[Behavior of the human organism in time zone flights. 2. Sequelae of desynchronization]. The responses of the human organism to time zone flights are reviewed. The physical and biological principles which are connected with dysrhythmic phenomena following shifts of environmental time cues are demonstrated. Quantity and quality of desynchronotic symptoms of psychophysiological functions are described and their significance for performance ability and health of the air traveller, in particular with respect to the possibility of pathogeneous effects, are discussed.


[Ambulatory treatment of arterial hypertension urinary the new combination "saluretic and beta-sympatholytic"]. 91 hypertensive patients were treated for 8 weeks with a combination of Trasicor80Esidrix. For the first 2 weeks the fixed daily dose was 2 X 80 mg Trasicor and 25 mg Esidrix. From the third week of treatment onwards, the Esidrix dosage was maintained; the dosage of Trasicor 80 was either maintained, increased, or later decreased, according to the results obtained. Following 8 weeks treatment, the systolic blood pressure decreased from 190,4 (+/- 23,0) to 156,0 (+/- 17,7) mmHg, the distolic pressure decreased from 105,9 (+/- 13,5) to 87,6 (+/- 8,3) mmHg. The most marked decrease was recorded after the first week of treatment. In 84% of the cases, the results of the treatment were classed as good and very good; in 11% of cases the treatment was moderately successful, and in 4 patients (5%) the treatment had no effect. The tolerability of Trasicor80Esidrix was remarkably good (in 94% of cases, according to the physician's assessment). 10 patients complained of side effects, and 4 of them discontinued the treatment. Tasicor80Esidrix has been shown to be a safe, simple and practical form of treatment arterial hypertension. It was possible to maintain the selected initial dose of 2 X 80 mg Trasicor and 25 mg Esidrix in 2/3 of the patients.


Evidence of an enzymatic 17alpha leads to 21 hydroxyl transfer in the biosynthesis of cortexolone from 17alpha-hydroperoxyprogesterone by adrenal cortex microsomes. The concept of a possible biogenetic intramolecular relationship between several pairs of hydroxylated positions of corticosteroids, in particular between positions 17alpha and 21, has been proposed by us some time ago. We now present evidence that to a certain extent such a relationship can indeed exist. 18O-labelled 17alpha-hydroperoxyprogesterone was incubated under ordinary oxygen atmosphere with the microsomal fractions of bovine adrenal cortex. Following extensive purifications by thin-layer chromatography, we have isolated a metabolite with mobility characteristics corresponding to those of authentic 17,21-dihydroxy-4-pregnene-3,20-dione (cortexolone). According to its mass spectrum, this metabolite has a molecular weight of 350, i.e. 4 atomic mass units higher than the molecular weight of non-labelled cortexolone. No conversion of 17alpha-hydroperoxyprogesterone to cortexolone was observed with a previously heat-inactivated preparation. The presence of 4 additional mass units in the cortexolone metabolite means that the latter has preserved two 18O-labels in the molecule, one at position 17alpha and the other one at position 21. This can only be explained by a rearrangement reaction of the hydroperoxide group in such a way that it is accompanied by a C-17alpha to C-21 hydroxyl transfer. In the inverse case, when non-labelled 17alpha-hydroperoxyprogesterone was incubated under 99% 18O2-atmosphere, non-labelled cortexolone of molecular weight 346 was also found.


Isolation and some observations of the properties of a bovine neurohypophysial milk-ejecting factor. A substance possessing milk-ejecting activity has been isolated from an acetone powder preparation of bovine posterior pituitary glands by Sephadex G-25 chromatography of the neurophysin-neurohypophysial hormone complex. While the material possessed an oxytocic activity of 2.8 IU/mg as measured on the isolated rat uterus, the milk-ejecting activity was more than three fold greater, 9.6 IU/mg. The peptide had an antidiuretic activity of 0.133 IU/mg and a pressor activity of 0.083 IU/mg. Neither the uterine-stimulating action nor the pressor activity was destroyed by incubating the peptide with 0.01 M sodium thioglycollate at 65 degrees C for 5 min. The oxytocic activity was antagonized neither by 1.4 X 10(-6) M atropine nor 3.3 X 10(-7) M phenoxybenzamine.


The effect of maternal hypothyroidism on maternal and fetal tissue glucose-1-14C incorporation in rats. These experiments were conducted to help elucidate the mechanism for the impaired fetal development occurring during maternal hypothyroidism. The disposition of glucose was measured using glucose-1-14C. Maternal hypothyroidism depressed glucose utilization in thematernal-fetal system. Maternal net glycogen synthesis from the labeled glucose was impaired. However, while the fetal glycogen storage system may be capable of at least relatively normal glycogen synthesis, abnormally low levels of glycogen were measured. If, as the data suggest, enzymatic deficiencies do not exist, the low liver glycogen might be a result of the inability of the maternal-placental system to provide adequate substrate to the fetus.


Studies on the minimal dosage of melatonin required to inhibit pineal antigonadotrophic activity in male golden hamsters. Blinding adult male golden hamsters was followed by atrophy, within 12 weeks, of the testes and accessory sex organs (seminal vesicles and coagulating glands) and by a significant reduction in pituitary prolactin levels. In experiment 1 blind hamsters received subcutaneously implanted melatonin-beeswax (1:24 mg) pellets at the following intervals: once per week, per 2, 3, 4, 6 weeks, or only one pellet during the 12-week experimental period. The melatonin-beeswax pellets, regardless of the frequency of implantation, overcame completely the inhibitory effects of blinding on reproduction and nearly completely the depressant action of light deprivation on pituitary prolactin levels. In the second study the melatonin-beeswax pellets were implanted subcutaneously into blind hamsters every 2 weeks. The pellets contained either 1 mg, 500, 100, 50, or 1 mug melatonin. With the exception of the 1-mug dosage, melatonin again negated almost totally the inhibitory action of darkness on the gonads and accessory organs and also, for the most part, prevented the drop in pituitary prolactin levels. Based on these studies, when melatonin is chronically administered subcutaneously in a beeswax pellet the minimal dosage of melatonin required to counteract the inhibitory effect of darkness on reproduction seems to be less than 3.6 mug/day. The effects of chronic melatonin treatment are similar to those of pinealectomy.


Validity of a screening test for typing serum cholinesterase variants among Greek populations. A screening method for determining the abnormal phenotypes of human serum cholinesterase variants in a population survey was investigated. The test appeared to be satisfactory in detecting abnormal genotypes, but not assigning them into correct classification. The results of the population survey indicate that there may be a higher frequency of ChU1ChD1 genotype than those reported earlier. Family studies of the suxamethonium-sensitive propositi in this population demonstrate that abnormal genes ChD1, ChF1 and ChS1 are segregating, according to the usual Mendelian type of inheritance pattern. The possibility of a relatively high frequency of these abnormal genotypes among the Greek population has been indicated.


Partial D 15 trisomy. A case and general review. A profoundly retarded girl with cyanotic congenital heart disease, recurrent myoclonic seizures, an external strabismus and not very unusual facial features was found to have a 47, XX chromosome complement. The extra chromosome is a small G-size chromosome with small projections extending from the ends of the long arms and no satellites observed on the short arms. By Geimsa-trypsin banding techniques this aberrant chromosome appears to be a partially deleted D 15 chromosome. A comparison of the clinical features is made with those described in the nine other reported specifically identifies cases of 'partial trisomy 15'. For clinical and chromosome morphology reasons, this was felt not to be trisomy in the G group nor an extra Y. We speculate that the long arm projections are satellites derived from a ring-type intrachromosomal translocation.


A, 1;6, translocation associated with congenital glaucoma and cleft lip and palate. A translocation of a part of the long arm of a chromosome No. 1 onto the long arm of a chromosome No. 6 was observed in a 2 1/2-year-old boy with mental retardation, harelip, cleft palate and congenital glaucoma. Different banding methods revealed that the translocation t(1;6)(q23;q27) apparently was balanced. The conncection between the patients' symptoms and the chromosomal rearrangement might be fortuitous or produced by the chromosome aberration.


Suxamethonium sensitivity and segregation of human serum cholinesterase variants at locus, Ch1, among twelve British families. Sera from 39 individuals with suxamethonium apnoea have been examined. The likelihood of the ChU1ChD1 heterozygotes developing suxamethonium apnoea has been calculated. The results indicate that 1 in 4,000 of normal homozygotes and 1 in 400 of ChU1ChD1 heterozygotes develop suxamethonium apnoea. The period of suxamethonium apnoea in these individuals has been found shorter than that usually seen in ChD1ChD1 homozygotes. An approximate estimate of the frequency of the ChF1 and ChS1 genes has also been calculated. Twelve British families of these suxamethonium apnoea propositi have been examined. The inheritance pattern in all these families was found to be of the Mendelian type. Three of these families have been found to be segregating for the rarer ChF1 gene and two for ChS1 gene, respectively. This present study provides an additional piece of support to the hypothesis that the ChF1 and ChS1 are alleles determining the synthesis of usual and atypical cholinesterase together with the likelihood of ChU1ChD1 heterozygotes having occasional suxamethonium apnoea. In addition, the present report indicates that there may be cholinesterase variants besides dibucaine and fluoride-resistant, 'silent' and C5.


A boy with 46, X, del, Y, due to a de nove mutation. A newborn male referred for genetic investigation because of a large sized head and dysplastic ears, but with apparently normal male genitalia was found to have a deletion of all of the brightly fluorescent part of the long are of chromosome Y and absence of the Y fluorescent body on buccal smear. His father and his two brothers had normal Y chromosomes. Social and family history as well as marker investigation make illegitimacy most unlikely and leaves an occurrence of a new chromosomal mutation in the father the most probably interpretation. Follow-up of the infant to the age of 9 months revealed a large baby with normal development.


Consanguinity and demography in some Chilean populations. Spatial and temporal changes in the rates and the patterns of consanguinity are studied in some (indigenous as well as admixed) populations of Chile. Relationship between the variation of infant mortality and late fetal death rates with the degree of inbreeding is also explored. The need of a temporal study of these demographic variables is also emphasized to elucidate the influence of marriage structure or determined reproductive patterns on the genetic and demographic aspects within these populations.


Linkage studies in Lenz microphthalmia.

Linkage studies in Lenz microphthalmia. Glucose-6-phosphate dehydrogenase (G6PD) phenotype studies were done on a black family with X-linked heredofamilial bilateral microphthalmia (HBM). Three crossovers and three non-crossovers were detected in three informative matings of four generations yielding a recombination value of 0.5. These findings do not provide evidence for linkage between the G6PD and HBM loci, suggesting either that the G6PD and HBM loci are far apart on the X chromosome or that HBM in this family is inherited as an autosomal dominant male sex-limited trait.


Haptoglobin type Hp-Jo and hypohaptoglobinaemia in a Danish family. Preliminary report. The occurrence of the rare Hp 2-Jo type in a Danish family is reported. By subtyping procedure the 2alphaJ polypeptide chain was demonstrated for the first time in an HP 2-Jo sample. Apparently independent of the transmission of the HpJo gene hypohaptoglobinaemia was found in a rather high proportion of the members of the kindred.


Parathenar palmar pattern: a dermatoglyphic sign of possible clinical significance. The frequency of a 'double proximal axial triradius' (DPAT), which results in a palmar parathenar pattern, has been reported to be increased in those with ventricular septal defect (BSD). We scored the presence of this pattern in 313 patients with congenital heart defects (including 86 with isolated VSD), 176 with cystic fibrosis (CF) or relatives of those with CF, and 333 with no known clinical disease who were unrelated to individuals with CF. The frequencies in these three groups were 1.6, 2.3, and 0.6%, respectively. None of those with isolated VSD defect had a DPAT. All five individuals in the heart defect group with a DPAT had pulmonic stenosis. Of the total of eleven individuals in our series with DPAT patterns, eight were affected only on the right hand. The frequency of DPAT in individuals with no known disease in this series was 4/406=1.0%, more than double the frequency in a control series, published previously by DAVID, 5/1,129=0.4%. If the 73 relatives of those with CF are excluded from our own 'control' group, the frequency of DPAT in this group is then 0.6%, closer to the results in DAVID's control series.


Incidence of congenital heart disease in Hungary. A survey was planned for establishing the point prevalence at birth of congenital heart disease and for assessing at the same time the efficacy of a screening for such anomalies. This model included: (1) exact determination of the population under survey; (2) approximately complete ascertainment of all persons in the population studied; (3) identical principles of cardiologic screening; (4) application of modern cardiologic diagnostic methods, and (5) a sample of over 2,000 persons. 23 cases of congenital heart diseases were found among 2,259 children born 1963 in a defined Hungarian territory. This means a point prevalence of 10.2+/-2.1% live births. (An additional 6 doubtful cases were not taken into account.) From the 12 cases diagnosed in vivo, 10 were detected by the screening.


Distributions, sex and age effects, and joint associations between phenotypes of 14 genetic systems in an Australian population sample. The distribution of phenotypes of 14 polymorphic systems in a Melbourne sample have been determined. Some differences between males and females were found and the proportion of males of each PGM phenotype was shown to depend on the gene dosage in a linear manner. Among the more prominent effects of age noted, the median age of P1+ females was higher than for P1--females and this finding was associated with a positive linear regression of the proportion of P1+ women on age. No age effect was observed in males in this system. Some evidence for associations between phenotypes were found in 9 pairs of polymorphic systems.


The psychosomatic approach in the practice of medicine. The psychosomatic approach requires of the practitioner broad knowledge and skills relevant to the psychosocial, metabolic and physical responses of patients. The approach, being holistic, becomes appropriate in many different clinical situations (and should not be restricted to a few so-called psychosomatic diseases). Wise physicians and perceptive laymen have recognized the validity of an holosomatic approach for over 4000 years. Although the prevalence and incidence of psychosomatic disturbances are difficult to estimate (and probably underestimated in many surveys), data support the statement that family physicians should employ a psychosomatic approach in at least 15 per cent of cases. The general internist will probably encounter primarily psychosomatic disturbances in about 30 per cent of his patients; for example, many common presenting symptoms such as fatigue and chest pain arise in a setting of psychological stress. Apart from a sound knowledge of the genesis and manifestations of metabolic and structural changes, the physician must be familiar with the causes and symptoms of psychological disorders. Skillful interviewing and histroy-taking provide the data necessary to analyze and unravel psychosomatic interplay. Psychotherapeutic interviews often enable both the patient and the physician to understand the clinical problem: this understanding appears to aid recovery.


The doctor-patient relationship in the practice of medicine. The patient-doctor relationship is based on the principles of interaction, collecting data and integration of both interaction and data into an overall diagnosis/therapy. Patients with functional abdominal disorders are seen as representatives of today's general patients and a study of their management in present medical practice is reported, as revealed through literature. The literature reveals an almost complete neglect of intractional and intergrational principles. This holds true even for psychosomatically oriented literature, which offers some crude clinical guidelines at best. Thus the primary physician gets little support from psychosomatic medicine in understanding the full meaning of the doctor-patient relationship. The clinical implications of the relationship are demonstrated through a short case history and implications for future training are described which are based on the primary physician's actual working experiences.


Bodily communication and psychotherapy: a psychosomatic approach. In the management of patients it is often important to combine physical and psychotherapeutic treatment methods according to the individual patient's needs. In analytically oriented psychotherapy more attention can usefully be paid to the patient's bodily attitudes and behavior than has been customary. A psychosomatic approach which can be applied to the psychotherapeutic process is described, and theoretical considerations are discussed.


Management of the persistent somatizer.

Management of the persistent somatizer. Patients who suffer and complain of symptoms for which no adequate organic pathology is found present serious management problems. Patients who display somatization phenomena are discussed with respect to incidence, psychopathology and predisposing factors-social and cultural, early life experiences, personality characteristics and individual psychodynamics. Although primary prevention of somatization is not yet feasible, early recognition and treatment are possible. The role of the psychiatrist includes:  formulation of diagnosis; assessment for therapy; planning of treatment; and, at times, becoming the primary therapist. The family physician has the best opportunity for early detection and prevention of chronicity of somatization phenomena. Pharmacotherapy, behavior modification and some newer approaches in the management of these persistent somatizers are discussed.


Teaching psychosomatic medicine to medical students, residents and postgraduate fellows. The teaching objectives of a psychosomatic program are discussed--in particular, to teach skills and methods of observation; to help students to acquire information about mind-body relationships in health and disease; to help future practitioners develop the capacity for clinical reasoning which includes psychological and social considerations; to effect modifications in attitudes and behavior towards patients and their families; and to present to students the model of a physician who has a major interest and considerable competence in two areas of medicine--the psychosocial and the physical-physiologic-biochemical. A description of the general organization of the liaison service is presented, and the specific aspect of teaching programs for medical students, medical interns and residents, psychiatric residents, and liaison fellows are outlined. Implications for the future of liaison teaching are mentioned.


Epilogue: meditations on psychosomatic medicine. Presented are some personal views on the state of psychosomatic medicine as a science. It is suggested that the field needs more precision in language including exorcism of value judgments from certain dimensions, less circularity in stress-strain reasoning, more complex hypotheses, more emphasis on social support as a central variable and more acceptance of divergent research styles.


Neonatal herpes simplex virus infection. These results suggest that Ara A, within its nontoxic dose range, may be efficacious in the treatment of neonatal HSV infection, provided the drug is given early in the course of the disease. Such studies as this have prompted a large scale multi-institutional study, which hopefully will provide a greater insight into the natural history of this usually devastating disease. The information gathered undoubtedly will lead to better and more specific antiviral agents as well as diagnostic techniques for earlier identification of neonatal HSV disease.


Chlamydial eye disease.

Chlamydial eye disease. In the United States, chlamydial (TRIC) agents cause a small but important segment of infectious ocular disease. Elsewhere in the world, trachoma still represents the single greatest cause of blindness. The description of these diseases in this chapter is a brief introduction to a subject about which volumes have been and will continue to be written. Barring unforeseen developments, these agents will continue to plague humankind beyond the end of the twentieth century.


Selective solubilization of hemagglutinin and neuraminidase from influenza viruses. A novel approach is described for the isolation of hemagglutinin and neuraminidase from influenza viruses. In contrast to published procedures, the two glycoproteins are selectively solubilized, leaving an intact viral subparticle which contains lipid, RNA and non-glycoproteins. The pronounced differences in size allow a simple separation of the solubilized proteins from the virus 'core'.


Polyacrylamide gel electrophoresis of the genomes of two orbiviruses: D'Aguilar and Eubenangee. The orbiviruses D'Aguilar and Eubenangee were shown to possess RNA genomes separable into ten segments by electrophoresis on polyacrylamide gels. Although there were minor differences in the molecular weights of corresponding genome segments of the two orbiviruses, the overall patterns were more similar to each other than to that of the reovirus type 3 genome.


Development of standard reference materials for air quality measurement. The National Bureau of Standards is engaged in a continuing program involving gaseous Standard Reference Materials for air pollution measurements. Preparation of such materials requires definition of the stability, homogeneity, and accuracy of the samples. This information is obtained by long term studies of the gas systems, by development of absolute methods of analysis, and by analysis of large numbers of samples prepared in bulk. The results of studies, extending over several years, of low concentration of carbon monoxide in nitrogen and nitric oxide in nitrogen are reported. Over one thousand samples of these materials have been analyzed and the stability with time and the within-batch homogeneity have been characterized. Accuracy is achieved by use of gravimetric standards and with dynamic dilution systems. Accuracy attainable by either method is described. The use of permeation tubes of sulfur dioxide and nitrogen dioxide is necessary in some situations because of the reactivity of the gases. Data covering the stability and accuracy of these devices has been collected over a period of several years.


Effect of population and health care environment on hospital utilization. A path analytic test of a causal model linking a county population's demographic and socioeconomic characteristics, the way its hospital services are delivered, and the health care resources available to it with its rate of short-term general hospital utilization is performed using data from 56 New York State counties. The results generally support the model and point to the central importance of an area's hospital bed supply for an understanding of its hospitalization rates. The path analysis reveals the patterns of direct and indirect effects of population and health care environment variables on hospitalization rates and supports the contention that health care environment characteristics intervene between population and hospitalization. The practical implications of these results for those in the health care field are discussed.


Costs of providing dental services for children in public and private practices. This study compares the costs of providing children's dental services in three practice settings: private practices, public mobile clinics, and public fixed clinics. Some 15,000 children were provided comprehensive dental care over a three-year period. Results indicate that costs per visit and per child were lowest in mobile clinics and highest in private practices. The differential was partially explained by differences in productivity but mostly by the fact that the price of services in public practices represented costs of production, whereas in private practices they represented market values.


Predicting demand for publicly dispatched ambulances in a metropolitan area. A model to predict demand for publicly dispatched emergency ambulance service in Los Angeles County is constructed using 1970 census tract and land usage data and 1973 population and utilization data. Although data were not available for many communities within the county, results indicate that the mode, which uses four socioeconomic variables, can accurately explain actual variations in ambulance demand for individual communities in Los Angeles County and for larger regions within the county.


Determinants of hospital utilization in the Netherlands. Hospital use in the Netherlands is examined in a cross-section analysis of 1969 and 1971 data for 120 service regions. Elasticities of admissions with respect to bed supply and supply of general practitioners are calculated, and the substitutability of first level care (by general practitioners) for hospital care is considered. Substitution effects found indicate that the Dutch government's plan to reduce the ratio of hospital beds to population is feasible.


Analysis and control of nurse staffing.

Analysis and control of nurse staffing. An information and reporting system based on a regression analysis of historical nurse staffing data is described. The system provides a concise monthly report from which administrators can evaluate the efficiency of scheduling procedures used by nurse supervisors to meet varying patient loads.


The inverse Gaussian distribution as a model of hospital stay. Properties of the inverse gaussian distribution are presented with comments on fitting the distribution to lentgh-of-stay data. A conceptual framework for the hospitalization process is described; it suggests that the inverse gaussian distribution has considerable potential as both a descriptive and prescriptive model of length of stay, especially in the setting of psychiatric hospitals.


The gingivitis iron test.

The gingivitis iron test. Mixed saliva stimulated by mastication was sampled under standardized conditions in 50 recruits before and after a 10-day period of intensified oral hygiene. The degree of gingivitis was assessed (1) with the Sulcus Bleeding Index and (2) with the spectrophotometric determination of blood iron in the saliva samples. Oral hygiene reduced (1) the SBI from 1.1+/-0.6 to 0.6+/-0.4 and (2) salivary iron from 0.6+/-0.5 to 0.3+/-0.4 mug, both differences being highly significant (PF is less than 0.001). SBI and iron data were significantly but not strongly correlated (r=51).


Plaque inhibition and staining by hibitane and vantocil. In a first 2-day experiment, inhibitions of plaque formation by 0.05% Hibitane and Vantocil rinses were similar. In a second 7-day test, the same 2 antimicrobials again showed similar degrees of plaque depression. The Vantocil group exhibited significantly more severe tooth surface staining than the Hibitane group.


The precision of three enamel biopsy methods for fluoride determination. 3 different enamel biopsy methods were tested on 2 maxillary permanent incisors on each of 90 schoolchildren. In methods A and B the round biopsy field was bordered by copalite varnish, while method C utilized a scotch tape border. The biopsy itself resulted from etching the enamel surface with 2N perchloric acid for 7 sec for method A, and 14 sec for methods B and C. Flouride was measured with the fluoride activity electrode. The doubled etching time caused only a 30 to 40% increase of enamel removal. Method C showed the best reproducibility.


Uptake and retention of fluoride by intact and etched enamel. 180 fluoride biopsies were taken in 30 children from the labial surfaces of the 6 maxillary anterior teeth. The average thickness of the biopsied surface enamel was 8.35+/-0.75 mjm. Intact, not treated enamel had an average F-content of the integral of 550 ppm. 7 days after one 3-min topical application of amine fluoride on intact enamel the average F-concentration was the integral of 1150 ppm. 7 days after one amine fluoride application on enamel previously etched with pyruvic or orthophosphoric acid, the average F-content was the integral of 3400 ppm and the integral of 2800 ppm respectively.


Fluoride retention after rinsing with sodium fluoride and amine fluoride. Fluoride retention from fluoride rinses (250 ppm F), calculated from F-concentrations and volumes of expectorates, and fluoride clearance, determined in whole saliva samples collected 1, 5 and 10 minutes after rinsing, were studied in 70 adults. F-retention from a 1:1 oleylamine-cetylaminefluoride rinsing solution (15 ml. 15 sec) was 410 mjg F, from a sodium fluoride rinse 343 mug F. 563 mug F were retained from a 30-sec amine fluoride rinse. Fluoride clearance was significantly slower after cetylaminefluoride rinses than after NaF rinses. Prerinsing with sodium lauryl sulfate or cetylaminechloride annihilated the F clearance superiority of cetylaminefluoride over NaF.


Facilitatory effect of lingual nerve stimulation on masseteric EMG Activities of the cat. Unitary EMG activities in masseter muscle of decerebrate cats were recorded during repetitive stimulation (20-50 Hz) of the lingual nerve and during vibration. These two kinds of stimuli facilitated EMG activities, whereby their effects could summate. Masseteric EMG response was also obtained during jaw opening phase of the cyclic jaw movement. With the jaw cyclically moved at a widely opened position: motor units discharged even at the jaw closing phase during simultaneous lingual nerve stimulation or during vibration. Based on the results obtained, two possible pathways for lingually induced excitation of masseteric EMG can be speculated on: an excitatory pathway from the lingual nerve to the masseteric motoneurons, secondly a direct pathway to masseteric motoneurons. As facilitation of masseteric EMG was obtained with the threshold lower than that of jaw opening reflex, separate afferent fibers concerning these two reflexes should also be considered.


[The management of intratemporal facial nerve lesions (author's transl)]. Intratemporal lesions of the facial nerve can be divided into operative lesions, lesions due to birth trauma, trauma through the external auditory canal, gunshot injuries, lesions caused by fractures of the temporal bone and lesions due to intratemporal tumours. Bell's palsy and palsies due to inflammation are not included in this paper. The lesions caused by fractures are discussed in more detail. In longitudinal fractures the nerve is always damaged at the site of the geniculate ganglion and not at the pyramidal segment, as accepted until now. Of the lesions caused by tumours the neurinomas are discussed. A very rare case of a combined extra- and intra-temporal neurinoma is presented. The progress of the electrophysiological findings (nerve excitability test, electroneurography) are most important for the indication for exploration of the nerve, especially in lesions due to fracture. Surgery is necessary only in cases of imminent or complete denervation and not in cases of neuropraxia. The methods of intratemporal facial nerve surgery are: 1. anastomoses (cross-over) between the facial nerve and other cranial nerves (IX, XI, XII), 2. decompression, 3. suture (including rerouting), and 4. nerve grafting. The oldest method of anastomosing with the hypoglossal nerve, is a useful technique if other techniques of nerve repair have failed. Since the introduction of transtemporal surgery of the internal canal decompression can bedone from the stylomastoid foramen to the porus acousticus. The end-to-end suture of a severed nerve gives good results. Nerve defects can be corrected by shortening the nerve bed. The following methods are used: 1: rerouting of the pyramidal segment (Bunnel, Martin), 2. rerouting at the stylomastoid foramen (Mundnich), 3. transtemporal rerouting of the first genu (Ganglion geniculi) with preservation of the labyrinth (one case is demonstrated). 4. transmastoidal-translabyrinthine rerouting in cases of a destroyed labyrinth. Nerve grafting is the method of choice with large defects. In the temporal bone special suture techniques are unnecessary. The approximation of the stumps must be free of tension.


[Ventricular cord hyperplasias of the larynx-pathogenesis and treatment (author's transl)]. Primary hyperplasia of the ventricular cords can produce voice disturbance or can be a secondary change caused by a primary voice disorder. Primary hyperplasia, besides inflammation or tumour, arises in aging people by a metaplastic process of the glandular epithelium of the ventricular cords. These lesions are called "grandular-cystic ventricular cord hyperplasias". Secondary hyperplasias are mainly of a fibrous nature. These "fibrous-vicarious hyperplasias" arise in hyperkinetic functional voice disorders, in pareses or in some cases of extensive chronic hyperplastic or oedematous laryngitis if the vocal cords can no more be used for normal phonation. Endolaryngeal microsurgical excision from the ventricular cords followed by voice exercises enables us to treat the "ventricular cord voice" successfully within a short time.


[Light and electron microscopy of rhinoscleroma (author's transl)]. The authors report the case of a 50 year old male patient whose rhinoscleroma, localized to the upper respiratory tract, was demonstrated by the isolation of Klebsiella bacilli and histologically. Electron microscopically the Mikulicz cells were characterized by fused vacuoles occupying the largest portion of the cytoplasm and displacing the damaged cytoplasmic organelles. Phagosomes and dense bodies reminiscent of Russel bodies also occurred in the Mikulicz cells, in the vacuoles of which formations representing Klebsiella rhinoscleromatis were demonstrated. A light halo was visible around some of these formations. It could not be, however, decided whether these halos represented the mucous sheath of the bacillus or an artifact only. In the plasmacells the authors observed the bag-like dilatation of the ergastoplasm and the presence of Russel bodies. Transitory forms were not seen among the plasma and Mikulicz cells. As a result of the treatment, Klebsiella disappeared from the nasal mucosa of the patient. The authors wish to follow by means of electron microscopy the changes of the granulation tissue and pathogens following antibiotic therapy.


[Orbital decompression (author's transl)]. Decompression of the orbit for retro-orbital haematoma is not usually performed. On the other hand it is recommended when ophthalmoscopy shows impending thrombosis secondary to a massive orbital haematoma. In such cases both surgical decompression of the orbit and splitting of the optic nerve sheath should be done. The indications for the surgical exposure of the optic canal are: 1. When there is progressive change on perimetry of the visual fields; 2. When there is radiological evidence of narrowing of the optic canal; 3. When there is papilloedema. Because of the magnitude of the surgery it is only rarely utilized, and a conservative management is most frequently better.


[Microcoagulation in the treatment of facial spasm (author's transl)]. A method for the surgical treatment of facial spasm is described. The nerve trunk is exposed in the mastoid region and the sheath is opened. With a bipolar electrode, microspots are burnt spirally round the nerve trunk and also at a few places in the centre of the nerve after pulling the bundles apart. Three cases are reported and assessed in comparison with the methods of Miehlke, Fisch, Rosemann and Schaupp. The more rapid and easier delineation of the nerve trunk in the event of a recurrence are considered an advantage compared with the extratemporal methods.


[The use of plastic prosteses in laryngeal and tracheal stenoses (author's transl)]. A "T" shaped polyvinylpyrrolidine tube was used to resolve cicatricial stenosis of the larynx and trachea. The plastic prosthesis is softened by heat. According to clinical experience the prosthesis insures unhindered respiration, free expectoration, speech and deglution. A number of successes are demonstrated.


Asthmatic children away from home: a comparative psychological study. The essential difference that emerged from a comparison of the fantasies of Rapidly Remitting and Nonremitting asthmatic children was found to be in the area of emotional awareness. The children who lost their asthmatic symptoms when separated from home were found to have some awareness of angry feelings toward parental figures whom they experienced as hostile and/or rejecting. They were also found to be aware, to some extent, of longings for a relationship with a person who would provide nurturing care or guidance. The Nonremitting children, on the other hand, were found to be lacking in any awareness of either angry feelings or longings for a nurturing relationship. A study of the test materials of both groups of children reveals that these feelings are present in all eight children. Yet they have been totally repressed in the Nonremitting children, while the Rapidly Remitting children have, apparently, not felt the need to resort to such massive repression. Thus a second area of difference, implied in the first, emerges when we compare these two groups of children in terms of defensive ego functioning. Abramson's emphasis on the central importance of the period in which the child's emotional conflict arose proved to be valid for this study. He predicted that those children whose asthma begins at or near the period of toilet training will be the same ones who will have most difficulty giving up their asthmatic symptoms. Although I have not been able to validate dates for onset of asthma, it's clear, I hope, from the foregoing discussion that the Nonremitting children all suffer from conflicts arising in the anal period of development. This is not so (or much less so) for the Rapidly Remitting children who, however, often have conflicts which are just as severe. Each of the Nonremitting children, on an unconscious level, is waging a battle with mother over who will get the upper hand: this is the central conflict. Though these children are outwardly compliant much of the time, they betray their inner antagonism by withholding and being stubborn. Each has developed very skillful, though passive, methods for resisting adult authority. What are the implications for these findings? Our Nonremitting children do not always show obvious signs of emotional disturbance. Because they tend to be well behaved, they are often considered healthy and well adjusted. While the Rapidly Remitting children are insisting (often dramatically) on getting help, the Nonremitters are busy "fitting in". Though they are slow to respond to individual psychotherapy and milieu treatment, they need it as much as do those who are more immediately reponsive to our therapeutic efforts.


Assembly of tobacco mosaic virus in vitro. Improved model for the elongation process by protein subunits. The in vitro assembly reaction of tobacco mosaic virus (TMV), especially the elongation process of partially reconstituted RNA (PRR) by protein subunits, was observed by electron microscopy. After addition of TMV-protein subunits, the PRR appeared as rods with a clump at one end, believed to be a complex between added protein subunits and the RNA tail protruding from PRR. The subunits entrapped on the RNA tails in the forms of clumps were progressively incorporated into the growing rods on incubation, ending with the formation of completely reconstituted rods. The clumps were also observed after addition of cucumber green mottle mosaic virus (CGMMV) protein subunits to rods partially reconstituted from RNA and TMV-protein. In this case, the protein subunits, seen as clumps, did not become incorporated to form elongating rods. An improved model for the elongation of TMV rods is proposed. The elongation process is composed of two steps, with the first step being the interaction of protein subunits with the RNA tail protruding from the growing rod. Any protein having a specific binding site for TMV-rna, not limited to TMV-protein, will react in the first step. The second step is the incorporation of the protein on the RNA tail into a rod-shaped structure, with consequent elongation of the growing rod. It appears that only protein homologous with that in the partially reconstituted rods can partake in the second step.


The disulfide bridges of ribonuclease U2 from Ustilago sphaerogena. RNase U2 was partially hydrolyzed with chymotrypsin [EC 3.4.21.1] and sulfuric acid, and in each case the resulting peptides were separated by gel filtration, ion exchange column chromatography and paper electrophoresis. From the results of amino acid analysis of cystine-containing peptides and their oxidized components, the three disulfide bridges were located between the cystine residues at positions 1 and 53, 9 and 112, and 54 and 95.


Dephosphorylation of tubulin-bound guanosine triphosphate during microtubule assembly. 1. Tubulin purified from porcine brain in the presence of GTP contained 0.16 mole of GDP and 0.73 mole of GTP per 60,000 g of protein. 2. Microtubules reconstituted from the purified tubulin contained 0.43 mole of GDP and 0.41 mole of GTP per 60,000 g of protein. Guanine nucleotide bound to the exchangeable site of tubulin was converted to GDP during microtubule assembly, while GTP at the non-exchangeable site remained intact. 3. Guanine nucleotide which had been bound to the exchangeable site of tubulin before microtubule assembly was also exchangeable during disassembly.


Exchange of phospholipids between mitochondria and rough or smooth microsomes in vitro. Phospholipids in mitochondria can be exchanged with those in two microsomal fractions from rough endoplasmic reticulum (rough microsomes) and smooth endoplasmic reticulum (smooth microsomes) in vitro in the presence of cell supernatant. The amounts of phospholipids transferred from each submicrosomal fraction to nitochondria were slightly different. The compositions of the phospholipids transferred to mitochondria from both microsomal fractions were the same, though these two fractions actually had different phospholipid compositions.


Studies on the circadian rhythm of phosphoenolpyruvate carboxykinase. III. Circadian rhythm in the kidney. Phosphoenolypyruvate carboxykinase [EC 4.1.1.21] activity in rat kidney shows a circadian rhythm with the highest activity between 0200 h and 0800 h and the lowest activity between 1400 h and 2000 h. The rhythm was observed in both sexes and throughout the year. Actinomycin D and cycloheximide effectively blocked the circadian increase in enzyme activity. These findings suggest that the circadian increase in phosphoenolypyruvate carboxykinase activity is due to net synthesis of enzyme protein through newly synthesized mRNA. In experiments with kidney cortex slices, gluconeogenesis from the radioactive precursor, [14C]malic acid, was considerably higher at 0200 h than at 1400 h, varying in parallel with the change in the enzyme activity.


Comparison of the activities for polypeptide synthesis of polysomes prepared with different detergents from normal and regenerating rat liver. When prepared in the presence of deoxycholate, the activities for polypeptide synthesis of polysomes from normal and regenerating rat liver were similar. However, when the polysomes were prepared in the presence of either Triton X-100 or Lubrol WX, the polysomes from regenerating liver had about three to four times more activity than those from normal liver. On the other hand, the activities for polyphenylalanine synthesis of ribosomes from regenerating rat liver were similar irrespective of whether these ribosomes were prepared in the presence of deoxycholate or Triton X-100.


DNA dependent RNA polymerase from Ehrlich ascites tumor cells. V. Characterization of a factor repressing RNA polymerase II as a ribonucleoprotein. Previously we reported the isolation of a factor, named the R-protein, which strongly repressed RNA polymerase II [EC 2.7.7.6] of Ehrlich ascites tumor cells. In the present work this factor was found to contain much RNA (ratio of RNA to protein, 2.3 to 1). The RNA was G:C rich, with a very high content of guanylic acid (about 38%). On equilibrium density gradient centrifugation in Cs2SO4 solution, the RNA became distributed above free RNA, but after digestion of the R-protein with pronase the RNA cosedimented with free RNA. Thus the R-protein is a complex of RNA and protein.


Amino acid sequence of the alpha chain of chicken AI hemoglobin. Adult chicken hemoglobin is heterogeneous and contains two major components, AI and AII (1). The amino acid sequence of the alpha chain of the AI component from white leghorns (small A type) was determined and compared with that of the alpha chain of the AII component, previously determined by the authors (2). An unexpectedly large difference of 65 amino acids was found between these two chains.


Acceleration of intradermal catabolism of guinea pig IgG1 and IgG2 antibodies by challenge with antigen. The intradermal catabolism of antibodies injected in guinea pigs to provoke skin reactions was studied using 125I-labeled guinea pig IgG1 and IgG2 anti-ovalbumin antibodies. Disappearance of both the IgG1 and IgG2 antibodies from injected sites was accelerated by intravenous injection of the antigen. The antigen-antibody complexes produced in vitro were also catabolized more rapidly than free antibodies, when estimated using 125I-labeled antibodies. On the other hand, the catabolism of normal IgG2 was not influenced by local anaphylactic reaction elicited by IgG1 antiovalbumin antibody coexisting at the sites. Therefore, the enhanced catabolism of antibodies on challenge was not caused by increased vascular permeability due to anaphylactic reactions, but by more rapid elimination of immune complexes formed at the sites. The Fc parts of IgG1 and IgG2 antibodies played an essential role in the enhancement of catabolism since the catabolism of the F(ab')2 fragments was not accelerated by complex formation with ovalbumin, but rather reduced.


Circadian rhythms in digestive enzymes in the small intestine of rats. I. Patterns of the rhythms in various regions of the small intestine. The activities of the digestive enzymes, maltase [EC 3.2.1.20], sucrase [EC 3.2.1.26], trehalase [EC 3.2.1.28], Leucine aminopeptidase [EC 3.4.11.1], and alkaline phosphatase [EC 3.1.3.1] were measured in various regions of the small intestine of rats. The activities of all these enzymes were much higher in the jejunum than in the ileum, and in the distal regions of the ileum no sucrase, trehalase or alkaline phosphatase activity was detected. In the jejunum, the activities of all the enzymes tested exhibited clear circadian variations with the highest activity at 0000-0400 h and the lowest at 1200 h when the rats were fed ad libitum. In the ileum, maltase and sucrase also exhibited circadian variations, but the amplitude of the rhythm was smaller than that in the jejenum. Trehalase and alkaline phosphatase did not show any circadian variation in the ileum. Leucine aminopeptidase showed a circadian variation in the ileum with the same amplitude as in the jejunum. The phase of the circadian variations shifted about half a day when the rats were fed in the daytime, but the amplitude of the rhythm did not change.


A simple rapid separation of C1-esterase using an immunoadsorbent column. An immunoadsorbent-antibody (egg albumin-Sepharose-antibody) column was found to be suitable for the rapid separation of C1-esterase from normal human serum. About 1.54 mg of C1-esterase, with a specific activity of 447 units/mg was obtained in voer 80% yield from the 20 ml of human serum.


Studies on the substrate specificity of Taka-amylase A. XII. Investigation of the active site of Taka-amylase A by examining the properties of p-phenylazobenzoyl Taka-amylase A. 1. When p-phenylazobenzoyl Taka-amylase A (PhAB-TAA) was incubated at pH 6.5 with hydroxylamine for 3 hr at 20degrees, some of the p-phenylazobenzoyl residues that had been introduced into Taka-amylase A (TAA) [1, 4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1, Aspergillus oryzae] were liberated as a hydroxamic acid, and the activity pattern of PhAB-TAA changed to that of intact TAA. This result suggested that the p-phenylazobenzoyl residues liberated had been bound to the tyrosyl residue located near the active site in the enzyme. 2. The transferase action of TAA or PhAB-TAA was studied using phenyl alpha-maltoside as a substrate and maltotritol as an acceptor. Unlike intact TAA, PhAB-TAA was not able to transfer the maltose residue to maltotritol, and this suggested that the p-phenylazobenzoyl residue was located near one of the aglycone-binding subsites, causing steric hindrance.


Viscosity and molecular weight of hyaluronic acids. The intrinsic viscosity ([eta]) and the molecular weight (M) by sedimentation equilibrium were determined for hyaluronic acids of low (M=104--7.2X10(4)) and high (M=3.1X10(5)--1.5X10(6)) molecular weights. Double logarithmic plot of [eta] against M gave different lines for the two groups. The relationship between [eta] and M was [eta]=3.0X10(6)XM1,20 for the former and [eta]=5.7X10(-4)XM0.46 for the latter group. The molecular weight at the point of intersection of the two lines was about 1.5X10(5). The rheological behavior of the hyaluronic acids below M=2.1X10(4), for which the value of reduced viscosity was independent of concentration, was different from that of the hyaluronic acids above M=5.1X10(4), for which the value of reduced viscosity increased with concentration.


Studies on the substrate-induced spectral change of cytochrome P-450 in liver microsomes. The spectral changes of cytochrome P-450 caused by the addition of small molecules to liver microsomes were investigated precisely and the following conclusions were reached. 1. The Type I spectral change was entirely due to the interaction of the cytochrome with a hydrocarbon residue in a ligand. To induce the modified Type II spectral change, the presence of a hydroxyl group in a ligand was required. Compounds which contain a basic amino group induced the Type II spectral change. 2. The Type I spectral change was caused by the interaction of a ligand with the 419-nm form of cytochrome P-450, with its concomitant conversion to the 394-nm form. Whereas, compounds inducing modified Type II spectral change interacted with the 394nm form of the cytochrome. In this case, however, the 394-nm form was not converted back to the 419-nm form but was converted to a new state showing an absorption peak at 416 nm. The Type II spectral change-inducing interaction of a ligand with the cytochrome could occur with all forms of the cytochrome. 3. Both Type II and modified Type II compounds bound to the cytochrome at heme iron, and converted the cytochrome into modified ferrihemochromes. On the other hand, the Type I interaction occurred ina protein moiety of the cytochrome, and probably caused a conformational change of the cytochrome accompanied either by weakening of the internal ligand interaction or by displacement of the ligand with another one having a weaker field at the heme iron. 4. Type I and each of other two types of binding of compounds with cytochrome P-450 could occur simultaneously.


Isolation of L-dynurenine 3-hydroxylase from the mitochondrial outer membrane of rat liver. Outer membrane preparations of rat liver mitochondria were isolated, after the mitochondria had been prepared by mild digitonin treatment under isotonic conditions. L-Kynurenine 3-hydroxylase [EC 1.14.13.9] was solubilized on a large scale from outer membrane by mixing with 1% digitonin or 1% Triton X-100, followed by fractionation into a minor fraction I and a major fraction II by DEAE-cellulose column chromatography. The distribution of total L-Dynurenine 3-hydroxylase was roughly 20 and 80% in fraction I and II, respectively. Fraction I consisted of crude enzyme loosely bound to anion exchanger. In the present investigation, fraction I was not used because of its low activity and rapid inactivation. In contrast, fraction II consisted of crude enzyme with high activity, excluded from DEAE-cellulose column chromatography in the presence of 1 M KC1. In addition, fraction II was purified by Sephadex G-200 gel filtration and DEAE-Sephadex A-50 column chromatography with linear gradient elution, adding 1 M KC1 and 1% Triton X-100 to 0.05 M Tris-acetate buffer, pH 8.1. After isoelectric focusing, the purified enzyme preparation was proved to be homogeneous, since the L-kynurenine 3-hydroxylase fraction gave a single band on disc gel electrophoresis. The molecular weight of this enzyme was estimated to be approximately 200,000 or more by SDS-polyacrylamide gel electrophoresis and from the elution pattern on Sephadex G-200 gel filtration. A 16-Fold increase of the enzyme activity was obtained compared with that of the mitochondrial outer membrane. The isoelectric point of the enzyme was determined to be pH 5.4 by Ampholine isoelectric focusing.


Inhibition of 6-methylsalicyclic acid synthesis by the antibiotic cerulenin. Cerulenin, a specific inhibitor of beta-ketoacyl-(acyl carrier protein) synthetase [EC 2.3.1.41] and 3-hydroxy-3-methylglutaryl-CoA synthetase [EC 4.1.3.5], was studied to determine whether it inhibits 6-methylsalicylic acid synthesis, in which so-called "polyketide" formation, a condensation step similar to that in fatty acid synthesis, is involved. In fact, 100 mug/ml (4.5 X 10(-4) M) of cerulenin inhibited 60% of 6-methylsalicylic acid synthetase activity and 68% of fatty acid synthetase activity of Penicillium urticae.


Amino acid composition and physiochemical characterization of chondroitinase from Arthrobacter aurescens. The amino acid and carbohydrate compositions of chondroitinase AC [EC 4.2.2.5] from Arthrobacter aurescens were determined, and its physicochemical properties were examined. 1. The enzyme has been shown to be a glycoprotein containing mannose, glucose, glucosamine, and glucuronic acid (3:5:4:2). 2. Its molecular wieght was estimated to be 76,000 by gel filtration on Sephadex G-200, 75,000-80,000 by SDS disc electrophoresis, and 75,800 by sedimentation veolcity. No subunits were detected in the molecule. 3. The physicochemical properties determined include: sedimentation coefficient (s(o)20, w=5.14 S), diffusion constant (D(o)=6.09 X 10(-7) cm2/sec), frictional ratio (f:f(o)=1.19) and apparent partial specific volume (v=0.73 ml/g). 4. The optical rotatory dispersion and circular dichroism of the enzyme were investigated. The contents of alpha-helix and beta-structure of the enzyme were estimated to be 16 and 25%, respectively.


Inhibition of alpha-glucan phosphorylase by alpha-D-glucopyranosyl fluoride. Alpha-D-Glucopyranosyl fluoride was found to inhibit strongly the action of alpha-glucan phosphorylase b[EC 2.4.1.1] from rabbit muscle, and that of the enzyme from potato tubers rather weakly. The inhibition is highly specific, being competitive with respect to glucose 1-phosphate and noncompetitive with respect to polysaccharide, during polysaccharide synthesis. In the reverse process, it is competitive with respect to Pi. These results have been explained by assuming that the inhibitor binds to the glucose 1-phosphate site of the enzyme, occupying both subsites which normally bind the glucosyl and phosphate moities of the substrate, but does not directly interact with the polysaccharide site. Based on this assumption, the dissociation constants of the enzyme-inhibitor and enzyme-polysaccharide-inhibitor complexes have been evaluated (0.43 and 0.20 mM for the muscle enzyme, respectively; 24 and 23 mM for the potato enzyme, respectively). Glucosyl fluoride also acts as a noncompetitive inhibitor with respect to AMP. A high concentration of AMP causes an inhibitory effect on the action of the muscle enzyme, the effect being menifested in the presence of glucosyl fluoride.


Enzymic hydrolysis of di-D-fructofuranose 1, 2'; 2, 3' dianhydride with Arthrobacter ureafaciens. Enzymic hydrolysis of di-D-fructofuranose 1, 2'; 2, 3' dianhydride with the bacteria Arthrobacter ureafaciens was studied to elucidate its mechanism. Hydrolysis of the difructose dianhydride to D-fructose, which did not occur with yeast invertase [EC 3.2.1.26], was found to occur on incubation with an enzyme preparation from an autolysate of the above bacteria. However, incubation with enzyme which had been treated at 60 degrees for 30 min yielded an intermediate hydrolysis product. The product isolated was found to be inulobiose and to be hydrolyzed to D-fructose by the original enzyme, as well as by yeast invertase. It was thus shown that the hydrolysis of the difructose dianhydride to D-fructose with the crude enzyme took place not in a single step but in two separate steps at 2, 3' and 1, 2' linkages. It was not determined whether the entire process is mediated by one and the same beta-fructofuranosidase or by different enzymes.


Blood group A activities of glycoprotein and glycolipid from human erythrocyte membranes. It is known that ABO blood group substances in human erythrocyte membranes are sphingoglycolipids, but recently several authors have reported that the glycoproteins of the erythrocyte membranes also have ABO blood group activities in addition to MN blood group activities and virus hemagglutination inhibitor activity. We solubilized blood group A erythrocyte membranes with lithium diiodosalicylate and separated the glycoprotein fraction by phenol extraction and ethanol precipitation. This fraction was apparently not contaminated with glycolipid, but it showed weak blood group A activity. The activity of the glycoprotein of the erythrocyte membranes was one-sixth of that of the lgycolipid fraction from the same amount of membranes. The glycoprotein components were purified by Sephadex G-200 gel filtration in SDS. The main component isolated, PAS 1, still showed blood A activity.


A polysome-membrane binding system from rat liver. I. Basic characterization of the binding system. A simple reaction system was developed to examine the binding of polysomes to membranes of the endoplasmic reticulum and to investigate the fate of ribosomes and nascent chains during protein synthesis in vitro. The system conssited of Sephadex G-25 treated post-mitochondrial fraction prepared from rat liver (Sephadex-PM) as a source of membranes, and radioactive free polysomes prepared from another rat liver. The following results were obtained. 1. Nascent chains on free polysomes labeled in vivo were transferred to membranes in vitro. The process required protein synthesis. 2. This reaction occurred in two steps: a) Binding of the free polysomes to membranes in the absence of protein synthesis. b) Release of ribosomes, leaving nascent chains on the membranes, requiring protein syntehsis. 3. A portion of the ribosomes found on membranes in vivi (membrane-bound ribosomes) was also released from the membranes during incubation in vitro, leaving their nascent chains on the membranes. The significance of the transfer of nascent chains from free polysomes to membranes in vitro is discussed in the light of known polysome-membrane interaction in vivo.


On the activation of bovine plasma factor XIII. Amino acid sequence of the peptide released by thrombin and the terminal residues of the subunit polypeptides. A blood coagulation factor, Factor XIII, was highly purified from bovine fresh plasma by a method similar to those used for human plasma Factor XIII. The isolated Factor XIII consisted of two subunit polypeptides, a and b chains, with molecular weights of 79,000 +/- 2,000 and 75,000 +/- 2,000, respectively. In the conversion of Factor XIII to the active enzyme, Factor XIIIa, by bovine thrombin [EC 3.4.21.5], a peptide was liberated. This peptide, designated tentatively as "activation peptide," was isolated by gel-filtration on a Sephadex G-75 column. It contained a total of 37 amino acid residues with a masked N-terminal residue and C-terminal arginine. The whole amino acid sequence of "Activation peptide" was established by the dansyl-Edman method and standard enzymatic techniques, and the masked N-terminal residue was identified as N-acetylserine by using a rat liver acylamino acid-releasing enzyme. This enzyme specifically cleaved the N-acetylserylglutamyl peptide bond serine and the remaining peptide, which was now reactive to 1-dimethylamino-naphthalene-5-sulfonyl chloride. A comparison of the sequences of human and bovine "Activation peptide" revealed five amino acids replacements, Ser-3 to Thr; Gly-5 to Arg; Ile-14 to Val; Thr-18 to Asn, and Pro-26 to Leu. Another difference was the deletion of Leu-34 in the human peptide. Adsorption chromatography on a hydroxylapatite column in the presence of 0.1% sodium dodecyl sulfate was developed as a preparative procedure for the resolution of the two subunit polypeptides, a or a' chain and b chain, constituting the protein molecule of Factor XIII or Factor XIIIa. End group analyses on the isolated pure chains revealed that the structural change of Factor XIII during activation with thrombin occurs only in the N-terminal portion of the a chain, not in the N-terminal end of the b chain or in the C-terminal ends of the a and b chains. From these results, it was concluded that the activation of bovine plasma Factor XIII by thrombin must be accompanied by a limited proteolysis of the arginyl-glycyl bond located in the N-terminal region of the a chain, liberating the "Activation peptide." The possibility of activating Factor XII with other porteinases was examined using Factor Xa [EC 3.4.21.6], Factor XIIa, kallikreins [EC 3.4.21.8], urokinase [EC 3.4.99.26], trypsin [EC 3.4.21.4], ficin [EC 3.4.22.3], papain [EC 3.4.22.2], and bromelain [EC 3.4.22.4]. Among these enzymes, only bromelain and trypsin showed clear activating effects.


Retarding effect of dodecyl alcohol on polyacrylamide gel electrophoresis of SDS micelles and SDS-protein polypeptide complexes. Micelles of sodium dodecyl sulfate (SDS) are significantly retarded by the addition of a small amount of dodecyl alcohol to a sample solution in SDS-polyacrylamide gel electrophoresis. The phenomenon can be ascribed to the decrease in charge density due to the incorporation of dodecyl alcohol into SDS micelles. The effect is extended to SDS-protein polypeptide complexes when the amount of SDS micelles is insufficient to accomodate the dodecyl alcohol. A similar effect is likely to occur when SDS-polyacrylamide gel electrophoresis is applied to a sample containing lipophilic materials.


Tryptic peptides from the beta polypeptide chain of AII component of chicken hemoglobin. The aminoethylated beta polypeptide chain in AII component from the hemoglobin of adult chicken was digested with trypsin [EC 3.4.21.4] and the resulting peptides were separated and purified by ion exchange chromatography, paper chromatography, and gel filtration. Eighteen tryptic peptides, which were nonoverlapping, accounted for all of the amino acid residues in the beta polypeptide chain. The amino acid sequences of the tryptic peptides were established by a combination of enzymatic digestion and subtractive Edman degradation.


Degradation of rod outer segment proteins by cathepsin D. The degradation of proteins of the rod outer segment (ROS) fraction by partially purified cathepsin D [EC 3.4.23.5] from the retinal pigment epithelium was studied. The ROS fraction, prepared from bovine eyes by sucrose density gradient centrifugation, had little cathepsin D activity. Partially purified cathepsin D, obtained from crude extract of bovine retinal pigment epithelium using bovine serum albumin as a substrate, hydrolyzed the porteine of the ROS fraction. The rate of degradation of ROS proteins was proportional to both the enzyme concentration and the incubation time. With ROS proteins as substrate, the optimal pH of cathepsin D was about 3.5. The degradation of ROS proteins was inhibited by pepstatin.


Modification of the gas-liquid chromatography procedure and evaluation of a new column packing material for the identification of anaerobic bacteria. Gas-liquid chromatography has become a useful aid for the identification of anaerobic bacteria in the clinical laboratory. When many extracted samples are to be analyzed, time is of prime importance. By altering the operating conditions of the chromatograph, we have decreased the total elution time of the volatile fatty acids examined to approximately 12 min. There is, however, a decrease in the ability to resolve propionic and isobutyric acids. A new column packing material, SP-1220 (Supelco), was found to give excellent separation of propionic and isobutyric acids as well as demonstrating the presence of formic acid which was not seen with the previously used Resoflex. Extracts of clinical isolates of anaerobic organisms were processed using the altered conditions and new column packing material with excellent resolution of all acids. The use of SP-1220 in the clinical laboratory will facilitate the identification of anaerobic bacteria.


Uracil and pyruvate requirements of anaerobic growth of staphylococci. Sixty-six strains of staphylococci recently isolated from human skin and identified as members of the three recognized species of staphylococci, and 21 stock strains representing most of the Baird-Parker subgroups of staphylococci and micrococci were studied. All 16 skin strains of Staphylococcus aureus demonstrated weak to moderate anaerobic growth in the basal medium, growth stimulation by either uracil or pyruvate, and best growth when both were added. The 20 skin strains of S. epidermidis responded similarly to S. aureus but with a tendency toward heavier growth. The 28 isolates of S. saprophyticus generally gave little or no growth in the basal medium, no increase due to pyruvate alone, a weak response to uracil alone, and, with three exceptions, gave moderate to good growth when both supplements were present. The Baird-Parker strains from subgroups S-II and S-III responded like S. epidermidis; those from subgroups S-V, S-VI, M-1, M-2, M-3, and M-6 generally responded like S. saprophyticus; and those from subgroups M-4 and M-5 failed to grow anaerobically in all media.


A scheme for the identification of thermophilic actinomycetes associated with hypersensitivity pneumonitis. A scheme has been developed for the identification of thermophilic actinomycetes associated with hypersensitivity pneumonitis. Eighty strains, 10 Micropolyspora faeni, 6 Saccharomonospora viridis, 52 Thermoactinomyces candidus, 7 T. vulgaris, 4 T. sacchari, and 1 T. dichotomica, either isolated from patients' environment or received as authentic strains, were studied. In addition to the cultural and microscopic morphology in various media, each strain was subjected to an array of biochemical tests. These tests included decomposition of tyrosine, xanthine, hypoxanthine, gelatin, casein, esculin, and arbutin. Using a rapid thin-layer chromatography method, the isomer of diaminopimelic acid and sugar in the whole cell hydrolysate were studied. The thermophilic actinomycetes can be identified in a reasonable period of time using a combination of all these tests.


Wound infection by Prototheca wickerhamii, a saprophytic alga pathogenic for man. Biopsy of a wound infection of the palmar fascia in a young diabetic woman revealed characteristic periodic acid-Schiff-positive Prototheca species cells with a rosette configuration and internal septation. Prototheca wickerhamii was cultured repeatedly from the wound drainage and the biopsy tissue. Several diagnostic features distinguishing Prototheca species, saprophytic algae, from yeasts are: the formation of endospores by mitosis; greater variation in cell size (2 to 15 mum); the presence of cytoplasmic granules, particularly in old cultures; and the absence of budding forms and pseudomycelia. The organism was resistant to 5-fluorocytosine and the minimal inhibitory concentration of amphotericin B was 12.5 mug/ml. With the exception of the tetracycline group, all other 16 antibacterial agents tested appeared completely ineffective in vitro. A synergism between amphotericin B and tetracycline was clearly demonstrated by the use of the checkerboard method. Infection by Prototheca species may be more common than presently realized due to the common expedient of identifying yeast-like isolates as "yeast--not Candida albicans."


A space-saving media table.

A space-saving media table. A space-saving media table designed to facilitate pouring large quantities of plated media in a small area is described.


Evaluation of Aspergillus differential medium. The new Aspergillus differential medium distinguishes effectively between members of the Aspergillus flavus group and other Aspergillus species of interest in medical mycology.


Comparison of the reversed passive hemagglutination with radioimmunoassay methods for hepatitis B antigen. Radioimmunoassay for the detection of hepatitis B antigen has been accepted in many diagnostic laboratories now. The question of nonspecific positives has always been a matter of controversy. Two improved radioimmunoassay tests, namely Ausria II-125 by Abbott Laboratories and a radioimmunoassay method by Connaught Laboratories Limited (Hebria), were compared with the original Ausria 125I. Included in the comparison was the reversed passive hemagglutination test (Auscell, Abbott). Five hundred sera of clinical patients were tested. Fifty-five or 11% were found to have hepatitis B antigen. Three tests, Ausria 125I, Ausria II-125, and Hebria showed the same number of positive sera, whereas Auscell missed one. However, Ausria 125I indicated two additional false positives. Dilution experiments, however, indicated that Ausria II-125 and Hebria were the most sensitive tests, with the reversed passive hemaglutination showing the least sensitivity. Therefore, the new Ausria II-125 and the Hebria radioimmunoassay tests are preferable in view of their sensitivity and specificity.


Lichen striatus: a model for the histologic spectrum of lichenoid reactions. Three phases of lichenoid reactions are defined: 1) the primary phase, 2) the established phase; and 3) the senescent phase. Lichen striatus is characterized by a primary pattern that may be apparent in the epidermis, the hair follicles, and rarely the sweat glands and ducts. Focal areas of established lichenoid reaction, that are indistinguishable from lichen planus, are common. They usually are confined to the tips of elongated rete ridges. Established lichenoid patterns are occasionally present in hair follicles and are indistinguishable from those seen in lichen planopilaris. Eccrine hidradenitis, a feature of lichen striatus, is rarely seen in lichen planus. Lichen planus may be an adaptive epidermal response to a clone of aggressive lymphocytes and, as such, may be a manifestation of auto-immunity. In lichen striatus, senescent lichenoid patterns resemble those seen in lichen nitidus.


Recalcitrant pustular eruptions of the extremities. Forty-seven biopsies of pustules from patients with recalcitrant pustular eruptions of the palms and soles were examined blind and the results were subsequently compared among three clinical sub-groups: acrodermatitis continua, pustular psoriasis and pustulosis palmaris et plantaris. With the exception of three cases, it was not possible to make a diagnosis of psoriasis on the basis of histology alone. Histological findings were otherwise uniform and typical: intra-epidermal, unilocular, well-delineated pustules. No significant differences were found among the three subgroups. In view of the uniform histology, the unknown etiology and the uncertain clinical classification, the authors prefer the clearly descriptive term pustulosis palmaris et plantaris.


Lichen sclerosus et atrophicus: an electron microscopic study. The ultrastructural changes in seven cases of lichen sclerosus et atrophicus are described. An interesting epidermal alteration was the presence of collagen fibrils in the intercellular space; furthermore, the basal cells were altered by condensation and homogenization of the tonofibrils. The basement membrane was not uniform and often multilayered. The anchoring fibrils were numerous. In the cutis intertwining strands of fine filaments, bundles of immature collagen and normal collagen could be found. In lichen sclerosus et atrophicus the dermo-epidermal interrelationship is disturbed.


Modulation of dermal cell activity during hair growth in the rat. Interaction between connective tissue cells and hair growth in the rat has been studied by radioautography after in vivo and in vitro pulse labelling with thymidine, uridine, histidine, leucine and proline. The connective tissue, which surrounds and integrates the hair bulbs as a unit, contains cells of various types which have a cyclic metabolic activity. This cyclic activity is coordinated with the hair growth cycle. The number of nuclei which actively synthesize DNA in the dermal cells, mainly those of endothelial and migratory cells, significantly increases during the short and transient anagen 4 substage. RNA and protein synthesizing activities are also present in all cell types and seem modulated by the hair cycle although to a lesser degree. This data provides an important basis for the interpretation of similar studies in alopecia areata.


An electron microscope study of Darier's disease. An electron microscope investigation was performed on cutaneous biopsies from four patients with Darier's disease. Suprabasal lacunae with acantholytic cells a prominent feature. Basal cells and acantholytic cells showed an increase in tonofilaments. Corps ronds appeared as vacuolated cells.


The effect of alpha and beta adrenergic receptor stimulation on the adenylate cyclase activity of human adipocytes. The effects of the mixed agonist epinephrine and the beta agonist isoproterenol, each alone and in combination with the alpha adrenergic blocker phentolamine and the beta blocker propranolol on the adenylate cyclase activity of human adipocyte membrane fragments were determined in a calcium free buffer. Neither phentolamine (10 muM) nor propranolol (32 muM) affected basal adenylate cyclase activity. Epinephrine (10 muM) stimulated adenylate cyclase activity and this effect was slightly enhanced by phentolamine. The combination of epinephrine plus propranolol depressed adenylate cyclase below the basal level. Isoproterenol (10 muM) markedly stimulated adenylate cyclase; the addition of phentolamine caused an equivocal further increase while the addition of propranolol depressed adenylate cyclase activity to, but not below, the basal level. These findings are consistent with the hypothesis that human adipocytes have both alpha and beta adrenergic receptors and that these receptors are associated with the cell membrane adenylate cyclase system.


The effect of divalent cations on bovine spermatozoal adenylate cyclase activity. The effect of divalent cations on bovine sperm adenylate cyclase activity was studied. Mn2+, Co2+, Cd2+, Zn2+, Mg2+ and Ca2+ were found to satisfy the divalent cation requirement for catalysis of the bovine sperm adenylate cyclase. These divalent cations in excess of the amount necessary for the formation of the metal-ATP substrate complex were found to stimulate the enzyme activity to various degrees. The magnitude of stimulation at saturating concentrations of the divalent cations was strikingly greater with M2+ than with either Ca2+, Mg2+, Zn2+, Cd2+ or Co2+. The apparent Km was lowest for Zm2+ (0.1 - 0.2 mM) than for any of the other divalent cations tested (1.2 - 2.3 mM). The enzyme stimulation by Mn2+ was decreased by the simultaneous addition of Co2+, Cd2+, Ni2+ and particularly Zn2+ and Cu2+. The antagonism between Mn2+ and Cu2+ or Zn2+ appeared to have both competitive and non-competitive features. The inhibitory effect of Cu2+ on Mn2+-stimulated adenylate cyclase activity was prevented by 2,3-dimercaptopropanol, but not by dithiothreitol, L-ergothioneine, EDTA, EGTA or D-penicillamine. Ca2+ at concentrations of 1-5 mM was found to act synergistically with Mg2+, Zn2+, Co2+ and Mn2+ in stimulating sperm adenylate cyclase activity. The Ca2+ augmentation of the stimulatory effect of Zn2+, Co2+, Mg2+ and Mn2+ appeared to be specific.


Perceptual processing in dichotic listening. Subjects heard two lists of 4 items each presented simultaneously to the two ears at a rate of four pairs of items per sec. A recall cue presented immediately after the test list signalled report of 4 of the 8 items. In recall by spatial location, the cue indicated whether the items on the right ear on left ear should be recalled. In recall by category name, the cue indicated the superset category (e.g., letters or words) of the items to be recalled. Recall by spatial location was not significantly different than recall by category name. This results argues against the idea of a preperceptual auditory storage that holds information along spatial channels for 1 or 2 sec. The final experiment showed that recall by spatial location is significantly better than recall by category name when the report cue is given before, not after, the list presentation. These results show that spatial location can be used to enhance semantic processing and/or memory of 1 of 2 simultaneous items, but only if the relevant location is known at the time of the item presentation.


Order information in dichotic memory.

Order information in dichotic memory. Three experiments were performed using a recognition probe procedure to test the subject's recognition of the order of two items from a dichotically presented list. In all three experiments subjects were unable to recognize simultaneous items as having been simultaneous unless the critical pair was the last pair in the list. In contrast, they were able to identify the order of items not originally presented simultaneously at better than a chance level. Performance did not differ as a function of whether the two critical items were presented to the same or different ears. The data were interpreted as indicating that subjects divide attention between competing inputs in the dichotic memory task and that the eary-by-ear order of report is a result of the format in which the items are stored.


Electron microscopic study on the lens of riboflavin-deficient albino rat. Although cataract was recognized as a typical symptom of ariboflavinosis soon after the discovery of riboflavin, some reports appeared thereafter which denied its occurrence. In the present study electron microscopic examination of the lens of rat fed on synthetic riboflavin-deficient diet revealed swelling degeneration of mitochondria and vacuolation of cytoplasm of the epithelial cells of the lens. These changes are similar to those observed in the initial period of cataract caused by other agents.


The influence of thiamine deficiency on porphyrin synthesis and porphyrin proteins. 1. Studies carried out in cell-free rat-liver extracts showed an inhibitory effect of thiamine deficiency on porphyrin synthesis. 2. Extracts of normal and thiamine-deficient rat livers were incubated with the cofactors and substrates of the thiamine pyrophosphate-dependent enzyme, 2-oxoglutarate glyoxylate carboligase. There was a marked inhibition of porphyrin synthesis when the substances were added either individually or together. 3. Thiamine deficiency resulted in a decrease of haemoglobin concentration and catalase activity whereas a rise in tryptophanpyrrolase activity and cytochrome b5 and P450 concentration was observed.


Several properties of the partially purified proteinase inhibitor in eggplant exocarp. A proteinase inhibitor was isolated and partially purified from the exocarp of eggplant, Solanum melongena L., by means of acetate buffer extraction, heat treatment, salting-out and column chromatography on DEAE-cellulose. This preparation showed inhibitory activities on various proteinases; trypsin [EC 3.4.4.4] and Pronase were strongly inhibited while alpha-chymotrypsin [EC 3.4.4.5] and Nagarse were weakly inhibited. The inhibitor was a protein substance, and, therefore, it was gradually inactivated by the long-time incubation with Pronase. The inhibition mode was non-competitive on trypsin and competitive on Pronase on the basis of Lineweaver-Burk plots. The investigations on the inhibition behavior in the co-existence of two kinds of proteinases suggested that the inhibitor was not of multi-headed type.


Effects of dietary protein level on the energy metabolism of rats during exercise. The experiments were designed to study the effects of exercise of various intensities in albino rats fed diets containing 8 per cent or 20 per cent casein. Male rats about 7 weeks old were divided into exercise groups and control (non-exercise) groups. The exercise groups were forced to run 57 km or 76 km in total during a 28-day period. The oxygen uptake of rats was measured in order to study the influence of exercise on energy metabolism of rats and the effects of training. Body weight and food intake were also measured. 1. In all exercise groups the total amount of food intake and body weight gain during the exercise period were smaller than those of the control groups, regardless of the protein levels of the diets. but while the rats were kept at rest after the exercise period, the food intake and body weight of these groups increased and approached those of the control groups. 2. No difference in resting metabolism was observed both in the 8 per cent and 20 per cent casein groups. At lower speeds up to 1.5 km/hr the 8 per cent casein group indicated lower oxygen requirement during the exercise but at speeds higher than 2.0 km/hr the oxygen requirement was definitely higher than that of the 20 per cent casein group. The estimated optimum speed for rats weighing 300 g on the average is somewhere between 1.5 and 2.0 km/hr is calculated on the basis of oxygen requirement for running 100 m. 3. The obvious effects of training on oxygen uptake were seen in the 20 per cent casein group after four weeks' training, although no effect was found in the 8 per cent casein group.


The subependymal plate and the genesis of gliomas. A case of experimentally induced glioma in the rat is described, whose origin is clearly linked with hyperplasia of the subependymal plate.


An analysis of the effect of ischaemia on testicular ultrastructure. Permanent ischaemia of the rat testis results in the formation of fusion multinucleate cells and macrophages from cells of the innermost cellular layer, in the ischaemic testis. The macrophages are replaced by fibroblasts after 25 days of ischaemia. Similar changes are visible in the contralateral testis which also demonstrates the evolution of multinucleate spermatids by karyokinesis without cytokinesis. Binucleate spermatids and double-headed spermatozoa have only one acrosome, and spermatozoa with two middle pieces are enveloped by a single cytoplasm. The sequential ultrastructural changes following ischaemia are described and it is suggested that cells of the inner cellular layer can alter their characteristics according to demand.


The fine structure of the reticulum cells in lymph-nodes from cyclophosphamide-treated thymectomised mice. In mice depleted of lymphocytes by thymectomy and cyclophosphamide treatment the popliteal lymph nodes  showed macrophages, fibroblasts, endothelial cells and a heterogeneous group of cells here described as reticulum cells. Some of these both within and outside the germinal centres had fine long processes, i.e., were dendritic, and some had deep cytoplasmic invagination. Interdigitating cells were not a feature of the nodes and there was little evidence of migration of cells through post-capillary venules.


Fibrosis of the conducting tissue in infancy. The conducting tissue of the heart was studied in  a group of 38 cases of the sudden infant death syndrome and in a control group of 28 children dying of known causes. A variable amount of fibrous tissue was found in the atrioventricular complex in almost every case. There was a statistically significant increase in fibrous tissue with age in both groups and there was also significantly more fibrosis in the sudden infant death group compared with the controls. Possible explanations for these findings are discussed and it is suggested that the results might be of aetiological significance in the sudden infant death syndrome.


The ultrastructure of organising experimental mural thrombi in the pig aorta. This ultrastructural study of experimentally produced mural thrombi in the pig aorta has shown that at 3 days there are, amongst the other constituents, two distinct cell populations, macrophages and undifferentiated mesenchymal cells. Over the subsequent 2 wk the mesenchymal cells, which appear to be homogeneous initially throughout the thrombus, gradually differentiate on the surface to form an endothelial lining, in the superficial layers to form myointimal cells and ultimately smooth muscle and, in the deeper layers, to form new capillaries which join with endothelial lined clefts from the surface. The morphological evidence supports the postulate that the early stage of organisation of a mural thrombus in effected by pluripotent precursor cells from the circulating blood. The new endothelium, myointimal cells, capillaries, intimal smooth muscle and the extracellular tissues characteristic of an organising thrombus all appear to derive from this common source. In this study we saw no evidence to suggest that, at this stage, there was a contribution from the cells native to the vessel wall which, however, may be involved in the later stages of organisation.


Chronic gastritis--a simple classification. Gastric mucosal biopsy specimens from 241 patients with examined. Chronic inflammatory cellular infiltration of the gastric mucosa was found in 181 patients and this graded as mild, moderate or severe. The presence or absence of atrophy or intestinal metaplasia was noted. True superficial gastritis was observed in only three cases.


Primary adenocarcinoma of the female urethra. Three cases of primary adenocarcinoma of the female urethra are presented. The tumour in the first case was associated with urethritis glandularis and is thought to arise from previous glandular metaplasia of the urethral mucosa. The tumour in the second case resembled the clear-cell carcinomas of the lower female genital tract and is thought to be of embryonic rest origin. The tumour in the third case is thought to arise from the paraurethral glands.


Some remarks concerning the fetal heart rate total dip areas. It was ascertained whether the sum total of the dip areas 60 minutes prior to delivery is an evaluating parameter for judging the fetal state. The cardiotokograms of 62 deliveries with a normal newborn state (newborn index 1) and forty with a pathological newborn state (newborn index 2 and 3) were digitally computer [5]. By proper programming numerous decriptive dip parameter can be determined, e.g. the amplitude, duration, area, lag time, recovery time, fluctuation before, within, and after the dip. The sum total of the dip areas was calculated from the CTG 60 minutes before delivery. Only cardiotokograms with at least two decelerations were included. The pathological newborn group has a larger mean sum total of dip areas than the group with a normal index (Fig. 1). This difference, however, is not significant. Mean values were calculated for other descriptive parameters, e. g. dip fluctuations, lag time, dip amplitude etc. These also differ only slightly between the two groups. (Fig 2). Hence they give no satisfactory decription of the fetal state. By including several dip parameters simultaneously [7] an evaluating parameter can be determined for both decelerations. The various descriptive parameter are given different weights and are added up (discrimination analysis). In analogy to the sum total of the dip areas the sum total of the evaluating parameters was calculated. The difference between the two groups with respect to these evaluating parameter sums is significant. (Fig. 3). The sum of total dip areas alone does not appear to be a sufficient FHR parameter for evaluating the fetal state. Evaluation is significantly improved by considering simultaneously several descriptive parameters.


Smoking during pregnancy and placental weight: a multivariate analysis on 3759 cases. The analysis of a survey of 3759 births shows that the difference in placental weight between smokers and nonsmokers is, if not nil, at least minimal, and that is definitely less than might be expected taking birth weight and other factors into consideration in a multivariate analysis (Tab. II). The distortion between the fetal and placental weights, which are very closely correlated, assigns to smoking a peculiar place among the factors influencing these two weights, a result which may lead to various interpretations.


Individual correction of birth weight for parental stature with special reference to small-for-date and large-for-date infants. The aim of the present paper is to determine how parental stature measurements should be used to "correct" birth weight in order to improve the diagnosis of small or big-for dateness. A first approach, based on the pattern of coefficients of correlation between maternal and paternal weight and height, and birth weight (Tab. I), may be criticized for two reasons: 1) it does not take into account the possible variations of this pattern of correlations from one subcategory (for instance of age) of the sample to another and ii) it makes no difference between "genetic" and "environmental" components of parental influence on birth weight. A second approach takes into account the variations of parental stature measurements, of birth weight and of the pattern of correlations according to mother's age (Tabs. II and III). Briefly: The correlation between birth weight and mother's weight increases, the correlation between  birth weight and father's weight decreases when mother's age increases (except for mother's older than 34), and these coefficents have the same value in the youngest group (mothers less than 21). These observations are consistent with the hypothesis of the predominance of the "genetic" component in the youngest group, which leads to the establishment of the coefficients to apply to each parental stature measurement by means of a multiple regression analysis carried out on this only group (Tab. IV). For the whole population, the correction must finally be calculated using the weights of parents at 20 years (or, if unknown, an approximate value). The correction is about ten grams per kilogram of mother's and eight grams per kilogramm of father's weight deviations from the mean values of the population to which they belong.


An endocrine model for the diagnosis of intrauterine growth retardation as demonstrated by the determination of total estrogen and pregnandiol 24-hour urinary excretion in 222 at risk pregnancies. A reliable method for surveillance of chronic impairment of nutritive placental function is described. The techniques are simple, tested for their reliability, without need for isotopes or special apparatus and hence inexpensive. Using 222 pregnancies at risk it is shown that the simultaneous determination of a fetal (estrogen) and a placental (pregnandiol) parameter makes the early diagnosis of intrauterine growth retardation possible. Estrogen diagnosis alone has a reliability of 90.1% with 1.8% falsely pathological and 8.1% falsely normal findings (Tab. I). Simultaneous pregnandiol determinations increase the number of falsely pathological findings to 8.1% but reduce that of falsely normal ones to 2.7%. No small for date (SGA) infants are found here. It consists of 5 cases of imminent (3 times actual) premature delivery and one postmature one. Hence our technique indicates the risk of intrauterine growth retardation in all cases but not the risk of premature or postmature delivery. Early diagnosis (from week 20) indicates that impairment of placental function as indicated by decreased pregnandiol excretion, occurs weeks or months earlier than decreased estrogen excretion (Fig. 1). This can be explained only by assuming that the rate of estrogen excretion is usually not dependent on the placenta but on the capacity of the fetal adrenals and liver. Thus our results indirectly confirm those of others who claim that the fetus can synthetize estrogen precursors without the need for placental pregnenolon by using acetate. Thus it appears that the synthetic pathway is independent of the placenta at the beginning plays a quantitative role also. Since the placenta can form aromatic compounds even when its nutritive function is severely impaired, our finding is further proof that estrogen excretion reflects fetal and not fetoplacental well-being. It follows that pathological estrogen excretion indicates fetal injury that has already occurred. The requirement that a sensitive parameter of placental function be hence determined in time is met by pregnandiol assays. Low pregnandiol excretion often precedes low estrogen excretion which leads to a SGA infant, indicating that pregnandiol excretion is closely correlated to placental nutritive function. Synthetic reactions in the fetus require energy and hence depend on the placenta. Normal estrogen excretion frequently observed in the presence of prolonged decreased pregnandiol excretion must hence indicate that the fetus can compensate for placental insufficiency. In the placenta this can be demonstrated by hyperplasia of the capillaries. This is reflected in the undulating excretion of pregnandiol (Fig. 1), where compensation (new vessel formation) and depression (lesion of vessels) make these contradictory placental processes "visible". The functional unity  of the fetus and the placenta is finally also demonstrated by the fact that each prolonged compensatory phase of the placenta is reponded to by the fetus with a clearly compensatory excretion of estrogen (Fig. 1)...


Uterine hemodynamics and fetal response to vena caval occlusion in sheep. The present experiments should show if vena caval occlusion (V. C. O.) results in a decrease in uterine blood flow and increase in uterine vascular resistance (UVR). We are further interested to know, if V. C. O. influences fetal heart rate (FHR) and fetal blood pressure (BP).


The measurement of fetal growth during pregnancy by ultra-sound (B-scan). We have followed fetal growth by ultrasonographic B-scans. In addition to percentile curves of the biparietal skull diameter we have established percentile curves for measurements of the fetal trunk (sagittal thoracic diameter and length of trunk). The percentile curves for the biparietal diameter were obtained from 5400 individual measurements; the percentile curves for the trunk measurements utilized 1300 individual measurements. These cases were from almost entirely unselected material from our special prenatal clinic. This resulted in a larger variation than the percentile curves for biparietal diameter of other authors [Campbell and Newman]. However, these authors selected their material for "normal pregnancy" while we insured that neither "corrections" of the normal variation nor subjective criteria for exclusion have introduced a systematic error. The advantages of ultrasonography for monitoring of the pregnancy are self-evident: repeated examinations are possible, the examination takes little time, and the method is safe. The determination of the biparietal diameter for estimation of fetal development alone is insufficient because trunk measurements may indicate developmental disturbances (dystrophy and hypertrophy) before the growth of the biparietal diameter of the skull is affected. Furthermore, comparison of the fetal skull and trunk measurement may indicate errors in measurement or malformations (hydrocephalus, microcephalus). The following percentile curves are illustrated graphically: 1. Gestational age versus biparietal diameter (Fig. 1). 2. Biparietal diameter versus weeks of gestation (Fig. 2). 3. Length of gestation versus sagittal thoracic diameter (Fig. 3). 4. Length of gestation versus length of trunk (Fig. 4). 5. Sagittal thoracic diameter versus length of trunk (Fig. 5).


Homosexuality and the medical profession: a behaviourist's view. That a homosexual -- man or woman -- is neither a sinner nor a sick person is the thesis of this paper by an authority on sexual deviation. Therefore, such a man or woman neither needs penance and pardon nor cure in the medical sense. Nevertheless such individuals sometimes need the help of doctors and must be treated with understanding. The medical profession also has, in the view of the behaviourist school of psychiatrists, of which Dr Bancroft is a member, the duty of influencing social attitudes towards homosexuals. Obviously homosexuals who come into conflict with the law are special cases, and must be treated as such but this is not 'medical' treatment so much as social control even if drugs and other forms of therapy are used.


The teaching of medical ethics.

The teaching of medical ethics. The following description of the situation in Maastricht in the Netherlands is unique as this is a new faculty of medicine and the opportunity has been taken to build the teaching of medical ethics into the curriculum from the start.