Dinitrochlorobenzene contact sensitization in pulmonary tuberculosis. Skin sensitization with DNCB was carried out in forty-five untreated, 106 "on treatment" and fifteen fully treated patients with pulmonary tuberculosis along with fifty-five controls. Mantoux test with PPD was also carried out simultaneously. All the normal controls could be sensitized to DNCB and the degree of sensitization was 4+ in majority of the subjects. In contrast, in untreated patients only eighteen could be sensitized to DNCB and the degree of sensitivity did not reach 4+ in any patient. Similarly, fifty-five patients could not be sensitized with DNCB in the group of 106 subjects who were still suffering from active disease and were on therapy and none gave a 4+ response. The difference in the proportion of subjects who could be sensitized to DNCB in these two patient groups was significantly less in comparison to controls. Among fifteen patients who were fully treated and did not have active disease thirteeen could be sensitized with DNCB, but the degree of response was again found to be less than the controls. All the patients as well as the controls gave a high proportion of Mantoux positivity. These findings indicate that there is a subtle degree of immunodeficiency in pulmonary tuberculosis which improves simultaneously with the clinical improvement.


Presence of antibodies specific to cartilage-type collagen in rheumatoid synovial tissue. Synovial membranes of rheumatoid arthritis patients were examined by fluorescence microscopy for the presence of cells producing different classes of immunoglobulins and for the incidence of antibodies to human collagens. IgG and IgM immunoglobulins were detected while IgA, IgD and IgE were absent. When consecutive tissue sections were incubated with tetramethylrhodamine isothiocyanate-labelled collagen preparations, prominent cellular and extra-cellular staining was observed only with cartilage-derived Type II collagen.


Serum disappearance and catabolism of homologous immunoglobulin fragments in rats. The serum disappearance, metabolic clearance and whole body catabolism of homologous immunoglobulin fragments were studied in rats. The rapid disappearance of Fab fragments from serum in normal animals was no longer present after nephrectomy. In contrast, the serum disappearance curve of Fc fragments was not altered by nephrectomy. The results of three different experiments, however, indicated that similar to Fab fragments, some Fc fragments underwent filtration and degradation in the kidneys. First, the amount of intact Fc fragments excreted in the first day after injection increased from 6% of the injected dose in normal rats to 17% in rats pretreated with sodium maleate. Secondly, nephrectomy eliminated the rapid phase of whole body catabolism of inected Fc fragments. Thirdly, auto-radiographic studies showed localization of Fc fragments in the renal proximal tubule cells in the first 3 hr after injection. An identical localization was seen with Fab fragments. These results  support the conclusion that removal from circulation by glomerular filtration and subsequent reabsorption and degradation in proximal tubule cells represent the major mechanism for catabolism of Fab fragments. Although some Fc fragments undergo the same fate, most injected Fc fragments equilibrate with unknown sites where they are possibly bound and made unavailable for filtration in the kidneys.


Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution. The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority of the lymphocytes in this congenitally athymic mouse are relatively long-lived, although few cells live for 6 weeks or more. Differences in labelling percentages of blood, spleen and lymph node lymphocytes indicated a production of lymphocytes with a short residence time in the spleen. A similar production was not seen in the lymph nodes. While the lymphocytes in the spleen were evenly distributed according to life-span, the paracortical lymphocytes in lymph nodes were found to have a generally shorter life-span than those of the cortex, in opposition to findings in normal mice. The cortical cells which were by far the most numerous in the lymph nodes seemed to be more sessile than para-cortical lymphocytes. The life-span of these latter cells are comparable to those of thoracic duct lymphocytes, and the scarcity of cells in the paracortex reflects the small number of recirculating lymphocytes in nude mice.


Giemsa staining of the sites replicating DNA early in human lymphocyte chromosomes. A timetable for the initiation of DNA replication in human lymphocyte chromosomes has been established by a technique which allows detection of areas of chromosomes replicating at a given interval of the S-phase. The resolution of the method, using 33258 Hoechst-Giemsa staining, is more refined than that obtained with 3H-thymidine autoradiography. Early replicating regions coincide with R-bands. The timetable is rather coarse since replication may start asynchronously in the same region of homologous autosomes of the same metaphase and since even the sequence of bands appearing on individual chromosomes sometimes deviates from the rule.


The Giemsa banding pattern of the canine karyotype. The canine metaphase karyotype consists of 78 chromosomes. All autosomes exhibit telocentric or acrocentric configurations gradually diminishing in size. These features make identification of homologous pairs by conventional analysis difficult. Chromosome preparations were derived from short-term cultures of peripheral blood lymphocytes obtained from clinically normal dogs representing at least four breeds. Most components of the canine karyotype can be distinguished readily. No significant G-banding pattern variations were detected in the individuals screened. An idiogrammatic interpretation of the banding pattern is presented. Apart from bands, other characteristic morphologic features were found which aid in identification. The G-banding pattern of the canine metacentric X is quite similar to that of the banded human X. The canine Y is a minute metacentric having two positive bands.


Chromosomal banding patterns in Akodon arviculoides (2n=14),Akodon sp.(2n=24 and 25), and two male hybrids with 19 chromosomes. Chromosomal polymorphism resulting from two pericentric inversions in Akodon arviculoides (2n=14) has been described (YONENAGA, 1972a). In this paper the banding patterns are presented and identification of the inverted segments of the autosomal pairs 2 and 3 is made. The karyotype of Akodon sp., which varies in diploid number (2n-24 and 25), is described and shown to be due to the presence of a small submetacentric chromosome in the 2n=25 individuals. The karyotypes of two 2n=19 males studied show that they are hybrids between Akodon arviculoides (2n=14) and Akodon sp. (2n=24).


Antirheumatic drugs: clinical pharmacological and therapeutic aspects. There are many current concepts of the pathogenesis of rheumatic diseases which incorporate immunological, infectious and hereditary factors. Rheumatic diseases may sometimes become apparent after trauma, be associated with certain diseases and may be induced by nerve damage and serum sickness. Systemic lupuserythematosus may result from the use of a variety of drugs. At present the body of evidence tends to incriminate immunological factors as well as infectious agents as principal factors in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Just as there is uncertainty regarding the pathogenesis of rheumatic diseases, knowledge of the mechanism of action of the various drugs used to treat these diseases is also incomplete. Recent progress indicates that inhibition of prostaglandin biosynthesis and possibly lysosomal membrane stabilization are primary modes of action of the anti-inflammatory agents. Certain antirheumatic drugs have also been shown to exert some of their therapeutic effect by interfering with the kallikrein-kinin-kininase system...


Gonadotrophs following removal of the ovaries: a fine structural study of human pituitary glands. The fine structure of gonadotrophs has been investigated in surgically removed pituitary glands of 12 women who because of disseminated breast cancer, underwent bilateral ovariectomy at various periods before hypophysectomy. Compared with the adenohypophyses of 3 non-ovariectomized female subjects with diabetes mellitus, electron microscopy revealed that two cell types were affected by gonadectomy. These cell types corresponded to those which were regarded as FSH gonadotrophs and LH gonadotrophs in previous studies. In addition in the adenohypophyses stimulated by removal of the ovaries, intermediary cell types began to appear suggesting a transformation of LH gonadotrophs to FSH gonadotrophs. The most conspicuous change following gonadectomy  was the formation of castration cells. These cells arose from FSH gonadotrophs and exhibited ultrastructural features interpreted as representing the morphologic manifestations of sustained hypersecretion of gonadotrophins. It seemed that castration cells have a limited life span and in their advanced stages of development they show ultrastructural signs indicative of irreversible involution.


The influence of testosterone on brain cholesterol. Male sex hormone testosterone propionate induces esterification of brain cholesterol. Esterified cholesterol is absent in the brain of female rats, treatment with male hormone induces esterification. In castrated male rats the esterified cholesterol from brain disappears, whereas supplementation to those animals with testosterone helps in the re-appearance of esterified cholesterol.


Effect of thiourea on calcitonin cells of the Indian grey mongoose Herpestes edwardsi (Geoffroy). The thiourea treated mongooses display an increase in the number and size of the calcitonin cells. These cells sometimes are seen accompanied with desquamated epithelial cells within the colloid. The thyroid follicular cells also record an increase in their height.


[Radioimmunologic proinsulin determination in the serum using an "insulin-catabolizing protease" from the rat liver]. Proinsulin determinations in human serum are of particular interest, because proinsulin represents only a fraction of the biological activity of insulin. Proinsulin like components are determined by means of an "Insulin Degrading Protease" (ISP) which degrades insulin into non-radioimmunoassayable fission products. The radioimmunoassay before and after incubation with this enzyme provides values for the total-insulin and the proinsulin. The preparation of the ISP is done by homogenization and ultracentrifugation of fresh liver tissue followed by dialysation and dryfreezing. After further concentration by adsorption to a calcium-phosphate-gel the ISP degrades pure porcine insulin within 20' down to a rest of 9%, but only 7% of pure porcine proinsulin is altered. The proinsulin values provided this way are reproducible and exact enough for the clinical use. They correspond largely to those methods using chromatographic columns. In 13 persons the proinsulin fraction of the total insulin after stimulation with glucose and tolbutamid has been registered. The proinsulin shows in the oral glucose tolerance test compared to insulin a lower and delayed increase. After tolbutamid only minor changes of proinsulin values have been seen. As long as it is difficult to prepare a proinsulin specific antibody for a direct proinsulin radioimmunoassay, the ISP-method is even qualified for extensive proinsulin determinations in human serum.


The effect of alpha-melanophor-stimulating hormone on liver regeneration and incorporation of amino acid in rats' liver protein. Following 25 mug/day synthetic alpha-MSH administration, the liver regeneration of partially hepatectomized rats proved to be increased. The hormone treatment resulted in an enhanced alanine incorporation of the liver proteins, but this effect was uncertain on partially hepatectomized rats. Due to the hormone treatment the low liver protein content of the operated rats became normal. The pseudocholinesterase activity of the liver homogenate of alpha-MSH treated rats was also elevated. On the basis of these experiments authors are supposing some protein synthesis increasing effect of synthetic alpha-MSH.


H3-phenylalanine incorporation into protein in the pituitary, hypothalamus and cerebral cortex of male rats during postnatal development. Incorporation of H3-phenylalanine and concentration of protein in the anterior pituitary gland (APG), hypothalamus and cerebral cortex of male rats have been studied during postnatal development from day 21 to 120. APG and hypothalamus showed significantly higher rate of amino acid uptake and protein synthesis during the prepubertal phase, decrease at puberty and an age dependent variation thereafter. Protein concentrations and amino acid incorporation in the APG and hypothalamus are possibly influenced by the higher circulating levels of androgens during sexual maturation in marked contrast to their lack of effect on the cerebral cortex.


Significance of 3alpha, 17 alpha-dihydroxy-5beta-pregnane-20-one in the diagnosis of congenital adrenal hyperplasia. The 3alpha-17alpha-dihydroxy-5beta-pregnane-20-one (17-hydroxy-pregnanolone) excretion was found by gas chromatography to be as high as the pregnanetriol in urine of 4 virilising CAH female and 2 male patients. According to our results the significance of the determination of 17-hydroxy-pregnanolone is equal to that of the pregnanetriol in the diagnosis of adrenal hyperplasia. As the 17-hydroxy-pregnanolone is demonstrable after mild acid hydrolysis, too, it can be applied independently from the pregnanetriol determination. In five out of the six patients we found the excretion of the pregnanediol to be high, too. Its value reached, irrespective of sex, the characteristic quantity of the woman's luteal phase, so it undoubtedly originated from the adrenal cortex. We dealt shortly with the explanation of high pregnanediol excretion.


Extracellular enzyme system utilized by the fungus Sporotrichum pulverulentum (Chrysosporium lignorum) for the breakdown of cullulose.  Functional characterization of five endo-1,4-beta-glucanases and one exo-1,4-beta-glucanase. A strong synergistic response was observed between the five endo-1,4-beta-glucanases and the exo-1,4-beta-glucanase obtained from culture solutions of the rot fungus Sporotrichum pulverulentum (formerly called Chrysosporium lignorum), when these enzymes were allowed to degrade de-waxed cotton and Avicel.  No synergism was observed if Walseth cellulose, an acid-swollen cullulose, was used.  If de-waxed cotton was pretreated with endo-1,4-beta-glucanases, the exo-1,4-beta-glucanase enzyme released much more degradation products than from an untreated cotton...


A model for conformational coupling of membrane potential and proton translocation to ATP synthesis and to active transport. Acceptance of a membrane potential and/or a proton gradient as a possible means of transmitting energy from oxidations to ATP synthesis rests in part on a satisfactory hypothesis for how the potential or proton gradient could drive ATP synthesis. Recognition that energy input may drive ATP synthesis by change in binding of reactants at the catalytic site has led to the suggestions presented in this paper. These are that in oxidative phosphorylation and photophosphorylation, the requisite conformational changes may be coupled to exposure of charged groups to different sides of the membrane. The cycle of charged group exposure or movement may be driven by the membrane potential or, through protonation and deprotonation, may be coupled to proton translocation across the membrane. Effects of proton gradient and membrane potential may be additive. Similar conformational coupling suggestions may explain proton translocation coupled to ATP cleavage and active transport of metabolites coupled to membrane potential, proton gradients of ATP cleavage.


Effect of cytidine-5'-monophosphate on peptidyl transferase activity. The transfer reaction with pA-fMet as a donor substrate is strongly stimulated by CMP, whereas the transfer reaction with CpApCpCpA-acLeu as a donor substrate is inhibited by CMP. These results indicate that the donor site of peptidyl transferase contains specific binding sites for the terminal adenosine and for the cytidylic acid residue in the terminal sequence CpCpA of tRNA and that an attachment of proper nucleotides to the donor site induces a conformational change in peptidyl transferase.


Joint use of light, X-ray and neutron scattering for investigation of RNA and protein mutual distribution within the 50S subparticle of E. coli ribosomes. The values of the RNA and protein radius of gyration obtained in these studies corroborate the conclusion reported earlier [1] that on average the RNA is nearer to the center of the particle than is the protein. (It should be noted for comparison that the minimal Rg value of the RNA corresponding to its dense packing as a sphere in the center of the 52S subparticle is 49 A.) Moreover, such a great difference in the radii of gyration of RNA and protein implies a definite scheme of mutual RNA and protein arrangement in the 50S subparticle -- namely the distribution of the greater mass of proteins on the RNA surface.


Metabolism of systematically given corticosteroids. In the metabolism of a systemically administered corticosteroid, one of three possible main pathways is determined by the position in the molecule of the substituents which are added in the drugs to the naturally occurring ones. (I) Chiefly, hydrogenation in ring A and/or the 20-position: cortisol, cortisoine, prednisolone, prednisone, and 6alpha-methylprednisolone (II) In the presence of a substituent in the 16-position mainly 6beta-hydroxylation: dexamethasone, betamethasone, and triamcinolone. (III) In the presence of a substituent in the 16-position, and fluorine in the 6alpha-position principally defluorination in the 6alpha-position and 6beta-hydroxylation: fluocortolone and paramethasone. Complete metabolism, in long-term use, can be expected in the case of the substances mentioned under II and III, but not of those under I. Enzyme induction, both actively and passively, is negligible in group I and marked in groups II and III.


Antibodies with affinity for epithelial tissue in chronic dermatophytosis. Antibodies to dermatophytes which also had affinity for intercellular material of epithelial tissue, were detected in sera from 80% of patients with chronic dermatophytosis using an indirect fluorescent antibody test. The class of immunoglobulins reactive with both the dermatophyte and the epithelial tissue was identified as IgM. IgM antibodies with affinity for arthrospores of Trichophyton mentagrophytes and intercellular substance of epithelial tissue could be removed from sera with mycelium of Trichophyton rubrum.


The effects of some hair oils and unsaturated fatty acids on experimentally induced dermatophytosis. Antimycotic effect of mustard and coconut oils, oleic and palmitic acids on experimentally produced dermatophytic infection on hairy skin in the guinea pigs was studied. Mean Duration of Infection (MDI) was significantly reduced in all experiments where coconut and mustard oils or unsaturated fatty acid (oleic acid) were used. The significance of these results in realtion to Tinea capitis in humans is discussed.


[Reaction of epidermis after long-term action of urea]. The epidermis thins in response to short-term contact with urea, and the results of extensive enzymological and autoradiographical studies suggest that urea acts on processes involved in epidermal proliferation. After long-term exposure of skin to urea, lasting more than 2, 4, or 6 weeks, no further thinning occurs, and there is no tendency for atrophy to develop during this period. This assertion is made on the basis of biometrical, autoradiographical, and cytophotometrical data. It is likely, however that a reduced number of cells synthesizing DNA is not the only change in normal epidermal proliferation leading to the peidermal thinning that was measured. The urea could also alter factors regulating either cell entry into DNA synthesis or the synthetic process itself, or both. These findings clearly are of significance not only in industrial medicine but also in the use of urea in topical dermatological therapy.


Ichthyosis hystrix of 'porcupine man' type. Report of a case. Ichthyosis hystrix is a term used to describe an ichthyosiform dermatosis in which formation of hyperkeratotic, verrucose excrescences is a prominent clinical feature. This paper deals with an interesting case of ichthosis hystrix associated with a negative family history and two squamous cell epitheliomas.


Analyses in blood of dermatological patients. I. Glutathione and glutathione reductase. Glutathione was estimated in 98 blood samples from dermatological patients; in only two cases, both of contact eczema, a value considerably below normal was found. Glutathione reductase was assayed in blood samples from 139 different patients and 21 normal controls. The activity was significantly higher in atopic dermatitis (17 patients). A significantly greater variable was found among patients with non methotrexate-treated psoriasis (44), light sensitivity (12) and scleroderma (5). In the methotrexate-treated psoriatic group (24) and mean and variability did not differ significantly from normal. In most hospitalized patients a low glutathione reductase activity rose within a few weeks, but in a case of dermatitis herpetiformis a very low level persisted for 3 months. Blood samples with very low glutathione reductase activity, taken from a case of psoriasis and from a patient on griseofulvin treatment, gave a positive peroxide test and tended to hemolyze; these returned to normal together with the glutathione reductase activity.


Improvement of refractory psoriasis vulgaris after tonsillectomy. In order to ascertain what effect tonsillectomy may have in the treatment of children and adolescents with recurring psoriasis vulgaris, refractory to topical therapy and courses of penicillin, and triggered by infection, and also to test a possible correlation between tonsillitis and exacerbations of psoriasis, a retrospective study of the course of psoriasis after tonsillectomy, using charts and questionnaires, was undertaken in 74 psoriatic patients. Each patient served as his won control. The average age of the patients at tonsillectomy and the duration of psoriasis were 14.2 years and 4.5 years, respectively, while the average follow-up period was 4.5 years. The clearing of the psoriasis was statistically significant (p less than 0.01) as it occurred throughout the entire follow-up period in one-third of the patients, while an additional third noticed considerable improvement of their psoriasis. After trying tropical therapies of various sorts as well as courses of penicillin, tonsillectomy might be considered for recurring, refractory psoriasis vulgaris in children and adolescents.


Ultrastructural abnormalities in the skin nerves of a patient with scleredema adultorum (Buschke) and diabetes mellitus. In an electron-microscopic study of the skin of a patient with scleredema adultorum (Buschke) and diabetes mellitus, the unmyelinated nerve fibres showed accumulations of glycogen. On morphological grounds, these accumulations appeared to be located in the axons.


[Melanoacanthoma (author's transl)].

[Melanoacanthoma (author's transl)]. A 87-year-old Caucasian women had a recurrent pigmented tumor on the back. Histologically, the lesion was interpreted as being a melanoacanthoma. It was characterized by a proliferation of unpigmented basaaloid cells with aggregates of large prickle cells, forming small horn pearls; furthermore the tumor contained numerous large dendritic cells with large amounts of melanin granules. A short review of the literature is followed by the discussion of the relationship between melanoacanthoma and irritated seborrheic keratosis.


[A case of keratosis follicularis spinulosa decalvans (author's transl)]. The case of a 2-year-old boy with keratosis follicularis spinulosa decalvans is described. On of his sisters had keratosis follicularis of the upper arms, forearms, thighs and legs as well as blepharonconjunctivitis chronica catarrhalis bilateralis and was considered as forme fruste of the anomaly. His mother had sparse eyebrows. The mode of inheritance and the Lyon hypothesis are discussed.


A case of cutaneous amoebiasis.

A case of cutaneous amoebiasis. The present report concerns a patient with ulceration around an artificial anus. The condition had been treated for some time as pyoderma gangrenosum but finally proved to be cutaneous amoebiasis; the presence of Entamoeba histolytica was demonstrated. A cure was achieved with metronidazol (Flagy) and diloxanide furoate (Furamide) given orally.


Depigmenting action of corticosteroids. Experimental study on guinea pigs. The depigmenting action of corticosteroids was studied on the black skin of the guinea-pig by cutaneous applications followed by repeated histological sections. These experiments demonstrated the depigmenting action of triamcinolone acetonide and betamethasone 17-valerate. The results of this study show the influence of concentration and chemical formula of the corticosteroids on the process of depigmentation. The histological study did not reveal any particular morphological aspect of melanocytes capable of suggesting a mechanism of action by these chemical compounds at the cellular level.


A study of the immunological status of patients with dermatophytoses. 22 patients with Trichophyton rubrum infection were studied for some of their immunological parameters. The trichophytin skin test performed with commercially available Dermatophytin (Hollister-Stier) gave immediate positive reaction in 3 patients. All the other patients gave negative delayed and retarded reactions. In vitro response to PHA of the peripheral lymphocytes was significantly depressed in patients compared to the controls. No relationship could, however, be established between the severity, duration or extent of the disease and the depression of the lymphocyte response. IgG and IfA were found to be within normal limits. IgM levels were significantly depressed which was probably artefactual in nature.


[Ultrastructure of solid basalioma. A morphometric study (author's transl.)]. A morphometric investigation was made on mitochondria of basalioma cells and the cells of the basal layer of the epidermis lying over the tumor. The mitochondria of the basalioma cells occupy 4.7% and of the epidermal basal cells 5.3% of the cytoplasm. The number of mitochondrial sections yields a relation of 6.6:10 in favor of the epidermal cells. These results demonstrate an alteration in the size of the basalioma cell mitochondria. The possible causes of this mitochondria enlargement were discussed. An attenuation of the activities of the mitochondrial, membrane-bound enzymes in the basalioma cells is caused in all probability primarily by a reduction of the cristae material in comparison to the basal epidermal cells. The nucleus-cytoplasm relation amounts to 6.3:10 in the basalioma cells and 3.0:10 in the basal epidermal cells.


Botryomycosis.

Botryomycosis. A case of botryomycosis was studied in which a coagulase-negative, DNAsenegative Staphylococcus with wide antibiotic sensitivity in vitro was isolated and which could be classified as having a 'low pathogenic capacity'. Nevertheless, there was no improvement with appropriate therapy. IgG and complement (C3) were demonstrated in the grains. Botryomycosis can be considered as a state of 'equilibrium' between the host and the microorganism. It is not clear if this results from low pathogenicity of the organism or from some peculiar characteristic of the host.


Short-term changes in incubation temperature: behavioral and physiological effects in the chick embryo from 6 to 20 days. In 3 experiments we have attempted to determine the extent to which the chick embryo is behaviorally and physiologically responsive to short term changes (.5-2 hr) in the normal ambient incubation temperature. Embryos ranging in age from 6-20 days of incubation have been examined after exposure to temperatures ranging from 30.5 degrees to 44.4 degrees C (normal incubator and nesting temperatures are 37-38 degrees C). At 6,9 and 12 days of age the heart rate and the duration of amnion contractions were significantly altered by exposure to temperature either higher or lower than normal although overt neuromuscular activity (motality) remains unchanged. At 15 and 20 days, however, (hatching occurs on Day 21) the rate of neuromusclar activity is altered at both low and high temperatures. At 20 days, beak-clapping, vocalization, and respiration rates also change reliably upon short-term exposure to both high and low temperatures. The possibility is discussed that embryonic responsiveness to temperature changes in the environment during natural incubation may play some role in later behavioral capabilities.


Comparative ontogenetic features of skeletal muscles in physiologically mature and immature mammals. One series of experiments investigated the time required by such indices of the states of skeletal muscles as membrane potential (MP), action potential (AP), and content of total protein and dense residue to acquire values approximating those found in adults. We established that these indices acquire values approximating those found in adults at the beginning of sexual maturation in both rats and dogs. Chronologically, these values require one-fifth the time to become established in rats as they do in dogs. Another series of experiments investigated the same indices in physiologically mature and immature organisms (rats and dogs). We established that they are much lower in immature than in mature organisms. We conclude that under conditions of natural development the main objects of elimination through natural selection in early developmental periods are physiologically immature organisms.


Olfactory, thermal, and tactual influences on infantile ultrasonic vocalization in rats. The amount of time infant rats 3-13 days old spent emitting ultrasounds was greater when pups were placed in an empty dish than when placed in a dish containing clean bedding or soiled bedding from the nest. Pups from 5-13 days of age vocalized more when on the clean bedding than when on the soiled bedding. When placed on cloth covered dishes, pups vocalized most to the empty dish and least to the dish containing soiled bedding. The odor of clean bedding elicited less ultrasonic vocalization than the odor of the empty dish only when less than 7 days old. Pups vocalized more to room temperature than to heated conditions. The results indicate that olfactory, tactual, and thermal nest cues influence infantile ultrasonic vocalization in the rat.


Olfactory bulbectomy and nursing behavior in rat pups (Wistar DAB). To determine whether bilateral olfactory bulbectomy led to a change in nursing behavior, and thus death, we bilaterally bulbectomized (BX) pups from 14 litters at 2, 7, and 11 days of age. Litters treated on Days 2 and 7 consisted of 3 BX pups, 2 surgical control (SC) pups, and 2 handling control (HC) pups. Litters treated on Day 11 consisted of 1 or 2 BX, 1 or 2 incompletely bulbectomized pups (IBX), 2 SC pups, and 2 HC pups. These litters and 3 additional nontreated litters were observed on Days 4,7,10,13, and 16. A smaller number of BX pups survived through Day 10 than SC, HC, IBX, and nontreated pups. Differential treatment of the BX pups by females or littermates was not found. The females' mammary glands were functional but the BX pup stomachs had little or no milk. The BX pups spent less time nursing and more time away from the female and their littermates than did the other pups.


Neurological organization and visual fixation in infants at 40 weeks conceptional age. Neurological organization and visual fixation were found to be unrelated in a group of premature infants tested at their term date. These results are discrepant with those obtained with a sample of full term infants. Separate comparisons made of the neurological and fixation data revealed one significant group difference from the fixation data; all other analyses were nonsignificant. The discrepant findings may have occurred because prematures are subject to developmental disparities in the regulation of arousal, neuromuscular, and visual systems due to differential impact of preterm extrauterine life.


Preliminary evidence for the effects of environmental complexity on hybridization of rat brain RNA to rat unique DNA. Hybridization to unique DNA by RNA from brain or liver of rats given varying degrees of experience was investigated. RNA from brain of environmentally enriched rats hybridized to more unique DNA than did brain RNA from nonenriched controls. No significant differences were observed with liver RNA. This provides preliminary evidence for an increased transcription of the unique sequences of DNA in the enriched animals. The technique used has great promise for the investigation of experientially-induced alterations in gene expression.


Handling rabbits in infancy: in search of a critical period. In Experiment 1 rabbits were handled for the first 10 days of life while controls were not disturbed. In Experiment 2 rabbits were handled on Days 11-20. In Experiment 3 rabbits were handled on Days 1-10, 11-20, 1-20, or were not handled. Starting at 31 days the animals were given an open-field test, a test for exploratory behavior toward novel stimuli, and a test of social behavior. The data were not consistent with the critical period concept. Instead, handling during the first and second 10-day intervals appears to be additive and to approximate the effects of 20 days of handling.


Discrepancy from rearing conditions affects chicks' behavior in a novel situation. Chicks raised in small or large cages were exposed to a relatively large novel situation at 12 or 24 hr of age. At both ages, chicks from small cages had longer latencies to begin moving and lower activity scores. Age itself had no effect. Apparently, chicks learn the characteristics of their home cage shortly after hatching, and discrepancy from the home affects their response to novel situations.


Adaptation to novel environments by the rat: effects of age, stimulus intensity, group testing, and temperature. Adaptation of operant bar pressing in a dark 2-bar test box was determined during 2-hr tests for singly tested rats 16-18, 24-32, and 750-800  days old. Rats 16-18 days old failed to adapt during the test, although all other age groups did. Adaptation occurred more slowly for the 120-150 day-old group than for the remaining 2 age groups. Experiments with the 2 youngest groups showed that bright light lowered response levels of both age groups, compared with controls, but failed to alter the course of adaptation. In contrast, group testing resulted in lowered response levels and faster adaptation for 16-18 day-old rats, but higher response levels for 24-32 day-old rats compared with singly tested controls. High temperature (32.5 degrees C) resulted in adaptation for the 2 younger groups. The failure of 16-18 day-old rats to adapt may have been due to lower body temperature while in the test chamber than while in the home cage nest area.


Voluntary exposure to light by young and aged albino and pigmented inbred mice as a function of light intensity. Young (5 month) and old mice (23 and 26 months) of the inbred A/J and C5BL/6J strains (N = 80) were isolated in ventilation chambers with ad lib food and water for 1 week at a time. Each animal was allowed to select its own lighting schedule by pressing one lever to turn on a light of either 10.76 or 166.40 lux illumination and pressing another lever to turn the light off. Three-way analyses of variance for Age, Strain, and Illumination effects on parameters of bar pressing, stimulus change, and light duration patterns per circadian period (24 hr) indicate that old mice are less active than young mice and the A/J mice are less active than C57BL/6J mice. Young mice spent more time in the dark than old mice and the A/J albino mice spent more time in the dark than did the C57BL/6J pigmented mice. Other age and strain differences were noted as well and are discussed with respect to some theories of light exposure by nocturnal animals.


Effects of phenobarbital given to pregnant mice on behavior of mature offspring. Mature offspring of C57BL/6J mice (Mus musculus) injected daily with phenobarbital (40 mg/kg) for the last third of pregnancy differed from saline and untreated control animals on 3 measures of behavior. Offspring of phenobarbital treated animals had higher locomotor scores than controls during an open field activity test at 75 days of age. Male offspring were also tested on a 1-trial passive avoidance task and treated animals were found to be deficient. Finally, female offspring responded less than controls on fixed ratio schedules of reinforcement. The behavioral changes suggest that offspring of mice injected with phenobarbital during pregnancy are less responsive to the stimuli in their environment which maintain behavior.


Learning deficits in rats with malnourished grandmothers. Female rats (F0) were maintained on a protein-restricted or a normal diet 1 month prior to mating and throughout pregnancy. Their female offspring (F1) were maintained on a normal protein diet and mated with normal males. In previously reported studies, the 2nd generation offspring (F2) of the malnourished rats have been found at birth to have significantly lower cerebral DNA ( a measure of cell number), cerebral weight, and cerebral protein than normal controls. We now report that these F2 animals show marked learining deficits at maturity on 2  different successive reversal tasks, even though they themselves have never directly experienced malnutrition. Thus, certain behavioral as well as biochemical effects of malnutrition appear to the next generation of animals.


Variability of the effects of rearing in a large litter on the development of the rat. The variability in the effects of rearing rats in large litters was examined. Subjects reared in litters of 16 were stunted and delayed in the appearance of eye-opening and fur-eruption as compared with pups reared in litters of 8. However, the effects of the large-litter treatment were not uniform; pups in this group exhibited markedly higher variability with regard to all measures than did pups from small litters. In fact, some pups from the large litters were heavier and some exhibited developmental landmarks earlier than did most pups reared in small litters.


Experimental studies of the ontogeny of ultrasonic vocalizations in bats. The ontogeny of FM pulses emitted by bats is a process of maturation that is not easily altered by experimental manipulation during early development. Infants that were hand-raised and infants that were raised by mothers with altered voices (the superior laryngeal nerves were cauterized pre- and postpartum) emitted normal adult calls. Effects of pinching the superior laryngeal nerves of young bats with a cold forcepts on their vocalizations suggest that the development of this nerve and its associated musculature occurs early in the bat's postnatal life.


A comparison of live and videorecord viewing of infant behavior under sound stimulation. II. Six-week-old infants. Ten clinically normal 6-week old infants were presented with a series of sound stimuli while their behavior was assessed live by 2 sound-masked observers and simultaneously videorecorded. Two weeks later the same observers assessed the behavior from the videorecords. In both situations, observers were permitted to see the babies for 10 sec at each trial. The first 5 sec was a prestimulus observation period, and the second 5 sec might have contained a sound stimulus. Between trials the observers were allowed 20 sec in which to note (1) prestimulus activity, (2) confidence in response, and (3) facial, digit, and limb movements, and "wholistic" impressions (e.g., "stilling"). The agreement between the live and video situations was fair for prestimulus activity, modest for confidence in response, and fair to good for movement items. The use of videorecorded material for 6-week  old infants generally caused rather small losses of relevant information and apparently will not overly distort the findings of experimental or clinical work. This outcome was rather similar to that of our earlier study of neonates.


Neonatal thyroxine administration, behavioral maturation, and brain growth in mice of different brain weight. L-thyroxine in amounts of .5, 1, and 2 mug was injected daily from age 5 through 14 days in 3 lines of mice selected for high (H), medium (M), or low (L) brain weight. Controls (injected with vehicle only) of these lines differed in ages of eye-opening, first auditory startle, and perfection of a surface-righting response. Thyroxine at .5 mug/day accelerated the maturation of eye-opening, auditory startle, and aerial-righting response, but had no effect on a grasping response or open-field activity. Brain weights were depressed significantly in all thyroxine treated groups except in the 9k-mug dosage in  H mice.


Genetic variation in the development of mouse brain and behavior: evidence from the middle postnatal period. Six inbred strains and 3 F2 hybrid crosses of mice were assessed for developmental status at 32 days after conception (about 13 days after birth). Phenotypes measured included body weight, brain weight, maturity of 14 reflexive behaviors, myelination of 80 fiber tracts, and thickness of the external granular layer of the cerebellum. All measures of brain and behavior showed a similar pattern of results: hybrids were generally more advanced than either of their inbred parent strains; differences among inbred strains were large, but differences among hybrid crosses were quite small. Acceleration of F2 mice compared to their homozygous relatives ranged from .5 to 2.4 days mean difference. Developmental ages of inbred litters ranged from 28.7 to 32.2 days, whereas hybrid litters ranged from 31.5 to 32.7 days.


Alterations in consummatory behavior of mice produced by dietary exposure to inorganic lead. Mice suckled by mothers given tap water and by mothers given a 5 mg/ml lead acetate solution during lactation were given a choice between tap water and a lead acetate solution after lactation. All offspring demonstrated an immediate aversion to the lead acetate solution. The offspring from the mothers receiving lead acetate during lactation demonstrated a greater aversion to the lead acetate solution than did the offspring from mothers receiving tap water. In addition, the lead acetate offspring drank more total fluid (tap water plus lead acetate solution) after weaning than the control offspring. The results indicate both learned and unlearned changes in motivation for fluid following ingestion of lead via the mother's milk in infancy.


Effects on offspring of chronic maternal methamphetamine exposure. Twenty-five Sprague-Dawley derived rats were administered 1.0, 3.0 or 5.0 mg/kg of methamphetamine HC1 or saline twice daily throughout gestation beginning on Day 1 of pregnancy. Rats were allowed to deliver normally; offspring were culled to 8 and sexed on Day 7, and weaned on Day 21. All females had viable litters except at the 5.0 mg/kg dose where 4 of 7 failed to deliver. The rats given methamphetamine delivered earlier than did controls. Weight gain over gestation decreased as a function of increasing drug dose. No gross anomalies were visible in the offspring. Litter size decreased as a function of increased dose and eye opening was delayed in the drug groups; the 5.0 mg/kg offspring made more conditioned avoidance responses than did the 3.0 mg/kg and saline offspring.


Development of dustbathing in Bobwhite quail. II. Effects of early pecking experiences. The development of dustbathing was facilitated among groups of Bobwhite chicks allowed to peck into dust as compared to chicks allowed to peck at dust or those inexperienced with dust. A 2nd study found a consistent, but nonsignificant, facilitation among chicks pecking into dust on Days 1-3 as compared to Days 4-6. In Study 3, groups of chicks pecked into dust on Days 2,4, or 6. Dustbathing development was facilitated among chicks pecking on Day 2, and inhibited among chicks pecking on Day 4, as compared to those pecking on Day 6. The only difference, however, between each of these groups and chicks with no pecking experience in dust (Study 1) was an inhibition of dustbathing among chicks pecking on Day 4.


Effects of age and genotype on acquisition of an active avoidance response in mice. Two experiments were conducted in which inbred C57BL/6J and DBA/2J mice were trained in an active avoidance jump-up task under distributed practice conditions at a variety of ages comprising a large part of their life-span. DBA/2J mice were found to be basically an escaping strain and exhibited little change in behavior as a function of age. C57BL/6J mice developed consistent avoidance behavior when training was initiated at 31-36 days of age. Avoidance behavior appeared to reach a peak in the 45-day-old group and progressively decreased in 145- and 560-day-old groups. Increased footshock intensity in old DBA/2J mice enhanced escape responding without increasing avoidance responding. Increased footshock intensity in old C57BL/6J mice enhanced avoidance responding.


Effect of undernutrition on metabolic compartmentation of glutamate and on the incorporation of [14C] leucine into protein in the developing rat brain. The effect of undernutrition on the rate of protein synthesis and the development of metabolic compartmentation of glutamate in the brain was investigated by using [U -14 C] leucine as precursor. In the brain of normal rats the incorporation rate of [14C] leucine into protein was at a maximum during the 3rd week after birth, but in the undernourished animal this rate was markedly lower. The biochemical maturation of the brain, followed in terms of the age-dependent increase in the glutamine/glutamate specific radioactivity ratio, was severly retarded in the undernourished animals, mainly as a result of a marked depression in the conversion of leucine carbon into glutamine. However these biochemical effects of undernutrition were reversible: on rehabilitation from Day 21-35 the rate of conversion of leucine carbon, both into proteins and glutamate and glutamine, was restored to normal.


Development of visually evoked responses and visually guided behavior in kittens: effects of superior colliculus and lateral geniculate lesions. The development of visually evoked responses (VER's) and visually guided behavior was studied in kittens for 3 months after unilateral lesions of the superior colliculus (SC) or lateral geniculate nucleus (LGN) made at an early age. Of 37 kittens studied, data are presented for 6 which met 3 criteria: survival to at least 90 days of age; adequate lesion size and location; and technically satisfactory VER's and behavioral observations at appropriate intervals. The SC and LGN lesions markedly reduced or eliminated different VER components in infancy, but only the effects of LGN lesions persisted to 3 months of age. Visual field behavior deficits occurred following both types of lesions, but only those following SC lesions persisted to 3 months of age. These results are interpreted in terms of the functional status of the structures mediating the VER's and behavior at the time the lesions were made.


Autoradiographic studies on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and its effect on DNA synthesis in Swiss mice. Light microscopic autoradiographic studies were made on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride in Swiss mice and on the effect of 1,2-dimethylhydrazine dihydrochloride on DNA synthesis, using the 3H-thymidine incorporation technique. In the first study, 14C-1,2-dimethylhydrazine dihydrochloride was administered subcutaneously or orally. Large amount of silver grains were found in hepatocytes and substantially lower amount of silver grains observed in the endothelial cells and epithelial cells of colon. In the second study, repeated injections or oral administrations of 1,2-dimethylhydrazine dihydrochloride were given to mice which subsequently received 3H-thymidine treatment. A somewhat higher amount of thymidine incorporation in DNA was noted in the epithelial cells of the colon of subcutaneously and orally treated mice at two occasions and a substantially higher amount in the endothelial cells of blood vessels in liver of mice treated by both routes than in the corresponding controls. In three instances, however, the amount of incorporation decreased; in the hepatocytes and endothelium at 1 week and 24 hr, respectively, after oral treatment, and in the epithelium of the colon at 3 months, after subcutaneous administration. In the mice treated with 1,2-dimethylhydrazine dihydrochloride, a significantly high amount of 3H-thymidine incorporation was observed in the endothelial cells of blood vessel in liver from which tumors later arose, and somewhat high in the hepatocytes in which tumor did not develop. In the epithelial cells of colon, no apparent relationship can be seen between these events. No association was seen in the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and tumor development in various cells.


Immunotherapy of cancer:  induction of tumor immunity with a mixture of tumor cell-BCG, and the effect of intratumor injection of BCG and of nonliving BCG preparation. The effect of syngeneic tumor cell mixed with BCG on intradermal tumor growth and on specific tumor immunity was evaluated. (1) With the use of several early transplant generations of syngeneic mouse tumors, the ratio of 1:10 to 1:20 of tumor cell--BCG was confirmed as the best for the present mouse--tumor system. (2) The development of immunity capable of eradicating distant tumor deposit was tested by varying doses of tumor deposit inoculated at the same time as the mixture of tumor cell--BCG. The remarkable efficacy of the tumor cell-BCG mixture on local tumor suppression (7/8) and tumor immunity (5/7) was proved with tumor burden of 10(5) cells or less. Control mice receiving BCG contralateral to the tumor site (10(5)) were not able to achieve tumor immunity (1/8), but were able to reject the local tumor (8/8). (3) The tumor cell--BCG mixture was as effective in a line of rat lung carcinoma as it was in the mouse system in rejecting both the local tumor and the tumor challenge injected intramuscularly. (4) Intratumor injection of BCG or nonliving BCG preparation (in which whole cell wall of BCG is attached to oil droplets) in primary tumors in mice previously sensitized with BCG led to a few instances of complete tumor regression in animals having tumor nodules of 3 to 10 mm in diameter. The survival period of animals treated with BCG or with nonliving BCG preparation was significantly longer than that of saline-treated controls.


Phytohemagglutinin skin test: diagnostic value for showing immunodeficiency in patients with cancer. The skin response to 5 mug of purified phytohemagglutinin (PHA) was studied in 299 subjects, including 58 normal controls, 92 patients without malignancies, and 149 patients with nonlymphomatous cancer. Other immunological responses, such as in vitro lymphocyte stimulation (62 subjects) and skin response to purified protein derivatives (PPD) (95 subjects), were tested simultaneously to examine their correlation with the PHA skin test. A positive reaction was observed 24 hr after intradermal injection of 5 mug of purified PHA in 56 (96.6%) of 58 normal controls, 40 (49.4%) of 81 untreated patients with cancer, and 24 (35.3%) of 68 cancer patients receiving anticancer therapy. Among 32 patients with gastric cancer tested, impaired skin reactivity to purified PHA was noted in patients in stage III or IV. A correlation was found between in vivo and in vitro responses to PHA in 46 (74.2%) of 62 individuals (P less than 0.001). The PHA skin test was repeated 4 times over a period of three months in patients without malignancies, and no significant change in tehir skin reactivity was detected. In repeated tests, the skin reactivity to purified PHA of patients with lung cancer varied depending on the clinical status, and the extent and type of anticancer therapy the patients were receiving. It is concluded that the PHA skin test is a simple diagnostic method for screening for immunodeficiency in cancer patients before and during the course of anticancer therapy. Other advantages of this test are that no presensitization is required and that it can be used repeatedly.


Potentiation of cytostatic effect of sulfur- or chlorine-containing purines and related ribonucleosides by amphotericin-B on cultured mouse leukemia cells. Synergistic effects of sulfur-containing purines and related ribonucleosides (6-thioinosine, 6-thioguanine, 6-thiocyanatopurine, 6-methylthioinosine, 6-thiocyanatoguanine, 6-thiocyanatoguanosine, 6-phenacylthioinosine, 6-nitrobenzlythioinosine, 6-(p-chlorobenzyl)thioinosine, 6-(p-nitrobenzyl)thioguanosine, 6-benzylthioinosine, 6-ethylthioinosine, 6-benzylthioguanine, 6-benzylthiopurine, 6-methylthiopurine, and 6-thiocyanatoinosine) and chlorine-containing purine and its ribonucleoside, (6-chloropuine and 6-chloropurine riboside), in combination with the polyene antibiotic, Amphotericin-B, on cell survival and synthesis of DNA were examined in mouse leukemia L5178Y cells. 6-Methylthioinosine, 6-thiocyanatopurine, 6-thiocyanatoinsoine, 6-methylthiopurine, and 6-thiocyanatoguanine (or -guanosine) among sulfur-containing compounds were strongly potentiated by Amphotericin-B, and 6-chloropurine riboside, which is electronically analogous to methylthioinosine, was also enhanced by the polyene. Thiocyanoto or methylthio group at position 6 of the purine ring seems to be important for the polyene-mediated potentiation. 6-Methylthioinosine alone had much greater effect on DNA synthesis of HeLa cells than on L5178Y cells, and Amphotericin-B failed to potentiate the action of 6-methylthioinosine in HeLa cells.


Electron microscopic study on the response of the normal canine brain to boron-neutron capture therapy. The response of normal cerebral tissue of dogs to boron-neutron capture therapy by the currently available improved method was studied by electron microscopy. Peripheral blood capillaries of the neutron-irradiated area in the left cerebral hemisphere were compared with their counterparts in the shielded and non-irradiated right hemisphere. No ultrastructural changes, as those noted in classical method of boron-neutron irradiation by the improved technique of boron-neutron capture therapy. There was no swelling of endothelial cells, disappearance of cristae of mitochondria, increased pinocytosis, disappearance of ribosomes, enlargement of Golgi apparatus, or increased appearance of endoplasmic reticulum. Basement membrane was not disrupted and was uniform. Pericytes, synaptosomes, and other glial elements remained intact. In contrast to the old clinical trials up to 1961, the renewed boron-neutron capture therapy is regarded not to cause serious damage to the central nervous system.


Antitumor activity of carbamoyl derivatives of 5-fluorouracil by oral administration. Antitumor activity of 1-carbamoyl derivatives of 5-fluorouracil was tested in L-1210 system by oral administration with two reference compounds, 5-fluorouracil and tetrahydrofuryl-5-fluorouracil (FT-207). The compounds tested were methyl-, ethyl-, isopropyl-, phenyl-, and cyclohexyl-carbamoyl-5-fluorouracil, and the therapeutic ratios (ILSmax/ILS30) of these compounds were 1.9, 2.2, 2.3, 1.0, and greater than 3.3, respectively, those of the two reference compounds being 1.7 and 1.0. Cyclohexylcarbamoyl-5-fluorouracil was the most effective of these compounds.


Streptococcal preparation as an activator of host-mediated immune response: cellular immunity and alternate pathway of complement. Streptococcal preparation, OK-432, was examined for its ability to initiate a host-mediated immune response. Aged individuals with negative skin response to phytohemagglutinin (PHA), as well as reduced in vitro blastoid transformation of lymphocytes, were treated with OK-432, and the response to PHA appeared in two out of three cases. The preparation was also demonstrated to convert C3 proactivator of complement when incubated with fresh human serum, as tested by immunoelectrophoresis, indicating the possibility that OK-432 might activate the alternate pathway of complement.


Induction of esophageal cancer associated with gastric cancer in a dog by N-ethyl-N'-nitro-N-nitrosoguandine. The experimental induction of gastric cancer was studied in four dogs given oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in solution. Esophageal cancer with the regional lymph node metastasis was found in one dog at autopsy, with concomitantly existing gastric cancer. This dog, which ingested a total amount of about 38 g of ENNG, died of weakness on the 513th experimental day. Three remaining dogs are still living and under observation.


Combination of non-specific immunopotentiation with Corynebacterium liquefaciens and chemotherapy in tumor-bearing mice. The effect of combining chemotherapeutics (Mitomycin-C, cyclophosphamide, or 5-fluorouracil) and immunopotentiator (anaeobic Corynebacterium liquefaciens) against Ehrlich ascites carcinoma in mice was examined. Mitomycin-C and cyclophosphamide were given intraperitoneally 2 days after the inoculation of tumor cells. 5-Fluorouracil was administered intraperitoneally for 7 consecutive days beginning from the second day after inoculation of tumor cells. C. liquefaciens was given intraperitoneally in various time regimens before or after the drug. The best prolongation of survival was observed when C. liquefaciens was given after the administration of Mitomycin-C or cyclophosphamide but no effect was seen in the combination of 5-fluorouracil and C. liquefaciens. These results suggest that non-specific active immunotherapy using C. liquefaciens may be a valuable adjunct to the conventional cytocidal anticnacer chemotherapy with agents such as Mitomycin-C or cyclophosphamide and the most important variable seems to be the time at which the immunopotentiator is given during the therapy.


[A cytogenetic analysis of the antimutagenic action of alpha-tocopherol on spontaneous and radiation-induced chromosomal mutations]. The antimutagenic effect of alpha-tocopherol at concentrations of 1-10(-5)-1-10 mcC/ml was studied with respect to spontaneous and radiation-induced chromosome mutations in Allium fistulosum L. and Vicia faba L. It is established that at these concentrations alpha-tocopherol exhibits a significant antimutagenic activity, decreasing the frequency of chromosome mutations more than by 40-50%. No changes resulting from the antimutagenic effect of alpha-tocopherol were observed in the spectrum of structual mutations of chromosomes.


[A medico-genetic study of the population of Western Pamir. VI. Local genetic differentiation in the populations of Western Pamir]. The article comprises the results on the analysis of the structure of the great Pamirs' population (of a higher rank) and of one of its parts, the subpopulation of the valley of the river Bartang. Wright's F coefficient was used for the statistical treatment of the data obtained in the course of the analysis. The FST estimates were obtained from the variances of the frequencies of the genes located in 5 loci (ABO, MN, P, Rh and P.T.C.) culculated for 23 samples of the great populations of the Pamirs and for 9 samples of the population of the Bartang river valley. The general inbreeding coefficient for the Pamirs FIT=0,0323, its random component FST=0,0017 and the non-random component FIS=0.0306.


[Viral genome integration with nuclear DNA in chronic viral infection]. A possibility of the integration of tick-borne encephalitis virus RNA in the host cell genome is studied under the condition of long-term chronic infection of HEp-2 cells. Molecular hybridization of viral RNA, labelled with 3H-uridine, and of DNA from intact and chronically infected cells was performed in 50% formamide with 0,4 M NaCl with subsequent investigation of the hybridization product by means of equilibrium centrifugation in CsSO4. 0,3 and 0,5 mg of DNA were used in hybridization experiments. It is shown that RNA obviously forms hybrids with DNA from chronically infected cells, whose density varied from 1,55 to 1,46 g/ml, depending on the proportion of RNA and DNA in the hybrids. When the amount of DNA increased, the number of DNA-RNA hybrids increased as well. It is concluded that in nuclear DNA of cells chronically infected with tick-borne encephalitis virus, there are DNA sites, homologous to viral RNA, which are absent in intact cells.


[The effect of cystamine on the outcome of dominant lethal mutations and reciprocal translocations in sex cells of mice subjected to gamma-irradiation in different doses]. Protective effect of cystamine (150 mg/kg) against genetic damages induced by gamma-irradiation in germ cells of male mice of CBA strain (at doses of 100, 300, 600 r) was studied. The application of cystamine decreased the frequency of dominant lethal mutations induced by radiation in sperms, spermatids and spermatocytes. The degree of the protective effect of cystamine depended on a radiation dose. The protective effect of cystamine was the highest at the radiation dose of 300 r. It was negligible at the radiation dose of 100 r and was completely absent at the dose of 600 r. Cystamine did not affect the rate of induced reciprocal translocations in the spermatogonia at all the radiation doses used.


[Cultured human fibroblast enzymes. III. Enzyme activity in a triploid strain]. Complex investigation of 5 enzymes was carried out in a cell strain with triploidy 69, XXY, derived from a human spontaneous abortus. The activity of 3 enzymes (acid phosphatase, lactate and malate dehydrogenases) in triploid cells proved to be significantly increased as compared to those of 3 diploid strains, whereas the activity of alkaline phosphatase was decreased. The activity of glutamate-oxalacetate transaminase did not change. The absence of the pronounced genetic dose effect and different alteration of the activities of the enzymes studied may be considered as an expression of a disbalance of enzymes in cytogenetically defective cells.


[Heterogeneity and several clinico-genetic correlations in epilepsy under inbred conditions]. The types of inheritance and clinico-genetical correlatins of epilepsy in 291 probands in conditions of inbreeding were studied. The data obtained confirmed the multifactorial (gene-polygene+medium) inheritance of epileptic and convulsive predispositions and contradicted the hypothesis of primarily recessive inheritance of epilepsy. Together with family forms of the disease, which were communicated mainly according to an uncertained and dominant type (rarely recessive type), there were existed forms of eipilepsy with incomplete genetical hereditary predisposition (which were observed in relatives of 2-3 generations only by epileptic features) and phenotypical forms concentrated in sporadic groups. There were found the dependences onthe rate of occurrence of secondary epilepsy (with or without epileptoidness), epileptoid psychopathy and children convulsions in relatives, on the type of inheritance, the age of manifestations, the form, polymorphism of the attacks, the severity of the developement of epilepsy, the expressiveness of epileptoidness in probands and high severity of the disease with distinct epileptoidness inbreeding families. The hereditary heterogeneity of epilepsy, associated, perhaps, with pleiotropy of epileptic (with or without epileptoidness) genes, was assumed. The found clinico-genetical correlaltions mightbe taken into account in medico-genetical prognosis of families burdened by epilspsy in analogous populational-demographic conditions.


[A complex study of strains of human cells with karyotype anomalies. III. An immunoelectrophoretic analysis of water-soluble antigens]. Antisera to diploid, trisomic and triploid embryonic fibroblast-like cells were obtained after hyperimmunization of rabbits. Immunoelectrophoretic analysis with these antisera revealed up to 9 water-soluble antigens in embryonic cells, which were present in skin fibroblasts from adult donors as well. Trisomic and triploid strains did not differ from the diploid ones by the spectrum of water-soluble antigens. The content of the number of antigens (especially of cathode fractions) in trisomic cells was significantly low as compared with those in control diploid cells, whereas in triploid ones it differed slightly. All the strains were characterized by the presence of proteins immunologically identical to alpha-globulin of human serum.


[The genetic heterogeneity of hereditary human diseases]. The paper deals with the probability regularities of mutations arising in the same locus (or nucleotide) in human populations. It is shown that in a population of constant size the number of such recurrent mutations tends to an equilibrium value. It is demonstrated that dynamics of this number of recurrent mutations depends on the population structure essentially. This phenomenon is illustrated by comparing non-subdivided and hierarchy populations of the same size.


[A representative model of the hierarchic structure of human populations]. The paper deals with the concept of a hierarchy population. The population is hierarchial, if it can be divided into a certain amount of subpopulations in such a way that the set may naturally break into classes (levels). A migration may exist from each sub-population or into a higher one. Such population structures are frequently encountered among the human populations. It is shown that in a hierarchial population a selection is more efficient than in a non-subdivided one. In this respect the role of small populations in evolution is suggested. It was possible to demonstrate that in a hierarchial population there was a higher degree of polymorphism, a higher velocity of the evolutional process, that in a non-subdivided population of the same size. Besides, the level of polymorphism in the hierarchial population increases monotomously with the growth of the amount of generations during rather a long period of time.


[A system for assessment of chemical substances on mutagenicity in man: general priniciples, practical recommendations and further elaboration]. As a basis of the suggested test-system, the following conditions are observed: 1) the economy of fulfilment in a short time; 2) the analysis of gene and chromosome mutations in germ and somatic cells; 3) the evaluation of mutagenic effects of not only substance, but also of the products of its metabolism; 4) including in the system only the tests which give the minimal variability between separate experiments; 5) the evaluation of dose-effect relationship. The practical scheme of testing is divided into two parts: a screening and a complete one. The screening programme consists of two tests: a) a test on microorganisms with a metabolic activation in vitro; b) a cytogenetic analysis of bone marrow of mammals. The complete programme of testing includes 4 tests: a) a test on microorganisms with a metabolic activation in vitro and in vivo; b) a test of dominant lethal mutations on mammals; c) a cytogenetic analysis of bone marrow of mammals; d) a cytogenetic analysis in the culture of human lymphocytes. There are good reasons for the principles of selection of substance for testing according to the screening and complete programme: population occurence, economic (or medical) significance, information about relative chemicals showing mutagenic, carcinogenic and teratogenic effect. In the group of chemicals which are to be tested according to the screening programme, such ones can be included: industrial chemicals, phosphoorganic insecticides, drugs which are taken by a limited group of patients. The group of chemicals which are to be tested according to the complete programme consists of the following ones: pesticides, food additices, widespread drugs, the chemicals of the group 1, if during one of the tests of the screening programme a genetic effect is detected. At the genetic risk estimation it is advisable to keep to the following rule: a positive effect, identified in any object of the system must in the direct meaning extrapolate on men. The quantitative evaluation of the mutagenic danger of a chemical can be determined by the increase of the spontaneous level of mutations in the test-object on the basis of an average dose and exposition of the given chemical in the human population. Those chemicals are subject to the quantitative evaluation, which have shown a mutagenic activity during any of the test-objects; they are also widespread and because of their social or economic value can not be replaced or excluded from taking. From the point of view of genetics any substance with a mutagenic activity is dangerous and must be prohibited from using or replaced by any other non-mutagenic chemical, or limited by the contact of persons of non-reproductive age. As a temporary measure from a hygienic point of view, it is recommended to evaluate this chemical as especially mutagenic and prohibit or limit its using, when its average population dose produces 1/10 or more increase of the spontaneous level of mutations.


[Structure-function features of the long-arm iso-X-chromosome of 45, X/46X, i(Xq) patients]. Differences in the morphology of the human iso-X-chromosome differentially condensed by the treatment with 5-bromodeoxyuridine were revealed by means of quantitative morphometry. It is shown that these differences are not random and are correlated with the asynchrony of the reduplication of iso-arms. It is assumed that the differences in the structural organization and in the chronology of the reproduction of iso-arms are due to the different degree of their inactivation.


[Dermatoglyphics in beta-thalassemia major]. The features of dermatoglyphics in 39 children with beta-thalassemia major and in 47 their parents are studied. The control were 70 healthy children. The patients with beta-thalassemia had more often the prevailence of whorls over other finger patterns. There was an increase of the "atd" angle and some increase in the ridge of counts. Parents had also an increase of the amount of whorls, but this increase was less pronounced than under beta-thalassemia. The changes of the dermatoglyphics in parents of children affected with beta-thalassemia major are suggested to ba a phenotypic feature of heterozygous carrier of the mutant gene.


[A comparative study of the cytogenetic effect of a series of phosphoorganic pesticides]. A comparative study of the effect of 12 organophosphorus pesticides on mice was carried out. A statistically significant increase of  the frequency of aberrant metaphases in bone-marrow cells of mice was induced by dipterex, metaphos, phosphamidon and imidan. No correlation between the toxicity and the mutagenic activity of the compounds studied was observed. The pesticides studied can be regarded as substances with a slight cytogenetic activity with respect to animals.


[Isolation and properties of several auxotrophic mutants of a highly virulent strain of the plague microbe]. 2432 stable auxotrophic mutants were selected from high virulent Yersinia pestis strain 20b after treatment with nitroso guanidine. They were deficient in amino acids (arginine, aspartic acid, citrulline, glycine, glutamic acid, histidine, isoleucine, serine, leucine, lysine, ornithine, proline, tryptophan, tyrosine, valiney, pyrimidine and vitamins (riboflavin, thyamine, nicotinamide). Some mutants were two- and three-fold dependent. The leucine-, histidine-, purine-dependent mutants were isolated with the high frequency. All the mutants, like their original strain, grew in R-form; they were sensitive to diagnostic phages, had pesticine-fibrinolysin-coagulase sustem (fraction I) and were calcium-dependent. P+ cultures of auxotrophs were not virulent for laboratory animals.


[Reparative processes of damaged chromosomes in non-stimulated human peripheral blood lymphocytes by the fractionated irradiation method and temperature variation]. The fractionation experiments were carried out on resting lymphocytes. Non-stimulated lymphocytes were X-irradiated at the total dose of 200 r separated into two equal parts by either 5-hour or 20-hour intervals. The whole blood samples were kept during the intervals between the exposure at the temperature of 20degrees C or 37degrees C. All the cultures were made after the last radiation exposure at 37degrees C. Dicentrics and centric rings were scored. It is shown that a fractionation effect takes place in resting lymlf-dose at 37degrees C and is absent at the temperature of 20degrees C. It is suggested that there is the repair in lymphocytes at the stage Go, at least, from the dose of 100 r.


[The influence of a magnetic field on chromosome sets and cell division]. An effect of stable magnetic field on karyotype and cell division of human lymphocytes from peripheral blood was studied in tissue culture. Comparative investigations were carried out with lymphocytes, whoch were treated with magnetic field of different tension (0,179; 0,391 and 0,600 Ts) and continuance (30 sec, 30 and 60 min). Lymphocytes, treated with stable magnetic field, were suspended in donor plasma and immediately cultivated after the treatment. The stable magnetic field was found to have a distinct mutagenic effect on cultivated lymphocytes of human peripheral blood. The increase in structural impairements of chromosomes correlated with tension of magnetic field and continuance of its effect. In structural impairements of chromosomes the chromatid gaps and breaks were more often observed but chromosome ruptures and pericentric clearances occurred more rarely. The effect of stable magnetic field on lymphocytes proliferation was studie. Under weak and transient using of magnetic field the proliferation was stimulated, but in rigid conditions--mitosis and blastic transformation were decreased. Continuous effect of magnetic field with weak tension did not inhibite the blastic transformation but influenced on the survival rate of cells in tissue culture, enhancing their lethality.


[The biochemical-genetic mechanisms of learning. II. Selection for high and low rate of acquiring a motor conditioned reflex]. Using the model of feeding motor conditioned reflex, polymorphism for the rate of the formation of this response was found in a population of laboratory animals. Selection for high and low rate of the formation of this reflex resulted in significant differences inthis character between two strains already in the second generation. These differences are maintained in subsequent generations. The existing henerogeneity for the rate of the formation of conditioned rsponse in the population is shown to be genetically determined.


[The mutagenic effect of different types of irradiation on the sex cells of male mice. VIII. Frequency of development of reciprocal translocations in the spermatogonia of mice subjected to chronic gamma-irradiation]. The frequency of reciprocal translocations in mice spermatogonia after the exposure to chronic gamma-irradiation at doses of 100, 200, 300, 600, 920 r, at the dose rate of 4,2 r/day was investigated. It was shown that the mutation frequency increased insignificantly with the increase of the radiation dose (y =0,8+0.0011x). The comparison of the data obtained with earlier results revealed no changes in the yield of translocations at the reduction of the dose rate from 10 r/day to 4,2 r/day. The investigation of the genetic radiosensitivity of mice spermatogonia after a chronic gamma-irradiation showed a tendency to increase in their radioresistance.


Nitrite test for methaqualone.

Nitrite test for methaqualone. Details of a simple qualitative test suitable for detecting milligram quantities of methaqualone are presented. A similar reaction undergone by 2,4, 6-triaminopyrimidine suggests that the mechanism involves diazotisation of an intermediate product.


The significance of amylase in forensic investigations of body fluids. Amylase levels in body fluids are reported, and it is shown that high amylase levels may occasionally occur in body fluids other than saliva. Low amylase levels are reported in a saliva component which has been previously described as being rich in blood group active material. The use of amylase activity in the localisation and identification of saliva is discussed in detail and guidelines for the interpretation of results are proposed.


[Pulmonary lesions observed in victims of an aircraft accident]. The authors have studied the lungs of some of the victims of a recent important aircraft accident. The results have been compared to the literature and to an experimental study of decompression effects on animals. The observed injuries were those which are classically reported, consisting of pulmonary haemorrhage, acute traumatic pseudo-emphysema and laceration. There was no characteristic distribution except for the traumatic emphysema which was mostly subpleural and on the edges of pulmonary lobes. The general aspect can be called tiger-like-lung; the injuries had a very heterogeneous distribution. The comparison of this study to the literature and to our experimental work shows that the observed pulmonary injuries were not characteristic and could not indicate the cause. The peculiar aspect of these lungs is well named "traumatic lung". It seems very difficult to determine the etiology of each elementary injury.


The toxicology of twelve cases of death involving methadone: examination of postmortem specimens. The drug levels in postmortem specimens from 12 cases of poisoning involving methadone have been determined using a general toxicological extraction method. In 8 of the cases, drugs other than methadone were also found. The relevant known case histories are described.


The recovery of alkaloids after their location on thin layer chromatograms. A method was developed for the recovery of 29 alkaloids from TLC plates after they had been complexed with either potassium iodoplatinate (for tertiary amines) or carbon disulphide (for primary and secondary amines). A comparison was made between the percentage recoveries of these alkaloids from 5 different types of TLC plate. In addition, the stability of these alkaloids on TLC plates over a 7 day period was studied. Assays were, where possible, carried out by UV spectrophotometry but gas chromatography was used for alkaloids which possessed low UV absorbtivity values. All the alkaloids extracted from TLC plates were examined by low resolution mass spectrometry.


Scanning electron microscopy in the investigation of bite marks in foodstuffs. The purpose of the present study was to assess the value of utilizing SEM in the examination of bite marks in foodstuffs. Six students, whose front teeth showed no conspicuous irregularities, were asked to bite off a part of some selected foodstuff consisting of butter, cheese, Norwegian brown sweet cheese, apples, carrots, bananas, chocolate and chewing gum. The texture and the varying stickiness of the foodstuffs seemed to be of significance as far as the details of the bite marks were concerned. In butter, chewing gum and Norwegian brown sweet cheese, fine details were discerned, thus justifying the use of SEM. Both scratch marks of the front teeth and impression marks of the incisal edges were studied. Only the latter revealed details of value for the identification by means of the SEM. Often small enamel defects were found at the incisal edge of the front teeth. These defects showed a great number of individually characteristic details. Where dentin was exposed at the incisal edge, further characteristic details could also be found. Thus, the use of SEM seemed to be of value in special cases as a supplement to conventional investigation methods.


Dental identification of fire victims.

Dental identification of fire victims. In a recent review of 100 cases of dental identification, 60 were involved with fire. This figure excluded 3 air crashes in which 120 victims died, and in which fire was of a minimal consideration. This preponderance of burn cases prompted some observations and some queries, relative to fire, their type, temperatures and durations. Burn cases present a fund of useful knowledge in identification purposes.


Identification and differentiation between colored pencils. With pencils of any color, the first step certainly involves visual examination to distinguish between the color tints and to study the quality of the stroke itself. In many instances by this step alone, 2 pencils can be distinguished if they are the product of 2 different manufacturers. In other words, the most useful of all tests is the visual examination. In the case of red pencils, infrared luminescence reveals significant information and should be resorted to in those instances where two questioned strokes are extremely similar. Study under ultraviolet radiation may also help to establish similarities or differences which are not readily discernible by visual examination. However, reflected infrared examination and study with dichroic filters have no particular value when dealing with red pencil although chemical spot testing may be of some assistance. In the case of blue pencils, a number of brands absorbs infrared radiation to a different extent and some give off distinctive infrared luminescence, so that these 2 tests can assist in distinguishing between certain similar colors or tints. Also, study through dichroic filters has value. Thus, the combination of these 3 tests can be of some advantage, but in most instances, particularly with dark blues, examination under ultraviolet radiation is not particularly helpful. Chemical spot testing has some limited advantages but generally only in combination with all other tests. In the case of green pencils, the same pattern of testing may be used as with blues. Many of the greens absorb infrared rays and some have bright infrared luminescence. Ultraviolet radiation can cause certain greens to fluoresce in a distinctive way. Thus, with each color studied, differences can be revealed and similarities established. Colored pencils are a distinct group of writing instruments. Within any color classification, there is a variety of shades or tints. Although it is not psosible to determine the make of pencil used in any particular writing, it is possible under many circumstances to distinguish between the work of different makes and grades of red, blue and green pencils, as well as other colors which have not been covered by this paper. While visual examination will separate the many different makes, other tests are described which will further assist in grouping or separating colored writing strokes. For a number of reasons, and particularly because of manufacturing procedures of different companies, not every make of pencil is distinctive, but there has been found to be a definite variety within each color group, and many makes are distinguishable.


The significance of the postmortem discovery of gastric contents in the air passages. The significance of the finding of gastric contents in the air passages at postmortem examination is discussed and references quoted to indicate that without clinical corroboration of aspiration of gastric contents, the purely autopsy diagnosis of such aspiration is to be regarded with reservation. In a series of routine medicolegal autopsies, gastric contents were shown to be present in a quarter of all cases, irrespective of the cause of death. This figure also appeared to hold for autopsies upon infants and the special dangers of ascribing infant victims of the "sudden death in infancy syndrome" to the aspiration of vomit is pointed out.


Liability and compensation independent of medical negligence: the new Swedish system. On the 1st of January 1975 a new system of Treatment Injury Insurance was introduced in Sweden. (Until then the rules of tort law governed all liability insurances.) Almost all medical attendance within, and much of the attendance outside, hospitals is managed by County Councils (Landstingen). The new insurance is contracted by the managing County Council to a pool of Swedish Insurance Companies. The total amount of the premiums for this first year is calculated to be 16 milj Skr (4 milj $ = 1/2$ per inhabitant per year). By treatment injury shall be understood "injury or illness of a physical nature...as a direct consequence...of...treatment (excepting natural or probably consequences of an act justified from a medical point of view), or of incorrect result(s) of technical examination or clinical diagnostics, or of accidents in hospitals, doctors' offices or in connection with ambulance services".


[Local cryosurgical management of colonic and rectal cancer]. Complex experimental investigations created the basis for cryosurgical treatment of colon and rectum cancer. 27 patients were chosen for cryotherapy according to strict indication. Especially developed instruments and technique are presented. A three year-follow up-study shows 19 patients alive, most of them without recurrence or troubles. Immediately after starting with cryosurgical treatment patients recover remarkably. In collaboration with the Dept. of Microbiology (Rhein.-Westfäl. Techn. Hochschule Aachen) the possibility of a special cryoimmunological response is investigated.


[Therapy of malignant melanoma].

[Therapy of malignant melanoma]. The treatment of malignant melanoma is described (preoperative, one-time radiation with 10 000 roentgen, excision, endolymphatic radionuclid therapy in localisation of the tumor on the legs, following operative and radiological treatment in metastatic tumors). The statistical reports are analyzed. It seems that the survival rats is not dependent alone on the extent of the surgical intervention.


[Activation of the blood coagulation system during gram-negative infections and endotoxemias]. Blood coagulation may be activated by the extrinsic or intrinsic pathways. The extrinsic clotting system is put into action by tissue thromboplastin, originating from injured tissue cells, but also from damaged leukocytes and erythrocytes. Tissue thromboplastin is a phospholipoprotein with an enzymatic component, capable of converting the clotting factor VII to its activated form, factor VIIa, which in turn activates factor X. The factor Xa-complex (containing also factor Va, phospholipid, and calcium) is the prothrombinconverting principle. The intrinsic clotting system is based on factors which are contained in the circulating blood. Its activation requires the availability of phospholipid and of activated factor XII (factor XIIa), or factor XIa. Factor XII is activated by collagen, i.e., whenever the vascular endothelium is injured, and to a lesser extent also by "activated" blood platelets. Platelets in turn are activated primarily by thrombin, collagen, and, in a self-perpetuating process, since all these materials are released from activated platelets, also by adenosine-5-diphosphate, adrenaline, and serotonin. The activation of platelets leads to a variety of morphological and biochemical alterations, culminating in their aggregation and in the selective release from storage organelles of different substances, among them those mentioned above. Of particular importance is the fact that in the course of platelet alterations, procoagulant phospholipid also becomes available on the platelet surface. The significance of the activation of the intrinsic system is seen in the possibility of the initiation of a self-sustained process which, after a primary event, e.g. vascular or cellular injury, will continue to convert prothrombin into thrombin. The effects of endotoxin on the blood clotting system show striking species differences. In the rabbit, endotoxin, with the involvement of factors of the complement system, will directly act upon blood platelets and thus initiate intravascular, intrinsic coagulation. In man, endotoxin remains without a direct effect on platelets and alternative possibilities of initiating thrombin formation must be considered. One possibility is extrinsic activation via tissue thromboplastin from injured leukocytes. Another pathway, which is supported by several experimental findings, starts out with endotoxin-mediated endothelial damage. Endothelial cells are in fact severely affected by endotoxin and may even be removed from the vascular wall, thus making accessible the subendothelial activator of factor XII. Thrombin in turn affects the vascular endothelium: therefore, one initiated, the process of intravascular activation of coagulation will perpetuate, this the more as platelets in turn will be stimulated into activity. The possible intervention of other vasoactive factors must also be considered...


[Concentration of antibiotics in the human lung. Clinical studies of Reverin distribution in various pulmonary lobes]. On 12 patients with bronchial carcinoma serum and lung-tissue concentration levels of tetracyclin were measured. The concentration levels of the antibiotic were twice as high in the lung tissue as in the serum. In the lower lobe of the lung significantly higher values were measured than in the upper lobe. The demonstrated tissue levels of Pyrrolidino-methyltetracyclin (Reverin) in human lung are high enough to be effective in pulmonary bacterial infection.


[The keloid. Thoughts on therapy].

[The keloid. Thoughts on therapy]. The possibilities of treatment of prophylactic treatment of keloids are described based on results in 96 patients. First therapeutic trials should be conservative. If the external treatment is not successful, the treatment with X-ray in combination with surgical measures in the best therapy.


[Human genetics. Clinical and preventive aspects from the viewpoint of obstetrics and gynecology]. Clinical genetics and genetic counselling can be applied effectively only, if close cooperation is secured between the clinical geneticist and the physician in the field. The limited capacity of all institutes of human genetics makes it mandatory that general practicioners and the various specialists preselect patients for special genetic work-up and counselling. Quite often it is their obligation also to secure and document findings, prerequisite for effective genetic counselling, which would be lost otherwise. Special points are discussed and illustrated with typical cases.


[Treatment of heart-rhythm disorders in infancy and childhood]. According to own experiences and after a review of the literature a survey of therapy of cardiac arrhythmias in infancy and childhood is given. In this age group most of the occurring cardiac arrhythmias are harmless and pass without serious circulatory disturbances. Therefore in these cases no specific treatment is necessary, except of course the treatment and management of the disease which is causing the arrythmia. This report is concerned more detailed with the therapy of rhythm disturbances which are life threatening or will become fatal if they continue untreated for a longer period. In spite of the therapeutic recommendations given we are aware of the fact that it is impossible to predict the success of therapy. This turned out to be so especially in the case of tachycardias. The difficulties in long-term management of postoperative heart block are mentioned. Antiarrhythmic drugs, their indications, efficacy, side-effects and contraindications are listed in separate tables ("FdM-Tabellen für die Praxis" Nr. 30/1975, Fortschr. Med. 93, 30: 1447, 1975).


[Oto-vertebral syndrome].

[Oto-vertebral syndrome]. The oto-vertebral syndrome is supposed to be caused by an early embryonic exogenous damage which at the same time affects the development of the ear and vertebral column and possibly also causes cardiac anomalies. Animal studies showed that the malformation syndrome originates in the 6th-7th week of embryonic development. The extent of the malformations of the ear and the vertebral column varies. Frequently seen are dysplasia of the external ear and dystopia and atresia of the external ear canal as well as vertebral malformations, mostly involving the thoracic region. Only 4 case reports have been published in the literature. The differential diagnosis includes Goldenhar-syndrome, oculo-vertebral syndrome. Thalidomide-syndrome and chromosomal aberrations. Therapy depends on the extent of the malformations. In case of atresia of the ear canal hearing is first of all improved with a hearing aid, operative procedures are to be planned later on. Child development is promoted with acustic stimulation.


[Serum bilirubin determination in newborn infants. A new micromethod for the determination of serum of plasma bilirubin in newborn infants]. A micro-method for determination of bilirubin concentration (c) of plasma or serum from newborns was developed. Photometer-readings of the extinction (E) of diluted serum (S) at the bilirubin absorption-band were done against diluted serum as blank, made free from bilirubin by the oxydative power of Chloramin T. Reagents: 1/15 M Na2(HPO4)/K(H2PO4) buffer pH 7,4 (B) and 2 g/dl Chloramin T in B(C). Blank: 0,6 ml C + 0,02 ml S; sample: 0,6 ml B + 0,02 ml S. Reaction time: 4--8 min; filter Hg 436 nm; 1 cm light-path. c (mg/dl) = E X 43,5. Accuracy was determined by a calibration curve (x: mg/dl c of diazo-method; ): E of micro-method); b = 1,008. Reproducibility in series at 14,2 mg/dl resp. 47,9 mg/dl was 1,5% resp. 1,6%. Linearity between E and c is good up to 48 mg/dl c. Specifity was only reduced by serum hemoglobin (h). Sodium heparinate (50 E./ml S) and carotin (952 microgramm/1) had no effect upon E; plasma anticoagulated with heparinate therefore can be used instead of serum. Concentration of h is without importance for clinical purposes; 100 mg/dl h causes about 0,2 mg/dl wrong depression of c.


[Chronic pancreatitis].

[Chronic pancreatitis]. Chronic pancreatitis is considered a progressive damage of the anatomic structure of the pancreas. Alcoholism and diseases of the bile tract are to be considered in the first place among the many etiologic factors. The pathogenetic principle is an intrapancreatic activation of enzymes combined with autodigestion. The leading symptome is abdominal pain. Besides laboratory tests and X-ray examination the  main methods of diagnosis are the examination of endocrine and exocrine function of the pancreas, endoscopic-radiological cholangio-pancreaticography (ERCP) and sonography. More than half the patients with chronic pancreatitis can be treated satisfactory by a diet poor in fat, the abstinence of alcohol and the substitution of enzymes.


[Non-epileptic episodes of unconsciousness. Pathophysiology and clinical aspects]. Originally syncopes were defined as seizures without organic (W. Schulte), nowadays all periods of unconsciousness not caused by epilepsy but by primary or secondary cardiovascular diseases are included. Precipitating factors, pathophysiology, symptoms and differential diagnosis are discussed.


[Prognostic criteria in multiple sclerosis]. The clinical data of 812 patients with Multiple Sclerosis were recorded on optical mark reader-sheets and analyzed with the help of a computer program. In addition to statistical data on the sex ratio, mean age at onset, mean duration of illness the influence of some factors on prognosis were evaluated. The ability to work and walk was dependent on the duration of the disease and the type of the course, independent however of the age at onset and of the sex. The correlation between the clinical data and laboratory results is expected to give clues to the etiology and/or pathogenesis of the disease.


[Treatment of psoriasis. New possibility of psoriasis treatment using long-wave UV light and a photosensitizer]. Report about the effect of the therapy of psoriasis with topical application of Meladinine and blacklight as inaugurated by Mortazawi and Oberste-Lehn as well as Tronier. In a high percentage of patients treated a regression of the lesions could be observed. As this therapy is possible for ambulatory patients the number of cases in need of stationary treatment may be reduced.


[New method for the more precise differentiation of melanomas. Significance of formalin-induced fluorescence for the prognostic evaluation of malignant melanomas]. The value of formalin-induced fluorescence method in diagnosis of malignant melanoma. With this method in the case of malignant melanoma the melanin producing cells can be clearly demonstrated. Shape and arrangement of the tumor cells in the epidermis are to be judged accurately. It is possible to distinguish special cases of lentigo maligna melanoma from superficial spreading melanoma. In the first kind of tumor the cells mostly have long dendrites like melanocytes, whereas in superficial spreading melanoma we predominantly find round cells which only seldom show dendrites. Furthermore the fluorescence method is of great value in exact determination of the level of invasion. Only in this way it is possible to detect single tumor cells in connective tissue, in vessels and in fat tissue. Also in examination of lymph nodes even single cells or small clusters of melanoma cells can be detected.


[Acquired ichthyosis as a cutaneous symptom of Hodgkin's disease. Paraneoplastic syndrome]. A case-report of a patient with acquired ichthyosis is given. The symptoms of the main disease-ascites, heavy edema, cachexia and general dissolution-became manifest at the same time as the cutaneous manifestations. The histological examination of a neck lymph node showed metastases of a carcinoma of the gastrointestinal tract. The autopsy resulted in the diagnosis M. Hodgkin. The dermatosis (ichthyosis) is explained as cutaneous pareneoplastic syndrome. The pathogenesis of the disease and the possible role of A-vitaminosis resp. disturbance of vit. A metabolism in the manifestation of the cutaneous manifestations is discussed.