A mutational assay system for L5178Y mouse lymphoma cells, using hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) -deficiency as marker. The occurrence of a long expression time for mutations induced by X-rays and EMS. The development of a system for the detection of somatic cell mutation to hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) (EC 2.4.2.8) deficiency in L5178Y mouse lymphoma cells is described. The selection of mutant cells was not influenced by the concentration of the selective agent 6-thioguanine (6-TG). In addition, all the mutants selected, spontaneous as well as induced ones, showed a complete loss of HGPRT activity. In reconstruction experiments, in which mutant cells were mixed with wild-type cells, the recovery of mutant cells was only markedly influenced when wild-type cells were seeded in a cell density ten times higher than the one, 5-10(4) cells/ml, used in subsequent induction experiments. X-irradiation and treatment with ethyl methanesulfonate (EMS) increased in the mutation rate above the spontaneous background. A clear-cut dose-dependent mutagenic effect after exposure to X-rays was measured. The rate of induced mutations at the HGPRT locus in lymphoma cells was 1-3-10(-7) per R, as determined after exposures of 200, 300, 400, 500 and 600 R. The time the cells needed to express their mutations was much longer than 48 h. Further study of this phenomenon showed that the optimal expression time for TGr-resistant mutants in L5178Y cells was 6 to 7 days. No indication for a dose-dependent effect on the optimal expression of the mutants was found.


Private Initiative in PSRO.

Private Initiative in PSRO. Private initiative in PSRO (Pl) is a privately funded joint effort by five major professional organizations to influence the implementation of PSRO on behalf of the public interest. Working with five PSRO's, PI is testing a form of concurrent quality assurance and its effect on the immediate outcomes of hospital care. The project also promotes and evaluates participation in local PSRO's by representatives of the general public. The operating costs of PSRO's and their impact on hospital utilization and reimbursements by Medicare and Medicaid are being prospectively determined. A central issue addressed by PI is growing encroachment by the central administration of PSRO on private medicine's traditional responsibility for assuring the quality of care. PI seeks improved means of rendering a satisfactory public accounting in quality assurance as an alternative to federal regulation of this elemental professional function.


Expression of H-Y antigen in human males with two Y chromosomes. To determine whether the gene that controls the expression of H-Y ("male") antigen on human cells is Y-linked, we have compared the H-Y antigen level in normal males with that in three males with two Y chromosomes. Leukocytes from one XXYY and two XYY males express more H-Y antigen than leukocytes from normal XY males. We conclude that a structural gene or positive regulatory gene for H-Y antigen is on the human Y chromosome. Testing for the H-Y antigen may be of benefit in patients who have signs of masculinization but who lack an identifiable Y chromosome. Positive results for the H-Y antigen would be tentative evidence that the corresponding region of the Y chromosome was present, perhaps as part of a translocation, despite the absence of a typical Y chromosome.


Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex. By subcutaneous implantation of 2 or 13 morphine pellets (75 mg morphine/pellet), rats were made tolerant to, and dependent on narcotic analgesics. Occipital cortex slices from dependent animals and placebo-implanted controls were incubated with (-)-3H-noradrenaline and subsequently superfused with physiological salt solution. The accumulation of 3H-noradrenaline was not changed by pretreatment with 2, but was slightly decreased by pretreatment with 13 morphine pellets. The overflow of tritium evoked by electrical field stimulation was higher in slices from morphine-implanted rats than in those from placebo controls. Morphine and levorphanol, added in vitro, inhibited the stimulation-induced overflow of tritium at similar concentrations and to a similar degree in slices from morphineand placebo-pretreated animals.--It is concluded that, during chronic treatment with morphine, an adaptation takes place in the brain to compensate for the acute effect of narcotic analgesics, i.e. inhibition of the release of noradrenaline by nerve impulses. The chain of events from the drug-receptor interaction to the depression of the release process can be escluded as substrate of this adaptation. During withdrawal, the compensatory changes provoke an enhanced increase of extracellular noradrenaline during nerve impulses.


Visual perception of line direction in patients with unilateral brain disease. The accuracy of identifying the slope of briefly exposed lines was assessed in patients with lesions of the left or right hemisphere and in a group of control patients without history or evidence of brain disease. The frequency of impaired performance was remarkably high in the patients with right hemisphere lesions. In contrast, the patients with left hemisphere lesions did not perform differently from the control group. Visual field defect, aphasic disorder, and age were not related to performance level. The striking interhemispheric difference in performance on this visuospatial task suggests its further development for clinicodiagnostic purposes.


Fusariosis, myasthenic syndrome, and aplastic anemia. Fusarium, a fungus, produces a potent mycotoxin that, when ingested with contaminated cereal grains, produces a serious illness in man called alimentary toxic aleukia (USSR) and Akakabi-byo (Japan). The illness includes gastrointestinal symptoms and weakness and if ingestion of Fusarium contaminated grain persists, culminates in aplastic anemia. A 66-year-old woman had Eaton-Lambert syndrome and a clinical course similar to alimentary toxic aleukia. Several months before her death, pancytopenia, initially thought guanidine-induced, developed and progressed to aplastic anemia despite discontinuation of guanidine 2 1/2 months before death. Autopsy showed numerous granuloma in the liver, spleen, esophagus, and cecum from which Fusarium oxysporum was isolated. Although the unique finding of systemic fusariosis may relate to altered host resistance terminally, a causal relationship with her defect of neuromuscular transmission and/or aplastic anemia is a distinct possibility.


Neurofibrillary changes after acute experimental lead poisoning. Following acute tetraethyllead intoxication in rabbits classic neurofibrillary tangles develop. As studied by electron microscopy, such tangles develop in hydropic degenerating neurons and consist primarily of bundles of 200 A diameter smooth tubules of enormous length. In two of 16 animals a few twisted tubules (periodicity of 800 A) also could be found. The significance of these lead-induced twisted tubules, so characteristic of Alzheimer's pre-senile dementia in man, is discussed.


Cerebrospinal fluid acid-base and lactate changes after seizures in unanesthetized man II. Alcohol withdrawal seizures. Acid-base changes in arterial blood and lumbar cerebrospinal fluid were correlated with simultaneously determined lactate levels in patients admitted after alcohol withdrawal seizures. Arterial and cerebrospinal fluid lactate was elevated in association with a marked respiratory alkalosis in 13 patients studied 5 to 12 hours after the seizure. Similar elevations of arterial and cerebrospinal fluid lactate were found in five patients during delirium tremens without antecedent withdrawal seizure. The cerebrospinal fluid lactate determined on admission appeared to correlate best with the length and severity of the alcohol withdrawal syndrome that developed in patients after a withdrawal seizure.


Ocular bobbing: the myth of its localizing value. Ocular bobbing is a distinctive eye movement disorder seen in patients with pontine dysfunction. The typical phenomenon consists of abrupt, spontaneous downward jerks of the eyes with a slow return to the midposition in association with paralysis of spontaneous and reflex horizontal eye movements. Bobbing was present in a patient with acute cerebellar hemorrhage in whom no intrapontine lesions could be demonstrated. The myth that this sign is specific for intrapontine destruction has to be abandoned.


Neurogenic influence on local cerebral blood flow. Effect of catecholamines or sympathetic stimulation as correlated with the sympathetic innervation. Local cerebral flow was measured continuously in conscious rabbits (thermoclearance technique), and PaO2 and PaCO2 were recorded by mass spectrometry. Though inhalation of CO2 increased flow in caudate nucleus and lateral geniculate body, catecholamines only had effect on caudate nucleus where isoproterenol enhanced and epinephrine and norepinephrine reduced flow. Reduction by electrical stimulation of the neck sympathetic trunk was particularly evident in the caudate. Blood flow increased markedly in both regions after preganglionic conduction blockade. The effects were correlated with a significantly lower degree of sympathetic arteriolar innervation (fluorescence histochemistry) in the lateral geniculate body compared with the caudate nucleus.


Evidence of subnormal function of association cortex in presenile dementia. Regional cerebral blood flow (rCBF) was measured in 23 patients with organic dementia (17 patients with Alzheimer's disease and six with low-pressure hydrocephalus [LPH]). The flow of gray matter was significantly reduced, especially in occipito-parieto-temporal regions, as well as frontally in some patients. During activation with psychologic tests, reading, etc., the flow augmentation in the association areas in the demented patients was not as marked as in nondemented controls. Instead, in some patients, a flow diminution was recorded in the same regions (intellectual steal). Organic dementia appears to be accompanied by a low activity in the association cortex and a reduced ability to activate these regions during mental effort.


Macro square wave jerks.

Macro square wave jerks. Quantitative eye movement recordings in a patient with multiple sclerosis who had both macro square wave jerks and an internuclear ophthalmoparesis supported the concept of an internal brain-stem monitor that mediates corrective eye movements. A brain-stem model of this monitor illustrates the patient's motility disorder and the normal function of providing synergistic version and vergence corrections for dysmetric eye movements. Thus, the careful study of pathologic disturbances provides information relevant to the normal operation of the ocular motor system.


Electrophysiologic analysis of aberrant regeneration after facial nerve paralysis. The blink reflex, ordinarily elicited only in the orbicularis oculi and not in other facial muscles, can be used to detect synkinetic movements objectively. In 26 of 29 patients tested at least 4 months after facial nerve degeneration, an aberrant blink reflex was recorded in the orbicularis oris on the affected side. Of the remaining three, one had injury to only a peripheral branch of the facial nerve and experienced a return of function with no evidence of synkinesis; in the other two, the affected side of the face was totally paralyzed in the absence of facial nerve regeneration. Synkinetic movements ultimately will occur in nearly all cases following facial nerve degeneration provided that the facial nerve regenerates from a proximal site.


Subacute combined degeneration of the spinal cord with cystinuria. An 18-year-old man had noticed increasing difficulty in walking for 4 years. Examination disclosed spastic paraparesis and posterior column signs suggestive of subacute combined degeneration of the spinal cord. Urinalysis, urinary thin-layer chromatography, and intestinal biopsy disclosed typical cystinuria. Pernicious anemia and other known enteropathies were excluded. Although this could be a chance association of cystinuria and subacute combined degeneration, one other paper has reported a cystinuria patient with similar neurologic findings. A chance association between cystinuria and nonpernicious anemia subacute combined degeneration of the spinal cord should occur only once in 120 million individuals. Thus, identification of only a few more cases would suggest a pathogenetic link between the two disorders. These observations emphasize the need to search for neurologic signs in patients with cystinuria and to screen the urine of patients with spinal cord signs of obscure origin for cystinuria.


Studies in myasthenia gravis. Pyridostigmine-C14 metabolism after thymectomy. Pyridostigmine-carbon 14 (P-C14) excretion studies in myasthenia gravis patients who had had thymectomies failed to produce any significant difference from results observed in myasthenic patients who had not had thymectomies. Thus, change in P-C14 metabolism cannot help explain decreased anticholinesterase requirements and electromyographic changes observed in some patients following thymectomy.


Suppression of expulsion of Aspiculuris tetraptera in hydrocortisone and methotrexate treated mice. Hydrocortisone treated male and female mice, given a primary infection with Aspiculuris tetraptera, did not reject the worms during the third week of infection. Mice given hydrocortisone during the first week of infection had elevated worm burdens on day 10, suggesting that some worm loss was encountered during the anterior migration in control mice. Furthermore, this temporary period of treatment was sufficient totally to suppress rejection and to allow the parasite to persist until day 28. Methotrexate also significantly delayed rejection, but larval growth was retarded in treated mice. These results, it is suggested, add strength to the hypothesis that the loss of A. tetraptera in a primary infection in mice, is an immunological phenomenon.


Suppression of the immune response to Trichuris muris in lactating mice. Mice infected with Trichuris muris during lactation were unable to expel the infection at the normal time, but expulsion occurred when lactation was terminated. Suppression of expulsion was uniform in mice suckling more than five young but variable with smaller litters. Mice exposed to a primary infection while lactating were shown to have serum antibodies capable of passively transferring immunity to recipient mice and showed near normal immunity to a secondary infection given after lactation had ceased. Acquired immunity to T. muris was also suppressed by lactation, but the worms which became established in lactating resistant mice were fewer and smaller than those in non-lactating, non-resistant controls. It is suggested that the suppressive effect of lactation in this host-parasite relationship is exerted on the second, lymphoid cell-mediated phase of worm expulsion.


Effect of exteroceptive feedback in controlling electrodermal activity in pre-conditioned fears. Ss with a strong fear of snakes were taught to increase and decrease their skin resistance during practice sessions with a continuous visual display. Ss were not aware that they were increasing or decreasing their levels of skin resistance and attempted only to influence the magnitude of the multimeter display, the polarity of which was controlled by the experimenter. The study used a within-subjects reversal design to investigate whether bidirectional control could be acquired over skin resistance level. To investigate whether this acquired control could affect the magnitude of elicited pre-conditioned autonomic responses, a pre- and post-training comparison was made between the GSRs elicited during test sessions in which Ss viewed slides of snakes while attempting to influence their electrodermal activity with the assistance of the visual display. The results suggest that Ss are able to acquire voluntarily bidirectional control of their level of skin resistance with continuous visual feedback and that this control can either depress or facilitate the magnitude of pre-conditioned emotional responses as a function of visual feedback.


Cognitive and personality factors associated with the double trapezium illusion. 76 pairs of 9- to 11-yr.-old twins (41 female, 35 male) who were discordant on the magnitude of error for the double trapezium illusion were given the Children's Personality Questionnaire and the Wechsler Intelligence Scale for Children (WISC). The Wilcoxon matched-pair signed-ranks test was used to determine whether the twins with relatively smaller magnitudes of error than their co-twins also manifested systematic differences on the personality factor scores and the WISC subtest scores. Among the female pairs, twins with smaller magnitudes of the illusion were relatively more stable (Factor C), more shrewd (Factor N), obtained higher scores on Similarities and Digit Span, and had longer reaction times before responding to the figures. Among the male pairs, similar trends were found but the differences were not as pronounced. The results are discussed in terms of Piaget's theory concerning children's deployment of attention and Kagan's reflective-impulsive dimension in children's cognitive judgments.


Simple parametrizations of maximum expiratory flow-volume curves. Four elementary mono-compartmental lung models yield parametrizations of Maximal Expiratory Flow-Volume curves of normal subjects. The respective analytical functions are fitted to the measured curves and the mathematically derived ventilation indices are compared with standard measured data. While individual values of resistance and compliance seem devoid of a simple physical interpretation, their product indeed matches the models.


Glucose transport in the short loop of Henle of the rat kidney. Its characterisation by transport constants. Short loops of Henle in rat kidneys were perfused with proximal tubular equilibrium solutions containing radioactive D-glucose. The transport rates follow 2-parameter kinetics: Km = 5.7 mmol/I. Vmax - 145 X 10(-12) MOL/MIN-1; Phlorrhizin inhibits transport almost completely, indicating little passive diffusion of D-glucose. The glucose transport capacity in the short loops of Henle, presumably in the pars rects, is much smaller than that in superficial segments.


Metabolic changes in the quadriceps femoris muscle of obese people. Enzyme activity patterns of energy-supplying metabolism. 1. In biopsy samples of the lateral part of m. quadriceps femoris of 49 obese and 14 lean persons the activities of the following enzymes were investigated: triosephosphate dehydrogenase (TPDH), glycerolphosphate: nad dehydrogenase (GPDH), lactate dehydrogenase (LDH), hexokinase (HK), malate: NAD dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOADH). 2. The muscles of obese had an increased activity ratio of TPDH to CS and to HK, respectively, caused in muscles of female obese subjects by an increase of TPDH activity, in those of obese men rather by a decrease of CS and HK activities. 3. Cluster analysis brough to light the existence of three major groups. Group 1 (low activity-low LDH group), consisting of muscles of female obese subjects only, exhibited low activities of all enzymes investigated, that of LDH being so low as to possibly induce a serious deficiency of anerobic metabolism under working conditions. Group 2 (medium enzyme activity group) was characterized by medium enzyme activities, similar to that of lean controls (included in this group). This consisted of subjects of both sex. Group 3 (high enzyme activity group) consisted of obese of both sex. It was distinguished by high enzyme activities, especially of LDH. It is suggested that the groups of similar enzyme activity patterns might reflect different stages, types and/or genesis of obesity.


The spinal route of sympatho-inhibitory pathways descending from the medulla oblongata. 1. The effect of making discrete lesions in the cervical spinal cord on the brainstem elicited inhibition of a spinal somato-sympathetic reflex response has been studied in anaesthetized cats. 2. Electrical stimulation within three areas of the medulla caused an inhibition of the spinal component of the reflex response elicited in thoracic white rami communicantes by stimulation of intercostal nerves. The three medullary areas studied were the ventrolateral medulla and the caudal rephe nucleus, from where bulbospinal monoamine neurones originate, and the ventromedial reticular formation. 3. The inhibitory effects of stimulation in the ventrolateral medulla and raphe nucleus were abolished by the destruction of parts of the ipsilateral dorsolateral funiculus of the cervical spinal cord, whereas the inhibition produced by ventromedial reticular formation stimulation was abolished by lesions which included part of the ventral quadrant of the cord. 4. The time course of the inhibitory effects of electrical stimulation of descending sympatho-inhibitory tracts in the cervical spinal cord was studied in unanaesthetized decerebrate cats spinalized at C1. Inhibition obtained from the dorsolateral funiculus characteristically had a longer time to onset than inhibition obtained from the ventrolateral and ventral funiculi.


Effect of ouabain and potassium-free solution on mammalian thermosensitive afferents in vitro. Studies have been performed on the afferent fibers innervating the scrotal skin of the rat to test the hypothesis that the generator potential mechanism underlying cold thermosensitivity of these afferent fibers is an electrogenic sodium pump. In these experiments a pudendal nerve-scrotal skin preparation was isolated from the animal and maintained in oxygenated mammalian Ringer's where composition could be varied and drugs added. Application of ouabain resulted in an increae in the discharge of cold sensitive afferent fibers which was more pronounced at 38--41 degrees C than at temperature below 30 degrees C. In most of the cases transient accelerations on cooling were reduced, but often a transient response to warming appeared. The effects of ouabain administration were reversible. Removal of extracellular K at 35 degrees C resulted in an increased discharge of cold sensitive afferents. This observation is consistent with the effects of ouabain, since removal of extracellular K also block Na transport. The generator potential mechanism underlying cold sensitivity of these afferent fibers appears to be an electrogenic Na pump.


DNA replication in Physarum polycephalum: characterization of replication products in vivo. Synchronous plasmodia of Physarum polycephalum in DNA synthesis were pulse-labelled with [oH]- thymidine for time periods of 15 seconds up to 9 minutes, or given a 30 seconds pulse followed by chase periods of 9 minutes up to 6 hours. Sedimentation analysis in alkaline sucrose gradients revealed at least five species of single stranded DNA14 molecules in the pulse experiments. Co-sedimentation of [14C]-labelled phage-DNA gave relative S-values of 5-7, 13-15, 23-25, 30 and 33-35 for these DNA molecules, all of which can be chased into DNA of higher molecular weight.


[Immunogenic properties of S. choleraesuis for pigs]. The aim of this work was to determine pathogenic properties for white mice of 3 S. choleraesuis strains. Two of these strains (No. 6 and Ivanovice) were attenuated, and the third strain (No. 964) was isolated from a pig which died of salmonellosis. Pathogenic properties and shedder state of the attenuated strains were tested in pigs with special reference to the persistence of the shedder state in the lymph nodes and internal organs of pigs after their vaccination and subsequent challenge. Specific agglutinin level in pigs before and after administration of the attenuated S. choleraesuis strains was also determined. During the investigations the method for industrial production of the lyophylized vaccine was worked out. The vaccine, containing the attenuated Ivanovice strain, proved to be harmless for pigs, under laboratory conditions, and it protected pigs against experimental challenge 3 weeks after their vaccination. After this time no salmonellae were found in the lymph nodes and internal organs of pigs. No salmonellae were also detected in faeces of these pigs during 10 days after their vaccination. In pigs vaccinated and challenged 3 weeks later no salmonellae were found in the lymph nodes and internal organs, 3 weeks after the challenge, although these micro-organisms were detected in faeces of these pigs 2 to 5 days after challenge. The only exception was one pig; from its lymph node salmonellae were isolated. The three above-mentioned S. choleraesuis strains proved to be pathogenic for white mice.


[Effect of semen diluters containing egg yolk contaminated with DDT on the survival of bull spermatozoa]. In two experiments, hens received 200 (group I) or 100 ppm of DDT per day and per kg of live weight (group II), for 17 or 10 days resp. The eggs of experimental hens were collected, and a 3 or 6 day collection of eggs was used for preparing a sample of pooled egg yolks; one part of this sample was used for preparation of a 25% egg yolk-citrate diluent, the other for DDT determination. The egg yolks of experimentally poisoned hens contained 12 to 957 ppm of DDT (egg yolks of controls 1-4 ppm) in consecutive collection samples. However, the survival time and survival indexes of bull semen (90 ejaculates) preserved at 3 degrees C and 46 degrees C in yolk citrate diluent containing DDT poluted egg yolk did not differ from those preserved in control diluter.


The action of ionizing radiation on DNA in the presence of quinacrine. II. DNA strand breakage. Strand breakage of DNA irradiated in solution and in the dry state in the presence of quinacrine was investigated by sedimentation analysis. Determination of single strand breaks in solution combined with binding studies permits to conclude that bound quinacrine protects DNA more effectively than the free compound. In the dry state quinacrine is without detectable effect on both single and double strand break formation, neither under aerobic nor anaerobic conditions.


DNA-synthesis in synchronized L-cells after irradiation during the G1-phase of the cell cycle. Mouse fibroblast L-929 cells synchonized by mitotic selection were irradiated during the G1-phase of the cell cycle with a dose of 1000 rad. The rat of DNA synthesis was measured by 3H-thymidine incorporation, and the progression of the cells through the cell cycle was determined using a pulse-cytophotometer. Irradiation caused a decrease in the rate of DNA synthesis to half the control value, and an extension of the S-phase to twice its normal duration.


The action of ionizing radiation on DNA in the presence of quinacrine. I. UV absorption and fluorescence measurements. It is shown by UV absorption and absolute fluorescence spectroscopy of solutions containing both DNA and quinacrine that the components experience mutual radio-protection due to scavenging of water radicals. From measurements at different ionic strengths it is inferred that quinacrine bound to DNA is more efficiently protected than the free compound. Furthermore, release of bound quinacrine from DNA is observed at higher doses.


MMPI correlates of menstrual distress.

MMPI correlates of menstrual distress. The MMPI and Moos' Menstrual Distress Questionnaire (MDQ) were administered to 60 undergraduate women. Partial correlations between MMPI clinical scales and menstrual and premenstrual MDQ symptom scales were computed with intermenstrual (baseline) symptom reports and response set (Gough's F-K index) statistically controlled MMPI variables tended to correlate with some symptom scales (premenstrual pain, negative affect; menstrual behavior change) but not with others (water retention, arousal). Where correlations did occur, common MMPI scales (Sc, Hs, Hy, Pt) were involved. Results suggest that psychological factors are more closely associated with some areas of menstrual symptomatoloty than with others.


Changes in DNA secondary structure after gamma-irradiation. Native calf thymus DNA was gamma-irradiated at 500 mug/ml in 0.01 M NaCl in the presence or absence of oxygen. By irradiation, an increasing amount of DNA becomes reactive with a water-soluble carbodiimide-derivative (CMEC). In the DNA sections reactive with CMEC the nucleotide strands are separated, a phenomenon previously described as radiation-induced denaturation. The dose-effect curve for the formation of denatured DNA shows an upward-bent form; a distinct oxygen effect of about 2 is observed. By a comparative study with DNA samples, degraded partially with DNAse I, it was shown that a minor part of the radiation-induced denaturation results from the formation of the radiation-induced single strand breaks, whereas the major part is a local denaturation independent of the strand breaks. In these locally denatured regions 20 to 50 nucleotide pairs are separated.


Force breeding, social disorder and mammary tumor formation in CBA/USC mouse colonies: a pilot study. If the newborn of a socially organized CBA/USC mouse colony are regularly removed (force breeding), the social order breaks dowm. There is fighting among the males and the young are lost due to neglect and injury by the females (cronism). A high incidence of mammary tumor formation is observed during the disorder of such formerly socialized groups. In the pilot study being reported, force breeding initiated at the sixth month of colony life eventually at the ninth month led to fighting and the loss of young by cronism. All 12 female colony members developed tumors during the subsequent 5 months. Meanwhile, tumors developed in only 8% of the same age Study Siblings and in 46% of Study Breeders maintained under rapid breeding conditions. Force breeding is a knowm moderately effective tumorigenic technique. Since tumors did not occur in the population cage until its social system broke down, this suggests that the combination of force breeding and social disorder-induced neuroendocrine changes is peculiarly favorable to tumor development.


An outbreak of ornithosis.

An outbreak of ornithosis. An outbreak of ornithosis occurred in Lidköping, a small town in Southwest Sweden, in January 1967 through May 1969. 24 proved cases were known, aged from 10 to 72 years, 19 patients gave a history of contact with birds (parrots, canaries, parakeets), 13 of them with birds from the same pet shop. Five patients had visited the pet shop only once before their illness. Attempts to prove infection with ornithosis agent in 7 birds from the pet shop were unsuccessful. Three patients, 2 of them in the same household, had no contact with birds and infection from person to person was strongly suspected. All patients had pneumonia. Fever, cough and headache were predominant clinical symptoms. There were relapses in 4 patients and 2 patients had symptoms of encephalitis. No deaths occurred.


Neutralizing antibodies after rubella vaccination of newly delivered women: a comparison between three vaccines. Neutralizing (NT) antibody titres against rubella were determined in sera of 114 newly delivered women vaccinated with the Cendehill strain (Cendevax), the HPV-77 DE-5 strain (Meruvax) or the RA27/3 strain (Almevax). Blood samples were obtained before and 8 weeks as well as 2 years after the vaccination. Eight weeks after the vaccination NT antibodies were found in 56, 79 and 95% and after 2 years in 82, 94 and 100%, respectively. The differences between Cendevax and Almevax were statistically significant. Eight weeks postvaccination the median NT antibody titres were found to be 2, 4 and 4, respectively, while after 2 years the titres had further increased with one titration step. Levels of NT antibodies were observed to increase also after 8 weeks, i.e. during the period 8 weeks to 2 years postvaccination.


Changes in intracranial pressure and brain hydration during acute ethanolism. Intracranial hypertension and brain hydration were scrutinized during acute ethanolism for consideration in the combined head injury setting. Intraventricular pressures and whole brain water levels rose with moderate or high ethanol dosages. The most prominent alterations were associated with respiratory acidosis and hypoxia; less marked changes were found in their absence and point to a second mechanism. Elevated central venous pressures appeared as well in some instances to constitute a third action. It is accordingly suggested that ethanol may add significantly to the combined pathology with associated acute head injury in several ways. These include: contributions to edema formation, to respiratory depression, and to alterations in local hemodyamics.


[Vitamin E and selenium in the feed of farm animals (author's transl)]. A survey is given of vitamin E and selenium deficiency syndromes in farm animals. Some syndromes can be attributed to the exclusive deficiency of one of the above-mentioned feed components. In some cases with practically complete lack of both componentspathological symptoms can be cured by the addition of one of them to the feed in sufficient amount. A synergistic effect of vitamin E and selenium is sometimes found to recur. The most important theory about the functioning of vitamin E is that it acts as an antioxidant. This theory presumes that, in case of a vitamin E deficiency, peroxidation of unsaturated lipids can occur everywhere in the body leading to oxidative chain reactions. The free radicals thus produced might participate in non-specific reactions with functional and structural compounds. Vitamin E is considered able to reduce lipid peroxides or scavenge free radicals from chain reactions. The pros' and cons' of this theory are discussed. The role of vitamin E has further been associated with thenium is part of the enzyme glutathione peroxidase. This enzyme catalyses the reaction of reduced glutathione with peroxides, whereby hydroxy-acids and oxidized glutathione are generated. Most probably the glutathione peroxidase has its antioxidative action in the cytosol, whereas vitamin E is mainly located in the membranes of the cell.


The influence of oestradiol benzoate and progesterone on the secretory activity of the epithelium of the ampulla tubae in ovariectomized ewes: a light microscopical study. The influence of oestradiol benzoate and progesterone on the morphological and secretory characteristics of the epithelium of the ampulla tubae was studied in ovariectomized ewes. In untreated ovariectomized animals the epithelial height is minimal, the nuclei of the secretory cells are located in the most apical part of the cells i.e. in the cytoplasmic protrusions, and secretum (PAS positive material) is not present. The only change after progesterone treatment is a slight increase in epithelial height. After treatment with oestradiol benzoate, the epithelium reacts with an increase in height and with a withdrawal of the nuclei of the secretory cells towards the basal region of the cell. Two or three days after the treatment, the amount of secretum is comparable to that during D2 or D3 of the normal oestrous cycle. It is concluded that the rise in oestrogen levels on the day prior to the onset of oestrus in a normal oestrous cycle is responsible for stimulating the biosynthetic apparatus of the secretory cell, resulting in a maximal storage of secretum two or three days after heat. Progesterone does not seem to play an important role in the release of the stored secretum; 10 days after a 3 days oestrogen treatment, the amount appears to be similar to that in animals receiving progesterone after application of oestrogen. It is suggested that release takes place as a logic consequence of synthesis without a specific trigger. The results after a combined administration of the two steroids indicate that progesterone interferes with the action of oestradiol benzoate. The apical position of the nuclei of the secretory cells during the luteal phase of the cycle must be attributed to a diminishing oestrogenic influence rather than to an active intervention of progesterone.


[Quantitative changes in the uterine microflora during the puerperal period and conception in cows]. A total of 32 cows equal in terms of breed, annual milk productivity, feeding and tending regime were examined to determine the clearance of the uterine microflora during the puerperal period and establish the correlation between the conception rate and the bacterial clearance. The studies were carried out on the day of calving and on the 3rd, 6th, 9th, 12th and 15th day after that. It was found that in cows manifesting certain troubles during the puerperal period the bacterial count in the uterine discharges was 75.3% higher as early as the very first day following calving, and regardless of the drop after the ninth day, by the fifteenth day it was 64 per cent higher than in animals showing normal puerperium. In 40.8 per cent of the cows the discharge afterbirth on the day of calving showed no microorganisms. The rise of the microbial count was noted after the first day. It reached its maximum values by the 9 - 10th day after calving, after which it showed a dropping trend. The conception rate of cows with a normal puerperium at first service was 58.1 percent.


[Vaginal cytology at the end of pregnancy (author's transl)]. What information is permitted by cytodiagnosis was tested with reference to 2182 vaginal smear examinations in 882 pregnant women at the end of pregnancy. There is no cytological smear type from which the degree of fetal maturity can be determined beforehand with satisfactory certainty; in practice, one must work with diagnosis by exclusion, which, however, can be of great help: If a "before term" smear type is found, a genuine post-term birth can be excluded on the basis of the cytological examination alone with high degree of probability (98.3%). With an "at term" type of smear the birth of an immature child is nor very probable (1.7%); but an over-maturity may already exist (6.9%). A genuine post-term infant can only be expected in barely half of the cases (45.7%) with a "post-term" cell picture. A satisfactory assessment of the probable date of birth is only possible with the "at term" type of smear: in the great majority of cases (80.8%) a birth within 5 days can be counted on with this type of smear. The possibilities of "term cytology" in "programmed births" are referred to.


The levels of heavy metals (Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb, Hg) in fish from onshore and offshore waters of the German bight. With the intention of increasing our knowledge about the actual degree of heavy metal accumulation in fish, the contents of the elements manganese, iron, cobalt, nickel, copper, zinc, cadmium, lead and mercury in certain fish species (cod and plaice) from onshore and offshore waters of the German Bight have been determined. The measurements have been performed by atomic absorption spectrophotometry: Flame AAS was used as investigating procedure for the determination of Mn, Fe, Cu and Zn. A non-flame atomization system with a heated graphite tube was used for the determination of Cd, Pb, Co, and Ni. The concentration of total Hg was estimated according to the so-called "cold vapour atomic absorption method". In order to avoid errors in interpretation of measured values of Co and Ni, which occured as a result of matrix effects, a special technique has been developed. This based upon an selective separation and enrichment by chelate exchanger chromatography ("Chelex 100"). The analytical data obtained are plotted in a diagram with log.-log. scale. The content is shown on the x-axis, and the corresponding relative reproducibility (variation coefficient) of the method used is shown on the y-axis. For all elements investigated certain levels have been found out. From an examination of the results it appeared that there were comparatively small differences in the prevailing concentrations of transition metals Mn, Fe, Co, Ni, Cu, and Zn between samples of the same species from different areas. Likewise, the levels estimated for plaice did not differ from those estimated for cod. There is some evidence of elevated levels of Cd, Pb, and Hg in plaice from areas along the coastline.


[Lead-contents in mushrooms (author's transl)]. The lead-contents of canned and fresh mushrooms were analyzed by photometric determination after dry ashing and dithizone extraction. The average lead-content was found to be 0.49 ppm with extreme values of 0.10--1.0 ppm on fresh-weight basis resp. 5.5 ppm (2.0--13.5 ppm) on dry-weight basis. It appears that lead content increases with the size (age) of the mushrooms; the influence of canning upon the lead content is not yet finally clear, it seems, however, as if canning process has a lesser influence on the lead content than the size (age) of mushrooms.


Changes in a population of dikdik, Madoqua (Rhynchotragus) kirki (Günther 1880). In 1968/69 a small local population (deme)--11 to 17 animals on 42 ha--of Kirk's Dikdik was studied in the Serengeti area, East Africa. All animals were known individually and all territorial boundaries mapped. The population was revisited in 1972 and all animals and boundaries were recorded anew. 6 animals of 1968 were still present in 1972, 6 had disappeared and 4 were new. 2 territories were still the same, 1 had been divided up between 2 neighbouring ones, 1 had gained 1 ha. In the following summary of the results the generally formulated statements like "Dikdik do" always are short and stand for the specific statements like "the observed Kirk's Dikdik of the Soit ol Modison deme did". 1. Dikdik live in pairs in territories.--2. The young are expelled from the parental territory at the age of 6 to 9 months.--3. They then are able--nearly fully grown, but the horns of the male male only half of their final size--to establish their own pairbond and territory.--4. The female can produce her first young at the age of 15 to 18 months and is reproductive up to at least 6 years.--5. While the reproductive potential is 2/female/year (gestation period 25 weeks), the realized rate of raised animals in 1968/69 was 1/female/year.--6. Average population age lies around 5 years.--7. Maximum physiological age is 10 or more years.--8. The pair bond is independent of the territorial bond and lasts for life.--9. The territorial bond is independent of the pairbond but does not last for life.--10. Strategical lines of the territorial boundaries are marked by dung areas. The families of both territories each use their own places on these areas. The whole family urinates and defaecates together (one after the other) in a ritualized way.--11. The territorial boundaries can shift. The number of dungplaces along a disputed and/or shifting boundary is higher than along an undisputed stable one.--12. Only the male defends the territory and chases off the grown up male young.--13. The female who does not defend the territory is nevertheless bound to it directly, not only by her bond to the male.--14. The most important open question with respect to the social organization is: How is the grown up female young induced to leave the territory? Can there be circumstances when she can stay?


Displays of the honeyeater Manorina melanocephala. Investigated displays of Noisy Miners, Manorina melanocephala, in Australia. This unusual bird lives in colonies and many male male care for the offspring of each female. 3 flight displays, 11 non-flight displays, and several components of facial displays (including a variable eye patch) are discribed. The eye patch provides a large yellow and black augmented eye, important in intimidation. No stereotyped sequence of courtship behaviour precedes copulation. Displays are used to advertise nest locations. A greeting display, the corroboree, is extremely common. The possibility of the evolution of submissive display from threat is discussed. Special vocalisations of male male and female female are used in a duet. The maintenance of bonds among many individuals in a colony may be more important than strong pair bonds. Group cohesion is probably maintained by flight display, nest display, mobbing, and other communal activities. High interspecific aggression results in few resident species in colonies. This level of interspecific aggression might be maintained by incorporating much intraspecific mimetic display and ritualised submissive behaviour.


[Multiplication of coxiella burneti in different tissues and organs of embryonated eggs (author's transl)]. Multiplication and content of Coxiella burneti after infection of the yolk sac were studied in different tissues and organs of embryonated hen's eggs (yolk sac, CAM, allantoamnion, amniotic fluid, liver, muscles, spleen, and heart). Demonstration of the agent was performed from the 6th to the 11th day p.i. by direct microscopic methods (Stamp and auramine staining, fluorescent antibody technique); the Coxiella content was determined by titration in embryonated hen's eggs. Coxiellae could be demonstrated, apart from the yolk sac membrane, also in the intestine and CAM from the 7th day p.i., and in the other organs examined from the 11th day p.i. by means of microscopy. For the same period, embryonic death rates (ELD50) and egg infectivity (EID50) were determined separately. The highest numbers of Coxiella were consistently found in the yolk sac membrane (ELD50 10(4.0)-10(5.2); EID50 10(6.0)-10(7.8)). In the intestine, CAM, allantoamnion, and amniotic fluid, ELD50 values were between 10(2.0) and 10(2.8), EDI50 values between 10(4.8) and 10(5.2), on the 11th day p.i.. Titres were lower for muscles, liver, spleen, and heart of infected embryos.


[Serological examinations with apathogenic clostridia (M 55) (author's transl)]. Spores of the apathogenic clostridium butyricum (M 55) germinate after intravenous application in mammalians in tumor tissue only. On the basis of these earlier findings a diagnostic and prognostic procedure, used so far, namely the agglutinationtest with vegatative forms of this clostridium was improved by creation of a hemagglutination reaction. With different methods some different hemagglutinins have been isolated. Their efficacy was tested against specific antibodies in rabbits and mice. The higher sensitivity of these procedures was demonstrated.


[Bacteriological investigations and animal experiments with Mycobacterium ulcerans (Tübingen 1971) (author's transl)]. In 1972 we reported the first isolation of M. ulcerans in Germany and in 1973 we reviewed the epidemiology, clinical features and therapy of Buruli ulcer (6, 7). Initial isolation was done from swabs of the edge of the ulcer on Loewenstein-Jensen medium at 30-33 degrees C. Subcultures showed poor growth at 37 degrees C, and none at 22 degrees C or 42 degrees C or on Loewenstein-Jensen medium without glycerine. No acylamidase or lipolytic activity was detectable and the organisms were catalase positive, triphenyltetrazolium chloride reduction positive, nitrate reduction negative and nicotinic acid production positive (Table 2). Possibly our strain is a nicotinic acid positive variant, as is the strain described by RUNYON et al. (16). (The bacteriological characteristics are summarized in Table 2). Our strain was sensitive to dihydrostreptomycin, cycloserine, viomycin, rifampicin and a riminophenacin derivate (Lampren), but was resistent to isoniazid, para-aminosalicyclic acid, ethionamid and ethambutol (Table 3). White mice and rats but no guinea pigs are susceptible to infection with M. ulcerans. Injection into the foot pad is preferable to intraperitoneal or subcutaneous injection (Table 4). After such an injection of material from our patient, signs of disease appeared in the following order: 1. foot pad swelling; 2. redness and oedema of the whole leg; 3. ulceration of the dorsum of foot (fig. 1) with fluctuant, gross oedema of the subcutaneous tissue and loss of hair; 4. atrophy and contraction of the infected extremity with the development of further ulceration on the abdomen and tail. In the two months following an injection of a standard suspension of M. ulcerans the animals developed such gross oedema of the subcutaneous tissues of the abdomen that its progression could be followed by regular weighing (fig. 2). By the end of the two months, the total body weight was double that of control uninfected animals.


Effect of some autonomic drugs on heat defence in the pigeon. As compared to the time of median control death (i.e. the time inducing 50% death in untreated birds at 50 degrees C), exogenous noradrenaline afforded 100% survival in the blue rock pigeon, Columba livia. The survival percentages with the other autonomic drugs were: chlorpromazine 70%; reserpine 60%; adrenaline 60%; pentolinium 50% and dihydroergotamine 30%. The time of median control death at 50 degrees C was found to be 3.5 hours in the pigeon. During 10-day exposure at 45 degrees C all the birds pre-treated with noradrenaline survived, and 47% of those treated with adrenaline and 42% of the untreated birds survived the stress. It is concluded that noradrenaline acts definitely as a "heat protective" hormone in the pigeon.


Determination of measles virus-specific nucleocapsid antibodies by means of counterimmunoelectrophoresis. A counterimmunoelectrophoretic method for quantitative determination of antibodies against measles virus nucleocapsid is described. Unfractionated material from measles virus infected cell cultures was used as antigen, diluted to give only a nucleocapsid-specific precipitate. Purified nucleocapsid and a rabbit hyperimmune serum against this antigen was used to establish the specificity of the test. The measles virus specific antibody titres determined by the method were comparable to those found in nucleocapsid complement fixation tests. It is concluded that the technique described offers a simple and sensitive method to determine nucleocapsid specific antibodies.


Immunochemistry of a cell wall polysaccharide isolated from Eubacterium saburreum, strain L49. A polymer isolated from E. saburreum strain L49 contained O-acetylated glycero-galacto-heptose as the main constituent, and in addition an unknown aldose. The polymer was located at the outer part of the bacterial cell wall. The polymer reacted with antiserum to L49 microorganisms by precipitation and complement fixation. Two antigenic specificities were detected, one of which was destroyed by de-acetylation. The rabbit antibodies to both specificities were low-molecular-weight antibodies.


Diurnal variation in endogenous production of carbon monoxide. Effect of caloric restriction. The endogenous production of carbon monoxide (VCO) and total serum bilirubin (SB) have been followed in five healthy male volunteers during one baseline day and one day with no caloric intake. VCO in the morning studies was 11.2+/-1.7 (mean +/-1 S.E.M.) on the baseline day and 10.1+/-2.3 mumol/mmol total body heme (TBH) and day on the fasting day, respectively. In studies before noon, VCO increased significantly on both days, to values of 17.8+/-1.6 and 19.6+/-2.2 mumol/mmol TBH and day, respectively. In the first study in the afternoon, VCO differed significantly between the two days, amounting to 12.1+/-3.0 and 23.7+/-3.5 on the baseline and the fasting day, respectively. The difference was still significant in the evening, when VCO was 11.6+/-3.1 and 22.1+/-4.9 mumol/mmol TBH and day. SB followed the same pattern, with mean values of 4.0+/-0.3, 4.9+/-0.3, 4.2+/-0.9 and 3.0+/-0.3 mug/ml during the baseline day and 4.5+/-0.6, 5.4+/-1.2, 7.0+/-0.5 and 8.5+/-1.0 mug/ml, respectively, during fasting day. Only insignificant amounts of conjugated bilirubin were found. The studies confirm earlier reports on the effect of caloric restriction on VCO. Since this effect is simultaneous with an increase in SB, it is concluded that the changes are secondary to an increase in total heme catabolism. They might be due to an increase in intracellular hepatic heme turnover but it cannot be excluded that starvation affects erythropoiesis and/or red cell catabolism, thereby causing an increase in VCO and SB.


Alcohol withdrawal convulsions in genetically different populations of mice. Individual Swiss-Webster mice differed in the intensity of their withdrawal reactions after a standard regimen of alcohol administration, and offspring resembled their parents in this respect. Inbred strains of mice also differed in the severity of their alcohol withdrawal reactions. C57BL mice showed almost no convulsions on handling. These results indicate that a genetic factor participates in determining the severity of alcohol withdrawal seizures in mice. The sensitivity to excitant actions of reserpine paralleled the sensitivity to alcohol withdrawal reactions in three strains of mice but not among individual mice of a genetically heterogeneous stock. The strain correlation between these traits was therefore fortuitous and does not demonstrate a common biochemical lesion in alcohol-withdrawn and reserpine-treated mice.


Alcoholic liver injury: experimental models in rats and baboons. A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence upon withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis), and differed strikingly from the alterations produced by other models of liver injury. In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.


Cell models in the study of mechanisms of toxicity. Cell models, particularly in vitro systems, allow studies of toxicological mechanisms to be made under controlled conditions. One way that such mechanisms can be studied is by determining the reproducible changes that toxins induce, at the electron microscopic level, in the structure of cultured cells. A detailed description of such a study is given and includes preparation of the cell model, treatment of the cells, assessment of toxin-induced changes, and some general conclusions derived from experiments with this cell model. Other models which have been used for toxicological studies are also discussed with reference to advantages, limitations and potential applications.


Plasma lipid changes in young adult couples consuming polyunsaturated meats and dairy products. Twenty-five young couples consumed either a saturated or polyunsaturated fat diet for a 20-week period. The polyunsaturated beef, lamb and dairy products, high in linoleic acid, were produced by feeding ruminant animals "protected lipid" feeds which prevent hydrogenation of fats in the rumen. The experimental design provided for four dietary groups: A) saturated diet for 20 weeks; B) polyunsaturated diet for 20 weeks; C) saturated diet for 10 weeks then polyunsaturated diet for 10 weeks; and D) polyunsaturated for 10 weeks then saturated diet for 10 weeks. Polyunsaturated-to-saturated ratios (linoleic: total saturated fatty acids) for the diets were: prestudy, 0.43-0.56; saturated 0.11-0.14; polyunsaturated, 0.56-0.62. Factors other than diet that appeared to affect cholesterol responses were carefully considered. During the initial 3 weeks (regimentation period) plasma cholesterol concentration decreased in all groups irrespective of diet. This was followed by two experimental periods in which the effects of the prescribed diets were readily apparent (response periods I and II). The final 4 weeks of the study were characterized by diminishing compliance with the dietary discipline (abatement period). Subjects in each group (A,B,C,D) were subdivided into high and low on a basis of each group's initial median cholesterol level. Those in the high subgroups were very responsive to dietary changes whereas those in the low subgroups were not. Combined responses of high subjects were: polyunsaturated diet, -10.7 mg/dl (P less than 0.025), saturated diet, d8 mg/dl (P less than 0.05). Combined difference between saturated and polyunsaturated diets was 18.5 mg/dl or approximately a 10% cholesterol difference between the experimental polyunsaturated and saturated diets.


Lens changes in a galactosemic fetus.

Lens changes in a galactosemic fetus. The first child of a Spanish-American couple died presumbably from galactosemia. Early in the mother's fourth pregnancy, the parents' red blood cell levels of galactose 1-phosphate uridyl transferase were measured and both parents were found to be heterozygous (carriers) for transferase deficiency. A prenatal diagnosis of galactosemia in the fetus was made with the aid of amniocentesis and tissue culture. Abortion was induced when the fetus was 5 months old. Biochemical studies of lung and liver tissues confirmed the diagnosis of galactosemia. Cataractous changes were found by electron microscopy in both fetal eyes. Lens epithelial cells showed degenerative changes and a tendency to proliferate into two cell layers. Edema, liquefaction, and a variation in density characterized the lens cells.


PSRO and quality assurance: what is the occupational therapist's role? This article highlights the characteristics of the PSRO review process, looks briefly at the variety of patient care evaluation procedures and enumerates the ways in which occupational therapists can participate. There are two major steps the occupational therapists can take. The first is done on an individual or staff level. The second, involving a series of ongoing contacts, needs to be organized through a state or local occupational therapy association. Individual participation starts in your own service area with chart audit of the quality of occupational therapy care. The audit is based on criteria developed or adapted in the occupational therapy department. There are now many ways to gain the skills necessary for such a project. They are listed in the article. Occupational therapists can have input into the PSRO program through a PSRO committee of their state or local occupational therapy association. Selected representatives of the occupational therapy affiliates should contact all PSROs in their state. The area in which occupational therapists can interact with the PSRO are described.


The development of the circulating blood volume of the chick embryo. The circulating blood volume of the chick embryo was determined from the 4th up to the 18th day of hatching. In contrast to former studies, there was employed a radioisotope dilution method with albumin-bound I131. The findings are in close correspondence to those of the earlier studies. The blood volume does not display an entirely perfect curve of exponential growth, i.e., the doubling time increases steadily. The blood volume attains a peak value between the 16th and 18th day and decreases somewhat toward the end of the hatching period. There has been postulated a reduction of total red cell volume and hemoglobin caused by the involution of the extraembryonic circulatory system. The destruction of the erythrocytes seems to take place in the endodermal epithelium of the proximal yolk sac, where an accumulation of iron could be demonstrated on the 19th and 20th days.


Postnatal observations on the diurnal rhythm and the light-responsiveness in the pineal glycogen content in mice. In mice of both sexes ranging in age from five days to two years, the development and time course of diurnal rhythm and light-related variations in pineal glycogen were systematically studied by a semiquantitative histochemical method. When the animals were maintained under the usual diurnal lighting conditions (12L:12D), the diurnal rhythm and light-related changes in pineal glycogen appeared first at 22 days of age and persisted until two years. The glycogenic response was most prominent between 60 and 150 days, and declined slightly in mice older than one year. The glycogenic response and cell size tended to differ in the distal, middle and proximal portions of the body of the pineal. These regional differences change with the ages of the animals. When mice were kept in continuous darkness for seven days starting from 15, 23 or 60 days of age, the pineal showed a diurnal rhythm in pineal glycogen. When mice were kept in altered light regimens such as continuous darkness, continuous lighting or 6L:6D from birth up to 30 days, no diurnal variation in pineal glycogen developed.


Evaluation in the continuum of medical education-the GAP report revisited. Thirteenth annual Baxter-Travenol lecture. In 1971, the National Board of Medical Examiners appointed a Committee on Goals and Priorities, with a charge to provide advice, counsel, and recommendations relative to the Board's future directions. The report of the Committee, "Evaluation in the Continuum of Medical Education", was published as a monograph in 1973. It addressed itself to issues of evaluation, certification, licensure, and accreditation throughout the entire spectrum of medical education-undergraduate, graduate, and continuing. This paper, by the chairman of the Committee which authored the report, provides a review of: (a) the trends in medical eduction which formed the basis of the remmendations, (b) the recommendations themselves, (c) reactions to the report subsequent to its publication, and (d) actions taken by various groups relating to issues discussed in the report. It concludes with a discussion of anticipated changes in graduate medical education raises questions of the implications of these changes to the specialty of Aenesthesiology.


Propranolol and cardiac surgery: a problem for the anesthesiologist? Propranolol therapy has been implicated as a cause of myocardial depression and increased morbidity and mortality in patients undergoing coronary artery surgery. The authors reviewed 169 consecutive patients undergoing cardiac surgery, of whom 143 had been taking propranolol, with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Patients taking propranolol until 24 hours before surgery showed no increased incidence of hypotension or bradycardia before cardiopulmonary bypass. Hypotension after bypass was no more common in patients off propranolol 12 to 48 hours than in patients who either discontinued the drug over 48 hours before operation or had never taken the drug. Myocardial contractility as measured by systolic time intervals was normal 24 to 48 hours after stopping propranolol therapy. Five patients had preoperative myocardial infarctions within 48 hours of discontinuing the drug. The operative mortality rate was 4 percent in patients taking propranolol within 48 hours of surgery and 6 percent in all other patients. Seven risk factors, other than propranolol, were identified in those patients requiring inotropic support. The authors conclude that propranolol can be given safely within 24 to 48 hours of coronary artery surgery provided the patient is a satisfactory candidate for myocardial revascularization.


The effects of ketamine on cardiovascular dynamics during halothane and enflurane anesthesia. The cardiovascular effects of a single dose of ketamine administered during halothane or enflurane anesthesia were studied in 24 patients. During halothane anesthesia, ketamine caused a rapid and significant increase in arteriolar peripheral resistance (p less than 0.01) and a decrease in cardiac output, stroke volume, and systolic diastolic, and mean arterial blood pressures. Heart rate was not significantly changed. Ketamine resulted in similar, though less dramatic and slower developing, changes in patients anesthetized with enflurane. These results demonstrate that general anesthesia blocks the cardiovascular-stimulating properties of ketamine. They also indicate that ketamine has significant cardiovascular-depressant qualities when used during halothane or enflurane anesthesia.


Uneven epidural analgesia-early diagnosis and correction: case reports. Lateral displacement of the epidural catheter can cause uneven epidural analgesia. Early determination can be made by pulse-wave monitoring of sympathetic blockade of the lower extremities and by x-ray determination of the placement of the catheter tip. Withdrawal of the catheter tip to near the midline may correct uneven epidural analgesia.


Awareness, dreams, and hallucinations associated with general anesthesia. This incidence of mental aberrations (awareness, dreams, and hallucinations) in 490 adult patients undergoing a variety of surgical procedures was investigated. The total incidence of mental aberrations reported was 11 percent (awareness 1 percent, halluncinations 2 percent, dreams 8 percent). No statistically significant correlation was found between the incidence of unusual mental reactions and the anesthetic agents employed, the age or sex of the patients, or the duration or type of surgical prcedure.


Stellate ganglion block.

Stellate ganglion block. A modified low-dose paratracheal approach to stellate ganglion block at the C6 level prevents the possible complications of subarachnoid introduction of large quantities of local anesthetic, brachial plexus block, and toxic reaction to local anesthetics. It is a technically simple procedure with readily identifiable landmarks and can be performed on an outpatient basis with short recovery periods. Successful block can be readily evaluated. It is emphasized that a series of blocks is required to "disorganize" the reflex activity triggered in the internuncial pools of the spinal cord as well as in the sympathetic ganglia themselves.


Management of epiglottitis in children.

Management of epiglottitis in children. Because of our experience, as anesthesiologists, in the treatment of upper airway obstructions, we have been asked to see children with epiglottitis. Over a 5-year period, we have treated 28 such cases. Our hope that IPPB and nebulized racemic epinephrine would quickly relieve the obstruction, as it has in laryngotracheobronchitis, did not materialize. The obstruction from the edematous aryepiglottic folds and other hypopharyngeal structures was not relieved by such treatment, and half required an artificial airway, five by tracheal intubation. However, we documented two facts: (1) that the obstructed patient with epiglottitis can be ventilated and benefited by positive pressure by mouth or machine and that this ventilatory support can be life saving, rather than worsening the obstruction as was previously thought; (2) that with heavy-dose antibiotic-steroid therapy, the severe obstruction can be expected to improve significantly 8 to 12 hours after the onset of treatment. With this observation, we have extubated our patients at this time, rather than at 24 hours or later.


Behavioral consequences in rats from chronic exposure to 10 PPM halothane during early development. Albino rats were chronically exposed for 40 hours a week to 10 ppm halothane in air during early development (conception to day 60), adult life (day 60 to day 135), or both. An unexposed group served as a control. Rats exposed during early development made 30 percent more errors than rats unexposed during this period when tested on a shock-motivated visual-discrimination task, or a food-motivated spatial-discrimination task. However, the relative rate of learning was the same for all groups. Exposure during early development also lowered the jump and flinch thresholds to electric footshock as compared to animals not so treated.


Regional analgesia following epidural blood patch. During the period November 1972 through October 1974, 118 epidural blood patch procedures were performed for severe postlumbar-puncture cephalgia. Subsequently, in a period varying from 105 to 380 days, three patients, two of whom had twice undergone epidural blood patch, were readmitted for either surgical operation or delivery. Either epidural, caudal, or spinal block was successfully accomplished. During the epidural block, the epidural block the epidural space was easily identified and no resistance was felt either to injection of the local anesthetic or to advancement of the epidural catheter. During the spinal block, ligmentum flavum was distinctly felt from the dura. The extent of the blocks, the onset and duration of action ofpivacaine, mepivacaine, and lidocaine were within normal limits. It is, therefore, concluded that epidural blood patch does not obliterate the epidural space and should not preclude the use of regional block for later surgical or obstetric procedures.


Relation of anesthesia to total hip replacement and control of operative blood loss. Blood loss during total hip replacement has been reported as ranging from 500 to more than 4000 ml. To find reasons for this large variation, 167 case reports were studied. Blood loss was higher with nitrous oxide-oxygen-curare-morphine aneasthesia than with halothane-nitrous oxide-oxygen. Blood loss was also higher in patients with cups, prostheses, and neoplasms of the femoral head and neck than in patients with degenerative and rheumatoid arthritis. In patients undergoing bilateral total hip replacement, operative blood loss was significantly (p=0.05) higher during the second operation. However, the most striking correlation of blood loss was with intraoperative systolic blood pressure (r=0.84), a finding confirmed by a prospective study in 58 patients. Blood loss, operative time, the number of blood transfusions, and the hypotensive and hypoxic response to acrylic bone-cement application decreased when intraoperative systolic blood pressure was lowered by 20 to 30 percent of the preoperative value by the use of trimethaphan or sodium nitroprusside. This moderate reduction of blood pressure resulted in a saving of 2 to 3 units of blood in an average case and a considerably clearer surgical field. The authors consider moderate lowering of blood pressure to be a useful adjuvant in anesthesia for total hip replacement.


Train-of-4 quantitation of competitive neuromuscular block. Thumb twitch in response to "train-of-4" nerve stimulation was observed in 34 anesthetized patients receiving d-tubocurarine. Over the range of 75 to 100 percent block of the 1st twitch in the train, the 4th, 3rd, 2nd, and 1st twitch become undetectable, in that order. The reappearance of twitch by spontaneous recovery also occurs predictably, following the reverse order. Counting the number of visible twitches remaining in the train (0 to 4) permits quantitative assessment of the competitive neuromuscular block 75 to 100 percent, thereby facilitates provision of profound relaxation and safeguards reversibility.


Comparative effects of dextroamphetamine and reserpine on halothane and cyclopropane anesthetic requirements. Cyclopropane minimum alveolar concentration (MAC) values in dogs following intravenous administration of 0.5, 1 or 2 mg/kg of dextroamphetamine were 27.8, 28.4, and 28.4 volumes percent, respectively. Those values did not differ significantly from each other but were 44 percent greater than average control (no dextroamphetamine(MAC values. Halothane MAC values following the same dextroamphetamine doses were 1.51, 1.71, and 1.64 volumes percent. These values were 75 percent greater than average controls, and this increase was significantly more than the 44 percent noted with cyclopropane. In contrast, 2 mg/kg of reserpine decreased halothane MAC 20 percent vut decreased cyclopropane MAC 40 percent- the difference between the two anesthetics again being statistically significant. These results suggest that alteration of anesthetic potency by centrally active adrenergic drugs depends on the sympathetic activity induced by the anesthetic. Conversely, this suggests that anesthetics may influence their own potency by altering central nervous system adrenergic activity.


The role of profound hypothermia in infants undergoing surgical correction of complicated heart defects. A series of 110 children, ranging in age from 2 days to 4 years and in weight from 2.4 to 12.9 kg, underwent total surgical correction of complicated heart defects with the aid of profound hypothermia and total circulatory arrest. Combined surface and core cooling, in conjunction with light general anesthesia, proved to be a safe and effective method to provide optimal working conditions for the surgeon. The technic of cooling and rewarmining, as well as hemodynamic and metabolic parameters monitored, are important, and factors such as type of heart defect, age, weight should be considered in relation to postoperative morbidity and mortality.


The source of increased plasma potassium following succinylcholine. Increases in plasma potassium following succinylcholine have been reported by many workers. In the present studies, these are greater when Althesin is used as the induction agent than after thiopental, and the rise is particularly marked in patients given halothane, occurring earlier in patients having electroshock therapy, and being reduced by the prior administration of a small dose of tubocurarine. These findings suggest that  the rise in potassium is due to muscle trauma indiced by the relaxant during the period of fasciculation, and this is confirmed by an increase in creatine phosphokinase enzyme activity. Althesin and halothane are best avoided with succinylcholine in chronic catabolic states where an excessive rise in plasma potassium could lead to dangerous cardiac dysrhythmias.


Increased cerbrospinal fluid pressure during laryngoscopy and intubation for induction of anesthesia. Intracranial pressure (ICP) was recorded in 12 patients undergoing craniotomy and 2 patients for carotid arteriogram. ICP did not change in response to the injection of contrast medium but rose significantly and dramatically in response to laryngoscopy and intubation. The increase appeared related to initial ICP and thus may represent exhaustion of compensatory mechanisms in these patients. Special attention must be given to this factor during manipulation of the larynx in neurosurgical patients with raised initial ICP or space-occupying intracranial lesions.


Candihexin polyene macrolide complex: physicochemical characterization and antifungal activities of the single components. The candihexin complex produced by a natural mutant of Streptomyces viridoflavus has been resolved into eight components. At least six of them, having hexaene chromophores, can be separated directly by thin-layer chromatography. The four major components, candihexins A, B, E, and F, account for about 90% of the total complex. They have been isolated and purified to homogeneity. All the major components were found to have macrolide lactone rings with all-trans hexaene chromophores. Candihexins A and B have compositions and molecular weights similar to candidin, the heptaene polyene macrolide produced by the parent S. viridoflavus, whereas candihexins E and F show smaller molecular weights and rather different elementary compositions. Candihexins A and B yield the amino sugar mycosamine upon hydrolysis, but no sugar was found in hydrolysates of candihexins E and F. Candihexins A and B have high antifungal activity against yeasts and filamentous fungi. The amino sugar-lacking candihexins E and F show no antifungal activity at levels of 100 mug/ml.


Fungal growth on C1 compounds: a study of the amino acid composition of a methanol-utilizing strain of Trichoderma lignorum. The amino acid composition of the C1-utilizing fungus Trichoderma lignorum, growing at the expense of methanol as the sole source of carbon, was determined. With the exception of an insufficient content of methionine, the essential amino acid composition of this novel protein source appears adequate in terms of the Food and Agricultural Organization Reference Protein for both direct and indirect use in the human diet as a food or animal feed, respectively.


Feed refusal factors in pure cultures of Fusarium roseum 'graminearum'. Isolations from 1972 Wisconsin feed refusal corn yielded predominantly cultures of Fusarium roseum 'graminearum.' With one possible exception, none of the selected isolates of this fungus induced emesis in pigeons, whereas six of nine isolates produced feed refusal responses in all test animals. A single isolate of F. roseum 'equiseti' also induced a severe refusal response and possibly slight emesis. None of the other fungi isolated from this corn (F. moniliforme, Acremoniella atra) or controls caused either emesis or feed refusal. Zearalenone was detected in all isolates and was shown to be partially responsible for refusal activity. The remaining activity was ascribed to one or more nonvolatile, neutral, relatively polar molecules. T-2 toxin, although not detected in these isolates, was shown to have dramatic refusal activity in rats.


Amino acid requirements and proteolytic activity of Streptococcus sanguis. The growth response of Streptococcus sanguis groups 1:A and 1:B in a complete chemically defined medium was not influenced by the oxygen concentration of the growth atmosphere. All of the cultures required cysteine and arginine; tyrosine and branched-chain amino acids were frequently required. Proteolysis of casein, mucin, and the anionic proteins of germfree rat saliva by S. sanguis was demonstrated. Hydrolytic activity toward casein was found in the soluble contents of the cells and in the cellular debris after disruption of the cells, with the soluble fractions exhibiting greater proteolytic activity toward casein. The soluble fractions from S. sanguis did not hydrolyze mucin, but this substrate was hydrolyzed by the cell debris fraction. When the amino acid requirements and proteolytic activity of S. sanguis and S. mutans were compared, these two oral streptococcal species exhibited distinct and characteristic differences.


Adaptation of BHK-21 cells to growth in shaker culture and subsequent challenge by Japanese encephalitis virus. Baby hamster kidney (BHK-21) cells were adapted to grow in shaker culture using Waymouth medium 752/1 containing 20 mM N-2-hydroxyethyl-piperazine-N'-2'-ethanesulfonic acid buffer and supplemented with 2.5% (vol/vol) calf serum, 0.002% (wt/vol) sodium oleate, and 0.2% fatty acid-free bovine serum albumin (WO2.5). Infectivity of Japanese encephalitis virus grown in the cells adapted to WO2.5 approached 2 x 10(8) plaque-forming units per ml. The culture volume of infected cells was reduced fivefold 12 h after infection. This step resulted in a 10-fold increase in infectivity over that obtained from infected cultures not subjected to volume reduction.


The effects of volatile compounds from nematodes on trap formation by a nematode-trapping fungus. Although the presence of prey induced trap formation by nematode-trapping fungi, it is improbable that the activity was associated with volatile compounds of nematode origin.


Surgical correction of unusual double-outlet right ventricle. This paper presents the case history of an 8-year-old girl who had total situs inversus and double-outlet right ventricle with pulmonary stenosis and severe tricuspid insufficiency in the presence of dextrocardia with ventricular discordance. A successful repair was performed using the Rastelli technique in conjunction with replacement of the tricuspid valve with a Bjork-Shiley prosthesis. The postoperative course was uneventful, and follow-up catheterization revealed a good operative result. However, the patient died suddenly during an emotionally upsetting period about two months after the operation. Postmortem examination revealed only signs of moderately severe cardiac decompensation. Some anatomical and embryological comments are made.


Structure-action relationships of histidine decarboxylase inhibitors. Substituted phenols were found to be more potent inhibitors of histidine decarboxylase than were the correspondingly-substituted benzoic acids. Regression analysis, though indicating that potent inhibitors of histamine formation are unlikely to be found among simple, substituted phenols, enables tentative conclusions to be drawn regarding the nature of the interaction between these compounds and the enzyme.


Genetic determinant of lithium ion distribution. An in vitro and in vivo monozygotic-dizygotic twin study. In previous research, evidence was provided of genetic control of in vitro red blood cell (RBC) uptake of lithium ion following a 24-hour incubation using a monozygotic (MZ)-dizygotic (DZ) twin study method. To extend these data, in vitro RBC lithium ion concentrations were assessed for five MZ and five DZ twin pairs. To extend this line of research on genetic control of lithium ion distribution to in vivo conditions, these twin pairs were administered lithium carbonate for seven days during which time RBC and plasma lithium ion concentrations were assessed. In this limited sample, the data provide evidence of genetic control of distribution of lithium ion across the RBC membrane in vivo as well as of in vitro RBC uptake of lithium ion.


[Hodgkin's disease: an epidemiological study on 140 children--urban/rural relation, profession of parents, domestic animal contact]. In Northern Germany (Schleswig-Holstein, Niedersachsen, Hamburg and Bremen) 140 children aged 2-14 years who had developed Hodgkin's disease after World War II were identified with the help of all 54 children's hospitals, the 101 local public health offices, and the Hamburg Cancer registry etc. Only histologically confirmed cases were included. For boys, comparison by urban and rural residence showed a preponderance of cases in rural areas (places with less than 2000 inhabitants). This urban-rural difference became statistically significant (P less than 0.05) when the cases reported from Hamburg (with its greater registration intensity) were excluded. For girls, there was no difference in the urban/rural distribution. Personal interviews were conducted with 133 case families. One third of the parents had been engaged in agricultural occupations. In the retrospective studies contacts with domestic animals was most impressive, especially those with rabbits (84.2%). But there was also contact with large animals, most frequently with pigs (45.9%). The difficulties of getting suitable controls--because of the widespread and changing keeping of animals--are discussed. A matched pair analysis of the 21 children from Hamburg confirmed significance (P less than 0.05) for contact with domestic rabbits.-- Furthermore, multiple cases (in family or in neighbourhood, "cluster") could mostly be linked together by contacts with the same herd. The epidemiological results from the basis of a hypothesis that Hodgkin's disease is a zoonosis. The possibility of a synergistic action of two factors--transmitted by two different species--is discussed.


Electron microscopic observation of feline kidney cells infected with a feline calicivirus. An electron microscopic study of kitten kidney cells infected with a feline calicivirus (a member of the family Picornaviridae) has been carried out. Although cells appeared to be synchronised by the light microscope, electron microscopic changes were extremely variable. The first observable and consistent changes occurred in the nucleus followed by the formation of membrane bound vesicles in the cytoplasm. A variety of arrangements of virus particle accumulation were observed in infected cells. These included crystalline arrays, membranous cisternae and accumulation of particles in fine fibrillar material. The finding of accumulations of virus particles in association with smooth membranes is of importance in respect of the recent biochemical evidence of poliovirus assembly in relation to smooth membranes.


Induced corneal vascularization remission with argon laser therapy. Vascularization was induced in rabbit corneas by the application of silver nitrate. Argon laser photocoagulation was applied to the entire length of these corneal vessels with relatively long pulses of energy. Untreated areas of vascularization were used as controls. There was a decrease in the corneal vascularization in the treated areas that exceeded any natural tendency toward remission. The results suggest the efficacy of inducing a remission of corneal vascularization with argon laser photocoagulation.


Variation of energy density in argon laser photocoagulation. The power density at the retina provided by presently available laser photocoagulators is subject to variation. Three factors contribute to making the retinal image of the laser beam substantially different from the spot size indicated on the selector of the photocoagulator. These are the operator's variable accommodation, the astigmatism introduced by the contact lens, and the depth of focus of the observation system. The assumption that the same setting on the instrument regularly produces the same power density at the retina will lead to errors in comparing lesions. The safest procedure is to start from the threshold in every location.


The diagnosis and management of keratomycoses. I. Cause and diagnosis. Causative isolates, clinical features, and laboratory studies are reported for sixty-one cases of culture-proved mycotic keratitis. Isolates are categorized into four groups, including 36 Fusarium solani, 11 other Moniliaceae species, seven Dematiaceae, and seven yeasts. Of the 61 patients, 42 were men. Mild outdoor trauma was sustained in 14 of 24 cases. Patients were often referred with a clinical diagnosis of presumed fungal keratitis, within one week of symptom development, and usually had not received topically applied steroids prior to referral. Laboratory diagnosis necessitates prompt corneal scrapings, preferably stained with Giemsa or Gram, and culture on Sabouraud and blood agar maintained at room temperature, with growth usually evident by 48 hours.


The pediculate bone graft as treatment for the aseptic necrosis of the femoral head. We believe that if an early diagnosis is stated and therefore its treatment, the final prognosis is considerably better. When faced with a coxarthropathy, presumably an aseptic necrosis of the hip, we believe that the hemodynamics of the femoral head plus a biopsy should be carried out, even in the cases where the radiology is negative. The simplicity of the technique in addition to the fact that the mechanics of the hip remain unaltered in view of any future operations, leads us to the point where the pediculate bone graft is the technique of choice in those cases with similar conditions to the above described.


Further observations on hormonal support of pregnancy in the ovariectomized rabbit. While the necessity for progesterone administration throughout pregnancy in the ovariectomized rabbit is not questioned, the roles of 20alpha-dihydroprogesterone and oestradiol are still in doubt. 20alpha-dihydroprogesterone was shown to be a weak inducer of implantation with less than one-tenth the potency of progesterone. The significance of its high level of production on the day after mating remains obscure. In combination with the earlier results of Kwun and Emmens (1974), further work with oestradiol suggests that at no stage is it clearly needed for successful maintenance of pregnancy. However, in low doses (0.125-0.2 mug/day prior to implantation, 0.2 rising to 1.6 mug, or remaining at 0.2 mug/day thereafter) it produced slight but sometimes significant improvements in implantation and foetal development percentages. Birth processes were abnormal if progesterone injections were continued beyond day 29. Foetuses were most frequently retained in utero or born dead after a somewhat prolonged pregnancy. The cessation of injections on day 29, whether or not a low dosage of 0.2 mug of oestradiol per day were continued, resulted in 94-98% normal parturition, but the percentage of live births was still significantly below that of controls unless oestradiol was given.


Cardiomyopathy--the frequently forgotten mimic: clinical and open-chest myocardial biopsy studies. Attention is drawn to the cardiomyopathies, 25 idiopathic cases being presented and the features noted which may mimic other conditions, especially coronary heart disease. Subtle clinical manifestations may be misinterpreted unless these disorders are kept in mind. The diagnosis can usually be suspected at the bedside but specialized tests may be required to confirm it. Open-chest myocardial biopsy has yielded exciting, but not yet apparently useful, results in six instances. Recognition of cardiomyopathy in aviation cardiology is important because of the high incidence of cardiac arrhythmia and sudden death associated with the condition.


The equilibrium position of the reaction of bovine liver glutamate dehydrogenase with pyridoxal5'-phosphate. A demonstration that covalent modification with this reagent completely abolishes catalytic activity. 1. The activity of bovine liver glutamate dehydrogenase incubated with pyridoxal 5'-phosphate declined to a steady value reached within 30--60 min. The residual activity depended on the concentration of modifier up to about 5 mM. Above this concentration, however, no further inactivation was produced. The minimum activity obtainable in such incubations was 6--7% of the initial value. 2. Km values of the modified enzyme were unaltered, whereas Vmax. was decreased. 3. Activity was fully regained on dialysis against 0.1 M-potassium phosphate buffer. 4. Reduction with borohydride rendered the inactivation permanent but did not alter its extent. 5. Enzyme permanently inactivated in this way to the extent of 90% and dialysed was re-treated with pyridoxal 5'-phosphate. In this second cycle activity declined from 10 to 1% of the original activity. 6. This strongly suggests that the failure to achieve complete inactivation in a single cycle reflects a reversible equilibrium between inactive Schiff base, i.e. covalently modified enzyme, and a non-covalent complex. 7. The re-inactivation reaction occurring on dilution was demonstrated directly and a first-order rate constant obtained (0.048 min-1). This, in conjunction with an estimate of the forward rate constant for Schiff-base formation, obtained by approximate pseudo-first-order analysis of inactivation at varied modifier concentrations, gives a predicted minimum activity very close to that actually obtained in a single cycle of treatment. 8. The dissociation constant of the non-covalent complex is given by two methods as 0.90 and 1.59mM. 9. The results indicate that covalent modification with pyridoxal 5'-phosphate completely abolishes the activity of glutamate dehydrogenase.


The nature of the binding site for aromatic compounds in glycogen phosphorylase b. The inhibition of rabbit muscle glycogen phosphorylase b (1,4-alpha-D-glucan--orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) by aromatic compounds was examined with 15 compounds. The relative effectiveness of the inhibitors correlated well with increasing substituent constant, pi, indicating the hydrophobic nature of the binding site. The inhibition was not affected by the ionic-strength variation of the assay mixtures. The results predict that the course of chemical modification of this enzyme and the properties of the derivatives depend on the nature of the reagent and on the incorporated groups. Many of the dissimilar and sometimes contradictory results reported for chemical-modification studies and for chemically modified phosphorylase b are explained by the findings presented in the paper.


Co-operative binding of oxytocin to bovine neurophysin II. The interaction of oxytocin with bovine neurophysin II in 0.1 M-sodium phosphate, pH 5.8, was investigated by equilibrium-dialysis and sedimentation studies. Sigmoidality of the binding curve is attributed to isomerization, either hormone-induced or pre-existing, with preferential binding of oxytocin to one isomeric state. Results are consistent with a binding equation of the form r = (2P[S]+2PQ[S]2)/(1+2P[S]+PQ[S]2) and values of 0.7 X 10(5)M-1 and 1.3 X 10(5)M-1 for P and Q respectively. The significance of these two parameters in relation to current theories of allostery is also discussed.


The reaction of penicillin with proteins. The mode of reaction of benzylpenicillin with two proteins was studied, with particular reference to the allergenicity of penicillin. These reactions, with pig insulin, and with hen's-egg-white lysozyme, were carried out in neutral solution at 37 degrees C. High concentrations of penicillin are needed to label the proteins, owing to concurrent hydrolysis of penicillin. Evidence has been obtained that the penicillin-reactive sites on the insulin molecule are the alpha-amino group at the N-terminus of the A chain and the epsilon-amino group of the lysine residue; whereas a site of reaction with lysozyme appears to be the epsilon-amino group of lysine-116.


The chemistry of the collagen cross-links. The mechanism of stabilization of the reducible intermediate cross-links. The periodate-degradation technique was used to demonstrate the mechanism by which the reducible cross-links of collagen are stabilized. In all the tissues examined, Smith degradations of the 3H-labelled cross-links indicated that dihydroxylysinonorleucine is derived solely from hydroxylysino-5-oxonorleucine, the Amadori-rearranged product of the original condensation reaction. Monohydroxylysinonorleucine exists in both keto and aldimine forms, the former being derived from hydroxyallysine and the latter from allysine. Their relative proportions are tissue-dependent and are related to the degree of hydroxylation of the specific lysine residues in both the telopeptides and the triple helix.


Short communications.

Short communications. A ribosome crystal is an aggregate of ribosomes which are packed in a regular array. Preliminary experiments analysing the proteins from ribosome crystals by two-dimensional gel electrophoresis show that, although most proteins appear similar to those from polyribosomes, four extra proteins also seem to be characteristic of ribosome crystals.


Fatty acid synthesis in liver and adipose tissue of normal and genetically obese (ob/ob) mice during the 24-hour cycle. 1. The synthesis of long-chain fatty acids de novo was measured in the liver and in regions of adipose tissue in intact normal and genetically obses mice throughout the daily 24h cycle. 2. The total rate of synthesis, as measured by the rate of incorporation of 3H from 3H2O into fatty acid, was highest during the dark period, in liver and adipose tissue of lean or obese mice. 3. The rate of incorporation of 14C from [U-14C]glucose into fatty acid was also followed (in the same mice). The 14C/3H ratios were higher by a factor of 5-20 in parametrial and scapular fat than that in liver. This difference was less marked during the dark period (of maximum fatty acid synthesis). 4. In normal mice, the total rate of fatty acid synthesis in the liver was about twofold greater than that in all adipose tissue regions combined. 5. In obese mice, the rate of fatty acid synthesis was more rapid than in lean mice, in both liver and adipose tissue. Most of the extra lipogenesis occurred in adipose tissue. The extra hepatic fatty acids synthesized in obese mice were located in triglyceride rather than phospholipid. 6. In adipose tissue of normal mice, the rate of fatty acid synthesis was most rapid in the intra-abdominal areas and in brown fat. In obese mice, all regions exhibited rapid rates of fatty acid synthesis. 7. These results shed light on the relative significance of liver and adipose tissue (i.e. the adipose 'organ') in fatty acid synthesis in mice, on the mino importance of glucose in hepatic lipogenesis, and on the alterations in the rate of fatty acid synthesis in genetically obese mice.


The value of sequential bone marrow biopsy and laparotomy and splenectomy in a series of 127 consecutive untreated patients with non-Hodgkin's lymphoma. The information derived from sequential routine bone marrow biopsies and exploratory laparotomy with splenectomy in 127 consecutive untreated protocol patients with malignant lymphomata other than Hodgkin's disease is reviewed. Of the 61 patients with diffuse lymphomata, 36% changed stage after these diagnostic procedures, usually to a more advanced stage. Of the 66 patients with nodular lymphomata, 62% had a change in stage, almost all to more advanced stages, usually as a result of bone marrow biopsy. The correlation of pathological stages to clinical stages is presented for each of the Rappaport classification subgroups and for several age groups. The precise indications for exploratory laparotomy with splenectomy cannot yet be defined. These will have to await the results of current clinical trials, which may reveal to what degree an improvement in therapeutic results has been achieved as a result of a better knowledge of the extent of disease.


Adnexal polyp of neonatal skin.

Adnexal polyp of neonatal skin. The adnexal polyp of neonatal skin is a small, usually solitary tumour of the skin occurring mostly on the areola of the nipple of the neonate. Our statistics reveal an incidence of 4-0% in 3,257 newborn infants. Histologically it always contains hair follicles, eccrine glands and vestigial sebaceous glands, hence the term 'adnexal polyp of neonatal skin' is proposed. No similar report has been hitherto recorded.