Numerical taxonomy and laboratory identification of Actinomyces and Arachnia and some related bacteria.

A numerical taxonomic study was made on 49 facultative anaerobic Gram-positive filamentous and/or diphtheroidal organisms isolated from dental plaques, carious dentin and faeces, together with 63 reference strains belonging to the genera Actinomyces, Arachnia, Bifidobacterium, Actinobacterium, Propionibacterium, Eubacterium and Lactobacillus. They were examined for 90 unit characters covering a wide range of tests and properties. The data were subjected to computer analysis in which the simple matching coefficient (SSM) and the similarity index  (SJ) were calculated, and the results of single linkage techniques and an unweighted average linkage cluster analysis technique were compared. The strains fell into six major groups (phena). The Actinomyces strains were recovered in two phena; the first contained Actinomyces israelii and the other facultative anaerobic Actinomyces, including subclusters equal to taxospecies of A. odontolyticus and A. viscosus/A. naeslundii, while the other phenon corresponded to the genera Arachnia, Actinobacterium, Bifidobacterium and Propionibacterium. The groups of Arachnia and Actinobacterium each contained one species, representing taxospecies of Arachnia propionica and Actinobacterium meyerii. Taxonomic criteria, both constant and discriminative, were selected to form a diagnostic table useful for laboratory identification of this group of organisms. Immunofluorescence supported the numerical data.


DNA base sequence homologies among strains of Streptococcus sanguis.

DNA was isolated from 19 strains and substrains of Streptococcus sanguis and analysed for guanine plus cytosine (GC) contents and base sequence homologies. Three groups could be discerned: group 1 strains had 40-8 to 42-8 mol % GC; group 2, 42-7 to 44-0 mol % GC; group 3, 43-8 to 46-4 mol % GC. DNA homologies between groups 1 and 3 were 40 to 60% at 67 degrees C and 40% at 72 degrees C. The homologies of group 2 towards groups 1 and 3 were much lower. Strains in groups 1 and 3 hydrolysed arginine and aesculin and fermented inulin; group 2 strains did not. Groups 1 and 3 could be considered subspecies of S. sanguis. Group 2 should not be considered S. sanguis.


Adult onset scapuloperoneal myopathy.

Six cases are described of muscle weakness and wasting of scapuloperoneal distribution with an onset in early adult or middle life and a relatively benign progression. One case also showed mild facial weakness. Four cases were probably sporadic but in two, a mother and daughter, autosomal dominant inheritance was likely. Electromyographic studies demonstrated myopathic features in all, and this was confirmed by muscle biopsy in five. Electrocardiographic abnormalities were present in three cases, but their significance is uncertain. It is considered that adult onset scapuloperoneal myopathy constitutes a clinically distinct condition.


Electrophysiological study of amyotrophy associated with acute asthma (asthmatic amyotrophy).

A girl developed acute amyotrophy of the left arm five days after onset of an acute attack of bronchial asthma. Slow improvement in muscle power began nine months later. There was severe denervation with preservation of sensation and normal motor nerve conduction velocities when these were measurable. The patient is similar to 10 patients reported by Hopkins (1974).


Absence of activation in frontal structures during psychological testing of chronic schizophrenics.

The distribution of activity in the dominant hemisphere was measured with the regional cerebral blood flow (rCBF) technique in 27 chronic schizophrenics and 15 non-schizophrenic control subjects (alcoholics) at rest and during phychological testing. In the non-schizophrenics, an increase of rCBF was observed during the test in frontal regions. In the chronic schizophrenics, on the other hand, no or only a very limited increase was recorded. In postcentral structures the flow response during the testing was, by and large, equal in the psychotics and the controls. The findings support the hypothesis advanced previously by the authors that in chronic schizophrenia there is defective transmission in the mediothalamic frontocortical projection bundle. This defect also appears responsible for the abnormally low resting flow (activity) in the dominant hemisphere in chronic schizophrenia which we have described previously.


Use of computerized tomography in senile dementia.

Computerized tomography was used to evaluate 35 patients with senile dementia and proved to be a simple and practical screening procedure. Those patients with moderate or severe cerebral atrophy had a poorer short-term prognosis than those with questionable or mild atrophy. Two patients with potentially treatable illnesses (hypothyroidism and pernicious anaemia) and only questionable atrophy had reversal of the dementia with treatment. A single patient with moderate atrophy had a potentially treatable illness (hypothyroidism) which only partially resolved. Those patients with dementia but relatively little atrophy by computerized tomography may represent a unique group with a better prognosis who require particularly careful evaluation for potentially treatable illnesses.


Optic ataxia: clinical-radiological correlations with the EMIscan.

After coronary by-pass surgery, a 47 year old, right-handed man developed Gerstmann's syndrome, a visual-spatial perceptual deficit, and a gross impairment of movememt under visual guidance ("optic ataxia"). Visual fields and extraocular movements were intact; he had a left hemiparesis. The EMIscan showed three lesions: a left parietal-occipital lesion; a posterior callosal lesion, and a right frontal lesion. It is hypothesized that optic ataxia in both visual fields requires bilateral lesions which, in the present case, were strategically placed so as to effectively disconnect motor cortex from visual input.


Conduction velocity along human nociceptive reflex afferent nerve fibres.

The conduction velocity along the nociceptive flexor reflex afferent nerve fibres was investigated in human subjects. The posterior tibal nerve was stimulated at two sites by single painful electrical shocks of 1.0 ms duration and with adequate intensity and the reflex EMG discharges were recorded from the short head of the biceps femoris muscle. The fastest reflex conduction velocity along the posterior tibial nerve between the ankle and the popliteal fossa was about 10-25 m/s. Thus the fastest flexor reflex afferent fibres associated with a painful sensation were thought to be included in the A-delta group of cutaneous afferent nerve fibres.


Delayed decrement of the nerve impulse propagation during induced limb ischaemia in chronic hepatic failure.

Sensory thresholds for vibrations and electrical shocks and the sensory nerve conduction velocity (median nerve) were measured during 30 minutes of induced limb ischaemia in 10 normal subjects and 15 patients with chronic hepatic failure. Sensory action potentials were recorded simultaneously at the wrist and elbow. Seven patients (group A) had a normal perception time for vibrations. As in normal subjects, the potential amplitude decreased from the onset of ischaemia, more pronounced at the elbow than at the wrist, and the conduction velocity became reduced more rapidly in the wrist-elbow than the first digit-wrist segment, indicating impulse propagation with decrement. Eight patients (group B) had a markedly prolonged perception time for vibrations. The reduction of potential amplitude and conduction velocity was considerably delayed, and the impulse propagation showed no evidence of decrement for 20-25 minutes of ischaemia. A rise of the threshold for electrical shocks was absent or very delayed. As in the two other groups, the rise was abrupt and occurred at the moment when the potential below the occluding cuff (elbow) was extinct. In both groups of patients there was an increasing temporal dispersion of action potentials and in patient group A a desynchronization of the late phase of the potential took place early in the course of ischaemia. Differences between groups A and B could not be predicted from the pre-ischaemic nerve conduction data.


Pathophysiology of aganglionic colon segment: an experimental study on aganglionosis produced by a new method in the rat.

Experimental aganglionosis was produced successfully in a colonic segment proximal to the peritoneal reflection by intraluminal filling under tension of the colorectum of rats with 0.01% corrosive sublimate in normal saline solution. Where the length of aganglionic segment was more than 3 cm, ileus appeared and megacolon proximal to a narrow segment was observed. Histologically and histochemically, a total denervation state was observed in the aganglionic segment, in contrast to findings in narrow segments of Hirschsprung's disease, in which intramural extraneous nerves are known to be increased. The fact that a definite narrow segment like that seen in Hirschsprung's disease appeared at the portion of the colon in which experimental aganglionosis was produced indicates that a narrow colonic segment certainly can be produced without presence of any intramural extraneous nerves, although the possibility that the presence of such nerves may exaggerate the narrowing cannot be denied. The fact that the cases in which length of aganglionosis was less than 2.5 cm did not have an ileus suggests that there may be some contributing factors other than aganglionosis in the etiology of Hirschsprung's disease of ultrashort segment, if this entity of the disease really exists. Aperistalsis observed in experimental aganglionic segments and that observed in aganglionotic segments of Hirschsprung's disease seem to be based on a common main factor, i.e., absence of the nonadrenergic, noncholinergic nerves.


Pharmacologic studies of Hirschsprung's disease on a murine model.

In studies of the pharmacology of a murine model of aganglionosis, the contracted aganglionic portion of the terminal bowel showed slow regular contractions of high amplitude in comparison to the rapid low-amplitude contractions of a normal segment of bowel. An absence of the nonadrenergic inhibitory system was demonstrated in the aganglionic, contracted portion of the bowel. This lack of the nonadrenergic system confirms previous findings in human tissue. It is proposed that absence of this inhibitory system in the aganglionic portion of the bowel results in the principal pathophysiologic findings in Hirschsprung's disease.


Hypercoagulability in childhood cancer.

Thirty-two children with solid tumors (lymphangioma, fibrosarcoma, hepatocarcinoma, osteogenic sarcoma, rhabdomyosarcoma, lymphosarcoma, mesenchymoma, hepatoma, Ewing's sarcoma, reticulum cell sarcoma, neuroblastoma, Hodgkin's disease, and brain tumors) were studied for alterations in coagulation by means of platelet counts, platelet aggregation, thrombelastogram, procoagulant and antigenic factor VIII, fibrin split products, and antithrombin III level. Results indicated hypercoagulability as shown by abnormally short thrombelastograms and elevated factor VIII levels and platelet counts in approximately one-half of the group. With the exception of increased fibrin split products in a third of the patients, little laboratory or clinical evidence for disseminated intravascular coagulation was seen. Hypercoagulability, as noted in adult carcinoma patients, can also occur in childhood sarcoma patients.


Immediate and long-term results of superior mesenteric vein-inferior vena cava shunt for portal hypertension in children.

Experience with 46 superior mesenteric vein-inferior vena cava shunts in children is reported, with postoperative follow-up of from 2 to 15 yr. The first procedure used as an end-to-side implantation of the vena cava into the right side of the superior mesenteric vein or portal vein after ligating the cava above the iliac vessels (16 cases). In the next 30 children, the vena cava was lengthened using the left or right common iliac vein, thus obtaining better anastomosis and reversed portal flow. Patency may be definitely assumed when the esophageal varices have disappeared within 3 mo; this was observed in 33 children. Results are nearly the same with superior mesenteric vein-inferior vena cava shunt, splenorenal shunt and portacaval shunt when the respective veins of the portal system are more than 1 cm in diameter. When it is less, the superior mesenteric vein-inferior vena cava shunt is more successful than others; this is the case in children under 7 yr of age. No serious trouble was observed after the interruption of the venous circulation of the limbs and pelvis when a superior mesenteric vein-inferior vena cava shunt was performed when the patients were less than 15 yr of age.


Inflammatory processes mimicking bladder tumors in children.

Tumor-like proliferative lesions were discovered on cystourethrography and cystoscopy in two children, one with severe bacterial urinary tract infection and the other with painless terminal hematuria. Histologically, these lesions were characterized by inflammatory infiltration and proliferative changes of the bladder epithelium. Appropriate treatment, including antibiotics, resulted in complete disappearance of the bladder lesions in both patients. The development of such lesions is related to the potential for nonneoplastic proliferation and metaplasia of the bladder epithelium and is considered to be the result of irritation associated with infection or other chemical and physical factors. The known malignant potential of such bladder pathology indicates a need for careful, long-term follow-up in such patients, including children.


Aldosteronoma in a child with localization by adrenal vein aldosterone: collective review of the literature.

Hyperaldosteronism due to aldosteronoma is a rare but potentially curable form of pediatric hypertension. We have presented a patient who had symptoms of enuresis and fatigue, and in whom the diagnosis was suggested by low serum potassium and persistent hypertension. Diagnosis was confirmed by increased plasma and urinary aldosterone and decreased plasma renin. The tumor was localized with the aid of adrenal venography and catheterization, which showed greatly increased plasma aldosterone levels in the right adrenal vein. The pathologic findings were totally reversed by right adrenalectomy. The clinical picture and results following surgical removal of aldosterone-producing tumors in six children are reviewed.


Correction of transposition of the great vessels with previous Baffes procedure.

Twenty-four patients with transposition of the great vessels who underwent a Baffes procedure in infancy were totally corrected by a modified Mustard procedure. There were three postoperative deaths and one major complication. All survivors have been followed from 2 to 8 yr and have done well except for one patient who required a tricuspid valve replacement because of tricuspid insufficiency. It is our conclusion that this group of patients can be corrected with a relatively low mortality and a favorable outcome.


Angiographic diagnosis and treatment of bleeding by selective embolization following pelvic fracture in children.

Angiography has been used successfully in adults for evaluation following major trauma and to subsequently control hemorrhage associated with pelvic fracture by selective embolization. This report illustrates that the technique is applicable in the evaluation and treatment of children with similar injuries.


Intestinal atresia in fetal dogs produced by localized ligation of mesenteric vessels.

Experimental ileal atresia and stenosis were produced by a localized ligation of the mesenteric vessels in fetuses from 13 pregnant mongrel dogs having gestational ages of 45-55 days. The intestinal infarct in the fetus was characterized by an aseptic coagulation necrosis selectively limited to the mucosa and submucosa, and also by intense hyperemia and minimal cellular reaction in the adjacent tissue. Eleven days after the devascularization, type 2 intestinal atresia, in which there is a long cord between the blunt ends microscopically similar to that seen in humans.


Fatal outcome in a child with pseudomembranous colitis.

The clinical and histologic changes occurring with antibiotic-associated pseudomembranous colitis are usually reversible with discontinuation of the causative medication. The spectrum of disease patterns ranges from a benign form to a very fulminant and occasionally fatal one. This report describes a child with a severe form of the disease. Despite recognition and sigmoidoscopic confirmation of this syndrome and cessation of antibiotics, his course continued to deteriorate. Sepsis, leukocytosis, refractory diarrhea, and abdominal distension led to exploratory laparotomy. A proctocolectomy was performed for necrosis of the entire colon; however, the patient died of sepsis.


Concurrent validity of the Wheeler signs of homosexuality in the Rorschach: P (Ci/Rj).

The Rorschach protocols of 43 males consecutively admitted to a university outpatient clinic were scored for frequency of the 20 Wheeler signs of homosexuality. Based on case history data, patients were assigned to homosexual, sex-role disturbed, or normal-control groups. In addition to the traditional group comparison the results were analyzed to yield P (Ci/Rj); that is, the probability of criterion group membership given test indicator. Both the homosexual and sex-role disturbed group displayed significantly more Wheeler signs than normals. Furthermore, given a Wheeler sign score of 15%, .75 of the predicted-homosexual group would be correctly classified compared to a .21 baserate prediction. It was suggested that expressing results as P (Ci/Rj) provides information more relevant to the clinician than is provided by the traditional practice of reporting significant differences between groups.


Validity of the Overcontrolled-Hostility (O-H) Scale: a brief report.

In order to further assess the validity of the MMPI O-H (overcontrolled hostility) Scale, high and low O-H youthful offenders were administered the Rosenzweig Picture-Frustration Study and their responses classified as extrapunitive, impunitive or intropunitive. Results indicated that high O-H subjects were significantly more impunitive than low O-H subjects and conversely, that low O-H subjects were more extrapunitive than high O-H subjects. Such findings are consistent with the O-H personality typology and lend further support to the construct validity of the Scale.


Personality differences among child molesters.

This study compared the MMPI profiles of two groups of child molesters, those with no prior arrests versus those with one or more prior arrests, in order to assess certain clinically derived inferences about these offenders. The sample consisted of 33 persons convicted of child molestation. The group with prior arrests showed more psychopathology than the group with no previous arrests.


Time experiences, self-actualizing values, and creativity.

The Personal Orientation Inventory (POI), the Inventory of Temporal Experiences (ITE), and the Adjective Check List (ACL) were administered to 80 subjects. Sixteen scores were derived from the POI, 4 from the ITE and a Creativity score for the ACL. The resulting intercorrelations were interpreted in the light of the theories of Maslow and Hugenholtz which postulate a convergence of self-actualization, creativity, and certain experiences of time. The present study presents some evidence for the expected convergence and contributes to the construct validity of several of the variables studied.


Locus of control and voluntary heart-rate change.

Investigated the effects of locus of control on voluntary control of heart-rate change. The 32 subjects were randomly assigned to one of two heart-rate change groups: Increase or decrease. The groups were counterbalanced for locus of control and sex. No heart-rate feedback was provided to subjects, and all subjects performed the appropriate task for two sessions. Results indicated that during the initial session, internals were better able to increase their heart-rates than externals; the externals were better able to decrease their heart-rates internals. This association, however, diminished to nonsignificance in the second session.


Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.

1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously  indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current.


Extracellular potassium activity, intracellular and extracellular potential responses in the spinal cord.

1. Microcapillary electrode assemblies of two or three channels were used to record extracellular and intracellular potentials together with the extracellular activity of potassium ions, from essentially single locations within the substance of the decapitate spinal cord of cats. A liquid ion exchanger filled the tip of the potassium sensing microprobe. Activity was evoked by electrical stimulation of afferent peripheral nerves (ventral roots were cut). 2. Within the substance of the spinal grey matter increments of extracellular potassium activity evoked by repetitive afferent volleys were precisely correlated with magnitudes of sustained shifts of extracellular electric potential. Raising [K+]o from 3 to 4 mM was associated with a negative shift of potential of 2-5 +/- 0-5 mV, regardless of the position of the electrode in the tissue, and regardless of treatment by convulsant or depressant drugs. 3. The spatial distribution of the responses of potassium activity was mapped by the spatial distribution of the negative sustained potential shifts. 4. Depolarization shifts of potential recorded from within neuroglia cells ran parallel with changes of extracellular potassium potential. Even though the magnitude of extracellular sustained potential shifts was precisely correlated with the responses of both extracellular potassium and intracellular glial potentials, the trajectory of sustained potential shifts did not exactly mirror the two other variables. Onset and offset of sustained potential shifts were faster than those of glial potentials or of extracellular potassium. 5. The responses of the true transmembrane potential (intracellular less extracellular potential shifts) of neuroglia cells in the spinal grey matter can fully be described by the Nernst equation. 6. Membrane potentials of neurones, potentials recorded from dorsal root filaments, or from white matter, appeared unrelated to the activity of potassium ions in extracellular fluid. 7. The results are compatible with the suggestions that changes of the membrane potential of spinal neuroglia cells are fully determined by the change of the activity of extracellular potassium, and that glia cells supply most of the current which generates sustained shifts of the extracellular potential of spinal grey matter. The results are hard to reconcile with suggestions that under conditions of moderate excitation (i.e. in the absence of convulsive neuronal activity) changes of extracellular potassium would significantly influence the membrane potential of spinal neurones, or of primary afferent nerve fibres.


Readjustment of retinotectal projection following reimplantation of a rotated or inverted tectal tissue in adult goldfish.

1. The pattern of visual projection from the retina on to the optic tectum following reimplantation of a piece of the tectal tissue was studied with neurophysiological mapping methods in adult goldfish. 2. When a rectangular piece of the tectum was dissected, lifted free, and then reimplanted to the same tectum after rotation by 180 degrees around the dorsoventral axis, the re-established visual projection later showed a complete reversal of retinotopic order within the reimplanted area with reference to the normal projection on to the intact surrounding area of the same tectum. The localized reversal was observed as early as 65 days, and also as late as 721 days after the 180 degree rotated reimplantation. 3. If a square piece of the tectal tissue was reimplanted after rotation by 90 degrees anticlockwise around the dorsoventral axis, the restored visual projection later showed a corresponding localized 90 degrees rotation within the reimplanted ares. 4. When the entire laminar structure of a dissected tectal tissue was inverted, and the reimplanted upside-down along the same rostrocaudal axis of the tectum, the restored visual projection on to the inverted tectal reimplant was found to be organized in a reverse retinotopic order along only the mediolateral axis within the reimplanted area. The restored visual projection retained a correct retinotopic order along the rostrocaudal axis. The same trends were also observed after regeneration of the optic fibres following section of the contralateral optic nerve. 5. If the inverted tectal tissue was reimplanted along the same mediolateral axis of the tectum, the re-established visual projection showed a localized reversal of retinotopic order along only the rostrocaudal axis within the reimplanted area. Sectioning the contralateral optic nerve made no difference to the result. 6. These results suggest that a piece of adult tectal tissue retains its original topographic polarity regardless of the orientation of reimplantation after either a rotation or an inversion. Furthermore the retention is not a short-lived transitory phenomenon. It persisted as long as the reimplanted tissue survived. 7. Histological examination of the operated tecta revealed that the reimplanted tectal tissues underwent a severe derangement in their laminar structures. It was impossible to identify the main target zone of retinotectal projection (the stratum fibrosum et griseum superficiale) or the central cellular layer (the stratum griseum centrale) in the reimplants. The prominent feature of the deranged tectal tissue was irregular vortices of tangled fibre bundles. Sparse tectal neurones of bipolar and granular types were irregularly scattered in the deranged structure of the reimplant. 8. Thus, the retention of original topographic polarity did not require an integrity of the cytoarchitectonic structure of the reimplanted tectal tissue.


The actions of volatile anaesthetics on synaptic transmission in the dentate gyrus.

1. The action of four volatile anaesthetics on the evoked synaptic potentials of in vitro preparations of the hippocampus were examined. 2. All four anaesthetics (ether, halothane, methoxyflurane and trichloroethylene) depressed the synaptic transmission between the perforant path and the granule cells at concentrations lower than those required to maintain anaesthesia in intact animals. 3. The population excitatory post-synaptic potential (e.p.s.p.) and massed discharge of the cortical cells (population spike) were depressed at concentrations of the anaesthetics lower than those required to depress the compound action potential of the perforant path nerve fibres. None of the anaesthetics studied increased the threshold depolarization required for granule cell discharge. Furthermore, frequency potentiation of the evoked cortical e.p.s.p.s was not impaired by any of the anaesthetics studied. 4. It is concluded that all four anaesthetics depress synaptic transmission in the dentate gyrus either by reducing the amount of transmitter released from each nerve terminal in response to an afferent volley, or by decreasing the sensitivity of the post-synaptic membrane to released transmitted or by both effects together.


Transfer of fatty acids across the rabbit placenta.

1. Transfer of fatty acids across the placenta was studied in anaesthetized rabbits at 28-days gestation by measuring umbilical venous-arterial differences, by injection of labelled palmitate into the mother and observing its appearance in the foetus, by injection of labelled palmitate into the foetus and measuring its appearance in the mother and the foetal clearance rate. 2. The release of fatty acids and glycerol by foetal adipose tissues was investigated in vitro by measuring the effect of addition of noradrenaline to the incubation medium and in vivo by measuring the effect of noradrenaline infusion into the foetus on circulating glycerol and free fatty acid concentrations. 3. In anaesthetized rabbits at 28-days gestation the maternal circulating free fatty acid concentrations were high and there was a positive umbilical venous-arterial difference. High maternal free fatty acid concentrations were associated with high umbilical venous-arterial differences. 4. Label was present in the foetus in 2 min and reached a peak in 3 min after injection of labelled palmitate into the mother. Label appeared in the maternal circulation in 1 min after injection into the foetus. The half-life of labelled palmitate was of the order of 30-60 sec in both mother in foetus. 5. Foetal white adipose tissue released both free fatty acids and glycerol into the medium and the rate of release increased four to five fold after addition of noradrenaline. Infusion of noradrenaline in the foetus led to a rise in glucose and glycerol concentrations, but the change in free fatty acid concentrations was not significant. 6. It was concluded that (i) free fatty acids can cross the rabbit placenta in amounts sufficient to provide the fatty acid components of stored triglyceride and structural lipids; (ii) placental transport of free fatty acids depends in part on maternal blood concentration and on foetal uptake; (iii) foetal circulating free fatty acids are continually exchanging with fatty acid pools in the placenta and with the maternal circulating free fatty acids.


Ionic mechanism of the excitatory synaptic membrane of the crayfish neuromuscular junction.

1. The reversal potential for the excitatory neuromuscular junction of the crayfish (Cambarus clarkii) was measured using the voltage clamp method. The potential change was recorded with an intracellular microcapillary and the negative phase of the output of the feed-back amplifier was connected to the stainless-steel wire which was inserted longitudinally into the muscle fibre. 2. When the excitatory nerve was stimulated, a transient feed-back current flowed inwardly through the membrane. This current was called the excitatory junctional current (e.j.c.). 3. Reversal potentials were determined by extrapolating the e.j.c.s measured at different membrane potentials. They were about 10-20 mV positive with respect to the bath solution (11-5 +/- 1-2 mV, mean +/- S.E.). 4. The reversal potential for the iontophoretically applied glutamate was identical with that for the e.j.c. 5. In hypertonic solutions, the reversal potentials for e.j.c. and glutamate became more negative. 6. When the sodium concentration of the bath solution was decreased, the reversal potential became more negative. 7. When the chloride and potassium concentration were altered, little, if any, change was observed in the reversal potential. 8. It was concluded that the e.j.c. was carried mainly by sodium ions. Contribution of other ions, possibly calcium ions, was discussed.


A comparison of radioactive thallium and potassium fluxes in the giant axon of the squid.

1. The influx and the efflux of 204Tl and 42K were measured in intact squid giant axons. 2. The resting efflux of 204Tl was found to be about one half of 42K and to have a temperature coefficient (Q10) of 1-3 as compared to 1-1 for K. 3. The extra efflux of 204Tl associated with nerve impulses was 30% greater than 42K. 4. From either Cl or NO3 sea water, the resting influx of 204Tl was about three times that of 42K. Ouabain reduced the influx of either isotope by about two thirds without changing the Tl/K ratio of the fluxes. This indicates that the Na pump can transport Tl. 5. From NO3 sea water the extra influx of 204Tl assoicated with nerve impulses was about the same as 42K. From Cl sea water there was no detectable extra influx of 204Tl. 6. The flux ratio, ouabain-insensitive influx/efflux, was different for the two ions. The resting flux ratio for Tl was consistent with a passive non-interacting flux, whereas K movements were consistent with 'single file' passage through the membrane. 7. The extra flux associated with nerve impulses is different from the resting flux both in Tl/K selectivity and in the effect of anion in the sea water. There is also a much higher flux per unit time during the nerve impulse. These differences suggest differences in the mechanisms underlying ion permeability at rest and during nervous activity.


The effect of saline and hyperoncotic dextran infusion on canine ileal salt and water absorption and regional blood flow.

1. The unidirectional Na and H2O fluxes, vascular pressures and total and absorptive site blood flows in the canine ileum were determined before and during I.V. saline infusion and subsequent I.V. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of I.V. saline or I.V. hyperoncotic dextran infusion were generally the same for both luminal solutions. 2. Continuous I.V. infusion of saline caused a continuous increase in the unidirectional flux of Na and H2O into the ileal lumen, an increase in total blood flow, and an increase in venous pressure. 3. The net absorption of Na and H2O was decreased by I.V. saline infusion. 4. The unidirectional fluxes of Na and H2O out of the lumen, arterial pressure, and absorptive site blood flow were not affected by I.V. saline infusion. 5. I.V. hyperoncotic dextran infusion reversed most of the effects of saline infusion. 6. The unidirectional fluxes of Na and H2O into the lumen were significantly correlated with Starling forces during I.V. saline infusion. 7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.


Evolution of the mammalian middle ear.

The structure and evolution of the mandible, suspensorium, and stapes of mammal-like reptiles and early mammals are examined in an attempt to determine how, why, and when in phylogeny the precursors of the mammalian tympanic bone, malleus, and incus (postdentary jaw elements and quadrate) came to function in the reception of air-borne sound. The following conclusions are reached: It is possible that at no stage in mammalian phylogeny was there a middle ear similar to that of "typical" living reptiles, with a postquadrate tympanic membrane contracted by an extrastapes. The aquamosal sulcus of cynodonts and other therapsids, usually thought to have housed a long external acoustic meatus, possibly held a depressor mandibulae muscle. In therapsids an air-filled chamber (recessus mandibularis of Westoll) extended deep to the reflected lamina and into the depression (external fossa) on the outer aspect of the angular element. A similar chamber was present in sphenacodontids but pterygoideus musculature occupied the small external fossa. The thin tissues superficial to the recessus mandibularis served as eardrum. Primitively, vibrations reached the stapes mainly via the anterior hyoid cornu, but in dicynodonts, therocephalians, and cynodants vibrations passed mainly or exclusively from mandible to quadrate to stapes and the reflected lamina was a component of the eardrum. In the therapsid phase of mammalian phylogeny, auditory adaptation was an important aspect of jaw evolution. Auditory efficiency, and sensitivity to higher sound frequencies were enhanced by diminution and loosening of the postdentary elements and quadrate, along with transference of musculature from postdentary elements to the dentary. These changes were made possible by associated modifications, including posterior expansion of the dentary. Establishment of a dentary-squamosal articulation permitted continuation of these trends, leading to the definitive mammalian condition, with no major change in auditory mechanism except that in most mammals (not monotremes) the angular, as tympanic, eventually bcame a non-vibrating structure.


Evidence for a structural relationship between successive parallel tubules in the SR network and supernumerary striations of Z line material in purkinje fibers of the chicken, sheep, dog and rhesus monkey heart.

The striations and the intervening filaments observed in the present study have been variously designated in the literature as: prodomal pattern, leptomeric myofibril, microladder, leptomeric organelle, leptofibril and zebra body. Electron microscope examinations of Purkinje fibers from the septa, papillaries, trabeculae carneae and small endocardial strands from chicken, sheep, dog and monkey hearts have revealed a close association between densely stained striations of supernumerary Z line material and successive parallel tubules in the network formed by the sarcoplasmic reticulum (SR). The striations appear to be linked together by filaments that somewhat resemble the part of thin filaments attached to Z lines in normal fibrils. The evidence for a close association of striations and SR tubules is derived from a similarity of spacing between striations and successive parallel tubules in the SR network and from a resemblance of striation and SR network patterns. The evidence for a structural relationship between striations and SR tubules is derived from the observation of electron-opaque strands traversing the space between striations and SR tubules.


Oocyte differentiation in Urechis caupo (Echiura): a fine structural study.

The fine structure of oocytes of Urechis caupo is described for seven arbitrary stages ranging from the smallest oocytes (7 mum in diameter) in the coelom to the mature oocytes (115 mum in diameter) in the storage organs. Although most types of cytoplasmic organelles accumulate more or less continuously, yolk granules do not appear until oocytes reach a diameter of 35 mum, and there is stage-specific synthesis of cortical granules in 60-80 mum oocytes. In the nucleus a single nucleolus first appears when an oocyte is 15 mum in diameter. Then a nucleolus satellite, which is about 3 mum in diameter, forms in 30 mum oocytes; this nucleolus satellite later (60-70 mum oocytes) becomes surrounded by 750 nm dense spherical bodies. Large (2-4 mum in diameter) juxtachromosomal spherules occur only in the nuclei of mature oocytes. Microvilli become progressively more numerous and longer until the oocyte reaches a diameter of 90 mum; their tips project 1 mum beyond the fibrous surface coat, which is 2 mum thick when well developed. Near the end of oocyte growth, the microvilli retract into the surface coat leaving their pinched-off tips adhering to the outside of the coat.


Linear and inverted repetitions in protein sequences.

An extensive search for internal regularities in amino acid sequences has been made, using both the genetic code and the relative frequencies of amino acid alternatives in homologous proteins. The two methods give very similar results and strongly suggest the occurrence of significant linear and inverted repetitions (similar sequences of opposite polarity) in several proteins. A hypothesis is developed to explain the occurrence of such internal regularities in proteins. This hypothesis is based on a process of duplication of an ancestral loop in which a symmetrical arrangement of amino acid allows stabilization by interaction between the amino acid side chains.


The amino acid sequence of myoglobin from skeletal muscles of red deer (Cervus elaphus).

Red deer myoglobin has been fragmented by restricted tryptic digestion and by treatment with cyanogen bromide. The fragments have been separated by gel permeation. The core peptide derived from cyanogen bromide cleavage have been further digested with trypsin and the resulting peptides have been separated on Dowex 1X2. All fragments have been characterized by their amino acid composition, by determination of their N-terminal sequence using automatic Edman degradation and of their C-terminal sequence following the kinetics of amino acid cleavage by carboxypeptidases A and B. The complete sequence has been found to be identical with the already known sequence of sheep myoglobin except for residue 145 which is Gln in red deer globin and Glu in sheep globin. Reinvestigation of the corresponding sequence in sheep globin has shown that residue 145 of sheep globin is also Gln.


Symmetries of genetic code-doublets.

The fact that 64 base triplets code only about 20 essential amino acids implies a strong degeneracy of certain base doublets. It is shown that the set of degenerate base doublets and the set of non-degenerate base doublets are highlly structured. A mathematical formalism is introduced which allows a systematic description of the consequences of an exchange of bases in a doublet. By this formalism it is shown that the two mentioned set have in fact the same structure.


Five simultaneous steady states in a flipping two-compartment-system with optical antipodes.

The previously given systems-theoretic model for the synthesis of optical antipodes (AD and AL) in strongly asymmetric yield, which shows mono-bistable behaviour depending on the degree of "openess" of the chemical reaction system is reconsidered for two equal compartments (subscripts 1 and 2 on A) with coupling by diffusion. In this configuration three threshold values, j1, is less than j2 is less than j3, for the influx j of the common precursor substance appear. For j is less than j1 only one steady state (s.s.) with no optical activity (ADi = ALi, i-1;2) and equal distribution of the antipodes in both compartments (AD1 = AD2, AL1 = AL2) exists. For j is greater than j 1, this totally symmetric s.s. becomes unstable and a pair of s.s. with optical activity (AD1 is less than AL1, AD2 is less than AL2 or AD1 is greater than AL1, AD2 is greater than AL2) but no spatial asymmetry emerges (parallel flipping), i.e. both compartments be8have as a whole, showing a preponderance of either the D- or the L-form. For j is greater than j2 in addition two new s.s. are possible with antiparallel flipping (AD1 is less than AL1, AD2 is greater than AL2 or AD1 is greater than AL1, AD2 is less than AL2), i.e. in one compartment the D-form has the majority and in the other one the L-form, but these are stable only beyond a third threshold value j3. A third thinkable pair with no optical activity, but different sum concentrations in both cells, does not exist in this special circuitry, but can be obtained in a slightly changed arrangement. So for j is greater than j2, 5 different (4 stable, 1 unstable) s.s., exist for the same set of parameters, one of which is chosen by the system.


Present status of enantiomeric analysis by gas chromatography.

The development of selective chiral solute-solvent systems showing separation of enantiomers by gas chromatography is reviewed. The enantiomeric analysis of alpha-amino-acids and its application to various problems, including notably the analysis of meteorites, is discussed. Some recent results with the highly efficient diamide phases, which permit resolution on packed columns, are presented. Some new ideas on the mechanism of resolution are briefly mentioned.


Neutral currents in weak interactions and molecular asymmetry.

Weak interactions are parity violating forces, i.e. they differentiate between mirror images. Therefore it is a very attractive hypothesis to invoke weak interactions in explaining the origin of molecular asymmetry. It is, however, not clear whether weak interactions may operate between electrons and/or between electrons and protons? For these types of interactions so called neutral currents are needed. Recent experiments with muon neutrinos at CERN gave some evidence for the existence of neutral currents. Thus we may suppose that parity violating forces are active in molecules. In the first part of this paper a very elementary theory of weak interactions is outlined with special reference to the discovery of neutral currents. In the second part we show how weak interactions may differentiate between mirror image molecules. The asymmetrically distributed static charges in chiral molecules represent a helical potential field. This potential field may exert an effect on the orbital electrons and therefore coupling of spins and momenta occurs. Thus the enantiomers are parity transformed images not only as geometrical bodies, but their orbital electrons are parity transformed too as "a helical electron gas". Weak interactions will differentiate between L and D forms because their orbital electrons have a nonzero spin polarization with respect to their velocity.


On the origin of molecular "handedness" in living systems.

Elementary particle effects (beta-decay) provide at best only a weakly handed radiation in the biologically effective energy ranges. Global magnetic effects coupled to sunlight are randomized by paleomagnetic reversals. Hence a persistent terrestrial handed bias at possible local biopoetic sites offers a more promising explanation for the origin of the "handedness" of the molecules found among living systems on earth. Magnetite in lava flows maintains a handed bias for surface catalysis through many magnetic reversals. Magnetite contaminated with sulfur has already been proposed by Granick as a biopoetic site because it provides a weak source of chemical energy derived by photochemical conversion. Indirect evidence for this hypothesis has been provided by the molecular structure of ferredoxin - a single strand of the 14 primordial amino acids wrapped around an FeS core. Lava flows have been suggested as biopoetic sites by Fox, since their temperature and chemical composition might allow for the rapid synthesis of prebiotic compounds at the surface of the primitive earth. The additional fact that magnetite in lave flows also provides a persistent handed site for surface catalysis offers a further argument for the experimental investigation of this specific biopoetic environment.


Crystallization and solid-state reaction as a route to asymmetric synthesis from achiral starting materials.

Many molecules which are achiral can crystallize in chiral (enantiomorphic) crystals and, under suitable conditions, crystals of only one chirality may be obtained. The formation of right- or left-handed crystals in excess is equally probable. Lattice-controlled (topochemical) photochemical or thermal solid-state reactions may then afford stable, optically active products. In the presence of the chiral products, achiral reactants may preferentially produce crystals of one chirality, leading to a feedback mechanism for the generation and amplification of optical activity. Amplification of optical activity can also be achieved by solid-state reactions. The optical synthesis of biologically relevant compounds by such routes may be envisaged.


Renal trauma and retroperitoneal hematomas-indications for exploration.

One hundred nineteen patients with renal trauma documented at laparotomy or by an abnormal excretory urogram were followed up sufficiently to allow assessment of their postinjury course. One-fourth of these patients had a laparotomy and Gerota's fascia was opened; one-fourth had a laparotomy and Gerota's fascia was not opened; and one-half had no laparotomy. Gerota's fascia was opened only after vascular control of the renal pedicle was obtained. Nonetheless, the loss of renal tissue in this group was high. Twenty-three of 34 patients (68%) required nephrectomy or partial nephrectomy, indicating the severity of their renal injuries. The loss of renal tissue was low in the two groups in which Gerota's fascia was not opened. Six of 85 patients (7%) developed complications eventually requiring nephrectomy or partial nephrectomy; an additional three patients (4%) demonstrated loss of renal tissue on followup urograms, the loss being minimal in all three cases. The relatively low morbidity in these 85 patients indicates that their original renal injuries were, for the most part, less serious than the injuries in the group in which Gerota's fascia was opened. This low morbidity also indicates that retroperitoneal hematomas in the area of the kidney which are nonexpanding, contained, and nonpulsatile need not be routinely explored.


Diagnostic laparotomy in the patient with multiple injuries.

Seven hundred consecutive patients with multiple areas of injury requiring surgical repair outside of the abdomen were subjected to laparotomy. Five hundred sixty-one patients had intra-abdominal injury: 139 patients were found to have no intraperitoneal damage. The morbidity in the 139 patients with negative findings at laparotomy was 2%. In patients with multiple areas of trauma, the abdomen is almost always suspect. The proliferation of diagnostic tools to detect intraperitoneal damage have, in some ways, helped physicians decide as to laparotomy. However, when multiple injuries are present, particularly of the central nervous system, classical findings of peritoneal damage are difficult to elicit. A diagnostic laparotomy does not add significantly to the overall morbidity or mortality, and in 25% of the patients in whom intraperitoneal pathology was not strongly suspected, damage requiring surgery was found. We think there is still a place for diagnostic laparotomy in patients with multiple trauma.


Two-level disruption of the ankylosed spine: a case report.

An unusual two-level fracture dislocation of the spine in a patient with rheumatoid spondylitis is presented. Thorough clinical and roentgenographic examination of the entire vertebral column in recommended in patients with rheumatoid spondylitis who have sustained injury.


Alkali lability of bacteriophage phi W-14 DNA.

The molecular weight of bacteriophage phi W-14 DNA, determined by velocity sedimentation in neutral sucrose gradients, was 92 +/- 6 X 10(6). The DNA showed marked fragmentation in alkaline sucrose gradients. This fragmentation was not a consequence of preexisting single-strand interruptions in the DNA, since thermal denaturation of DNA yielded intact single strands. The alpha-putrescinylthymine groups in phi W-14 DNA appeared to be labile; some, or parts of some, of these groups were cleaved from the DNA in alkali.


Bacteriophage T4 baseplate components. III. Location and properties of the bacteriophage structural thymidylate synthetase.

Two T4D thymidylate synthetase (td) temperature-sensitive mutants have been isolated and characterized. Both mutants produce heat-labile phage particles. This observation supports the view that this viral-induced protein is a phage structural component. Further, antiserum to td has been shown to block a specific step in tail plate morphogenesis. The results indicated that the td protein is largely covered by the T4D tail plate gene 11 protein. Since the phageinduced dihydrofolate reductase (dfr) also is partially covered by the gene 11 protein, it appears that td was adjacent to the tail plate dfr. This location has been confirmed by constructing a T4D mutant which is dfrtstdts and showing that these two tail plate constituents interact and give altered physical properties to the phage particles produced. A structural relationship for the tail plate folate, dfr, and td has been reported.


Characterization of the mRNA of influenza virus.

The kinetics of the appearance of influenza mRNA, the distribution of mRNA between free and membrane-associated polyribosomes, its poly(A) content, and the extent to which the genome was transcribed into mRNA early in infection were determined. Polyribosomes were prepared from influenza virus-infected cells labeled for 30-min periods at various times after infection with [3H]uridine. Most of the 3H-labeled RNA extracted from these polyribosomes sedimented as a heterogeneous 8S to 20S peak in sucrose gradients, and it was largely complementary to virion RNA. By the following criteria, the complementary RNA had properties normally ascribed to mRNA: (i) it labeled rapidly with [3H]uridine; (ii) after glutaraldelyde treatment, it banded with polyribosomes in CsCl density gradients; and (iii) it contained poly(A). In chick cells at 37 C, virus mRNA was first detectable at 45 min postinfection and reached its maximal rate of appearance at 2 to 2.5 h postinfection. The free and membrane-bound polyribosomes of infected cells were separated and were found to contain the same classes of mRNA. There was no absolute segregation of mRNA sequences into either polyribosome class although each probably contained distinct ratios of the different mRNA's. From 45 min postinfection onwards, both membrane-bound and free polysomal poly(A)-containing RNA contained sequences complementary to at least 80% of the genome RNA, whereas poly(A)-minus RNA contained sequences complementary to 90 to 100% of the genome. There was no evidence for the temporal control of transcription of influenza mRNA. At 31 C, when virus development was slowed relative to 37 C,complementary RNA first appeared at 1 h postinfection. At this time, total polysomal RNA contained sequences complementary to the whole genome.


Complementation between temperature-sensitive and deletion mutants of reovirus.

A very low level of complementation has been found in conventional crosses between various classes of temperature-sensitive (ts) mutants of reovirus. A more definitive test for complementation was devised through a plaque assay on cell monolayers mixedly infected with defective reovirions lacking the L1 segment and prototype ts mutants from one or other of the known classes of reovirus mutants. An increase in the number of plaques on the mixedly infected plates over that on control plates infected with defective virions or ts mutants alone indicated that the ts mutant had been complemented by the defective virus. Class A, B, D, F, and G mutants were complemented at 39 C by the defective viruses, whereas class C and E mutants were not. In tests to determine whether complementation was reciprocal it was found that the defective virions were complemented by a class G mutant but not by the class C mutant. This and previous work (D.A. Spandidos and A. F. Graham, 1975) has therefore shown that of the seven known classes of ts mutants the class C mutant is the only one that neither complements nor is complemented by the defective virions. For this reason the class C ts mutation has been assigned to the L1 segment of the viral genome.


Purification of influenza viral complementary RNA: its genetic content and activity in wheat germ cell-free extracts.

Influenza viral complementary RNA (cRNA) was purified free from any detectable virion-type RNA (vRNA), and its genetic content and activity in wheat germ cell-free extracts were examined. After phenol-chloroform extraction of cytoplasmic fractions from infected cells, poly(A)-containing viral cRNA is found in two forms: in single-stranded RNA and associated with vRNA in partially and fully double-stranded RNA. To purify single-stranded cRNA free of these double-stranded forms, it was necessary to employ, as starting material, RNA fractions in which cRNA was predominantly single stranded. Two RNA fractions were successfully employed as starting material: polyribosomal RNA and the total cytoplasmic RNA from infected cells treated with 100 mug of cycloheximide (CM) per ml at 3 h after infection. In WSN virus-infected canine kidney (MDCK) cells, the addition of CM at 3 h after infection stimulates the production of cRNA threefold and causes a very large increase in the proportion of the cytoplasmic cRNA which is single stranded; double-stranded RNA forms are greatly reduced in amount. Total cRNA was obtained by oligo(dT)-cellulose chromatography, and single-stranded cRNA was separated from double-stranded forms by Sepharose 4B chromatography. The cRNA preparation purified from polyribosomes consists of 95% single-stranded cRNA, with the remaining 5% apparently being double-stranded RNA forms. The cRNA preparation purified from CM-treated cells (CM cRNA) is even more pure: 100% of the radiolabeled RNA is single-stranded cRNA. Annealing experiments, in which a limited amount of 32P-labeled genome RNA was annealed to the cRNA, indicate that the purified cRNA contains at least 84 to 90% of the genetic information in the vRNA genome. Purified viral cRNA (CM cRNA) is very active in directing the synthesis of virus-specific proteins in wheat germ cell-free extracts.


Regulation of macromolecular synthesis in reovirus-infected L-929 cells I. Effect of L-histidinol.

The histidine analogue L-histidinol, reported by Vaughan and Hansen (1973) to establish a potent, readily reversible inhibition of eukaryotic protein synthesis in vivo, was used to investigate the regulation of macromolecular synthesis in reovirus-infected L-929 cells. The addition of L-histidinol to normal L cells led to a total inhibition of protein synthesis. The inhibition appeared to be a consequence neither of isotope dilution resulting from elevated endogenous amino acids nor of an inability of treated cells to accumulate exogenous amino acids. Addition of L-histidine to histidinol-arrested cells resulted in a complete recovery of protein synthesis. Similarly, protein synthesis in reovirus-infected L cells examined 17 h postinfection (31 C) was totally inhibited by histidinol treatment and was readily reversed by the addition of histidine. Reovirus-infected cells treated with histidinol had an essentially unaltered capacity to synthesize reovirus single-stranded RNA relative to unperturbed cultures but a diminishing ability to maintain genome RNA synthesis. Addition of L-histidine to arrested cultures led to a complete recovery of genome RNA synthesis. The L-histidinol-mediated arrest of protein synthesis was both very effective and easily reversed, suggesting the general applicability of this novel inhibitor to investigations of regulation of macromolecular synthesis in both normal and virus-infected eukaryotic cells.


Physical properties of moloney murine leukemia virus high-molecular-weight RNA: a two subunit structure.

The high-molecular-weight RNA of Moloney murine leukemia virus (MuLV) was analyzed by sedimentation equilibrium ultracentrifugation. Molecular weights of 7.2 x 10(6) and 3.4 x 10(6) were found for the native and subunit forms, respectively, indicating that the native structure is a dimer. S20,w and frictional coefficients were determined for MuLV RNA by analytical velocity centrifugation as a function of ionic strength. The apparent S20,w of native MuLV RNA was 47.3, 57.4, and 66.5 in 0.01, 0.1, and 0.20 M Na+, respectively; the corresponding frictional coefficients were 5.44, 4.48, and 3.87. Native RNA was estimated by circular dichroism to be 85% helical, whereas denatured RNA was 54% helical. Thermal denaturation profiles were obtained from uv absorbance scans. Melting temperatures of 57 and 68 C were obtained for high-molecular-weight RNA in 0.01 M Na+ and 0.122 M Na+, 1mM Mg2+, respectively. van't Hoff plots of the thermal denaturation data gave enthalpies for the helix-coil transition of 21,600 cal (ca. 90,500 J) per mol of cooperatively melting unit in high salt and 19,600 cal (ca. 82,100 J) per mol in low salt, consistent with both base stacking and pairing. The melting of Mu LV RNA occurred over a broad temprange and van't Hoff plots were linear over most of the melting range, indicating a noncooperative process of helix stabilization.


Relationships among the polypeptides of Newcastle disease virus.

We have studied the relationships among the polypeptides of Newcastle disease virus by using both kinetic and tryptic peptide analyses. The results of our tryptic peptide analyses suggest that there are at least six unique viral polypeptides--L, HN, FO(F), NP, M, and a 47,000-dalton polypeptide. The small virion glycopolypeptide F is related to FO, a glycopolypeptide found only in infected cells. In addition, several smaller polypeptides, including a 53,000-dalton polypeptide found both in purified virions and in infected cells, are related to the nucleocaspid protein. Kinetic analysis of each viral polypeptide reveals that all of the major viral polypeptides, with the possible exception of L, are stable after an amino acid chase. A precursor-product relationship between FO and F was not demonstrable by pulse-chase experiments. Also, almost the same relative amount of F, the putative product, was present in infected cultures after either 5 or 30 min of radioisotopic labeling. These results suggest that FO is processed rapidly.


Tryptic peptide analysis on nonstructural and structural precursor proteins from Semliki Forest virus mutant-infected cells.

Analysis of [35S]methionine-labeled tryptic peptides of the large proteins induced by temperature-sensitive mutants of Semliki Forest virus was carried out. The 130,000-molecular-weight protein induced by ts-2 and ts-3 mutants contained the peptides of capsid protein and of both major envelope proteins E1 and E2. The ts-3-induced protein with molecular weight of 97,000 contained peptides of the capsid and envelope protein E2 but not those of E1. Two proteins with molecular weights of 78,000 and 86,000 from ts-1-infected cells did not contain the peptides of the virion structural proteins. They are evidently expressions of the nonstructural part of the 42S RNA genome of Semliki Forest virus.


Identification of P48 and P54 as components of bacteriophage T4 baseplates.

The involvement of two bacteriophage T4 gene products in the initiation of T4 tail tube and sheath polymerization on mature baseplates has been studied by radioautography of acrylamide gels of various partially completed tail structures. The products of genes 48 and 54 (P48[the nomenclature P48 refers to the protein product of bacteriophage T4 gene 48] and P54), which are known to be required for the synthesis of mature baseplates, have been shown to be structural components of the baseplate. These gene products have molecular weights of 42,000 and 33,000, respectively. The addition of P54 to the baseplate not only permits the polymerization of the core protein, P19, onto the baseplate, but also caused the disappearance of a polypeptide of molecular weight about 15,000 from the supernatant fraction of infected cells. Another gene product, P27, has been identified in the crude extracts of infected cells. This gene product, which is required for the synthesis of baseplate structures, has the same mobility as one of the unidentified structural polypeptides of the baseplate and is therefore probably also a baseplate component.


Adenovirus assembly: self-assembly of partially digested hexons.

Papainic hydrolysis of adenovirus type 2 hexon capsomers was apparently limited and induced self-aggregation of hexons in a preferred oligomeric species, hexon trimers, sedimenting at about 19X, and retaining their immunological properties. These hexon trimers were composed of two classes of trimer molecules with different electric charges. The relevance of this trimer aggregation phenomenon to the adenovirus assembly process is discussed.


Lethal effect of fresh sea water on Vibrio parahaemolyticus and isolation of Bdellovibrio parasitic against the organism.

Halophilic Bdellovibrio, which is parasitic and lytic to Vibrio pharahaemolyticus, was ioslated from fresh sea water in the winter. It had a lethal effect on V. parahaemolyticus. The optimum temperature ofr multiplication ranged from 25 C to 30 C and growth was not observed at 35 C. Plaque numbers of the isolate reached a maximum in 17 hr under conditions of shaking at 25 C in autoclaved sea water supplemented with V. parahaemolyticus cells, and were as high as ten times the number of host cells. With respect to the host-suspended medium, the isolate multiplied in natural sea water ten times more than in Herbst's artificial sea water but did not grow in saline. V. parahaemolyticus, Vibrio alginolyticus and several species in the Vibrio genus were susceptible to the parasite on the basis of plaque formation but Escherichia coli and Staphylococcus aureus were not.


Permselectivity of the glomerular capillary wall: III. Restricted transport of polyanions.

The clearance of albumin relative to that of inulin is greatly exceeded by that of uncharged dextrans of the same effective molecular radius (approximately 36A), less than 0.01 vs. 0.20 in normal hydropenic rats. This marked difference in fractional clearances of albumin and neutral dextran suggests that some factor in addition to molecular size retards the transglomerular passage of albumin. Since albumin is a polyanion in physiological solution, we tested the effect of charge on macromolecular permeability by infusing the anionic polymer, dextran sulfate (approximately 2.3 sulfate groups per glycosyl residue), into seven normal hypropenic Munich-Wistar rats. For dextran sulfate with an effective radius of approximately 36A, the fractional clearance was reduced essentially to that found for albumin (approximately 0.01). This enhanced restriction of dextran sulfate, relative to neutral dextran, was also noted for smaller and larger dextran sulfate molecules. These differences in the transport of dextran sulfate vs. dextran suggest electrostatic repulsion of charged macromolecules by some component of the glomerular capillary wall, perhaps the negatively charged sialoprotein which coats glomerular epithelial cells. Loss of this polyanionic coat, as has been reported to occur in proteinuric disorders, might thereby account for the enhanced transmural passage of albumin.


Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man.

The effects of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone (iPTH) were studied. Acute metabolic acidosis induced by administration of ammonium chloride (NH4Cl) produced a barely detectable increase in serum iPTH. Chronic NH4Cl administration produced a marked elevation of serum iPTH that was well correlated with the magnitude of acid-induced hypercalciuria but not with the degree of acidosis. Acetazolamide administration produced an equivalent degree of acidosis, but hypercalciuria was minimal and iPTH increased only marginally. Methionine administration caused moderate hypercalciuria and a significant but moderate increase in iPTH. Chronic NH4Cl-induced acidosis produced no hypercalciuria when dietary sodium intake was rigidly restricted, and under these conditions serum iPTH remained normal. When sodium intake was suddenly increased while maintaining the acid load, hypercalciuria appeared and was followed by progressive rise in serum iPTH equivalent to that observed during chronic NH4Cl-induced acidosis in subjects consuming salt ad lib. These results indicate that chronic acidosis elevates iPTH mainly by producing hypercalciuria and that acidosis itself is not a primary stimulus to PTH secretion.


[Vascular pseudopapillitis (author's transl)].

Besides the true ischaemias of the optic nerve, which explain the post-haemorrhagic amaurosis, the low tension glaucoma and the open angle glaucoma, there are two varieties of vascular pseudopapillitis. First the variety due to arteriosclerosis, which is characterized by a palid oedema of the disc, followed by optic atrophy, a diminution of the vision field, as well as by signs of arteriosclerosis at the biopsy of the temporal artery. The second variety is the temporal arteritis, which is also characterized by a palid oedema of the disc, followed by optic atrophy, a visual loss, which is often complete, a marked rise of the erythrocyte sedimentation rate and a typical granulomatous arteritis at the biopsy of the temporal artery. These two varieties are due to an involvement either of the short posterior ciliary arteries or of the central vascular or pial system of the optic nerve.


[Long-term results of laser-trabecular-puncture (author's transl)].

A report on 38 eyes with glaucoma simplex that were treated by laser-trabecular-puncture 2 years ago is given. By this method one attempts to perforate the trabecular meshwork by means of a laser beam. Gonioscopy revealed that the pores had become occluded by scar tissue and goniosynechiae. In only 3 eyes (7.9%) was the intraocular tension lowered. The hypothesis is made, that in these cases contracture of scar tissue in the iris tissue led to a pull on the trabecular network and hence to an improvement of liquor drainage.


[Contribution to the therapy of epiphora (author's transl)].

A temporary displacement of a fold of the conjunctiva for the under lacrimal point is a cause for epiphora.


[Progressive lethal ulceration of the nose (Kraus-Chatellier) (author's transl)].

Following attacks of maxillary sinusitis and pneumonia ocular signs (epiphora and diplopia) developed in a 39-years-old female patient. An ulceration of the skin over the left lacrimal sac with destruction of the lacrimal bone gave way to a fistula to the nose; and simultaneously a left sclerokeratitis developed. Later a similar fistula on the right side occured together with destruction of the nasal bones, left phthisis bulbi and skin ulcerations on the lower lid. Histologically there was a non-specific chronic inflammation compatible with the diagnosis granuloma gangraenescens nasi ("progressive lethal ulceration of the nose") but no evidence for Wegeners granulomatosis. Under immunosuppressive therapy the condition improved and the patient was able to return to work.


[Case report on a Toxocara-canis infection of the human eye (solitary granuloma) (author's transl)].

Description of one case of an intraocular Toxocara-canis infection. It deals with a so-called solitary granuloma at the posterior pole of the eye. An infection with this parasit of world-wide distribution is probably more frequently than commonly supposed. The prognosis of the disease is unfavourable in most cases. The diagnoses of a larva migrans visceralis infection is possible by Lamina's Microprecipitation-Test on the living larva. It is an immune-biological and species specific test. The treatment is Minzolum¿ perhaps in combination with a corticosteroid or photocoagulation.


[Improvement of visual acuity in lens opacities using an optic aperture (author's transl)].

A diaphragm, placed in front of the eye acts as an artificial pupil as well as a field stop. The improvement of visual performance in the presence of opacities is due to its action as a field stop.


[Retinoblastoma in an adult (author's transl)].

A rare case of late occurrence of retinoblastoma in a 42-year-old man is described. In conformity with similar findings in the literature difficulties in clinical diagnosis and complications typical for late manifestation of this tumour are given. Similarities and differences in histological picture compared with retinoblastoma in childhood are presented. Considering the tumour's late occurrence the histological peculiarities of the place of origin as one of the factors of possible histogenesis is stressed.


[Chamber-angle photos with the Zeiss fundus camera (author's transl)].

A new device for holding a Zeiss Fundus Camera (Bed-Statif) is described. This device overcomes earlier difficulties, through which too much distance between the patient and the photo resulted. This appliance allows perfect goniophotos to be taken -- as shown by the numerous illustrations.


[Experimental findings and clinical experiences with diamond knives (author's transl)].

This is a report about two clinically and experimentally tested new diamond knives. With special polishing methods one can get such a sharpness that the necessary cutting pressure is two to three times less than with the usual razor-blade.


[An eye-model to show fundamental optical properties as related to refraction and glasses-testing (author's transl)].

A new model of the eye is presented, that can demonstrate quantitatively the principal optical concepts such as focal distance, refractive power, principal point, nodal point etc. Ametropias and their correction can be shown. This model can be used to illustrate the dependence of the vertex distance on the effective refractive power of a spectacle lens and the influence of a spectacle lens on the image size on the retina. The phenomena of retinoscopy can also be demonstrated very clearly. An instruction manual for the model exists that contains theory, control tests and suggested experiments.


[Experiences with the non-contact-tonometer (author's transl)].

The Non-Contact-Tonometer as developed by the American Optical Corporation, is in use superior to the traditional methods of intraocular-pressure measurements according to Schiötz and Goldmann: Without any manipulation on the eye the intra-ocular pressure can be measured rapidly and easily. Owing to the construction of the tonometer however measurements are only possible with smooth corneae. In addition to this the results of measurement with the NCT are not as exact as those of the traditional methods. Finally there is up to the present no possibility of standardising the new tonometer.


[Lasermicrosurgery in glaucoma (Lasertrabeculopuncture I1LTP], tangential irisbasecoagulation [TLC], removal of miosis and shifting of pupils) (author's transl)].

The long-term results of Lasertrabeculopuncture (LTP) and of tangential irisbasecoagulation (TIC) according to experience of 4 years are presented and critically discussed in comparison with the reports of other authors. The removal of miosis and the shifting of displaced pupils in glaucomatous and cataract eyes is demonstrated. The long-term results of other interventions in glaucoma by lasermicrosurgery are announced.


[Principle and results of a new "non-contact-tonometer" are discussed (author's transl)].

Comparing measurements with Non-Contact-Tonometer and handapplanation tonometer on 462 eyes with normal and elevated intraocular tension are statistically evaluated. The 2-s-limits for normal i.o. pressure at +/- 6.52 mm Hg (+/- 8.6 mbar), for elevated intraocular pressure +/- 13.2 mm Hg (+/- 17.6 mbar). This means less reliability than conventional applanation tonometers or even Schiötz-tonometers. The unability to read the tension when the corneal surface is rough means remarkable disadvantages to clinical use.


[Soft contactlenses in general practice (author's transl)].

In contrast to the hard lenses the soft lens has enough permeability for oxygen and water-soluble substances, whereas high molecular substances, bacteria and virus cannot penetrate the soft lenses, so long as their surfaces are intact. The two principal production methods, the spin cast method and the lathe-turned method are compared. The duration of wearing of the soft lens depends on the deposits of proteins from the tears on the surface of the lens and the desinfection method. The daily boiling of the lenses shortens their useful life, while chemical desinfection causes besides bacteriolysis, damage of the corneal cell protein. The new cleaners on the base of proteolytic plant enzymes promise good results. For the optical correction of astigmatism with more than 1 cyl, soft lenses with conic outer surface are used or combinations of a soft and a hard lens (Duosystem). The therapeutic use of soft lenses has as aim: protection of the cornea against mechanical irritation, release of pain, protracted administration output of medicaments. Further indications for use: aseptic corneal inflammation and corneal defects.


[Chiasma injury following skull trauma (author's transl)].

After a discussion of the pathomechanism of frontobasal cranial injury with a consecutive chiasmal lesion and diabetes insipidus due to a fracture of the basis of the skull, a personal observation of bitemporal hemianopia with a transient diabetes insipidus after a frontal motorcycle crash is recorded. A short survey of the literature shows the controversial opinions on traumatogenic lesions of the chiasma, which may be injured directly or the bitemporal hemianopia is due to a posttraumatic vascular disturbance. For the case described by the author primary tearing of the chiasma due to sudden applanation of the skull in the frontal region with burstfractures in the anterior cranial fossa is assumed.


[Temporal arteritis, clinical picture, treatment and prognosis (author's transl)].

32 patients are described, who 1971-1974 were hospitalized because of temporal arteritis. The admissions diagnoses were: 5 temporal arteritis. 7 Neuroretinitis. 4 Blood vessel obstruction. 2 Cerebral tumor. 14 Vision disturbances up to sudden blindness of unknown cause. In the early stages when intermittent visual disturbances with vague headaches of older patients (average age 68 years) are present, a temporal arteritis is often not recognised. In the region of the papilla the retinal arteries show obvious luminal narrowing. The papilla is already early on somewhat blurred and oedematous. The complaints continue bilaterally with intervals from days to months. Hence the treatment: bilateral resection of the temporal artery. Histologically: from our 32 patients 27 showed the classical picture of "giant-cell arteritis" with chronic inflammatory reaction of all layers of the wall and partial to complete obstruction of the vessel lumen. Local therapy: parabulbar application of cortisone. General therapy: Daily rheomacrodes infusions, Soludecortin, 100 mg per day (with latter "tailing off") and strophantin when the patient is not already digitalised.


[A light-independent function of the retina of rabbits. Examination on the energetic part of the visual pathway (author's transl)].

In this study a light-independent function of the retina of rabbits could be proved. For this purpose, the energetic part of the visual pathway was utilized, and its influence on the maturation of the testicles was examined. As a criterion of maturation, the pattern of the phosphatid-fatty acids was ascertained. The subdivision of the energetic part of the visual pathway into a photo-energetic and an autonomic-energetic component is proposed.


[Investigation of the state of the cell membrane and the mechanism of autolysis of the cornea in the process of conservation (author's transl)].

Questions of the mechanism of autolysis of the corneal tissue were examined on 72 dog eye balls, which had been kept in a damp chamber for 3 hours, 2 days and 15 days. The method of chemoluminescence found especial importance here, because it made possible to analyse the state of the functioning cell membrane and to gain information of bio-energetic processes which take place in the lipoprotein complexes of the cells and their organelles in the corneal tissue. From the results obtained it can be assumed, that in the mechanisme of autolysis disturbances of the self-regulating oxidation of the lipoidstructure-elements are of great importance in the process of survival and the conservation of corneal tissue.


[Hydrostatic pressures within the eye (author's transl)].

In the eye all membranes are more or less under tension, as elsewhere in the body. Hence the hydrostatic pressure in the choroid is less than in the retina. The available pressure difference within the bloodvessels would be less for the retina than for the choroid, if the arteries to the retina did not have a much larger bore than those to the choroid. Hence the bloodstream for the retina is slower and fluorescein appears later in the retina than in the choroid. There is a flow of tissue fluid from the choroid to the retina. It is absorbed by the retinal vessels. The larger the flow, the larger are the retinal veins, till retinal oedema occurs. Then the tissue pressure within the retina rises sharply and the capillaries become strangulated. But a few capillaries remain open and are blown up to arterio-venular shunts. Micro-aneurysmata arise as abortive vessel sprouts. It is plausible that lightcoagulation sticks the lamellae of Bruch's membrane together, to the extent that the development of oedema is arrested.


[Echographic studies in cases of excentric posterior scleral ectasias (author's transl)].

Excentric posterior scleral ectasias are rarely recognized correctly. They can cause uncharacteristic visual disturbances and refractive scotomas, which may cause a mis-diagnosis of bitemporal hemianopia. In this report 10 such cases are shown. The diagnosis was verified by the ultrasonographic measurement of the meridional length of the eye. Posterior scleral ectasias of maximum 4.5 mm were found.


[The relationships between left ventricular volumes and ejection fraction in mitral and aortic regurgitation (author's transl)].

In 2 groups of patients with mitral valvular incompetence (MI, n equals 20) and aortic valvular incompetence (AI, n equals 22) intracardiac pressures as well as left ventricular volumes (enddiastolic volume, endsystolic volume, stroke volume, ejection fraction, regurgitant volume) were determined during routine left heart catheterization and left ventriculography. Data obtained were compared with a normal group (N, n equals 20). 1. Enddiastolic volume was increased by 32 per cent (MI) and 180 per cent (AI) respectively in comparison to normal. Endsystolic volume was increased by 85 per cent (MI) and 113 per cent (AI). Total stroke volume exhibited increases by 11 per cent (MI) and 86 per cent (AI) respectively. Regurgitant volume averaged 64 per cent (AI) of total stroke volume, and 47 per cent in MI. Left ventricular ejection fraction was reduced in both groups by about 12-14 per cent. 2. enddiastolic volume was significantly dependent on the amount of regurgitant volume in both groups (MI, AI). Likewise total stroke volume increased with increments in enddiastolic volume. This increase was far mor pronounced (up to 250 per cent of normal) in AI in comparison to MI and may be referred to an effective contribution of the Frank-Starling-Straub-mechanism, induced by increased preload following regurgitation. There existed no correlation between enddiastolic volume or regurgitant volume and the effective forward stroke volume and other parameters of forward pump function (effective cardiac output, cardiac index, external cardiac work). Left ventricular compliance, as determined by diastolic pressure-volume relationships, was nearly the same in the 3 groups (N, MI, AI). 3. Left ventricular ejection fraction was nearly unchanged with increments in enddiastolic volume over a range of enddiastolic volumes up to 400 ml. At higher enddiastolic volume (is greater than 400 ml) decreases were found. In the failing heart with AI left ventricular ejection fraction was reduced even at low enddiastolic volume, exerted by decreases of fibre shortening and contractility. In contrast, in MI ejection fraction decreased with increments of enddiastolic volume over the whole range investigated. The increase in total stroke volume in both groups therefore was produced by increases of enddiastolic volume and to a very small extent by an increase of the ejection fraction. 4. The large contractility reserve in compensated AI may be referred to the altered contraction mechanism in aortic valvular regurgitation associated with i) decrese of isovolumic pressure development and increase of isotonic contraction, ii) increase of diastolic fibre stretch (preload) and iii) decrease of mean wall tension. Contractility reserve was essentially influenced by myocardial contractility. With decreases of contractility consecutively decreases of the total and the effective pump function of the left ventricle may occur despite unchanged contraction form and left ventricular dimensions.


[Hemodynamics, left ventricular volumes and compliance in 167 patients with congenital and acquired heart disease (author's transl)].

In 167 patients with congenital and acquired heart disease (ventricular septum defect (VSD), atrial septum defect (ASD), mitral stenosis (MS), mitral insufficiency (MI), combined mitral stenosis and insufficiency (MV) aortic stenosis (AS), aortic insufficiency (AI), combined aortic stenosis and insufficiency (AV), idiopathic hypertrophic subaortic stenosis (HOK) hemodynamic measures (arterial pressure, right and left heart pressures, cardiac output, cardiac index, stroke volume, cardiac work), left ventricular volumes (endiastolic volume, endsystolic volume, ejection fraction, regurgitant flow) and diastolic pressure-volume relationships (on the basis of diastolic pressure-volume changes) were determined during routine right and left heart catheterization and left ventriculography. 1...


[Serum lipase and amylase activity after endoscopic retrograde pancreatography (author's transl)].

Serum activities of lipase and amylase were measured in 11 patients at short time intervals (-10 min; + 10, 30, 60 min; 2,3,4,6,8,24,48 hours) after an endoscopic retrograde pancreatography. Lipase activity increased rapidly in 9 patients in 10 min after the contrast instillation and obtained its maximum at the first hour of investigation. Amylase activity elevation occurred in 5 patients only and was significantly lower than that of lipase with a flat peak at 1-6 hours.


Regulation of circulating parathyroid hormone levels: normal physiology and consequences in disorders of mineral metabolism.

A review of the chemistry, the biosynthesis, the regulation of the secretion and the metabolism of parathyroid hormone (PTH) provides a background to problems related to the determination of immunoreactive PTH levels in the blood of normal subjects and of patients suffering from disorders of mineral metabolism. Immunoreactive PTH measurements have to be interpreted in the light of the immunoheterogeneity encountered and the occurrence of several circulating PTH species with different molecular weights and immunological properties.


Giant mitochondria in the epithelial cells of the proximal convoluted tubules of diseased human kidneys.

Electron microscopy of 100 renal biopsies obtained at random from patients with various renal disorders revealed gigantic mitochondria in the cytoplasm of the epithelial cells of the proximal tubules in 36 cases (36 per cent). These giant mitochondria are usually round, ovoid, spindle-shaped or rod-shaped often reaching the size of the cell nucleus, and appear singularly and sporadically in the epithelial cell lining of the tubules. Once recognized by electron microscopy they are easily identified in routine histologic preparations and show the same staining characteristics as other mitochondria. In electron microscopy, giant mitochondria have a double limiting membrane, abundant matrical substance, and few remnants or cristae. In addition, they are characterized by (1) intramatrical irregularly branching fibrils approximately 35 A thick, (2) intramatrical bundles of straight filaments approximately 60 to 70 A thick, (3) intramatrical electron-opaque globules up to 0.6 mum., and (4) helical filaments in focally dilated spaces of the outer compartment. The significance of such a remarkable morphologic change of tubular mitochondria and the nature of the unusual components are at present unknown, but an abnormal metabolic condition is considered in its pathogenesis. Nothing specific has yet been found in the relationship between the positive appearance of giant mitochondria and types of renal disorders or clinical and laboratory data. It may be postulated from the present study that "giant mitochondrial tubulopathy" is a rather common, characteristic, and noteworthy change in the histopathology of renal tubule.


Foreign serum-induced pancreatitis in mice. I. A new model of acute pancreatitis.

Within a few hours after one injection of fresh human serum by the intraperitoneal route only, mice developed pancreatic acinar cell necrosis and inflammation, fat necrosis, elevated serum amylase and a shocklike state. The extent of these lesions and mortalities were roughly dose dependent and were not noticeably modified by either different fasting cycles or pilocarpine. Acinar cell changes and necrosis usually developed first in subserosal acini. The earliest ultrastructural change detected was nonspecific swelling of cytoplasmic compartments which was reversible but also preceded the cytoplasmic degradation that developed in cells undergoing necrosis. Notably, zymogen granule dissolution neither preceded nor accompanied this swelling, but developed pari passu with cell degradation. Occasionally, intact granules were found in necrotic cells. Serum was cytotoxic for isolated acinar cells in vitro, even in the presence of soybean trypsin inhibitor. These results (1) indicate that the injury mechanism in vivo is directly initiated through contact of serum with acinar cell surfaces and is independent of zymogen secretions and trypsin activation, and (2) suggest that a rapid disturbance in cell membrane permeability results, the magnitude of which being the primary determinant of cell death. Pancreatic toxicity of human serum was abolished by aging, heating, ethylenediaminetetraacetic acid, heparin, zymosan, cobra venom factor, and absorptions with mouse red blood cells, against which fresh, unabsorbed serum was hemolytic. Pancreatic toxicity in vitro and, to a much lesser extent, in vivo was reconstituted by combining the red blood cell-absorbed serum with either heated serum, or with IgM-enriched, but not IgG serum fractions. Fresh cord serum was virtually nontoxic and could substitute for absorbed serum in such reconstitutions. These results indicate that the injury mechanism involves at least two serum components. By both circumstance and analogy, other results and a review of other examples of foreign sera toxicity suggest that they are components of a complement-dependent, cytotoxic heterophile antibody system. The relevance of this odd phenomenon is that it offers a simple model of acute pancreatitis, contributes to the debunking of traditional notions of the pivotal role of zymogens in the initiation of acute pancreatitis, and hints at a potential pathogenetic connection between pancreatitis and products of immune or related reactions.


Primary demyelination in Theiler's virus infection. An ultrastructural study.

Theiler's virus infection in SJL/J mice was studied ultrastructurally at subsequent intervals after intracerebral inoculation. Extensive spinal cord lesions consisting of leptomeningeal and white matter mononuclear cell infiltrates with concomitant primary demylination were seen by 15 days. Stripping of myelin lamellae by invading mononuclear cell processes and vesicular disruption of myelin were demonstrated to be the patterns of myelin breakdown. Oligodendrocytes in the vicinity of demyelinating lesions never showed degenerative changes, and viral inclusions could not be found in any cells in the central nervous system. Remyelinating axons, first detected 21 days after infections, were more frequently seen in the late phase of the disease when conspicuous gliosis was also present. Active demyelination could still be observed as late as one year after infection at which time inflammation was decreased. However, plasma cells were relatively more numerous at later times after infection. These ultrastructural findings are similar to experimental allergic encephalomyelitis, and suggest an immune-mediated mechanism of demyelination in Theiler's virus infection.


Effects of variations in calcium concentration on parathyroid morphology in vitro.

Morphologic examinations, including the use of the potassium pyroantimonate-technique and x-ray analysis for ultrastructural localization of cations, were carried out on parathyroid glands from Mongolian gerbils cultured for 2 to 6 days. At a high calcium concentration most (suppressed) chief cells were characterized by a moderate or high cytoplasmic density, inconspicuous endoplasmic reticulum and Golgi complex, numerous often enlarged mitochondria, and the occasional occurrence of accumulations of secretory granules, storage granules, and lysosomal bodies, whereas other (atrophic) cells were smaller and still more dense. At a low concentration of calcium some (stimulated)  chief cells were characterized by a low cytoplasmic density, normal or structurally altered mitochondria, and smooth surface vacuoles occasionally connected with mitochondria, whereas the main features of other (active) chief cells were a moderate or low cytoplasmic density and a prominent endoplasmic reticulum and Golgi complex. Calcium-containing precipitates were found both inter- and intracellularly; the latter were mainly localized to nuclei, mitochondria, and rough surfaced vacuoles, and in stimulated cells also to the smooth surfaced vacuoles and the cytosol. Degenerative changes were seen, mainly in the suppressed cells; massive calcium loading in mitochondria seemed to precede degeneration and necrosis of whole cells. The findings indicate that clear differences exist between the different chief cell variants both as to the distribution of calcium-containing precipitates and to the structural appearance, and that these differences are influenced by the ambient calcium concentration. Suppressed cells occasionally seem to accumulate hormone which later may undergo lysosomal digestion. Calcium might be accumulated intracellularly, mainly in mitochondria of suppressed cells.


Induction of unusual tumors in vivo by rat fibroblasts treated with diepoxybutane.

Diploid rat embryo fibroblasts exposed to diepoxybutane, a carcinogenic alkylating agent, exhibited chromosome aberrations and a high proportion of tetraploid cells immediately after treatment. Following a prolonged period of carcinogen-free growth, a diepoxybutane-treated cuture showed morphologic transformation and produced transplantable malignant tumors upon inoculation into neonatal rats. Morphologic and histochemical characteristics of the tumors derived from cells exposed to diepoxybutane in culture were also found in tumors of animals exposed directly to this carcinogen. The tumors from diepoxybutane-treated cell cultures were composed of highly anaplastic giant cells with centrally located cytoplasmic inclusions. Clusters of identical cells were found in some of the tumors obtained by direct in vivo treatment of rats with diepoxybutane. The morphologic similarities of these tumors suggest that similar processes of cellular evolution to malignancy occur in cell culture systems and in vivo.


Crescents in diabetic glomerulopathy. Incidence and clinical significance.

Crescents, defined as any proliferative or fibrous space occupying reaction of the parietal layer of Bowman's capsule, occur as a regular and integral feature of the glomerular changes of diabetes mellitus. The frequency of crescents and adhesions to the capsule increases with increasing total severity of diabetic glomerular and vascular disease in glomeruli with mild-moderate diffuse glomerulosclerosis (GS), severe diffuse GS, and nodular GA. The high frequency (greater than 90 per cent) of crescents and adhesions in glomeruli with exudative lesions is unrelated to over-all severity of diabetic renal disease. The 8.73 per cent of glomeruli with exudative lesions had 45 per cent of the total crescents observed. The mechanism of crescent formation in diabetes is probably similar to the proposed pathogenesis of crescents in other renal diseases. The underlying injury in the glomerular capillaries in diabetes is mainly the "exudative lesion." The percentage of diabetic glomeruli with crescents correlated better with blood urea nitrogen and creatinine that did the percentage of end stage glomeruli (a measure of severity of vascular disease), the percentage of diabetic glomeruli with severe diffuse GS, the percentage of diabetic glomeruli with nodular GS, or the percentage of diabetic glomeruli with exudative lesions. The percentage of diabetic glomeruli with crescents correlated better with severity of vascular disease than did any of the other diabetic glomerular changes. No correlation existed between incidence of crescents and "capsular drops."