Anticonvulsant action of cannabis in the rat: role of brain monoamines. The role of brain monoamines in the anticonvulsant action of Cannabis indica resin (CI), against maximal electroshock-induced seizures in albino rats, was investigated by using pharmacologic agents that influence brain monoamine activity. Delta-9-tetrahydrocannabinol content of cannabis resin was estimated to be 17%. The anticonvulsant action of CI (200 mg/kg, i.p.) was significantly inhibited after pretreatment with drugs that reduce brain serotonin activity but not by drugs that reduce brain catecholamine activity. Similarly, the anticonvulsant action of a subanticonvulsant dose (50 mg/kg, i.p.) of CI was potentiated by serotonin precursors but not by catecholamine precursors. Potentiation of the anticonvulsant action of CI by nialamide or by imipramine was inhibited after pretreatment with 5,6-dihydroxytryptamine. The results suggest that the anticonvulsant action of CI in the rat is serotonin- and not catecholamine-mediated.


Barbiturate withdrawal and magnesium deficiency in mice. C57BL/6J male mice rendered physically dependent on phenobarbital exhibited significantly lower whole-brain and serum-magnesium concentrations than did control mice. The symptoms of phenobarbital withdrawal were remarkably similar to those seen in magnesium-deficient mice exposed to a low-magnesium diet without drug exposure. These findings suggest that brain magnesium deficits produced by chronic phenobarbital withdrawal could contribute to the observed phenobarbital withdrawal syndrome. Administration of MgSO4 during withdrawal significantly reduced the incidence of tonicclonic and lethal tonic seizures.


Naloxone-reversible analgesic action of SKF 525-A in mice. SKF 525-A, given i.p. to mice at doses from 50 to 100 mg/kg, had analgesic activity approximately 40% the analgesic potency of d-propoxyphene HCl, a chemically similar narcotic. While the analgesia produced by propoxyphene was totally antagonized by naloxone, however, that produced by SKF 525-A was only partly reversed. We suspect that SKF 525-A may exert its antinociceptive actions partly by an interaction with CNS narcotic receptors and partly by a nonspecific sedating action.


Effects of furosemide and spironolactone on the behavior of morphine-tolerant rats. In morphine-tolerant rats, a reappearance of morphine catalepsy and a disappearance of the turning behavior characteristic of brain-lesioned tolerant animals were observed under the influence of furosemide and spironolactone. The administration of spironolactone together with daily morphine treatment resulted first in an intensification of the morphine symptoms as measured by catalepsy and a retarded appearance of tolerance, typically characterized by a shift from catalepsy to turning movements in animals with single-sided brain lesions. Nontoxic doses of spironolactone raised the sensitivity of morphine-tolerant rats so that previously tolarated morphine doses become lethal.


Test for oral and postingestional factors mediating differential acceptability of morphine, methamphetamine, and chlordiazepoxide drinking solutions. The relative degrees to which aversive oral (presumably gustatory) and postingestional variables attenuate the voluntary drinking of morphine, methamphetamine, and chlordiazepoxide solutions by rats were assessed by comparing immediate acceptability with subsequent acceptability. Results indicated that morphine solutions (0.01--0.05%) are avoided primarily because of unpalatability, while methamphetamine (0.005--0.02%) and chlordiazepoxide solutions (0.02--0.08%) are avoided primarily because of aversive postingestional effects.


Generalization study with some narcotic and nonnarcotic drugs in rats trained for morphine-saline discrimination. Rats were trained to lever-press on an FR-10 schedule for food reinforcement, and to respond differentially on two levers while discriminating the effects of morphine (10 mg/kg) injection from those of saline (1 ml/kg). Following discrimination training, the morphine stimulus was generalized to propoxyphene, methadone, fentanyl, and sulfentanyl in a dose-dependent manner, and saline was generalized to alcohol, pentobarbital, azaperone, clonidine, naloxone, and p-chloroamphetamine. p-Chloroamphetamine failed to block the morphine stimulus.


Effect of a specific 5-HT uptake inhibitor, citalopram (Lu 10-171), on 3H-5-HT uptake in rat brain synaptosomes in vitro. The uptake of 3H-5-HT in synaptosomes from rat brains was investigated. Addition of DA or NA had only a slight or no effect on the uptake. When the uptake into NA and DA neurons was inhibited by the addition of high concentrations of NA and DA, the uptake of 3H-5-HT was unchanged. This was also found after destruction of NA and DA neurons by 6-hydroxydopamine treatment. Furthermore, the uptake of 3H-5-HT was almost equal in different brain parts containing NA and DA in very different amounts. These observations show that the uptake measured with 3H-5-HT is specific for 5-HT neurons. The present study revealed that citalopram and chlorimipramine inhibited uptake competitively, and in this respect the two drugs were equipotent. Compared with a series of tricyclic thymoleptics, the two drugs were the most potent inhibitors of 5-HT uptake, about 20 to 35 times more active than imipramine and amitriptyline. The metabolites of citalopram were also rather potent. The results obtained in the present study correlate closely with those obtained using inhibition of 14C-5-HT uptake in blood platelets, or using the inhibition of H 75/12-induced 5-HT depletion in rat brain. When rats were treated orally with citalopram or chlorimipramine, the inhibition of 3H-5-HT uptake in synaptosomes derived from these rats was two times greater after citalopram than after chlorimipramine.


A comparison of the discriminative stimulus effects of ethanol, barbital, and phenobarbital in rats. Five different groups of rats were trained in a food-motivated, bar-pressing task to discriminate from the nondrug condition (physiologic saline, i.p.) the effects produced by i.p. injections of ethanol (330, 660, or 990 mg/kg), sodium barbital (80 mg/kg), or sodium phenobarbital (25 mg/kg). The establishment of highly effective discriminations required 20--40 training sessions for all drugs, with the exception that rats trained with 330 mg/kg of ethanol required 80--100 training sessions. After the drug-nondrug discriminations were well established, cross tests revealed that ethanol did not elicit drug-appropriate responding in the groups trained with sodium barbital or sodium phenobarbital. However, both barbiturates elicited drug-approppriate responding to some extent in rats trained with ethanol as the discriminative stimulus. With barbital, the greatest generalization was observed in rats trained with the low dose of ethanol (330 mg/kg). The findings emphasize the need for the use of several training doses and for transfer tests in both directions when the stimulus effects of drugs are compared.


Toward the development of a potent, nonsedating, oral analgesic. The separate and combined analgesic effects of 10 mg of oral amphetamine sulfate and 25 mg of oral anileridine dihydrochloride were studied in 24 healthy, adult, male volunteers. Tolerance of progressively increasing pain produced by the Submaximum Effort Tourniquet Technique was tested four times in each subject: after amphetamine, after anileridine, after the combination, and after a matching placebo. Treatments were administered double blind and in counterbalanced order. Elapsed time to report of slight, moderately distressing, very distressing, and unbearable pain was recorded on each trial. The four oral treatments differed significantly for very distressing and for unbearable pain. At each of the three upper pain levels, the mean tolerance times for anileridine and amphetamine were similar; each was longer than placebo but shorter than the combination; and the effect of the combination was approximately the sum of the effects of the two components.


Tolerance to alpha-methyl-p-tyrosine in rats: studies on the antagonism of amphetamine-induced motor activity and excitatory behaviour. Rats were treated chronically with alpha-methyl-p-tyrosine methyl-ester HCl (alpha-MT) twice daily for 0--14 days. At 1 h after the (last) alpha-MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of alpha-MT markedly reduced the activity response after amphetamine. After 1--3 days of alpha-MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7--14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the alpha-MT tolerant rats with an early (at 0--1 h) and a late (2--4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of alpha-MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of alpha-MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.


Increased feeding in rats treated with chlordimeform and related formamidines: a new class of appetite stimulants. Low doses of the formamidine pesticide, chlordimeform (CDM) induce voracious daytime feeding in non-food deprived rats. Following CDM (10 mg/kg), food intakes were five times control intakes after 3 h and 1.1 times control intakes after 24 h. Other selected formamidines, such as the N-demethylated metabolite of CDM, and amitraz, increased 3-h food intake by two and five times control intake, respectively. Anorexia accompanied by excessive CNS stimulation was noted with higher doses of CDM (above 40 mg/kg) and other formamidines. This contrasts with the sedation usually observed with high doses of other structurally diverse appetite stimulants. In addition, hyperphagia was not observed with other CNS stimulants or local anesthetics such as amphetamine, cocaine, and holocaine. Thus the formamidines constitute a new class of appetite stimulants, which should prove to be useful agents for the study of feeding behavior.


Noradrenergic influences on catalepsy.

Noradrenergic influences on catalepsy. Widespread depletion of forebrain noradrenaline, produced by the intracerebral injection of 4 microgram of 6-hydroxydopamine into the fibres of the dorsal noradrenergic bundle, potentiated the catalepsy induced by 20 mg/kg of morphine and severely attenuated the catalepsy induced by two separate cholinergic agonists, arecoline and pilocarpine. It did not, however, affect haloperidol catalepsy at any of the four doses tested. These results suggest that cholinergic catalepsy may be critically dependent on an intact noradrenergic substrate, perhaps through cholinergic receptors located either presynaptically on noradrenergic terminals or on the cell bodies of origin in the locus coeruleus. Noradrenaline appears to play a modulatory role in morphine catalepsy, although other sites of action must also be involved. Ascending noradrenergic systems do not appear to influence haloperidol catalepsy.


Accelerated development of tolerance during repeated cycles of ethanol exposure. Adult male rats were subjected to 1--4 cycles of daily gastric intubation with ethanol (6 g/kg) for 16 days, separated by 17-day alcohol-free periods. Tolerance produced by this treatment (designated 'physiological tolerance') was measured by change in effect of a 2.2 g/kg i.p. dose of ethanol on the moving-belt test. It occurred in each cycle, disappeared completely in the drug-free periods, and developed more rapidly in the second and later cycles than in the first. Tolerance produced by the 'behavioral augmentation' technique (daily test practice under the influence of ethanol) also developed more rapidly on a second than on a first cycle. The progression from within-session to between-session tolerance was still evident, but accelerated. With 25-day alcohol cycles, separated by a one-month drug-free period, the 'carry-over' effect (i.e., more rapid acquisition of tolerance in the second cycle) applied equally, regardless of whether or not tolerance was produced by the same technique in both cycles, or by a crossover in either direction between the two techniques.


The effect of gamma-butyrolactone on locomotor activity in the rat. The effect of gamma-butyrolactone (GBL) on locomotor activity in the rat was studied. Low doses of GBL (100 and 200 mg/kg) had a biphasic effect on activity. Initially, the activity of the rats was reduced, and this reduction was then followed by a period of hyperactivity. The effect of alpha-flupenthixol (50 microgram/kg alpha-FPT), atropine (10 mg/kg), benztroine (25 mg/kg), protriptyline (15 mg/kg), and clomipramine (25 mg/kg) was investigated on this biphasic effect. alpha-FPT reduced the hyperactivity while benztropine potentiated it; atropine, clomipramine, and protriptyline had little effect. It is concluded that the increase in activity could be due to a release of dopamine.


Empirical separation of physiologic and expected effects of alcohol on complex perceptual motor performance. The role of expectancy in producing perceptual motor-performance deficits following alcohol consumption was investigated in a 2 X 2 factorial experiment. Forty male normal drinkers (1) either were or were not administered 0.414 g ethanol/kg body weight and (2) either were or were not instructed they were consuming an alcoholic beverage (regardless of actual beverage content). Performance on a divided-attention task requiring simultaneous pursuit rotor tracking and choice reaction-time responding provided the main dependent measures. Alcohol disrupted tracking performance and interacted with instructions regarding beverage content to influence choice reaction-time performance. Results confirmed previous reports of divided-attention task performance deficits induced by a low alcohol dose, but, more importantly, indicated that subjects' expectancies also influence performance levels. These findings demonstrate the importance of controlling for expectancy effects in alcohol research, and suggest that alcohol and expectancy may influence perceptual motor performance through different processes.


Acute effect of small doses of alcohol on the NSD parameters (normalized slope descriptors) of human EEG. The acute effect of ethanol upon the NSD (normalized slope descriptors) or Hjorth parameters of EEG were analyzed in 11 students. The maximal blood-alcohol concentration ranged from 1.0--1.7 mg/l. The activity (mean amplitude) increased and the complexity (frequency spread) decreased significantly as a function of time. The same effect was seen in control subjects, but to a lesser degree. The difference between the test and the control group was, however, significant only for the change in complexity. Changes in the mobility parameter (mean frequency) showed most prominently the interindividual differences: in some a transient increase during increasing blood-alcohol concentration, in others a steady falling tendency. It is concluded that changes in the NSD parameters reflect (1) the depressing effect of both alcohol and the test situation, which was more or less evident in most subjects, and (2) the individual degree of and type of CNS reaction to alcohol consumption. From a social and psychologic point of view, the individual reactions are at least as important as the reactions common to all.


The effect of dose, novelty, and exploration on amphetamine-produced stereotyped behavior. Four experiments are presented. The first experiment demonstrated that the incidence of steretyped behavior was a monotonic increasing function of amphetamine dose. Variations in the form of the response to dose are described. The next two studies examined the relationship between environmental novelty and amphetamine-produced stereotypy. This behavior was observed less among subjects placed into novel environments than among subjects placed into familiar environments. The ability of novel stimuli to evoke exploratory responses incompatible with stereotypy was suggested as the basis for this effect. This interpretation was supported in a final experiment, which observed exploratory behavior and general activity, as well as amphetamine-produced stereotypy in subjects exposed to a novel stimulus in an otherwise familiar environment. All four experiments were interpreted as supporting a unified conception of amphetamine-produced and pathological sterotyped behaviors.


The selection of patients for excretory urography. Symptoms, signs, and laboratory findings that indicated excretory urography in 1,622 patients, were compared with the radiographs. The chance that an indication would be associated with demonstrable disease was calculated. No "low-likelihood" indications could be identified. Elimination of the urograms obtained for any of the indications would not have been possible without simultaneously precluding detection of many diseased patients. The monetary cost of case-finding was low, and the efficacy of patient referral high.


The barium enema; evidence for proper utilization. A group of 1,041 patients was studied in an attempt to identify symptoms, signs, or laboratory findings (disease indicators) associated with either a high or low yield of abnormal barium enemas. A specific search was undertaken for subgroups with one or more statistically significant indicators of large bowel disease. If enemas were performed only for statistically significant indicators (fever, positive stool benzidine, rectal or abdominal mass, low hematocrit) or indicators of clinical importance (weight loss, constipation, diarrhea, etc.) only 13% of examinations would be eliminated. At the same time, however, 10% of patients with gastrointestinal disease would be missed.


Inhalation bronchography using powdered calcium ioglycamic acid. In 16 baboons, reproducible bronchograms could be achieved by inhalation of 400--800 mg of powdered calcium ioglycamic acid. Anesthesia, tracheal intubation, or premedication were not necessary. In patients and volunteers, the inhalation of the contrast medium dust caused strong cough. Local anesthesia allowed inhalation for about 10 minutes, which resulted in successful demonstration of the pharynx, larynx, and trachea with bifurcation. Lobular and segmental bronchi were demonstrated only after a longer inhalation time. The contrast medium was completely eliminated and did not cause any recognizable adverse reaction. Nonspecific inflammatory reaction of the bronchial mucosa was seen microscopically in baboons.


Whole body surface electron irradiation in the treatment of mycosis fungoides. An evaluation of 200 patients. The records of 200 patients with generalized cutaneous mycosis fungoides treated with whole body surface electron irradiation were reviewed. Type of skin lesion appeared to be the most important factor with respect to both survival and generalized skin disease-free interval. High-dose irradiation did not seem to influence prognosis significantly compared with a relatively conservative dose. The "cure" rate for the entire group was 7%. For a more homogeneous dose distribution, the eight-field technique is now used instead of the original four-field method. A new formula is proposed to standardize the reporting of doses.


Radiation therapy for metastases to the base of the skull. The clinical features and management of 46 patients with metastatic involvement of the base of the skull were retrospectively analyzed. Diagnosis could often be made on clinical grounds, with a limited number of investigations necessary. Local treatment with megavoltage radiotherapy relieved symptoms in 78% of patients, with improvement lasting until death in most. Field size and dosage are discussed. The likelihood of response dropped sharply the longer treatment was delayed. Therefore, if the clinical picture is suggestive, treatment should not be withheld even if radiographic investigations are negative.


Assessment of renal function following irradiation of the intact spleen for Hodgkin disease. Twenty-three patients with clinical Stage IA-IIIB Hodgkin disease underwent extended-field radiotherapy, including the intact spleen. In 17 of those patients, there was little evidence of renal dysfunction resulting from partial irradiation of the left kidney, which is inherent in such treatment. While isotopic images revealed an anatomic defect in the upper pole of the left kidney in one-third of the patients, dynamic studies showed that this anatomic alteration was not accompanied by any demonstrable dysfunction. Consistently normal serum BUN and creatinine levels in all patients tended to affirm that conclusion.


Total-body superficial electron-beam therapy using a multiple-field pendulum-arc technique. A technique using pendulum-arc rotation is presented for electron-beam treatment of generalized superficial malignancies. The technique consists of six arcing fields symmetrically dispersed around the body surface for circumferential coverage. The arc angle is selected to scan the height of the body fully. Beam uniformity within 10% over a height of 180 cm is achieved at a treatment distance of 385 cm. Randophantom dosimetry, using an 8 MeV electron beam degraded by 3/8 in. Plexiglas, indicates a surface dose uniformity within +/- 7% over most of the body surface. Underdosages occur at regions obstructed by adjacent body parts.


Adjustable compensators for whole-brain irradiation. A compensator for use in irradiating the whole brain with parellel opposed lateral fields was made from a stack of thin tempered aluminum plates. This configuration gives a wide latitude of degrees of compensation and can accommodate a broad range of head sizes. Dosimetry studies indicate that overcompensation may be desirable to reduce the dose to the mid-coronal plane of the skull and scalp without seriously affecting the dose uniformity in the treatment volume.


Neoplastic proliferation and natural history of B-cell neoplasia. In this analysis, I have concentrated on advances in immunology, kinetics, and clinical oncology which have provided a substantial basis for identifying major common features in the natural history and pathophysiology of B-cell neoplasia as diverse as MM, MG, BMG, and NL. Observations on the natural history of both experimental and clinical myeloma as well as studies of kinetics of proliferation of MM and BMG in man provide the basis for reasonable hypotheses. Firstly, malignant variants of B-cell neoplasms may result from a two-hit evolution. In this scheme, the first hit is a triggering by specific antigen which leads to a required monoclonal expansion, while the second hit is the oncogenic event. Some cases of BMG seem to be examples of an unusually prolific response to the first hit, while others appear to be minimal deviation malignancies after the second hit. In this latter circumstance, the neoplastic clone in BMG usually retains a significant degree of sensitivity to tumor mass-related feedback inhibition. This may occasionally be lost during subsequent subcloning. Significant future testing of these hypotheses may prove feasible through the application of the in vitro tumor colony-forming assay system as it lends itself to study of a number of the salient features of these disorders.


Effect of deoxycholic acid on 7,12-dimethylbenz(a)anthracene-induced, two-stage mouse skin carcinogenesis. The effect of deoxycholic acid on 7,12-dimethylbenz(a)anthracenecroton oil carcinogenesis in mouse skin was tested. Painting deoxycholic acid in addition to croton oil during promotion resulted in the earlier appearance of tumors, a greater tumor incidence, and a larger number of tumors per animal. DMBA initiation followed by either deoxycholic acid or solvents during the promotion period produced no tumors. Animals receiving deoxycholic acid or solvents alone developed no tumors.


[Genetic analysis of a population with abnormalities of gene frequencies]. Nineteen out of the 53 blood donors of french village with 241 inhabitants (Cezay Loire) are Rh negative (D--). This discrepancy in the distribution is analysed. 1.--The study of the genetic erythrocyte markers (ABO and Rh system for 158 inhabitants, Kell, Rautenberg, Duffy, Kidd, MNSs, P1 Lutheran, PGM1, PGM2, 6 PGD, AK, ADA, Acid phosphatase systems for 104 inhabitants) show significant abnormal gene frequencies (No. 10%) compared with a control population from Saint-Etienne, for A1, Ms, r, P1 alleles; conversely rare alleles do not seem to exist. HLA system was not tested. 2.--The genetic study led to: a) a demographic study which implied 7840 registrar's certificates and the building up of 1364 families to which the 5096 subjects belonged identified and having lived in Cezay since 1607 (this date corresponds to the earliest registrar's certificate). b) it also led to the analysis of the origin and evolution of the genetic inheritance throughout the 13 generations of known inhabitants. The calculation of the chances of each generation having passed on its genetic material to following generations shows that: Cezay has an integrated population; 30% of the genes are renewed for each generation the average value of each founder can vary according to the various generations but there seems to exist a "founder effect" of the Rh--(D--) having been and lived in the village before 1860. Although they represent 68% of the total population, the tested samples can be contested for certain systems, in its constitution (formation, choice) which prevents from ascertaining the foundation effect observed. The authors underligne the contribution of immunogenetics to the genetics of populations, and show the incidence of the choice of samples in the method used.


[Incidence of monoclonal gammopathies in blood donors]. A routine screening of monoclonal gammopathies (M.G.) was performed in the serum from 36, 015 blood donors by cellulose acetate electrophoresis. The incidence of M.G. was estimated to 0.14 per cent. About 86 per cent of cases can be classified as asymptomatic M.G. and 14 per cent as malignant M.G. (myeloma or Waldenström macroglobulinemia). In asymptomatic forms, heavy chain classes are only IgG or IgM with a large predominance of IgG (86,4%). It is suggested that donors in whom M.G. have been detected should not be allowed to give blood. A yearly clinical, hematological and an immunoglobulin check-up is recommended to these patients in order to defect the first sign of a malignant process.


Serum sulfhydryl levels in rheumatoid patients treated with gold thiomalate and penicillamine. Twenty-six patients with rheumatoid arthritis were treated with sodium aurothiomalate (16 patients) and penicillamine (10 patients) for 9 months. During both treatment periods the content of serum sulfhydryl groups increased and erythrocyte sedimentation rate, rheumatoid factor titre and number of swollen joints decreased.


Trace elements in serum and urine of patients with rheumatoid arthritis. Patients with rheumatoid arthritis were found to have elevated urinary copper excretion rates. They also had increased serum levels of coeruloplasmin and presumably also of a non-coeruloplasmin copper fraction. The zinc levels in serum and urine did not differ significantly from control values. Serum selenium and serum iron were decreased as compared with those of the healthy controls. It is suggested that an increased copper-to-selenium ratio may be of pathogenetic signficance. Biochemical changes induced by copper may be antagonized (at least partly) by the treatment with gold thiomalate and D-penicillamine. If serum selenium deficiency in RA can be confirmed in larger materials, selenium supplementation as a therapeutic measure should be considered.


Risk of infection from heavily contaminated air. In a factory processing shea nuts the dust concentrations were found to be up to 145 mg/m3 [80% respirable (1--5 micrometer)]. Bacterial examination of the dust revealed that under the worst conditions observed a worker might inhale 350,000 bacteria per 8 h. Of these, 3,000 were Ps. aeruginosa and 1,500 Salmonella spp. of nine different types. The possible health effects of these findings are discussed.


[Usefulness of the immunoglobulin-albumin ratio compared to electrophoresis in the diagnosis of multiple sclerosis]. The results obtained with gel electrophoresis on CSF samples of multiple sclerosis patients are compared with measurements of CSF IgG indexes (IgG/alb and IgG/total protein). The correlation between these parameters is good, provided the upper normal limit of the IgG/alb index is over 35% and an "overlapping" zone between 21 and 35% is introduced where the IgG/alb index has not the same diagnostic value.


[Fetal hydantoin syndrome in siblings].

[Fetal hydantoin syndrome in siblings]. The two children of an epileptic woman who underwent therapy with hydantoin during both pregnancies showed the characteristic findings of the fetal hydantoin syndrome: growth retardation, microcephaly, mental retardation, and a distinct hysmorphic pattern. Both exhibited a ridged metopic suture, hypertelorism, a short nose with a broad base, hypoplasia of the distal phalanges and nails of the toes, and inguinal hernias. In addition the 18-month-old girl exhibited epicanthal folds, strabismus, ptosis, and a small ventricular septal defect; she had been exposed in utero to 300 mg mesantoin daily. Her 6 1/2-year-old brother was more severely retarded, lacking speech and presenting with infantile autism. During pregnancy the mother had taken 400 mg mesantoin daily. About half of the offspring of epileptic women treated with hydantoin during pregnancy are mentally retarded, and 11% exhibit in addition the pattern of dysmorphic findings known as the fetal hydantoin syndrome. Hydantoin should therefore be strictly avoided in epileptic women of child-bearing age unless safe contraceptive measures are taken. In the event of pregnancy, therapeutic abortion should be considered if hydantoin therapy must be maintained.


A systematic assessment of early African hominids. A large sample of Pliocene fossil hominid remains has been recovered from the African sites of Hadar in Ethiopia and Laetolil in Tanzania. These collections, dating approximately between 2.9 and 3.8 million years ago, constitute the earliest substantial record of the family Hominidae. This article assesses the phylogenetic relationships of the newly discovered fossil hominids and provides a taxonomy consistent with that assessment. A new taxon, Australopithecus afarensis, has been created to accommodate these Pliocene hominid fossils.


Electromagnetic muscle stretch strongly excites sensorimotor cortex neurons in behaving primates. Responses of single units in primary motor and sensory cortex of behaving primates to electromagnetic stretch of the muscle flexor carpi ulnaris are comparable in latency and intensity to responses to wrist extension. Thus, muscle stretch appears to be a major factor in cortical response to limb displacement during performance and probably has an important role in motor control at the cortical level.


The major histocompatibility complex of the mouse. Like physicists striving to develop a unified field theory, immunologists are attempting to bring order to the microcosmos of defense reactions. Indications are that one of the most important constants in this microcosmos is the major histocompatibility complex (MHC) of the species. A test of any interpretation of the MHC's role in immunity is how well it explains this system's polymorphism. One of the most crucial questions an MHC hypothesis must answer is: Why are there so many alleles at this complex?


Eye malformations in rats: induction by prenatal exposure to nickel carbonyl. Exposure of pregnant rats to inhalation of nickel carbonyl on days 7 or 8 of gestation frequently causes the progeny to develop ocular anomalies, including anophthalmia and microphthalmia. The incidence of extraocular anomalies is very low. The specificity of nickel carbonyl for induction of ocular anomalies in rats appears to be unique among known teratogenic agents.


Survival associated with hepatorenal syndrome. We have described an advanced case of type A2 hepatorenal syndrome with subsequent recovery. The renal failure in this syndrome is secondary to the hepatic failure. In this patient, renal support was afforded by peritoneal dialysis, while hepatic recovery was facilitated by takedown of a jejunoileal shunt and by intravenous hyperalimentation. As liver function returned toward the normal range, renal function improved. Reversal of hepatic dysfunction is critical for reversal of hepatorenal syndrome of the type A2 variety.


Failure of routine methods in the diagnosis of chronic brucellosis. A young man who was raised on a farm and developed recurrent subcutaneous abscesses is described. Multiple cultures revealed either no growth or normal skin flora. Routine serologic evaluation for Brucella agglutinins was negative, including serial dilution to greater than 1:1,000 of the patient's sera. Brucella abortus infection was documented by the use of a binding antibody assay to measure the patient's class-specific serologic response and obtaining a positive culture by incorporating methicillin into the culture media to suppress overgrowth of staphylococci. Thus, the potential difficulty in making the diagnosis of brucellosis is demonstrated, and the use of extraordinary means, namely, specific selective media and a binding antibody assay, to make the diagnosis is emphasized.


Epidemic listeriosis. Report of 14 cases detected in 9 months. During the period August 1977 to April 1978, 14 Black patients in Johannesburg area had systemic infections caused by Listeria monocytogenes. Nine of these patients were neonates who presented with septicaemia (5 cases) or septicaemia and meningitis (4 cases) and 5 were adults, all of whom had meningitis. The mortality rate was 43% (6/14), with 4 neonatal and 2 adult deaths. All isolates of L. monocytogenes were type 4b. Only sporadic cases of human listeriosis have previously been reported in South Africa, and the cases reported here constitute the first epidemic in this country.


Enteric fever caused by Salmonella paratyphi C in South and South West Africa. This article documents 53 cases of Salmonella paratyphi C infections in humans in the Eastern Transvaal (47 cases) and South West Africa (6 cases). Ninety-two percent of patients (49 cases) had enteric fever, 1 patient was asymptomatic, and 3 had localized urinary infections or were carriers. Most patients were successfully treated with chloramphenicol and only 1 relapsed. The South West African strains were identified as S. paratyphi C var. east africa. The organism is probably spread by water, and 70% of patients who had enteric fever were under the age of 20 years.


Nutritional support of the burned patient. Patients with major thermal injury exhibit hypermetabolism as a result of neurohormonal alterations. Thus caloric requirements are exaggerated. Failure to provide supranormal caloric intake by both enteral and parenteral routes is associated with pronounced weight loss, delayed wound healing, decreased host resistance, and cellular dysfunction. Special dietary programs delivered early in the course of treatment must be utilized to prevent these complications of acute postburn malnutrition.


Alterations in the coagulation and fibrinolysis system in pregnancy, labour and puerperium, with special reference to a possible transitory state of intravascular coagulation during labour. Various tests of hemostasis were carried out during pregancy, labour and the puerperium in a group of 259 women. Determinations were carried out in the 1st, 2nd and 3rd trimesters, in the period of dilatation, the expulsion period, the period of expulsion of the placenta and the immediate postpartum period of labour and on each of the first 5 days of the puerperium. It was confirmed that during pregnancy there is an elevation of the fibrinogen degradation products (FDP) levels with a proportional increase in the numbers of positive protamine sulfate and ethanol tests. The proportion of positive protamine sulfate and ethanol tests reaches a maximum in the expulsion of the placenta coinciding with the presence of soluble complexes heavier than fibrinogen as detected by polyacrylamide gel electrophoresis and by column chromatography. All this indicates that there is a transitory intravascular coagulation produced during labour reaching its maximum at the time of birth and tending to become normalized in the first few days of the puerperium.


Abnormal growth hormone responses to CB-154 and thyrotropin-releasing hormone (TRH) in patients with acromegaly. CB-154 (2-Br-alpha-ergocriptine) stimulates growth hormone (GH) release in normal subjects. In acromegaly, however, this agent often decreases plasma GH level paradoxically. In order to examine the mechanism of the so-called "paradoxical decrease" in plasma GH with CB-154, GH responses to CB-154 were compared with GH responses to thyrotropin-releasing hormone (TRH), arginine, and luteinizing hormone-releasing hormone (LH-RH) in 20 cases of acromegaly. CB-154, as well as L-dopa, elicited decrease in GH in those patients whose GH secretion was more responsive to TRH and less responsive to arginine. These results suggest that, like L-dopa, CB-154 has similar dual actions of TRH antagonistic GH decrease and GH-RF (GH-releasing factor) facilitative GH increase. Moreover, it was speculated from this study that CB-154 has no significant effect on LH-RH release. The value of (increase ratio of GH on TRH)/(increase ratio of GH on arginine) can be used as an index for the indication of chronic CB-154 therapy in patients with acromegaly.


Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. I. Simultaneous oral and subcutaneous administration for 28 days. A toxicological investigation was performed with the linear alkylbenzene sulphonate (LAS) using 4 groups of 3 male and 3 female monkeys. Dosages were 0, 30, 150, 300 and 0, 0.1, 0.5, 1.0 mg/kg/day by simultaneous oral (p.o.) and subcutaneous (s.c.) administration respectively, for 28 days. At 300 p.o. and 1.0 s.c. mg/kg/day, the monkeys vomited frequently and usually within 3 hours of administration. An increased frequency of loose or liquid faeces was recorded for animals receiving 150 p.o. and 0.5 s.c. and 300 p.o. and 1.0 s.c. mg/kg/day. Fibrosis of the injection sites was found among all the test groups, the incidence and severity being dose related. Ophthalmoscopy, laboratory examination of blood and urine, organ-weight analysis and histopathological investigation did not detect any further treatment related responses. Previous reports concerning oral administration of tetrapropylene benzene sulphonates (ABS) to dogs record prompt emesis ascribed to local gastro-intestinal effects. Vomiting observed during this investigation was considered to be of possible central origin.


[Contribution to combined therapy of the Ewing-sarcoma (author's transl)]. The techniques and results from the treatment of 15 own cases with Ewing-sarcoma having undergone different therapeutic schemes are reviewed with the help of universal literature. These tumors are shown to need individual treatment which has to be adapted to the present data in each case.


The course of infection of trypanosoma cruzi in gamma-irradiated rats. The course of infection of both blood and tissues by the Sonya strain of Trypanosoma cruzi in gamma-irradiated rats has been investigated. The blood infection was dimorphic; slender and broad forms were present throughout, though broad forms predominated at high parasitaemias. Both total blood parasitaemia and numbers of slender forms increased progressively in a series of waves with a periodicity of about four days. The rate of increase in the numbers of intracellular parasites corresponded with this, suggesting that the intracellular development cycle is also about four days. Tissue infection appeared to originate at the site of subcutaneous infection but subsequently occurred in the heart, and then later in the muscle of the hind limbs and alimentary tract.


Heavy metal nephropathy of rodents.

Heavy metal nephropathy of rodents. Heavy metal nephropathy is a pathologic entity of the renal tubular epithelium of rats, evoked by lead, gold, and other heavy metals. It is characterized acutely by coagulative necrosis, subacutely by cortical fibrosis, and chronically by cytomegaly and karyomegaly. Finally, adenomas develop, some of which become malignant.


Pulsed pattern of proliferation in liver parenchyma of young mice. Natural synchronization of DNA-synthesizing hepatocytes. The present investigation is concerned with natural synchronization of DNA-synthesizing hepatocytes in the growing liver of young mice. It has been found that in individual specimens, 30--40% of all the parenchymal liver cells pass through the S phase within about 22 h. These cells are grouped into two large synchronous fractions, so-called "S-pulses". The time interval between the formation of these "S-pulses" is assigned by the duration of the S phase. It is shown that the maximum separate "S-pulse" involves 20% of the total hepatocyte population.


Studies of erythrocyte sequestration. I. Spleen homing of heat altered erythrocytes. Heat altered erythrocytes are taken up by spleen macrophages without any signs of mechanical strain as revealed by light and scanning electron microscopy. There was no scintigraphic evidence for changed flow rates within the spleen after sequestration of erythrocytes.


Studies of erythrocyte sequestration. II. Liver homing. Xenogeneic and enzyme-treated erythrocytes rapidly home to the rat liver as measured by scintigraphic procedures. Histology and scanning electron microscopy revealed that pronase digested erythrocytes are taken up as whole cells by liver histiocytes.


Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine. The parenteral administration of 1,2-dimethylhydrazine to rats caused the development of colonic neoplasms in about 90% of animals by 24--30 weeks of treatment. Usually there were multiple tumours with a mean of 2.7 per rat. The lesions have been classified histologically into adenomata (26% of all tumours) and carcinomata, the latter showing varying degrees of differentiation. No completely anaplastic tumours were seen, and there were none originating in connective tissue. The distributions of the different tumour types along the length of the colon varied. The more benign lesions were situated predominantly in the distal half of the colon, while the poorly differentiated adenocarcinomata were concentrated in the proximal third of the colon. There was good evidence to suggest that adenomata often progressed to frank malignancy in the distal colon. In the proximal part, however, it appeared that tumours frequently developed de novo as poorly differentiated carcinomata. Perhaps regional variations in the kinetic organisation of the normal colonic mucosa somehow influence the nature of the neoplastic change induced by DMH, thus accounting for the differences in tumor distribution. After 24 weeks of DMH treatment there was only a small increase in the mean number of tumours per rat.


Amyloid P component--a special type of collagen? The localization of amyloid P-components is demonstrated by immunofluorescence microscopy in normal human tissue (kidney, spleen, liver). The relation to collagen and to amyloidosis is discussed.


[Regional intra-arterial chemotherapy of malignant tumors of the maxillofacial region]. The writers treated 36 cases of maxillofacial malignant tumors in stage III--IV, cancer--in 35 cases, osteosarcoma--in 1, confirmed histologically, and 31 of them were treated through art. temporalis superfacialis, others--were treated by partial chemotherapy by thiophosphamide (260--320 mg) through art. caroticus externa. The results of the treatment are described. In 27 of 36 patients an antitumor effect was gained, in 3 cases a complete regression was noted, in 17--a 50% regression, in 6--from 25 to 50%, in 1--less than 25%. No effect was observed in 9 cases.


[Stucture of PhiKZ bacteriophage particles]. The structure of the particle of a new bacteriophage Pseudomonas phiKZ was studied. The particle of phiKZ bacteriophage was shown to have some features distinguishing this phage from all those known heretofore: a large size of the head and DNA and the presence in the head of a special structural formation named the central body. The central has a cylindrical shape and may be isolated from the head of the phage by repeated freezing-thawing the phage preparation. The structure of the central body is complicated. Possible functions of the central body are discussed.


Metabolic disposition of 6-ethyl-3-(1H-tetrazol-5-yl)-chromone, a new antiallergic agent, in the rat, guinea-pig, rabbit, dog and monkey. 1. [14C]Ethyltetrazolylchromone ([14C]ETC) was promptly absorbed from the rat small intestine by the portal route. 2. The maximum plasma concn. of unchanged drug after oral administration (10 mg/kg) was highest in dogs (456 microgram/ml), followed by monkeys (287 microgram/ml), guinea-pigs (146 microgram/ml) and rats (55 microgram/ml), and lowest in rabbits (09 microgram/ml). The half-life of the drug in plasma varied with the species, ranging from 13 to 133 h. The drug was highly bound to plasma protein. In dogs and rats, the plasma 14C was predominantly the unchanged drug, whereas in guinea-pigs, rabbits and monkeys it was mainly metabolites. 3. At 10 min after oral administration of the drug to rats there was a wide distribution of the 14C in the tissues. At this time, the 14C concn. were the highest in stomach, followed by kidney, liver, plasma, heart and lung, and lowest in brain. 4. Almost all administered 14C was eliminated from the body in 72 h. The major route of excretion was via the urine except with guinea-pigs, in which animal the 14C was almost equally divided between urine and faeces. 5. only trace amounts of the unchanged drug were found in urine and bile. The major urinary metabolites were as follows: I (1-hydroxyethyl ETC), II (acetyl ETC), III (IIIa, 2-hydroxyethyl ETC) and IV (1,2-dihydroxyethyl ETC) in rats, I and VI (5-carboxymethylsalicylic acid) in guinea-pigs, I, III (IIIb, carboxymethyl ETC) and VII (ETC-N-1-glucuronide) in rabbits, I and VII in dogs, and I and IV in monkeys.


Effects of some inorganic elements on nitrogen-fixation in blue-green algae and some ecological aspects of pollution. Nitrogen-fixation by two species of Nostoc, one of them a lichen phycobiont, was generally stimulated by low concentrations of arsenic, cadmium, nickel, lead, palladium, and zinc. Higher concentrations (0.025 to 0.125 ppm) of arsenic, nickel, and palladium were also stimulatory; however, higher concentrations of cadmium, lead, and zinc tended to inhibit fixation. With the exception of palladium and zinc at low concentrations these six tested elements tended to inhibit nitrogen-fixation in Chlorogloea fritschii and Westiellopsis sp.


Effect of rifampicin (3-(4-methylpiperazinyl-iminomethyl)rifamycin) on heterocyst differentiation in the blue-green algae Anabaena and Calothrix. Chains of multiple heterocysts form in Anabaena und Calothrix filaments on treatment with rifampicin. The multiple heterocysts form irrespective of whether the rifampicin treatment is given in combined nitrogen-free or supplemented medium. This suggests the possibility of involvement of a species of RNA or of protein as intracellular heterocyst inhibitor and indicates that some latent pattern-determining mechanism may operate in the combined nitrogen medium.


[Search for nucleic acid influencing, as well as membrane active, potential cancerostatic fungal metabolites using microbiological and cytological screening methods]. A prescreening program including microbiological and cytological assays was employed in search of potential cancerostatic antibiotics in crude extracts of mushrooms. The microbiological tests based on agar diffusion techniques consist of prophage induction test and BIP-test. All active compounds selected by these microbiological models are potential inhibitors of nucleic acid metabolism. Cytological assays on leukemia L 1210 cells have been carried out by microscopic examination and by evaluation using an electronic particle counter. Activity was expressed as decrease of the number of single cells caused by agglutination or lysis of cells, changes in cell surface area, dye exclusion, and increase of cell volume. A wide variety of mushrooms was demonstrated to exhibit interesting activities in some of these screening systems. The influence of primary metabolic products of mushrooms on microbiological models was studied additionally. In vivo assays have not yet been accomplished.


Some aspects on liver enzymes in protein-energy malnutrition. Liver enzymes alkaline phosphatase and transaminases (GPT & GOT) were studied in cases of protein-depleted rats. Alkaline phosphatase activities were determined with and without Mg addition to the incumedia, since it is the essential metal for this enzyme. The liver transaminases were also determined before and after pyridoxine injection, which is the coenzyme for this group. Both liver alkaline phosphatase and transaminases activities were increased on protein depletion. The study indicates that the increased activities of liver alkaline phosphatase in protein-depleted animals is suggestive of increased enzyme protein synthesis. On the contrary, high activities of liver transaminases are suggestive to be a result of some regulation mechanisms between the enzyme protein and its coenzyme.


[Lymph node tuberculosis--today].

[Lymph node tuberculosis--today]. The peripheral tuberculosis of the lymph nodes on the neck, in the axilla and on the groin is described in its present epidemiological situation, its pathogenesis, diagnosis and therapy. Nowadays the tuberculosis of the lymph nodes most frequently occurs at older age and in women. In most cases the M. tuberculosis is the causative organism. The differential diagnosis must take into consideration many possibilities and sources of error--also for the following therapy and expert opinion--, in most cases it demands a histological and bacteriological examination of the exstirpated lymph nodes. This is at the same time the first step to therapy which consists in the removal of all enlarged lymph nodes in the area of the disease and in a 2-phase-chemotherapy for the duration of one year.


A model of experimental endotoxin shock in monkeys and its therapeutic control. The course and therapy of endotoxin shock were studied in 34 monkeys Macaca mulatta. E. coli endotoxin was infused intravenously to conscious animals. The individual responses to a dose of 3 mg . kg-1 exhibited a considerable variability. A part of shocked animals were successfully rescued by a combined infusion of dopamine, hydrocortisone, and dextran; untreated animals died of endotoxin shock. Morphological changes in their parenchymatous organs were little marked in the acute experiment.


[Additional tocolysis via inhibition of prostaglandin synthetase with indometacin (author's transl)]. Indometacin was administered as additional tocolyticum in 42 women between the 27. and 36. week of pregnancy. Patients received indometacin oral, of a complete tocolysis could not be achieved by application of beta-sympathicomimetica. A complete tocolysis always could be achieved with a daily dose of 200 mg indometacin. The mean time of therapy was 7,5 days, the mean total dose 1100 mg.


Studies of Sarcocystis in Malaysia. II. Comparative ultrastructure of the cyst wall and zoites of Sarcocystis levinei and Sarcocystis fusiformis from the water buffalo, Bubalus bubalis. The two species of Sarcocystis--S. levinei and S. fusiformis from the water buffalo, Bubalus bubalis, show some ultrastructural similarities in their cyst wall and zoites. The zoites of both species are of about the same size, banana-shaped and have 22 subpellicular microtubules, numerous micronemes, eight rhoptries, a micropore in the region of the micronemes, an elongated mitochondrion, and a nucleus. S. levinei has 200--300 micronemes and S. fusiformis has about 400. The sarcocysts of both species are trabeculated and their cyst walls have cytophaneres containing annulated fibrils and coarse, electron dense granules. The cytophaneres of S. levinei are sloping, with irregular, wavy outlines, whereas S. fusiformis has the cauliflower-type of cytophaneres. This difference in the appearance of the cytophaneres, together with the difference in size of the sarcocysts and their definitive hosts, further confirms that S. levinei and S. fusiformis are two distinct species in the water buffalo.


Haemoproteus columbae: course of infection, relapse and immunity to reinfection in the pigeon. Studies were performed on the course of infection, relapse, and immunity to reinfection in 11 young pigeons infected with the avian malaria parasite Haemoproteus columbae Kruse. The prepatent period in our experiments varied between 22 and 37 days. The intensity and length of the initial infection period showed wide variations. During this period an initial periodicity of gametocyte production of about 12 days with peaks at about 6-8 and 18-20 days after patency was observed. The various modes of infection (fly bite, intramuscular, intravenous, or intraperitoneal inoculation of sporozoites) did not influence the intensity of the initial infection. No pathogenicity due to heavy infection with the parasite was observed. There was no periodicity of relapse occurrence, nor any correlation between the frequency of relapse and the intensity of the initial infection, and the phenomenon was not influenced by seasonal changes. Pigeons (Columba livia) that had recovered from previous infections were susceptible to reinfection, whereas pigeons with chronic infection acquired immunity (premunition).


[Comparative review of the developmental biology of the genera Sarcocystis, Frenkelia, Isospora, Cystoisospora, Hammondia, Toxoplasma and Besnoitia (author's transl)]. A review is given of the advances in our knowledge of the developmental biology of the so-called cyst-forming coccidia in the years from 1974 to 1978. Until 1970 only 6 Isospora species were known to occur in cats, dogs and men. After the discovery of the coccidian nature of the genera Toxoplasma, Sarcocystis, Besnoitia and Frenkelia, and after the discovery of the new genus Hammondia the number of known species rose to over 30. In addition it could be shown that also birds of prey, owls and reptiles serve as final hosts for several Sarcocystis and Frenkelia species. The coccidia with isosporoid oocysts can be classified into two major groups: Species with gamogony and sporogony in the final host (Sarcocystis, Frenkelia) and species with schizogony and gamogony in the final host and sporogony on the ground (Isospora, Cystoisospora, Hammondia, Toxoplasma, Besnoitia). The subdivision of the first group into the genera Sarcocystis and Frenkelia based on the localization of their cysts in the musculature and in the brain, respectively, cannot be upheld in the future. Their classification into organisms with small cystozoites of about 7 microm with birds or reptiles as final hosts (Sarcocystis and Frenkelia species of rodents) and those with large cystozoites of about 15 microm and mammals as final hosts (Sarcocystis spp. of domestic animals and rodents) would be more significative. The second group can be subdivided into monoxenous species (Isospora), species with an optional intermediate host in which no or only slight multiplication occurs (Cystoisospora) and in genera with a multiplication in two phases in the intermediate host (Hammondia, Toxoplasma, Besnoitia). The nomenclature of single species is very controversial. As an example the controversial apprehension of the taxonomy of the Sarcocystis species of cattle is discussed. An application has been submitted to the International Commission for the Zoological Nomenclature to delcare a number of names as nomina dubia and to introduce unambiguous names for those organisms for which type specimens are available.


[Lipoxygenases from pears, strawberries and gooseberries: partial purification and properties (author's transl)]. Membrane-bound lipoxygenases (EC 1.13.11.12) were partially purified from the fruits by centrifugation and gel chromatography. The enzymes have a pH-optimum at 6.0 (pear) resp. 6.5 (strawberry, gooseberry). Linoleic acid is oxidised to 9- and 13-hydroperoxides in a ratio of 3:7 (pear), 2:8 (strawberry) and 1:1 (gooseberry). The enzymes from gooseberries and from strawberries co-oxidise canthaxanthine with a higher specific activity than the lipoxygenases from pears and apples.


[Political aspects. Prevention and political realities]. Present health legislation in Switzerland is largely concerned with the protection of our inhabitants from biological, chemical and physical risk of the environment. More and more it extends to economic aspects and to the behavior of the individual. Also in this respect a legal basis not only for the coverage of the consequences but also for the prevention of ill health is needed. Responsible citizens of our nation devoted to freedom and democracy merit that such a basis does rely as little as possible on bureaucratic enforcement but mainly on information and health education, controlled by science and experience and oriented towards the human needs and values of our society.


[Economic instruments for promotion of prevention]. The classical economic instruments for influencing individual behaviour are regulatory and sumptuary taxes as well as subsidies. Regulatory taxes are forced payments, which are fixed exclusively to influence a group of individuals in the manner required by the government. Sumptuary taxes are levied in order to eliminate differences between private and societal costs (e.g. with smoking). Here the externality tax takes first place. Subsidies, finally, are a special aid, which should motivate the recipient to behave in a certain way. They can--in the same way as regulatory and sumptuary taxes--, by influencing the price structure, be employed in various ways to partronize preventative behaviour.


Hemolysin of Myxococcus fulvus NK 35 i. production and isolation. Myxococcus fulvus NK 35 has been shown to produce a soluble hemolysin which lysed rabbit, human, horse, and sheep erythrocytes. A medium (Varghese's medium) was devised in which a maximum of hemolysin was produced in 6 days at 28 degrees C under static conditions. The lysin was precipitated by complete saturation of the culture filtrate with ammonium sulphate, followed by dialysis against saline. Other enzyme systems were destroyed by heating at 100 degrees C. Further purification was achieved by passing through a Sephadex G-25 column, giving a single peak with 0.01 M of phosphate buffer, pH 6.6. Like the hemolysin of Pseudomonas aeruginosa, this hemolysin is non-proteinic and withstands 100 degrees C for 30 minutes.


[Haemorrhage from the upper gastro-intestinal tract; rare causes (author's transl)]. 839 patients with acute haemorrhage from the upper gastro-intestinal tract were treated in the last 14 years. In 72 cases the cause of bleeding was extremely rare. To find the correct diagnosis in acute situations the best is, to do emergency fiberoptic gastroscopy and in some special cases selective angiography. Without clear diagnosis the mortality rate in such cases will be too high.


Isolation of tubercle bacteria using Ogawa egg medium modified by addition of Tween 80. A modified medium was developed by altering the composition of 3 per cent Ogawa egg medium and adding Tween 80. Isolation of tubercle bacilli using this medium, in general, showed better growth and colines became visible earlier than the original medium, but there was no improvement in the positive rate.


Induced chain formation in Bacillus megaterium by suramin (Bayer 205). B. megaterium NCTC 5637 has been shown to grow into long chains in 1% glucose and 1% suramin (w/v). This effect was not noticeable in lower concentration of the inhibitor. The effect diminished in suramin free medium, indicating the change to be phenotypic.


On the interactions of Yersinia strains and cell cultures. Comparative investigations were carried out on the dynamics of invasion of cell cultures by strains Yersinia pestis EV and Yersinia pseudotuberculosis treated vitally with petroleum ether. It was established that the invasiveness of the strains studied was related to the presence of chemical structures of the bacterial surface sensitive to the action of either and whose synthesis was temperature dependent. The penetration and initial stages of intracellular multiplication of the Yersinia were accompanied with a certain activation of the RNA- and protein-syntheses in the host cells. That was clearly expressed in cell populations inoculated with Yersinia variants of high invasiveness. After the 24th hour of inoculation of the cell cultures a decrease of the rate of metabolic processes in invaded cells was observed due to the destructive changes in their cytoplasm. At the end of the investigation it reached values considerably lower than those of the controls.


Findings of enterotoxigenic Staphylococcus aureus strains in scarlet fever. From 48 out of 143 scarlet fever patients in the age range of 3-15 years, Staphylococcus aureus strains were isolated in the course of hospitalization or convalescence (isolation rate 33.6%). Staphylococcal enterotoxin (SE) was produced by 19 (39.6%) of these isolates. The most frequent SE types detected were A (47.4%) and C (36.8%); type B was produced by 2 strains, type E by 1, while type D, or a combination of SE types, was not detected at all (by means of immunodiffusion in a micromodification). So far no significant correlation has been found between the clinical course of scarlet fever or accompanying complaints and presence of SE-positive S. aureus strains. The significance of these findings is discussed.


[Studies about monocines (author's transl)]. By means of mitomycin induction monocine preparations were made from 162 Listeria monocytogenes strains. From tested strains of different serovars and antigen combinations altogether 76% were monocinogenic. Examination of efficiency was performed against 15 indicator strains of Listeria monocytogenes. Concluding from spectra of reaction 6 groups of monocines (A-F) could be differentiated. Serovar 5 (Ivanov) proved as an indicator strain particularly sensitive for all monocines.


Characterization of plasmids in bacteriocin producing strains of Streptococcus faecium. Four bacteriocin (enterocin) producing strains of Streptococcus faecium were examined for extrachromosomal DNA. Three strains proved to harbor minicircular plasmid DNA of uniform length as evidenced by CsCl ethidium bromide density centrifugation and electron microscopy. Molecular weight determination obtained through contour length measurements showed 2.4 X 10(6) dalton for S. faecium 25, 3.4 X 10(6) dalton for S. faecium 3 and 3.8 X 10(6) dalton for S. faecium 59. Elimination experiments for bacteriocin production with intercalating dyes proved sterile. The role of these plasmids remains for the time being unknown.


[Flagella specific H antigenic schema of Pseudomonas aeruginosa (author's transl)]. Serogrouping of P. aeruginosa on the basis of heat-stable somatic (O-)agglutinogens is well established, but H-typing on the basis of heat-labile agglutinogens is not accepted generally because of uncertain flagella specificity. In contrast to the agglutination reaction, the indirect fluorescent antibody technique allows the differentiation of soma and flagellum of P. aeruginosa cells at the morphological and serological level simultaneously, and thereby the specific analysis of flagellar (H-)antigens, even with OH-antisera. Using this technique the complex flagella-antigen a with the partial antigens a0, a1, a2, a3, a4 and the uniform flagella-antigen b are differentiated by cross absorption experiments. As the partial factors a1-a4 are independent determinants, a flagellar antigenic schema containing 17 H-types is devised. Type strains, immunization and absorption procedures for preparing diagnostic antisera are described. O-group and H-type show free combination. Completing the extended O antigenic schema of Habs (slide agglutination) with the flagella specific H antigenic schema (indirect fluorescent antibody technique), a detailed OH typing system of P. aeruginosa is obtained, by which clinical isolates are subdivided into 99 serovars.


Computer survey of antibiotic resistance--developments during 1973 to 1977. Results of antibiotic resistance of strains belonging to 9 species of so-called Problem bacteria, recorded by 10 District Public Health Laboratories in Slovakia during 6 months of 1977 (altogether 32641 strains) have been compared with results, obtained with identical computer-assisted system in 1973. The position of "Reserve antibiotics" (gentamicin, colistin, cotrimoxazole, oxacillin, lincomycin, spiramycin) remained favourable during precedent 4 years and even improved (with exception of gentamicin in P. aeruginosa). In classical antibiotics a typical steady-state situation was establishedin that period. Beta-lactam antibiotics in general deteriorated in gramnegatives, with certain improvements in special cases. In "specific pathogens", i.e. enteropathogenic strains of E. coli and in strains of P. aeruginosa, resistance to antibiotics generally increased. On the other hand, in S. aureus strains a better susceptibility to almost all antibiotics could be recorded. Surgical services still seem to use the bacteriological services infrequently and this should improve on an all-nation basis.


[Antinuclear antibodies (ANA) in patients with malignant diseases: frequency of occurrence and immunological characterization (author's transl)]. We report about the occurrence and importance of antinuclear antibodies in patients with malignant diseases. - We analyzed 110 sera of patients with tumors and found in 42% ANA. In contrast a corresponding control group contained ANA in 1.8%. - Patients with bronchogenic carcinoma and those of the digestive tract possessed ANA in a comparable percentage of 36 and 39, respectively. - Sera of patients with mamma- and uteruscarcinoma contained ANA in nearly 50%. - A connection between the type of the tumor and occurrence of ANA can be assumed. - Antibodies were directed against different antigens of the nucleus, often simultaneously occurring. Antibodies which we have detected, belong to different classes of immunoglobulins (IgG, IgM and IgA). In most cases we found a combination of antibodies. In 51% of positive cases antibodies were able to fix complement.


[Analysis of the biological effect of city smog extract IV. Growth inhibition of kidney cell cultures (cercopithecus aethiops) under the influence of a city smog extract and its polyaromatic fractions (author's transl)]. The cell growth of exponentially growing kidney cell cultures of Cercopithecus aethiops was determined by estimation of protein content. The effect of city smog extracts and its polyaromatic fractions on cell growth was examined. Based on the benzo(a)pyren-content the crude extract of city smog exerted the strongest inhibition of cell growth, followed by non purified and purified fraction of polyaromates. The inhibition of cell growth was dose dependent. Results indicate, that for cell growth inhibition are of importance concentrations of toxic substances and exposition time.


[Hygienic analyses carried out in a public sauna (author's transl)]. In a public sauna a considerable germ level was found to exist in all areas during rush hours. Although no specifically pathogenic germs were detected on the surfaces, the existence of E. coli would suggest that particular attention must be given to the hygiene of this type of bathing establishment. It is particularly important that the relatively high temperatures in the heated area of the sauna do not cause a hygienically decisive germ reduction. Apart from this, especially the foot-warming basins appear to be undesirable germ reservoirs, even for pathogenic germs (Staph, aureus, P. aeruginosa). Systematic daily disinfection, which is recommended as a basic requirement but which in practice is mostly omitted, proves indispensable. Proper use of the relatively harmless hydrogen peroxide allows the hygienic conditions to be clearly improved, shortly.


[Tele-electrosubcorticogram study of reactions to vestibular stimulation in neurosurgical clinical practice]. In connection with stereotactic examinations and operations, mainly in certain forms of epilepsy, the electro-subcorticogram under, vestibular stimulations was recorded by telemetry. The amount of informat ion obtained was analysed by electronic data processing. A number of vegetative parameters and the electro-oculogram could be recorded at the same time. Regular bioelectric reaction of the desynchronisation type or of the oscillation depression type were found. In the presence of focal or generalised convulsions, a weakening of the epileptic discharges were observed under labyrinthine stimulation. Also the sense of rotation leads to special influences. The method is also of importance for the postoperative phase as it represents an adaptation of the requirements of modern living conditions (acute accelerations, breaking and changes in direction). Finally, information about the dominance of interfocal relations can also be obtained.


Hyperprolactinaemia in the spontaneously hypertensive rat. A hypothalamic role in the aetiology of hypertension in the spontaneously hypertensive rat (SHR) has been suggested by prior observations. In an attempt to determine whether the central control of prolactin (PRL) release is altered in the SHR we have compared the PRL response to immobilization stress, thyrotrophin releasing hormone (TRH), haloperidol, and L-DOPA in the SHR and in normotensive Wistar control rats. Carotid artery catheters were inserted 48 h prior to the PRL response studies and the catheters were maintained patent with heparinized saline. Timed blood samples were obtained in SHR and control rats weighing 180-225 g. The SHR demonstrated elevated basal serum levels of PRL and greater PRL responses to stress. However, administration of L-DOPA resulted in a similar suppression of serum PRL in the SHR and in the normotensive controls. These findings suggest alteration in the central control of PRL release in the SHR. Observations of elevated basal PRL, exaggerated PRL in response to L-DOPA in SHR are consistent with normal pituitary responsiveness to dopamine suppression of PRL release, but defective hypothalamic metabolism of dopamine. Alterations in central dopamine control mechanisms in the SHR may play a role in the pathogenesis of essential hypertension in these animals.


Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease. In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.


Effect of clomifene on thyroid function in normal men. To study the effect on thyroid function 100 mg of clomifene citrate was given once a day to two groups of healthy male volunteers for 5 and 12 consecutive days, respectively. In both groups serum concentrations of TSH, thyroxine, triiodothyronine, T3 resin uptake test and thyroid hormone binding proteins were measured before, during and after oral administration of clomifene. The effect of clomifene treatment was evaluated in Group 1 by means of serum FSH and LH measurements. Further in Group 2 the serum TSH response to iv TRH (200 microgram) was also investigated. The mean per cent elevations in serum concentrations of FSH and LH were 145 and 200, respectively. In Group 1 a small but statistically significant decrease within reference limits in triiodothyronine (P less than 0.01) and free thyroxine index (P less than 0.02) was found on day 4 of clomifene. On day 5 a slight increase in TSH was observed (P less than 0.05). In Group 2 the response of TSH to TRH showed a non-significant increase after 5 days and a significant increase (P less than 0.01) after 12 days of clomifene. Eight days after discontinuation of the drug the response was restored to normal. No changes in the thyroid hormone binding proteins in serum could be demonstrated. Though the observed changes were slight, they indicate that clomifene exerts an influence directly on the thyroid function.


Morphologic effects of thio-TEPA on mammalian urothelium. Changes in abnormal cells. Morphologic changes induced by thio-TEPA were examined in animals with chemically induced neoplasms. Both toxic and metabolic effects were documented. Degeneration, vacuolization and increased exfoliation (toxic) were most prominent, occurred within 48 hours of exposure, and tended to subside after removal of the drug. Nuclear changes (metabolic) were rare and occurred late. Neither toxic nor metabolic effects were specific for thio-TEPA: both could be detected in control animals receiving saline. The metabolic effects of thio-TEPA are not sufficiently widespread to prevent tumor growth.


Appearance of histochemically detectable ionic calcium in degenerating primary sensory neurons. The effect of neonatal capsaicin treatment on the fine structure and localization of ionic calcium in sensory ganglion cells has been investigated in rats. Neonatal capsaicin treatment resulted in the degeneration of certain type B sensory neurons. At the same time ionic calcium was demonstrated histochemically in the perikarya of numerous small-sized ganglion cells. The appearance of histochemically detectable ionic calcium in these cells in relation to the pharmacologically evoked degeneration of certain primary sensory neurons is discussed.


[Calcium utilization in the neuromuscular junction after acetylcholin treatment (author's transl)]. In the site of the myoneural junction a liberation of Ca++ ions, which is similar to that described previously after an electric stimulation or use of cholinesterase inhibitor, can be revealed by histochemical methods (heavy metal substitution, tetracycline fluorescence technique and glyoxal-bis-(2-hydroxyanil) complex formation) using repeated acetylcholine and SCh administration. The possible aspecific reaction due to the presence of Mg++ ions can be excluded by means of the glyoxal-bis(2-hydroxyanil) method. It can be suggested that there is a correlation between the liberation of Ca++ ions an the function dependent mitochondrial energetic processes.


Glycogen changes in the liver cells of young rats following isoprenaline treatment. (Histochemical and ultrastructural investigations). Glycogen changes were investigated by light and electron microscopy in the liver cells of newborn rats following isoprenaline (IPR) treatment either for 1 day (2 intraperitoneal injections at 12 h interval), or for 8 days (2 intraperitoneal injections daily). On the day following the interruption of both treatments glycogen depletion was observed as compared to control rats, as evaluated by PAS reaction and confirmed by higher total phosphorylase activity. During this stage electron microscopy revealed mainly alpha-particles of glycogen associated to highly dilated smooth endoplasmic reticulum (SER) after 1-day-treatment, and to mostly increased SER after prolonged treatment. In the animals submitted to prolonged IPR administration and sacrificed at later times, glycogen masses intensely PAS-positive were strongly increased, while the activity of total phosphorylase proved accordingly lower than in the rats sacrificed at earlier times. Electron microscopy examination confirmed an increased amount of glycogen (alpha- and beta-particles) differently distributed: beta-particles were more numerous in the liver of the rats sacrificed on the last day of the experiment. At this time SER didn't appear modified as compared to control rats.


Comparative formaldehyde-induced and glyoxylic acid-induced fluorescence histochemical studies on the intrinsic adrenergic innervation of the intestine and the liver of normal and vagotomized cats. The inbuilt intrinsic adrenergic nervous apparatus of the intestine and liver of the cat was studied using 1. the formaldehyde-induced fluorescence histochemical method and 2. the glyoxylic acid-induced fluorescence histochemical method for serial microtome sections and whole mount tissue layers or smear preparations. In addition, the effect of I) total abdominal infra-diaphragmatic vagotomy with or without associated Finney-type gastro-duodenostomy and II) unilateral (left or right) and bilateral cervical vagotomy with or without tracheostomy on the intrinsic adrenergic innervation was tested. Fluorescing varicose axons, both "free" (i.e. unrelated to the blood vessels) and gathered to typical perivascular nerve plexuses were observed in all segments and all layers of the wall of the intestine. The density of the adrenergic innervation varied remarkably from an area to another, even in the same segment and tissue layer, which makes comparative estimations of the density of the innervation very difficult. However, the intrinsic adrenergic innervation of the circular muscle layer of the colon and the rectum seems to be consistently quite rich, and in the rectum, also the longitudinal muscle layer is relatively heavily innervated. It thus seems obvious that (in the cat) also the direct adrenergic innervation of the external smooth muscle layers is of considerable importance, specially in the rectum. In contrast, the results of the present study clearly indicate that the liver parenchyma (of the cat) is devoid of functional intrinsic adrenergic innervation. Vagotomies did not cause any changes in the intrinsic adrenergic innervation of the intestine and liver: even after complete vagotomy no reduction was observed in the number of fluorescing axons or in the intensity of the fluorescence. Consequently, the vagal contribution of adrenergic axons to the liver and the intestine must be negligible, at least in the cat. The use of the glyoxylic acid-induced fluorescence histochemical method and whole-mount tissue layers was found most suitable for mapping and comparative estimation of the density of the intrinsic adrenergic nerve net, and is therefore recommended for other similar or related studies.


[Thiotepa in the treatment of central nervous system leukemia in children]. The authors report beneficial effects of thiotepa on leukaemic involvement of the central nervous system. The drug was given to 4 children with central nervous system leukaemia refractory to methotrexate and cytarabine. Intrathecal thiotepa caused regression of changes in the cerebrospinal fluid and in the neurological status of these children. No side effects were observed during this treatment.


[The immunohistochemical demonstration of the Thiol: proteindisulfid oxidoreductase (TPO) in pancreas and isolated Langerhans'islets. A light-, fluorescent- and electron microscopic study (author's transl)]. Thiole: Protein disulfide Oxidoreductase (E. C. 1.8.4.2) is capable of catalyzing thiole-disulfid exchange reactions and might have an important function in both protein biosynthesis and degradation. By using histochemical methods we were able to demonstrate the localization of this enzyme in the Langerhans'islets and in the acinus cells of rat pancreas. The reaction of the acinus cells, however, was much weaker than that of the islets. Electron microscopic experiments revealed the enzyme to be located in the outer membrane of the nucleus, in the membranes of the endoplasmic reticulum and B-cell granules, and in the plasmalemma also. All these structures are known to be involved in the insulin biosynthesis and secretion. There is a good correlation between morphological and biochemical findings. In acinus cells there are a few reaction in the outer nucleus membrane, the membranes of the endoplasmatic reticulum, and the plasmalemm.


Occurrence of 7-dehydrocholesterol in the uropygial gland of domestic fowls. Histochemical studies on the uropygial gland of domestic fowls have shown the presence of sterols (among which cholesterol and its esters) in the lipidic fraction of the gland secret. beta-Glucuronidase activity beside A5 3beta- and 17beta-hydroxysteroid dehydrogenase activities suggests that uropygial gland might be involved in sterols metabolism. By thin layer chromatography cholesterol and 7-dehydrocholesterol can be separated from the uropygial extracts and these compounds can be identified in gas liquid chromatography.


Computer assessment of chromatin patterns on some germ line cells of the hemipteran, Triatoma infestans Klug. The digitized nuclear images of some Feulgen-stained primary and secondary spermatocytes of Triatoma infestans were analyzed with computer programs. Different cell types could be mathematically discriminated in terms of distance of the condensed chromatin areas from the center of the nucleus, relative circumference of these areas, and staining intensity ratio of the condensed chromatin areas with respect to the whole nucleus. The method appears promising for further comparative studies involving the whole spermatogenetic process of T. infestans. It is probably advantageous for the analysis of other hemipteran (and even non-hemipteran) spermatogeneses.


DNA content of cells in human buccal smears. A preliminary study. The DNA content of the cells from human buccal smears, stained by the Feulgen method, was estimated by absorbtion microdensitometry using a Quantimet 720 D image analyser. It was concluded from measurements that most of the cells in buccal smears contained 2C DNA; however, among the cells from male donors a substantial proportion of cells (about 17%) contained less than 2C DNA. This difference between population of male cells versus female cells was statistically significant. The mean value of DNA content was estimated to be 7.7% lower for male cells than for female cells. The conclusions are preliminary because relatively small samples of cells have been measured.


[Electron microscopical and ultrahistochemical investigations of erythrocytes from eel (Anguilla angiulla) and rainbow-trout (Salmo giardneri) under the specific consideration of the segregation apparatus and the marginal band (author's transl)]. Comparative studies were carried out on the fine structure of the erythrocytes of the European eel (Anguilla anguilla) and the rainbow trout (Salmo gairdneri) using electron microscopy and ultrahistochemistry. The cell organelles, the marginal band and the segregation apparatus were investigated. The 2 organelles revealed specific differences. An alkaline phosphatase activity was revealed by ultrahistochemistry at the cell surface only, while alternating activities between the nuclear membranes, in the Golgi complex and in the segregation apparatus were observed in the acid phosphatase depending on the differentiation stage of the erythrocytes. The results are being discussed relating to a function of the segregation apparatus and the marginal band.


Electron histochemical study on synthesis and breakdown of glycogen in the rabbit cornea. Glycogen synthetase and phosphorylase activity was studied in the rabbit cornea electron histochemically. Glycogen synthetase and phosphorylase were located in the cytoplasmic matrices of the corneal epithelium, but glycogen synthetase was found to be mainly in the superficial half of the epithelium, and phosphorylase mainly in the deep layer. Since the cells in the deep layer of the corneal epithelium contain rich cytoplasmic organelles which have carbohydrate metabolism from glycogen or glucose through the Embden-Meyerhof pathway to the TCA cycle, glycogen synthesized in the superficial half of the corneal epithelium by glycogen synthetase may be transferred to the deep layer of the epithelium and broken down by phosphorylase. Phosphorylase in the superficial half of the corneal epithelium may break down overproduced glycogen  so as to avoid the deposition of a large number of glycogen particles for maintenance of corneal transparency.


Histophysical and histochemical investigations on muscle arterioles in hypertensive arteriolosclerosis; an interference microscopical, polarization optical and histophotometrical study. In 50 formol fixed biopsies from the m. quadriceps femoris normal and hypertensive arteriolosclerotic arterioles were characterized by quantitative histophysical and histochemical methods. The interference microscopical measurements showed a real increase of dry mass concentration in the pathologically changed vessels. Additional histophotometrical results are interpreted as an increase of proteins with higher isoelectric point (globulins, actomyosin). An augmentation of actomyosin is compatible with the medial hyperplasia demonstrated histologically. Likewise a positive correlation was found between the fibrin incorporation proved histochemically and the quantitatively evaluated protein reaction with Fast green; Glycosaminglycans do not carry weight quantitatively. The polarization optical measurements yielded an alteration of the submicroscopical structure in arteriolosclerosis. It consists in a diminution of the submicroscopical volum of gaps and in a diminished orientated dye binding of Congo red. Thereby the pathogenesis of hypertensive arteriolosclerosis of skeleton muscle is above all characterized by an increase of heterogeneous proteins (blood plasma proteins, actomyosin) in the arteriolar wall, leading to a diminution of the submicroscopical volume of gaps and to an elevation of the dry mass concentration.


[Conformational alteration of the Antennulae microvillares (author's transl)]. Brush border cells of the rectal mucosa of the rat previously fixed with glutaraldehyde and OsO4 exhibit branched antennulae microvillares. This regular type of antennulae changes to become a cap-like layer at the tip of the microvilli following the incubation in 100 mM EDTA and 1 M guanidinium hydrochloride, respectively, of the native mucosa. During an incubation in isotonic sucrose the antennulae are transformed to moderately branched rod-like forms. The findings suggest a collaps of antennulae whose anchoring at the membrane of the microvilli appears to be resistant and, presumably, may prevent the loss of this mucosubstance.


Stimulating effect of leucine on the growth of M. leprae. M-Y 16j agar slant was prepared by modifying M-Y 14b which has hitherto been used most widely in our experiments by increasing the amount of Na pantothenate and adding leucine, and the growth stimulating effect was investigated referring to the foregoing subculture experiments. The results revealed that the growth of M. leprae was stimulated remarkably in the primary isolation quite similarly to the subculture. This seemed to be resulted from stimulated biosynthesis of fatty acids by the leucine metabolism. The authors are greatly indebted to the World Health Organization and the Comité Exécutif International pour l'Assistance aux Lépreux for their financial support and to Dr. S. Ishihara, the Director of the National Suruga Leprosarium, for his kind supply of the materials to be cultured and for the lepromin test in leprosy patients carried out by himself. The main point of this study was presented to the 50th Annual Meeting of the Japanese Leprosy Association.


Isolation of M. leprae using semi-synthetic solid agar medium. The primary isolation of M. leprae from leprous nodules was carried out using agar slant prepared by solidifying the basic compositions of M-Y series to confirm the reproducibility of the preliminary studies. Results revealed that L-Feb-75 strain represented thin membraneous growth from about 20th week and it crept up the culture tube wall at about 30th week of incubation at 37 degrees C. L-Jun-75 strain, on the other hand, exhibited numerous, white and rough colonies of submiliary size on various places of the lustreless, thin membraneous structure at the inoculation site. Thus, it was clearly demonstrated again that M. leprae could be isolated very well on the surface of agar slant of M-Y series. It is very interesting bacteriologically to note that L-Feb-75 strain formed wrinkled thin pellicle floating on the surface of liquid medium. Further, the fact that L-Jun-75 strain was isolated from a leprous nodule preserved for more than 3 months at -20 degrees C was very suggestive indicating a standard for the preservation conditions of pathological materials for at least 3 months from removal to cultivation without destroying the viability of M. leprae contained.


Grand mal-provoked hyperuricemia.

Grand mal-provoked hyperuricemia. A significant increase in S-urate was found postictally in 17 patients with two or more grand mal seizures within 24 h. In six patients S-urate was above the level at which hyperuricemic renal failure may develop. Impaired renal function was observed in two patients who had extremely high S-urates. It is proposed that prophylactic procedures against hyperuricemic renal failure should be carried out in all patients with repetitive convulsions.


Studies on acute and late stages of experimental central retinal artery occlusion in the Cynomolgus monkey. I. Intensity-amplitude relations of the D.C. recorded ERG with special reference to the c-wave. The main positive component of the c-wave of the ERG is generated by the pigment epithelium-receptor complex, which is supplied from the choroidal circulation. Occlusion of the central retinal artery (OCRA) causes serious morphological damage only to the inner retina. An effect on the c-wave is therefore not primarily to be expected. In this study on five Cynomolgus monkeys with unilateral, laser-induced OCRA the c-wave was decreased, slightly in the early stage and markedly in the late stage. A hypothetical explanation of the reduced c-wave amplitude, involving changes in potassium ion concentration, is discussed. The conflicting results in other reports may be explained by uncontrolled influence of slow c-wave amplitude oscillations, by differences between acute and late stages, and by possible surgical damage to the choroidal circulation in some cases.


Studies on acute and late stages of experimental central retinal artery occlusion in the Cynomolgus monkey. II. Influence on the cyclic changes in the amplitude of the c-wave of the ERG and in the standing potential of the eye. The slow (2-3/h) oscillations of the c-wave amplitude and of the standing potential of the eye (SP) were studied in the Cynomolgus monkey during the acute and late stages after experimentally induced (laser photocoagulation) occlusion of the central retinal artery (OCRA). Whereas the healthy control eyes showed large cyclic variations in both the c-wave amplitude and the SP, no oscillations in the c-wave amplitude were observed in the OCRA eyes at any stage, and the SP oscillations were barely detectable in these eyes. OCRA causes morphological damage to the inner retina but not to the pigment epithelium-photoreceptor complex, which generates the positive component of the c-wave, and where the SP is also believed to originate. The findings of the present study strongly indicate that the SP and c-wave oscillations are related, and that they are either dependent on an intact inner retina or that the pigment epithelium-photoreceptor complex is functionally affected by OCRA. If not taken into consideration, the marked difference in oscillations between the OCRA eye and the healthy eye may be a major source of error when comparing c-waves from the two eyes, and it seems that some of the conflicting results reported by others can be explained in this way.


Pathological studies on a long-term survived case of gamma heavy chain disease--a brief review of 30 reported cases and a proposal for histological typing. A pathological and brief clinical study on the eleventh case of gamma heavy chain (gamma-chain) disease who died at the age of 44 after a long course of 12 years from the assumed onset of the disease was presented. Clinicopathological observations of the case showed a neoplastic nature which caused her death complicated by asthmatic attacks. Autopsy findings were characterized by diffuse infiltration of lymphoplasmacytoid cells and a few large immunoblastic cells into various organs. Literatures of 30 cases reported in the past, and the modern concept of lymphoma strongly suggest that the classificatory position of gamma-chain disease as well as Waldenström's macroglobulinemia should be placed between multiple myeloma and classic malignant lymphoma as an independent disease entity belonging to the same category. A proposal of histological typing of the disease was made in order to simplify various diagnostic designations in the literatures:--gamma-chain disease, 1) reticular type, 2) lymphocytic predominance, 3) plasmacytic predominance, 4) lymphoplasmacytoid cell type, 5) immunoblastic type. The present case belongs to type 4.


Chondroitin 4- and 6-sulfate mucopolysaccharidosis--a morphological study. A 17-year-old patient clinically manifesting gargoyle face, dwarfism, skeletal bone deformity, mild mental retardation and benign course was presented. Biochemically, increased urinary excretion of acidic glycosaminoglycans was confirmed and chondroitin 4-sulfate and chondroitin 6-sulfate were substantiated to be the major components of the acid mucopolysacchariduria. Light microscopically, variable numbers of foam cells were observed in the biopsy materials of the lymph nodes, liver and skin, as well as in the smears of bone marrow aspirates. In the liver, the parenchymal cells appeared vacuolated. Histochemically, accumulation of sulfated acid glycosaminoglycans was demonstrated in the cytoplasm of the foam cells proliferating in these tissues, as well as in the liver cells. Electron microscopically, all of these storage cells were found to contain numerous, membrane-bound, vacuolar inclusions filled with flocculent, finely reticulogranular materials of low electron density similar to those seen in the storage cells of Hurler, Hunter or Sanfilippo's syndrome. Empty vacuoles were often coexistent. Accordingly, this case should be termed "chondroitin 4- and 6-sulfate mucopolysaccharidosis", with emphasis on the possibility of a new type of genetic mucopolysaccharidosis.


Pilot study on the growth inhibition by estramustine phosphate (Estracyt) of rat mammary tumours sensitive and insensitive of oestrogen. Rat mammary tumours induced by 7,12-dimethylbenz(a)anthracene had a higher concentration of 3H and 14C than muscle after injection of estramustine phosphate labelled with 3H in the oestrogen moiety and 14C in the alkylating moiety. Thin-layer chromatography showed that dephosphorylated estramustine phosphate was present in the tumours but no free oestradiol-17beta. The uptake of the drug in the tumours was parallelled by a dose dependant retardation of tumour growth and a prevention of tumour number increase. Estramustine phosphate also retarded growth of mammary tumours resistant to treatment with oestradiol-17 beta. It is concluded that estramustine phosphate has a greater effect on tumour growth than oestrogen.


Carbon disulphide induced activation of liver UDP glucuronosyltransferase in rats pretreated with phenobarbitone. Carbon disulphide (CS2) exposure has been shown to activate the UDP glucuronosyltransferase of liver microsomes in rats pretreated with phenobarbitone. Now the nature of CS2 induced activation of the enzymes has been studied further. Phenobarbitone pretreated rats were exposed to 0.15% CS2 for 2 hrs on two successive days. The activity of UDP glucuronosyltransferase was measured from the liver microsomes after the enzymes was activated by incubation of the microsomes with various concentrations of the detergents Triton X-100, digitonin and cetylpyridinium chloride. The exposed animals showed an increased enzyme activity at all applied concentrations of the detergents; therefore in addition to membrane destruction by CS2 exposure, some other mechanism must also be involved in the CS2 induced activation of liver microsomal UDP glucuronosyltransferase. The changes in membrane lipid-protein interactions with l-anilino-8-naphthalene sulphonate (ANS) were also probed. The CS2 exposed animals had more high-affinity binding sites for ANS in their liver microsomal membranes, and in addition the quantum yield of ANS fluorescence was enhanced by CS2. The changes differed from those found after carbon tetrachloride exposure and suggest that, even if the two drugs have some common effects on microsomes, e.g. UDP glucuronosyltransferase activation, P-450 destruction and lipid peroxidation induction, the changes they cause in the microsomal micro-environment differ.


Delayed hypersensitivity to tuberculin in rats: effects of antirheumatic drugs. The effects of different antirheumatic drugs administered according to various dosing regimes on tuberculin hypersensitivity in rats have been assessed quantitating the changes of exudate volume and mononuclear cells immigration at the site of challenge. Dosing at the time of sensitization with aurothiomalate and D-penicillamine enhanced the cell immigration which was decreased by similar treatment with levamisole. Cyclophosphamide increased the exudate formation. Indomethacin had no effect. Dosing at the time of challenge caused a marked reduction of both the parameters by aurothiomalate and cyclophosphamide and enhancement by levamisole. D-penicillamine increased only the cellular immigration and indomethacin the exudate formation. Long treatment with aurothiomalate and cyclophosphamide suppressed the responses. Similar treatment with D-penicillamine and levamisole produced a significant enhancement. Indomethacin had no effect. The relevance of these findings to the testing and mode of action of antirheumatic drugs is discussed.