Lack of mutagenicity of vinyl chloride in two strains of Neurospora crassa. No detectable induction of mutations could be found in two strains of Neurospora crassa after their conidia were treated with vinyl chloride, in ethanol solution and in its gaseous form. The results suggest that although N. crassa seems to lativating systems does not increase mutagenic activity of vinyl chloride in the two strains tested. At the same time these strains were mutated easily by UV and methyl methanesulfonate.


Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex. In an attempt to map the gene (or genes) controlling the synthesis fo the fourth component of complement (C4), we performed linkage studies in a family with hereditary C4 deficiency. The proband, a seven-year-old boy with lupus erythematosus, consistently lacked deteftable serum C4 by both functional and protein measurements. The complement defect was transmitted as an autosomal recessive disorder. Eight of 15 family members were considered to be heterozygotes, seven because of low C4 levels and one because of genetic data (obligate heterozygote). The gene (or genes) coding for C4 deficiency appeared to be linked to the major histocompatibility complex (A2,B12,DW2 on the maternal side and A2,BW15,LD108 on the paternal side) and to other markers known to be in close proximity to the histocompatibility complex on chromosome 6 (phosphoglucomutase-3, glyoxalase-1 and properdin factor B).


Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide. The effect of 6-aminonicotinamide (6-AN) on putative amino acid neurotransmitters, namely glutamate, GABA and aspartate was studied on brains of rats treated with this antimetabolite (35 mg/kg i.p.). After 6-AN application the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glucose, glucose 6-phosphate, fructose, glutamate, GABA, aspartate, ammonia, and 6-phosphogluconate. The alterations in the cerebral energy metabolism were found as reported in the literature (increased levels of glucose, glucose 6-phosphate, decreased levels of lactate and pyruvate) and could be interpreted as the result of a reduced glycolytic flux rate. After a prolonged period of 6-AN pretreatment (16-30 h) the GABA and glutamate concentrations were significantly reduced, whereas the level of aspartate remained unchanged. From the result presented the two following conclusions may be drawn: a) The changes in the concentration of neurotransmitters as GABA and glutamate could be responsible for some neurological symptoms produced by 6-AN. b) As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.


Glycolysis and glycogen metabolism after inhibition of hexose monophosphate pathway in C6-GLIAL cells. 1. 6-Aminonicotinamide (0.01 mg/ml) leads to a strong accumulation of 6-PG in C6 glial cells after 24h. 2. The accumulated 6-PG is dephosphorylated to gluconate which easily permeates the cell membrane. Extracellular gluconate is formed at a rate of 12% of the total glucose consumption. 3. 6-PG as competitive inhibitor of the PG1 caused a reduction of the glycolytic flux of about 40%. 4. The reduced glycolytic flux lowers the ATP concentration under anaerobic conditions to 75% of the controls. 5. The glycogen content after 6-AN is increased by 50%, probably by the activation of the glycogen synthetase due to the higher Glc 6-P concentration. 6. The fibroblast-like morphology of the C6 cell line has typically changed under 6-aminonicotinamide.


Differential effects of harmaline and ouabain on intestinal sodium, phenylalanine and beta-methyl-glucoside transport. Harmaline inhibits both the Na+ -K+ -ATPase activity and the uptake of L-phenylalanine in guinea-pig intestinal mucosa. The latter effect is not a direct consequence of the former, since higher concentrations are needed to inhibit the enzyme than the influx into the mucosa; Furthermore the uptake is still sensitive to harmaline when the Na+ -K+ -ATPase has been fully inhibited by ouabain. Harmaline can inhibit L-phenylalanine influx at a concentration at which it does not affect intracellular ion concentrations. Ouabain, however, inhibits the uptake of L-phenylalanine only after a 30 min preincubation period, when the intracellular sodium concentration reached the extracellular level. Harmaline also interferes with the influx of beta-methyl-D-glucoside in the mucosa of the dog colon. Addition of harmaline at the mucosal face of the tissue suppresses all net transport of sodium and chloride ions and L-phenylalanine across the mucosa. Thus the same mode of action appears to apply in both the guinea-pig ileum and the dog colon.


Exploration of affective illness.

Exploration of affective illness. This report deals with a series of experimental approaches carried out in clinical studies to attempt to examine the role of amines in relationship to affective state and the mode of action of thymoleptic agents. Attempts have been made to examine enzymes, amines and other metabolites in biological fluids to assess the role of catecholamines and indoleamines in these disorders. Synthesis inhibitors were employed in studies where antidepressant drug-induced remission was initiated and the effect of two inhibitors was assessed on the clinical state. The results are presented and discussed in regard to the significance of the role of serotonin in depressive states and the action of thymoleptic agents.


Long-term treatment of juvenile Huntington's chorea with dipropylacetic acid. Since the proposed mode of action of dipropylacetic acid, an anticonvulsant, is to increase central nervous system gamma-aminobutyric acid levels, we used this agent to treat identical twins with juvenile Huntington's chorea. Their clinical status did not improve immediately after they received dipropylacetic acid. Furthermore, long-term administration (over a year) of high doses of the agent (up to 2,400 mg per day; 92 mg per kilogram per day) did not seem to alter the slow progression of their disease. Prior to treatment with dipropylacetic acid, the twins had normal cerebrospinal fluid gamma-aminobutyric acid levels. In addition, cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid were determined before and after 18 hours of high-dose probenecid. The former showed a normal threefold to fourfold increase after probenecid administration, but homovanillic acid had a distinctly subnormal turnover after probenecid, with only a threefold rather than the normal tenfold increase.


Risks of laparoscopic fulguration and transection of the fallopian tube. The more common methods of laparoscopic sterilization involve transection of the fallopian tubes. There are, however, a number of cases accumulating in which coagulation without transection has been employed. The risks of bleeding requiring the use of laparotomy are considerably reduced with this technic. There is no increased risk of electrical injury. The pregnancy rate is essentially the same in both methods. It is suggested that failures with tubal transection may be secondary to fistula formation and an inherent problem, whereas the failures with coagulation without transection are secondary to inadequate coagulation and are therefore more easily prevented.


A new skin protecting ointment against acrylic resins. In order to protect the hands of dentists, dental technicians and dental nurses from direct contacts with acrylic monomer, a new type of protective monoglyceride containing ointment has been introduced. The monoglyceride-based ointment was found to prevent penetration of the monomeric part of an autopolymerising acrylic resin and was also shown to have significantly smaller decreasing influence on the ability to manipulate instruments and materials than a compared silicone-based ointment. Furthermore, even with addition of 1% by volume of the monoglyceride-based ointment there was no marked influence on the mechanical properties (elastic modulous and ultimate tensile strength) of an investigated acrylic tray material.


[Plasminogen determination, using a chromogenic tripeptidic substrate (author's transl)]. A simple, rapid and sensitive spectrophotometric method for the evaluation of plasminogen level is presented. After activation of plasminogen by streptokinase, plasmin is determined using its amidasic action on a tripeptidic substrate bound with paranitroanlin.


Biochemical studies on dacron arterial prostheses. Dacron arterial prostheses, treated or not with biopolymers (gelatin, glycosaminoglycans) were implanted in the abdominal aorta of dogs and the connective tissue synthetised inside and outside the prosthesis was studied. After 3 and 9 months of implantation the prosthesis, a joining portion and a piece of aorta were excised and put in organ culture with 14C-lysine for 3 days. Representative macromolecular extracts were then obtained by a  "chemical dissection" procedure. The radioactivity and the chemical composition of these extracts was studied. The DNA content of the prosthesis was higher than that of the adjacent aorta showing a dense cellular repopulation of the prosthesis. This was confirmed by histology also which revealed the presence of a newly formed limiting elastic membrane and the presence of numerous elastic fibrils. Collagen, elastin and glycosaminoglycans could be detected in the macromolecular extracts showing that the cells which repopulated the prosthesis expressed a complete biosynthetic capacity as far as matrix macromolecules are concerned. The distribution of proteins in the extracts was as follows: 4% of total proteins were extracted in a 1M CaCl2-buffer 80% of total proteins in the collagenase extracts, 10% in the 6M urea extract. Only 0,2% of proteins were in the final elastase extract, 10 times less than in the joining aorta fragment. The proportion of the other proteins was similar in aorta and in the prosthesis as well as the chemical composition (hexosamine and hydroxyproline content) of the extracts. The proportion of collagenase-extractable proteins decreased with the time of implantation (from 3 to 9 months) and the proportion of urea-extractable proteins increased. This type of modification is similar to that found in aging aorta wall. 14C-lysine was actively incorporated in all macromolecular fractions studied. The incorporation pattern of the prothesis tissue was similar to that found for the joining host aorta, showing a similar regulatory tendency for matrix macromolecules. It appears therefore that a valid hemocompatible vascular type of connective tissue can be synthesised on the dacron arterial prosthesis and nature of this connective tissue can be influenced by previous biopolymer treatment of the synthetic prosthesis. The described procedure (incorporation of labelled precursors in organ culture) appears to be a valid method for the exploration of the regulatory processes underlying the synthetic capacity for matrix macromolecules of the newly formed tissue in the synthetic prosthesis.


Developmental transformational capacity of children with Down's syndrome. This study examined the generative-transformational capacities of two groups of children with Down's Syndrome with mean mental ages of 3,6 yr. and 4,6 yr. respectively. A sentence repetition task was used to assess their knowledge of selected transformational sentence types (simple-active-affirmative-declarative, question, negative, passive and negative-passive). There were significant effects of groups and sentence types but a nonsignificant interaction of groups X sentence types. These results were taken as support for Lenneberg's "slow motion" hypothesis of language development in mentally retarded children. Children with Down's Syndrome appear to follow the same patterns of grammatical acquisition as normal children but at a reduced rate associated with the severity of their retardation.


[Megakaryocytes and platelets in congenital thrombopathies]. Different HT have been studied with the electron microscope and the findings compared to those in the literature. Five patients with thrombasthenia and three with Willebrand's diseases showed various disorders, usually anisocytosis and hypertrophic open canalicular system, in relation to regenerative states. Thirteen young children with 21-trisomy (2 with leukemia) and 13/15 trisomy (1 case) had enlarged platelets with abnormalities of membranes and vacuoles indicating some metabolic disorders and necrotic lesions. One child with Cooley's anemia showed a few granules and necrotic lesions. All these symptoms were related to regenerative or primitive megakaryocytopathias. The lesion of these latter cell appears in other HT: aberrations of membranes in giant platelets syndroms (J. Bernard and J. P. Soulier syndrome), disorders in membranes and/or granules in thrombopenic thrombopathias, the short platelet life span in May-Hegglin anomaly, storage pool disease in Hermansky-Pudlak syndrome. Finally the ultrastructural abnormalities of the platelets mainly help to distinguish several diseases of megakaryocytes.


Preventive cardiology. What should the clinician be doing about it? Candidates for a major cardiovascular event can be identified by ordinary office procedures and simple laboratory tests, and the degree of risk estimated. There are compelling reasons to believe that much is to be gained by lowering risk through preventive measures advocated for atherosclerotic cardiovascular disease.


The influence of serotonergic agents on the body temperature. The effects of serotonin precursors, tryptophan (TP) and L-5-hydroxytryptophan (5-HTP), administered together with peripheral decarboxylase inhibitor -- Ro 4-4602 on the rectal body temperature of rats was studied. TP caused a significant hypothermia which was prevented by pretreatment with p-chlorophenylalanine (PCPA), the serotonin synthesis inhibitor. 5-HTP did not influence the body temperature or slightly decreased it. However, the significant hypothermizing effect of 5-HTP was observed in rats pretreated with spiroperidol, haloperidol or phenoxybenzamine. Methysergide or cyproheptadine -- compounds regarded as potent serotonin receptor blockers -- did not prevent the TP-induced hypothermia. In methysergide pretreated rats 5-HTP produced a considerable hyperthermia. Cyproheptadine did not influence the effects of 5-HTP on the body temperature. The results obtained suggest that cyproheptadine and methysergide fail to block those central serotonin receptors which produce hypothermia after their stimulation.


Effects of drugs influencing serotonergic mechanisms on behaviour of insects. The present paper deals with effects of some drugs affecting brain serotonergic mechanism on behaviour in cockroach (Periplaneta americana) and immature form (larvae) of ant lion (Myrmeleon formicarius). The effects of para-chlorophenylalanine, LSD-25 and 5-HTP on simple learning mechanisms in cockroach and on behaviour of ant lion (building the funnel-shape traps) were studied. Both p-chlorophenylalanine and LSD-25 facilitated behaviour of insects whilst 5-HTP delayed responses. Our experiments indicate that serotonin may play an inhibitory role upon behavioural processes in some invertebrates.


A mechanism of duplex DNA replication revealed by enzymatic studies of phage phi X174: catalytic strand separation in advance of replication. The enzyme system for duplicating the duplex, circular DNA of phage phi X174 (replicative form) in stage II of the replicative life cycle was shown to proceed in two steps: synthesis of the viral (+) strand ]stage II(+)], followed by synthesis of the complementary (-) strand ]stage II(-)] [Eisenberg et al. (1976) Proc. Natl. Acad. Sci. USA 73, 3151-3155]. Novel features of the mechanism of the stage II(+) reaction have now been observed. The product, synthesized in extensive net quantities, is a covalently closed, circular, single-stranded DNA. The supercoiled replicative form I template and three of the four required proteins--the phage-induced cistron A protein (cis A), the host rep protein (rep), and the DNA polymerase III holoenzyme (holoenzyme)--act catalytically; the Escherichia coli DNA unwinding (or binding) protein binds the product stoichiometrically. In a reaction uncoupled from replication, cis A, rep, DNA binding protein, ATP, and Mg2+ separate the supercoiled replicative form I into its component single strands coated with DNA binding protein. In the presence of Mg2+, cis A, nicks the replicative form I; rep, ATP, and Mg2+ achieve strand separation with a concurrent cleavage of ATP and binding of DNA binding protein to the single strands. rep exhibits a single-stranded DNA-dependent ATPase activity. These observations suggest that the rep enzymatically melts the duplex at the replicating fork, using energy provided by ATP; this mechanism may apply to the replication of the E. coli chromosome as well.


Isolation and characterization of muscle membranes using surface-specific labels. Membranes were purified from rat muscle by a differential centrifugation method that avoids the use of salt extraction or incubations at elevated temperature. Three populations of membrane-limited vesicles were defined having average densities of 1.112 (fraction I), 1.141 (fraction II), and 1.158 (fraction III) g/ml in a continuous sucrose gradient. Lactoperoxidase-catalyzed iodination of intact muscle prior to isolation of membranes resulted in highest specific activity in fraction I, although all fractions could be equally labeled after isolation. 125I-Labeled wheat germ agglutinin incubated at low concentration with intact muscle preferentially labeled fraction I. Parallel studies on previously isolated fractions indicated that fraction I also contained the highest concentration of potential receptors for wheat germ agglutinin. In experiments on whole muscle, concanavalin A bound predominantly to sarcolemma with slight variable binding to T-tubular and nuclear membrane but no binding to sarcoplasmic reticulum or mitochondria. Parallel binding studies with isolated membrane fragments indicated heavy binding of concanavalin A by membranes in fraction I with scattered binding in fractions II and III. Na+K+Mg2+ ATPase was specifically enriched in fraction I but was also present in fraction II in a proportion similar to 125I labeling. Ca2+ ATPase was most active in fraction II but present in significant levels in fraction I. It is concluded from these and other data that fraction I contains predominantly sarcolemma membrane, while T-tubular membrane may represent a significant component of fraction II. Ca2+ ATPase activity in fraction I is intrinsic to the sarcolemma.


Effects of TRH on the central nervous system of the rabbit. Thyrotropin releasing hormone (TRH) administered intraventricularly to rabbits produces tachypnea, hyperthermia, behavioral excitation and, with larger doses, compulsive scratching. These effects of TRH were unaffected by various catecholamine and serotonin antagonists or depleting agents. When TRH was administered to pentobarbital-narcotized animals, tachypnea and rapid recovery of the righting reflex occurred. The antagonism of narcosis or sedation was evident against other barbiturates, diazepam, chlorpromazine, and reserpine, but not against morphine. Morphine actually appeared to antagonize the excitatory actions of TRH. Scopolamine pretreatment prevented the arousal from pentobarbital narcosis, but not the tachypnea or hyperthermia. TRH represents a new class of psychoactive chemical which may play a role in brain function.


The family in physical therapy.

The family in physical therapy. Family Focus is a training program implemented by the Division of Physical Therapy at Stanford University in cooperation with the Mental Research Institute of Palo Alto, California. Through this program, inpatients at the Stanford University Hospital and their families have the opportunity to live in a modular home on the hospital grounds prior to discharge and receive training in the activities they will need to carry out at home. Psychologists consult with the physical therapists on ways to help the family cope with stressful situations. The advantages of including the entire family in health care planning and treatment are described and suggestions are made for applying the principles in any physical therapy setting.


Comparative temperature dependence of (Na+ + K+)-ATPase. The temperature dependence of (Na+ + K+)-ATPase was measured, utilizing preparations of enzyme from heat and kidney of rats, hamsters, guinea pigs, ground squirrels, turtles, chickens, and ducks. The two hibernating species, hamsters and ground squirrels, were studied awake at normothermia and hibernating at 4 degrees C. The results for every species except the turtles showed the same temperature dependence established for (Na++K+)-ATPase from rabbit kidney with a quasi-linear dependence above 15 degrees C and little or no activity below 15 degrees C. Turtle enzymes showed a broad activity versus temperature curve with a fall-off at high and low temperatures. The data in all cases, including the turtle data, may be fitted by a previously described thermodynamic kinetic model. Further, the model will fith the turnover or decrease in enzyme activity at higher temperatures observed in a number of cases. These results do not support the widely imputed ion pumping role for (Na++K+)-ATPase.


A comparison of the central actions of prostaglandins A1, E1, E2, F1alpha, and F2alpha in the rat. II. The effect of intraventricular prostaglandins on the action of some drugs and on the level and turnover of biogenic amines in the rat brain. Prostaglandins (PGs) injected into the right lateral brain ventricle (i.v.c.) of the rat increased the sleeping time induced by hexobarbital, chloral hydrate, and ethanol. PGE1 and PGE2 intensified chlorpromazine-induced catalepsy, inhibited amphetamine hyperactivity, and significantly depressed the amphetamine-induced stereotypy. NA concentrations were decreased by PGE1 and PGE2 and were increased by PGF2alpha. PGF2alpha increased both 5-HT and 5-HIAA levels in rat brain. "Total" ACh concentrations were increased by PGF1alpha and PGF2alpha. PGE1, PGE2, and PGF2alpha enhanced the turnover of NA, DA, and 5-HT. PGE2 counteracted the decreased activity induced by alpha-MT and abolished the hypothermic action of alpha-MT. PGF2alpha had little effect on the activity of PCPA pretreated rats, whereas the higher doses of PGF2alpha increased body temperature in these animals.


[2 cases of arthrogryposis].

[2 cases of arthrogryposis]. The authors report two cases of arthrogryposis in two children of 7 1/2 and 13 years; the diagnostic criteria were those of Fisher, combining the joint limitations present since birth in at least two different regions, the absence of progressive neurological involvement, and evident amyotrophy. The different etiopathogenic theories are then discussed: review of the literature concerning cases of myopathic arthrogryposis is not very useful; the twelve cases mentioned in the literature are not homogenous, the histopathological findings were very variable, and the histoenzymological studies have been insufficient. The combination of neurological anomalies with arthrogryposis is undeniable (cerebral atrophy, depopulation of the anterior cornu, anterior radicular changes). They are not always present, however, and are insufficient to explain the symptoms. Consideration should be given to the question of whether the importance of the changes in the connective tissue are not underestimated: the proliferation of the connective tissue is, in fact, most of the time, the essential feature to be seen in a histological section. In connection with this "connective theory" it is important to recall the work of Ionasescu et al. (1970) who demonstrated in vitro the excessive synthesis of connective proteins in the muscles of patients with arthrogryposis.


[Echocardiography in hypertrophic obstructive cardiomyopathy]. The echocardiographic anomalies seen in 16 patients with proven hypertrophic obstructive cardiomyopathy (HOCM) are described. With use of a standardized technique and critical evaluation of the individual signs, echocardiography provides a simple and accurate means of confirming the diagnosis of HOCM, following the course and evaluating therapy.


[Effects of propranolol on pulmonary hypertension, right ventricular hypertrophy and metabolic myocardial changes due to acute hypoxemia due to high altitude]. In rats, a 3-day stay at an altitude of 3454 m (paO2 approximately 55 mm Hg) provokes a 50% increase in pulmonary pressure and a 20% increase in right ventricular weight, edema of both ventricles, particularly the right, and marked alterations in energy metabolism. Propranolol (4 mg/kg/day), administered 1 day before the transfer to high altitude and during the days of stay, prevents the increase in pulmonary pressure and in right ventricular weight and decreases myocardial edema, but has no effect on the metabolic alterations.


[Clinical course of congestive cardiomyopathy]. In 30 patients with the clinical, hemodynamic and angiographic findings of congestive cardiomyopathy, physical working capacity (PWC) and left ventricular (LV) ejection phase indexes at rest (EI), assessed by LV ejection fraction, enddiastolic volume, and mean rate of circumferential fiber shortening were determined. Based on PWC and EI, the following 3 functional groups were obtained: group 1 (n = 6) with normal PWC and borderline EI (subclinical congestive cardiomyopathy), group 2 (n = 10) with normal PWC and decreased EI, and group 3 (n = 14) with reduced PWC and severely depressed EI. The clinical course was followed for 24 months. In group 1 the functional state remained unchanged in all 6 patients. In group 2, 3 patients, changed to functional group 3 and 2 died during the observation period. In group 3, 3 patients improved and changed to functional group 2, 5 remained unchanged and 6 died after an observation period of 16 months. It is concluded (1) that PWC in congestive cardiomyopathy may be preserved despite depressed LV function, and (2) that the functional classification has important prognostic implications, in view of the fact that annual mortality in group 1 was 0%, in group 2 7% and in group 3 32%.


[The Sézary syndrome].

[The Sézary syndrome]. A case of the rare Sézary syndrome is described. The Sézary syndrome is a lymphoproliferative disorder of the skin, the lymph nodes, and to a smaller extent the bone marrow, which begins with erythrodermia. In the blood, strange circulating lymphocytes with a "cerebriform" chromatin structure and T-cell properties are found. The disease is primarly benign but may become malignant. The origin is unknown. Endogenic and exogenic factors are considered and relationships to other cutaneous lympho-proliferative diseases and treatment are discussed.


[Toxic reactions to gold salts with severe enterocolitis in a patient with rheumatoid arthritis]. A case of severe enterocolitis which occurred on initiation of chrysotherapy for rheumatoid arthritis is reported. The patient, a male aged 50 years, suffered from dramatic diarrhea for several weeks. Biopsy specimens from the stomach, ileum and colon revealed signs of inflammation. Later, general toxicodermia, mouth ulcers, blood eosinophilia and asymptomatic proteinuria were observed. After several months all the side effects disappeared. The toxicodermia was the most persistent.


[Kurschmann-Steinert myotonic dystrophia and Adams-Stoke attacks. Successful treatment of arrhythmia by means of pacemaker implantation]. The case is reported of a 39-year-old male with Steinert's dystrophia myotonica complicated by cardiac arrhythmias manifested by high-degree a-v block with Stokes-Adams attacks. Implantation of a demand-type cardiac pacemaker brought prompt relief from cardiac symptoms and the patient was able to resume work. The pathologico-anatomical findings in dystrophia myotonica are discussed, together with their possible connection with the type of arrhythmias described.


[Cardiac syncope].

[Cardiac syncope]. Clinical cases are presented on the general theme of cardiovascular syncope. A case is cited to illustrate the clinical picture of idiopathic hypertrophic obstructive cardiomyopathy, a frequently disguised and misinterpreted cause of syncope. Chief attention is focused on the concept of fascicular heart block causing syncope. In the light of 3 patients, the various possibilities with respect to etiology, evolution, clinical picture and prognosis of fascicular heart block are outlined. In this context the diagnostic, prognostic and therapeutic significance of His bundle electrocardiography is discussed. Finally, 2 cases are cited to illustrate the sick sinus syndrome as a major cause of syncope. The diagnostic procedure in patients with suspected lazy sinus node is discussed and the results are presented of 16 personally observed cases with this disorder.


[Clinical aspects and course of endomyocardial fibrosis]. In 6 women with the hemodynamic, angiographic and histological findings of endomyocardial fibrosis the clinical course was followed for 30 months. All six cases showed the typical partial obliteration of one (4 patients) or both (2 patients) heart chambers. Left ventricular pressure-volume relations elicited decreased distensibility of the left ventricle. The functional state in 2 patients with severe mitral insufficiency was improved following successful mitral valve replacement. One patient with left ventricular, and 2 patients with biventricular, obliteration were given drug therapy and in one case recompensation lasting 2 years was obtained. One patient with partial obliteration of the left ventricle and severe biventricular failure died after an observation period of 4 years. In summary it can be said that (1) endomyocardial fibrosis in Switzerland is observed mainly in females; (2) the clinical picture is dominated by severe congestive heart failure in which the heart size is only slightly enlarged; (3) systolic performance is normal or only moderately depressed despite severe restriction to filling and/or av-valve insufficiency; (4) partial obliteration of the right or left ventricle may be detected by echocardiography; (5) rheumatic fever may occasionally be the cause of endomyocardial fibrosis; (6) mitral valve replacement is accompanied by appreciable improvement in the patient's condition.


The assessment of peripheral vascular insufficiency with the doppler flowmeter. The author presents his experience of the Doppler ultrasound velocity meter in the repetitive serial assessment of patients presenting with chronic obliterative arterial disease. A close relationship between ankle pressure assessed by the Doppler apparatus and isotope muscle clearance studies was established. Pressure flow is directly related to the severity of the vascular occlusion. This fact has been applied in the study of 17 patients with varying degrees of vascular occlusion. The Doppler indices were measured at rest and after ischaemia or exercise. Constant reproducible patterns emerge reflecting gradations of peripheral vascular disorder. Doppler indices correlated well with the patients' exercise tolerance. Flow patterns were demonstrated by plotting the data. Unlike plethysmographic data obtained at rest, the Doppler index at rest was significant. The Doppler ultrasound velocity flowmeter is an effective method for the quantitative assessment during the follow-up of patients presenting with peripheral vascular disorders.


A pneumatic reduction device for gastroschisis and omphalocele. A new preformed pneumatic reduction device is available in two sizes, and it is recommended that a set be available for emergency use in any hospital which deals with the definitive emergency therapy of the newborn. The devices can be washed and flash sterilized as needed and, if properly cared for, can be reused repeatedly. The bag has facilitated the early care of newborns with omphalocele and gastroschisis and has allowed the rapid and effective reduction of eviscerated intestines. These bags can also be used for the controlled ventral hernias necessary in the treatment of infants born with large diaphragmatic hernias. It is hoped that the search for better techniques and materials will be continued, since the dramatic improvement in the survival rate of infants with gastroschisis and omphalocele has occurred not from a better understanding of the defects but by the application of improved techniques and materials in their treatment.


Use of Marlex mesh in acute loss of the abdominal wall due to infection. Closure of wounds of the abdomen with a minimal amount of foreign material is still the preferred method. However, in those instances in which loss of tissue is too great to effect closure or in which closure will place the suture line under tension, the use of a synthetic plastic mesh is an effective alternative. As described, the technique avoids the risks of further necrosis of the tissue, infection and dehiscence. In those instances of extensive loss of tissue, it is frequently the only practical method available to reconstruct the abdominal wall.


Immunological monitoring of long-surviving renal transplant recipients. In this study a variety of cell-mediated immunity responses were performed in long-term (2 to 12 year) human leukocyte antigen-A (HLA) nonidentical renal transplant patients. All patients showed mixed lymphocyte culture (MLC) stimulation against donor, indicating a lack of tolerance. Of successful long-term transplant patients, 73 percent showed high serum levels of MLC-blocking activity. A consistent association of successful long-term transplantation and a specific defect in recipient ability to generate cytotoxic cells against donor was seen at the 8 to 12 year level. A close association of lymphocyte-dependent activity (LDA) and clinical chronic rejection was found, and LDA could be identified prior to the onset of clinical chronic rejection in most cases. Four patients had a positive LDA assay prior to transplant and all four went on to develop chronic rejection. Recipients taking immunosuppressive drugs within 24 hours of testing had a deficient capability to generate cytotoxic effector cells against indifferent individuals. These findings demonstrate a consistent association of in vitro cell-mediated immunity parameters and in vivo transplant function and may represent a valuable immunological monitoring system for long-term recipient follow-up.


A clinicopathological study of fatal chronic airways obstruction. A clinicopathological study of 21 patients who died as a result of chronic airways obstruction was carried out. Thirteen patients had been in right ventricular failure for at least one year before death and the other eight patients did not have right ventricular failure. The patients with long-standing right ventricular failure died at a younger age, on average, than those without failure. There were no significant quantitative differences between the two groups in the length of history of chest disease, blood gas estimations, respiratory function tests or degree of polycythaemia. The group with right ventricular failure had significantly larger mean right and left ventricular weights than the group without failure, but there were no significant differences in amounts of emphysema, size of bronchial mucous glands, proportion of small airways lumen in the lung or number of thick-walled peripheral lung vessels between the two groups. The findings did not support the division of this series of patients, with fatal chronic airways obstruction, into two distinct groups broadly defined as 'emphysematous' and 'bronchitic', either clinically or pathologically. A history of right ventricular failure correlated well with the finding of right ventricular hypertrophy at necropsy. Electrocardiographic evidence of right ventricular hypertrophy was found to correspond with the size of the right ventricle at necropsy in 66% of cases. The radiographic diagnosis of emphysema proved an accurate assessment when compared to the necropsy findings, and radiographic estimations of right ventricular enlargement were  accurate in 65% of cases. Histological evidence of acute bronchitis was present in 20 of the 21 patients (95%), and five patients showed histological evidence of minor pulmonary thromboembolism. Ten patients in the series showed an increase in the weight of the left ventricular as well as the right ventricle.


Simultaneous ultramicroanalysis of both 17-keto-and 17beta-hydroxy androgens in biological fluids. Sensitive methods for quantifying androgens were lacking. Therefore, a relatively simple procedure for separating steroids was combined with highly specific assay methods so that eight androgens could be measured with high accuracy, precision and sensitivity. Semi-automated separations on Sephadex LH-20 columns used heptane:methylene chloride:ethanol:water (50:50:1:0.12) and a flow rate of 17.0 min/ml. The six peaks eluted contained androstenedine; androsterone, epiandrosterone and dihydrotestosterone; testosterone and dehydroepiandrosterone; 3alpha-androstanediol; 3beta-androstanediol; and androstenediol. Androstenedione, dehydroepiandrosterone and androstenediol were quantified using specific antisera (sensitivity less than or equal to 75 pg). Testosterone and dihydrotestosterone were measured by competitive protein-binding assays using rabbit TeBG (sensitivity less than or equal to 150 pg). 3alpha- and 3beta-androstanediol were similarly assayed using human TeBG (sensitivity approximately 150 pg). Androsterone was reduced with NaBH4 and the resulting 3alpha-androstanediol was assayed using human TeBG (sensitivity approximately 200 pg). Inter- and intra-assay variations were less than 10% for radioimmunoassays and less than 16% for competitive protein-binding assays over the entire dose response curve.


Effect of infusion of gonadotropin releasing hormone upon plasma concentrations of sex hormones in prepubertal and pubertal males. Plasma testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17OHP), androstenedione (A), estradiol (E2), and dehydroepiandrosterone sulfate (DHAS) were measured by radioimmunoassay after celite chromatography prior to and after a 3-hour infusion of the synthetic gonadotropin releasing factor, GnRH, in normal prepubertal and pubertal boys. Plasma T levels rose (p less than 0.001) in the pubertal but not prepubertal boys. 17OHP concentrations increased in those boys who had an increment of T. A, DHT, E2 or DHAS levels did not increase after GnRH. Basal levels of T, DHT, A and DHAS correlated with the peak and mean serum LH levels attained during the GnRH infusion. These data confirm the greater Leydig cell responsivity to transient rises of endogenous gonadotropin in pubertal males and also suggest that there may be a relationship between adrenal androgen production and maturation of the hypothalamic-pituitary-gonadal system.


[The growth of the skull and its importance for the occlusal conditions in Down's disease]. The teleradiographs and study casts of 68 patients with Down's disease were compared with those of 102 students. Pseudoprognathism, cross-bite and open bite were strikingly more frequent in the patients with Down's disease than in the students. The success of orthodontic treatment is very uncertain in patients with Down's disease. Mandibular prognathism needs in most cases surgical treatment. An open bite will be improved only if the position of the tongue is changed. Improvement of a cross-bite may be achieved by early expansion of the maxillae. In certain cases, normalization is accomplished. It is possible to reach considerable inprovements in patients showing a few or no occlusal surfaces though normal conditions cannot be established.


Relative role of factors associated with cerebral infarction and cerebral hemorrhage. A matched pair case-control study. Comprehensive ascertainment of all possible new cases of stroke appearing between January 1, 1970 and June 30, 1971, and admitted to three major hospitals in Winnipeg, Manitoba, has been achieved by reviewing the Manitoba Health Services Commission claim reports. The medical records of these cases were reviewed, pertinent data were abstracted, and rigid criteria for diagnosis were followed. Also, data were obtained from death certificates, autopsy reports and long-term hospital records. A total of 606 ascertained cases (410 infarction, 137 hemorrhage, and 59 undetermined type) were matched for age, sex, residence and year of admission with 606 controls from admissions for other than cardiovascular and cerebrovascular disorders. The data were analyzed for elucidating the possible risk factors for infarction (INF) and hemorrhage (HGE). The findings suggested that hypertension was the main risk factor in hemorrhage, whereas in infarction, along with hypertension, other factors such as diabetes, heart enlargement in chest x-ray, ECG abnormalities, and smoking were suggested as risk factors. There was an association also between infarction, on one hand, and the history of receiving anticoagulants, diuretics, and medications for the heart, and the occurrence of myocardial infarction, on the other hand. These features indicate that infarction and ischemic heart disease have similar risk factors. Hemoglobin and hematocrit were higher in infarction cases than in their controls only when measured at stroke admission. No difference was revealed when they were measured prior to stroke. Their association with infraction therefore may be secondary to other factors and of no significance for its risk.


Freezing of canine lymphocytes for use in mixed leukocyte culture and cell-mediated lympholysis tests. A satisfactory and reproducible technique of cryopreservation of canine lymphocytes for use in mixed leukocyte culture (MLC) and cell-mediated lympholysis tests has been developed. Dimethyl sulfoxide was used as the cryopreservation agent. Cells were frozen to -50 C at a controlled rate (-1 C/min) and stored at -169 C. The best preservation was obtained with a concentration of 10 x 10(6) lymphocytes/ml in Waymouth's MB-752/1 medium supplemented with 30% dog serum (MB-30). Before use in MLC or cell-mediated lympholysis tests, lymphocytes were rapidly thawed at 40 C and then rapidly diluted with MB-30 at room temperature. For best responses in MLC, one fresh component (either stimulating or stimulated cells or serum) was needed. The magnitudes of responses of frozen lymphocytes to phytohemagglutinin or in MLC were similar to those seen with fresh cells, but peak responses occurred usually 24 hr after those seen with fresh cells.


Induction of splenomegaly with stimulated leukocyte culture supernatants. Cell-free medium from stimulated murine leukocyte cultures induced spleen enlargement in vitro. Splenomegaly was measured by [3H]leucine incorporation of spleen fragments in tissue culture. Stimulatory cell-free medium were induced in leukocyte cultures with allogeneic or phytohemagglutinin stimulation. Supernatant activity has lymphokine properties, i.e., cell-free soluble factor(s), generated during specific lymphocyte activation, but which are expressed without reference to H-2 specificity.


Mixed heart cell-lymphocyte reactions and graft survivals in Ag-B-compatible rats. A method of dissociation of the rat heart cell for the mixed lymphocyte culture purpose is described. The treatment of the young rat heart with 0.1% collagenase-hyaluronidase solution yielded satisfactory heart cell suspension. The hear cells, thus obtained after mitomycin C treatment but not irradiation, stimulated allogeneic lymphocytes in the presence of 2-mercaptoethanol. In the Fischer to Lewis combination compatible at the Ag-B locus, strong reactions of Lewis lymphocytes to the dissociated heart and skin cells of the Fischer rat were related to the acute rejection of heart and skin grafts, while negative reactions by the kidney and spleen cells reflected a prolonged survival of the kidney graft. The role of skin- and hear-specific antigens in the rejection phenomenon is discussed.


Inhibition of the mixed leucocyte reaction by histocompatibility antibodies requires the Fc part. We have examined the effect in mixed leucocyte culture (MLC) with rat cells of the IgG fraction of alloantibodies against the major histocompatibility complex (anti-BN major) and against some of the minor histocompatibility antigens. Anti-BN major specifically inhibited the MLC response, both when BN cells were responding and stimulating cells. Absorption with BN erythrocytes completely removed the haemagglutinating antibodies but had no effect of MLC inhibition, while absorption with BN lymphocytes removed MLC inhibition as well as haemagglutinating antibodies. The F(ab')2 fragments of anti-BN major did not inhibit MLC, although they still had the capacity to combine specifically with BN lymphocytes. We therefore suggest that the inhibition of MLC responses by alloantibodies is either because of a cytotoxic effect (even if cytotoxicity could not be demonstrated in unmixed cultures) or a blocking of antibody-coated lymphocytes by Fc receptor-bearing cells. Antibodies against minor histocompatibility antigens did not inhibit MLC.


Humoral immunity in kidney transplant recipients. Sera obtained from kidney transplant recipients at various times after the graft were investigated for the presence of cytotoxic antibodies to B and T human lymphoid cells and for their ability to inhibit mixed lymphocyte reaction between allogeneic lymphocytes. More than 50% of sera from 35 such patients contained cytotoxic antibodies to B lymphocytes and 27 of 33 sera blocked and miced lymphocyte reaction by 25 to 75%. A statistically significant association between the presence of cytotoxic antibodies to B cells and the ability to block the mixed lymphocyte reaction was found in the group of patients with functioning grafts. However, the presence of cytotoxic antibodies to B lymphocytes did not correlate with the outcome of the graft.


In vitro correlates of rejection. II. Rat mixed lymphocyte reactivity in vitro and cardiac allograft acute rejection, hyperacute or accelerated rejection, and prolongation by active immunization. The relationship of F1 hybrid to parental strain cardiac allograft rejection rates to mixed lymphocyte reactivity in vitro has been studied in 10 strain combinations crossing the major histocompatibility barrier in three different models of acute rejection, accelerated or hyperacute rejection after skin graft immunization, and attempted active enhancement using 10(7) donor strain bone marrow cells. Although high and low reactivity could be discerned between the F1 hybrid and reciprocal parental strain in three of five instances in the one-way lymphocyte culturr reaction, low reactivity was only associated with prolonged graft survival in one combination. Two strain combinations giving high in vitro lymphocyte responses were associated with easily enhanced grafts. The BN strains was a low responder in vitro in the three combinations tested and as a recipient strain, allografts could not be actively enhanced. After skin graft presensitization, BN recipients rejected grafts hyperacutely in two of three combinations and with a median survival time of 2 days in the third combination. The association of poor in vitro proliferative responses, the inability to induce enhancement, and rapid graft rejection after skin graft presensitization could be related to genetic mechanisms controlling the amount and class or subclass of antibody or to the generation of suppressor cells and remains to be determined.


[Changes in the ATP-ase activity of skeletal muscle nuclei of rabbits with dystrophy and following their delipidation]. The level of the ATPase activity in the skeletal muscles nuclei with experimental muscular dystrophy and the sensitivity to bivalent (Mg2+, Ca2+) and univalent (Na+, K+) cations under conditions of delipidation were studied. It is established that among ATPases of the young rabbit skeletal muscles nuclei there is ATPase sensitive to monovalent cations: the presence of Na+ or K+ produces a 45% increase in its activity in some experiments as compared to the initial level. This activation is attributed to Mg2+, Ca2+-ATPase the action of which is not realized in the presence of EGTA-chelator of calcium ions. A decrease in the total ATPase activity in the skeletal muscles nuclei resulted from the experimental muscular dystrophy development occurs due to a decrease in the Mg2+, Ca2+-ATPase activity as the ability for activation by the monovalent cations is practically lost under these conditions. Delipidation of the skeletal muscles nuclei, which results in their loss of some phospholipids and cholesterin, is accompanied by the ATPase activity decrease. At the same time the nuclei ATPase activity lose its ability to activate by monovalent cations: Na+, K+. A conclusion is made that during delipidation the decrease in the total ATPase activity is due to a decrease in the activity of its Mg2+, Ca2+-part.


[Isolation of Na+, K+-ATP-ase].

[Isolation of Na+, K+-ATP-ase]. The data are discussed on the isolation of Na+, K+-ATPase from the membrane structures of a cell at functionally active state. The isolation of the membrane enzymes, particularly multicomponent enzymic systems, which might include Na+, K+-ATPase, is a rather complex task as their components are ordered in the membrane in a certain way. The disturbance of this ordering that is essentially maintained by membrane phospholipids, results in the inactivation of the enzymatic system. Different procedures are compared permitting the Na+, K+ATPase isolation and purification to be realized. It is noted that when realizing the Na+, K+-ATPase isolation and purification by means of a number of non-ionic detergents it is possible to obtain the "soluble" Na+, K+-ATPase preparations from the membrane structures, the preparations being a convenient initial material for the further purification of this enzymic system and its obtaining as a "functionally intact unit". The Na+, K+-ATPase isolation as a "functionally intact unit" would probably make an essential contribution to deciphering the molecular mechanism of the Na+ and K+ transport through biomembranes.


[Antitumoral activity of calusterone in advanced mammary carcinoma (author's transl)]. Thirty-one post-menopausal patients with advanced mammary carcinoma were treated with calusterone (7-beta, 17-alpha-dimethyl-testosterone), 200 mg daily per os for at least three months. Twenty-seven patients were avaluable. Eight patients (29%) had an objective response; two patients had a complete remission maintained for more than eighteen months by repeated three-month courses of therapy. In eight patients (29%), calusterone produced no objective response, without disease progression. The main side effects have been hirsutism, acne and gastro-intestinal distress; no libido modification was observed. Increased BSP retention was observed in one third of patients.


Thymolipoma simulating cardiomegaly.

Thymolipoma simulating cardiomegaly. A thymolipoma in an 8-year-old boy is reported. The tumour had appeared on a routine chest X-ray as a broadened heart shadow and a peculiar right heart contour. Cardiac hypertrophy was suspected primarily. At thoracotomy a thymic tumour was found.


[Organization and work experience of the endoscopy office in an emergency abdominal surgery clinic]. Within a five-year period in a special room intended for endoscopy 1934 investigations were performed, including 1318-on urgent indications. 77 esophago-gastroduodenoscopies were performed elsewhere-in the operating room, in the intensive care unit; 35 investigations were carried out under general anesthesia with the use of myorelaxants of a short effect. In 256 cases the neccesity of active infusion therapy and reanimation arose. In the paper, the authors' considerations concerning the need of organization, in large cities, of a mobile endoscopic team attached to the emergency medical aid are given with special reference to some features of the organization of endoscopy room in the clinic of emergency abdominal surgery.


[Surgical active laparoscopy and fibrocholedochoscopy in diagnosis and treatment of biliary tract diseases]. The authors have analysed the results of 120 laparoscopic cholecystographies and cholecystocholangiographies. In 48 patients laparoscopic cholecystocholangiography was terminated by laparoscopic cholecystostomy. This enabled the authors to eliminate jaundice in all 48-patients, while in 43 of them also to perform in later terms radical or palliative operation.


[Complex treatment of trophic leg ulcers]. During the recent 4 years, 135 patients (130 females and 5 males) with trophic persistent ulcers of the lower extremities, developed due to venous pathology, were treated conservatively. Eighty patients aged from 30 to 50 years, and only 55 patients were much older. The duration of the disease was from 6 months to 20 years. Ulcers were of different size from 3.2 to 180 cm2. The combined method of treatment of trophic ulcers enabled the authors to shorten twice the terms of the treatment as compared with other methods. The positive effect was gained in 89.6% of cases, in 59 patients (43.7%) complete healing of ulcers being gained. This method may be employed not only under stationary but also under outpatient conditions.


Proliferation of blood vessels and stroma in brain tumours. An enzyme-histochemical study. Proliferation of the vascular endothelium occurring in brain tumours is accompanied by a proliferation of histiocytes in the peripheral part of the vessel wall. These histiocytes infiltrate the tumour tissue in a very regular pattern. Enzyme-histochemically, there are marked differences between the activities of alkaline phosphatase, 5-nucleotidase, and ATPase in the normal and proliferating blood vessels. The whole process encompasses reactive changes evoked by the destroyed perivascular sheath of astroglial foot processes and the subsequent oedema in the tumour and the surrounding parenchyma. There are often tumour areas where diminished vascular permeability is established by proliferation of perivascular connective tissue. Here the oedema has completely disappeared. A clearcut influx of monocytes from the blood into the vessel wall is seen only in the vicinity of necrotic foci; the number of histiocytes is increased and their turnover is observed in swollen macrophages. In the rest of the tumour influx of monocytes and activity of macrophages are inconspicious.


[Laparoscopy in the diagnosis and differential diagnosis of ascites]. Ascites was found in 772 (30,89%) from all the 2500 laparoscopy examined patients. Ascites was due to liver cirrhosis in 57.78 per cent of the patients, to peritoneum carcinosis in 26.29 per cent and to primary and metastatic liver carcinoma in 12.95 per cent, to tuberculous peritonitis in 1.42 per cent and more seldom to some other diseases. A reliable diagnosis of liver cirrhosis, malignant tumors and the rest of the liver diseases, progressing with ascites is made by laparoscopy. Laparoscopy with a biopsy of peritoneum and liver is of decisive importance in the differentiation of peritoneum carcinosis and tuberculosisé. The clinico-laboratory diagnosis in carcinosis coincides completely with the laparoscopic one, the histologic--in 24.5 per cent, partially in 45.5 per cent and in 30 per cent it fails completely to coincide.


[Intensity of glycolysis and energy metabolism in erythrocytes in experimental hypervitaminosis A]. Administration of 60,000 i.e. of vitamin A into rats within three weeks caused an increase in amount of reticulocytes, in the rate of glucose utilization and in formation of lactic acid by erythrocytes. The activity of glycolytic enzymes was intensified. The activity of hexokinase was increased by 84.6%, activities of aldolase and phosphohexoisomerase were increased by 34%. But in the erythrocytes content of AMP, ADP and ATP was unaltered, probably due to activation of total and Na+, K+-dependent ATPase. The harmful effect of an excess of the vitamin A was manifested in an increased content of Na+ in erythrocytes and also in decreased stability of the cells to acid hemolytics.


[Organic dementia as a first symptom of infantile Huntington's chorea (author's transl)]. A loss of intellectual capacity at the age of 10 was the first symptom in a case of infantile Huntington's chorea. Subsequently a rigid hypokinetic syndrome occurred only at the age of 20. The dementia syndrome was confirmed in psychological tests. Auxiliary findings such as a diffuse abnornal EEG, as well as a dilatation of the lateral ventricles and an extension of the subarachnoid spaces in the PEG corresponded to a positive diagnosis of Huntington's chorea.


Preliminary clinical findings on the Kiel classification of malignant lymphomas. In 75 patients with non-Hodgkin Lymphomas the influence of the histopathological form, as judged by the Kiel classification, on the epidemiology and prognosis of the disease was examined retrospectively. The different forms of the Kiel classification influence in a typical way the age specific incidence rates and the prognosis of the disease.


Tumorigenic effects of chronic administration of benzylhydrazine dihydrochloride and phenylhydrazine hydrochloride in Swiss mice. Separate solutions of 0.015%  benzylhydrazine dihydrochloride and 0.01% phenylhydrazine hydrochloride were given continuously in the drinking water of 6- and 5-week-old randomly bred Swiss mice for the remainder of their life. The consumption of benzylhydrazine dihydrochloride significantly increased the lung tumor incidence from 21 to 42% in the females, while in phenylhydrazine hydrochloride-treated mice, the incidence of blood vessel tumors rose significanly from 5 to 22% in females and from 6 to 20% in males, as compared with the controls. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs and angiomas and angiosarcomas of blood vessels. The study thus proves for the first time the tumorigenicity of benzylhydrazine dihydrochloride. It also confirms the tumor inducing ability of phenylhydrazine hydrochloride, which is used in medicine for treatment of polycythemia vera.


Carcinogenic effects of skin transplantation and immunosuppression in mice. C3H and BlD2 mice received skin transplants from an animal of the other strain. Three groups were immunosuppressed for varying periods of time, and with different doses of vinblastine, cyclophosphamide, or azathioprine. Following transplantation, control animals received daily injections of NaCl. All animals developed tumours of lymphoreticular origin, which would indicate that immunosuppression is only a secondary cause for tumor development, with antigenic stimulation being the primary factor.


[On the cytostatic mechanism of action of N-methyl-N-beta-chloroethylhydrazine and its benzaldehydhydrazone (author's transl)]. N-Methyl-N-beta-chloroethyl-hydrazine and its bezaldehydhydrazone inhibit the synthesis of DNA and RNA in ascites cells in vitro faster and stronger than N,N-Dimethylhydrazine and procarbazina does. The benzaldehydhydrzone essentially inhibits influx and phosphorylation of nucleosides whereas N-Methyl-N-beta-chloroethylhydrazine acts directly on DNA synthesis.


The effect of fractionated exposure to thio-TEPA upon Chinese hamster cells in vitro. The dependence of the surviving fraction of Chinese hamster cells in vitro upon the concentration of Thio-TEPA, upon the duration of drug exposure and upon fractionation of drug exposure has been studied. Given a constant exposure time, the surviving fraction decreased according to a "shoulder" curve with increasing concentration. Given a constant concentration, the surviving fraction decreased exponentially with increasing exposure time. Splitting exposure of 60 min into two 30 minutes' exposures with drug-free intervals of several hours increased the cytostatic effect of Thio-TEPA.


Early X-ray detection of colonic and rectal tumours in European hamsters. Three groups of European hamster (EH) (Cricetus cricetus L.) were treated subcutaneously every two weeks for life with 1/10 or 1/20 LD50 DMH, while two other groups served as controls. Twelve weeks after commencement of treatment, radiological examinations of the colon and rectum were begun. The double contrast method was used. In this way it was possible to detect the earliest neoplastic alteration to take place in the above sites. This occurred in the 26th treatment week and was diagnosed as an adenocarcinoma. The technique used is simple, as well as being suitable for large numbers of animals. In addition, it allows for early experimental analysis of results in respect to latency period, growth rate, incidence and location of tumours.


The effect of 4-dimethylaminoazobenzene and azobenzene on the immune reaction of male Sprague-Dawley rats. The carcinogenic substance 4-dimethylaminoazobenzene and the non-carcinogen azobenzene were administered orally once a day to male Sprague-Dawley rats over several weeks at an equimolar dosage of 5-10(-5) moles/kg. Their immunological properties were examined in four different tests. The two substances suppress the cellular immune reactions of the rats already during the first month of treatment. The degree of efficiency of the immunosuppressive property decrease with the degree of antigenicity of the test antigen. Even a two-month treatment of the animals with the two substances had no evident influence on antibody formation. Correlations between the immune response and the carcinogenic effect were not demonstrable.


[Nitrosamin induced neoplasms of the colon and rectum. Investigations on the morphogenesis in rats (author's transl)]. The morphogenesis of neoplasms (carcinomas and pracecancerous polypoid lesions) induced by N-methyl-N-nitroso-N'-nitroguanidine (MNNG) was studied on 154 male Wistar rats (including controls), from which a group received a colostomy. Operated and non-operated rats were treated by intrarectal instillations of 2 mg per kg body weight MNNG twice a week during a period of 210 days.


[Pulmonary artery pressure and left ventricular  late diastolic pressure in rest and during dynamic load. Comparative studies on pressure transmission in the pulmonary circulation during simultaneous determination]. Left ventricular enddiastolic pressure (LVEDP), mean pulmonary artery pressure (PAPM) and enddiastolic pulmonary artery pressure (PADP) were simultaneously recorded in 19 subjects with normal left ventricular (LV) function, and in 109 patients with LV-dysfunction, 83 of whom were also studied during exercise. Patients with valvular heart disease or atrial fibrillation were excluded from this study. LVEDP and mean pulmonary capillary wedge (PCW) pressure were simultaneously recorded in 81 patients at rest, andin 16 patients also during exercise; the LV diastolic pressure prior to atrial contraction (LVPpreA) could accurately be identified in 45 patients at rest and in 23 patients with exercise. In contrast to the widely accepted opinion of others, the PADP (mean 8.2 +/- 2.2 mm Hg at rest and 12.3 +/- 3.4 mm Hg with exercise) showed a close approximation of LVEDP (10.0 +/- mm Hg at rest and 16.2 +/- 3.5 mm Hg with exercise) only in normal subjects at rest (p less than 0.05 and p less than 0.01 respectively). In patients with LV dysfunction there was no significant difference between PADP (11.7 +/- 4.5 mm Hg and 23.0 +/- 8.9 mm Hg), PCW (11.6 +/- 5.1 mm Hg and 24.1 +/- 11.9 mm Hg) and LVPpreA (12.5 +/- 5.5 and 21.5 +/- 7.7 mm Hg) at rest and during exercise. LVEDP could be estimated with sufficient accuracy only from the PAPM (18.9 +/- 6.5 and 35.7 +/- 10.8 mm Hg). The increase in LVEDP (14.7 +/- 7.7 mm Hg) with exercise was not significantly different from the increase in PAPM (16.8 +/- 7.1 mm Hg). There were highly significant correlations (p less than 0.001) between LVEDP and PADP (r = 0.85) as well as PAPM (r = 0.86) at rest and during exercise with the regressionline being closest to the line of identity for LVEDP and PAPM. The pressure gradient between LVEDP and PADP (LVEDP - PADP = 6.3 mm Hg with exercise) equaled the pressure increase in LV by atrial contraction (LVEDP - LVPpreA = 6.3 and 13.3 mm Hg). The pressure difference between PADP or PAPM and LVEDP remained constant despite marked variation of other hemodynamic parameters, e.g. stroke volume index (SVI), heart rate (HR) and cardiac index(CI). These data suggest that an elevated LVEDP is caused mainly by an augmented atrial contraction in patients with LV dysfunction at rest and with exercise. This mechanism precludes an enddiastolic pressure equilibrium between pulmonary artery and left ventricel. PAPM allows the best estimation of LVEDP independent from other hemodynamic variables.


[Identification of beta, beta-caroten-2-ol and beta, beta-carotene-2,2'-diol in the stick insect, Carausius morosus Br.; a reinvestigation study]. Two major carotenoids of the stick insect were reinvestigated and shown to be beta,beta-caroten-2-ol and beta,beta-carotene-2,2'-diol and not isocryptoxanthin (beta,beta-carotin-4-ol) and isozeaxaanthin (beta,beta-carotene-4,4'-diol). Both pigments are esterified with fatty acids. The identification is based on cochromatography with authentic 2-, 3- and 4-isomers of the mono- and dihydroxy pigment, mass spectra, and chemical behaviour. In acid solution beta-beta-carotene-2,2'-diol is specifically dehydrogenated and rearranged to ketones with retro structures in analogy to the reactionof beta,beta-caroten-2-ol as recently reported. The final product of the diol is 4,5-dihydro-4,5'-retro-beta,beta-carotene-2,2'-dione. This is the first demonstration of beta,beta-carotene-2,2'-diol in an animal.


Effect of substituted pyridazinone herbicides and of difunone (EMD-IT 5914) on carotenoid biosynthesis in green algae. The carotenoid biosynthesis of the green alga Ankistrodesmus braunii is blocked if these cells are cultured in presence of sublethal doses of pyridazinone herbicides (San 9789, San 6706, BASF 44521) or of the herbicide difunone (EMD-IT 5914). The amount of colored carotenoids normally found in these algae is reduced drastically and the precursors phytoene and phytofluene are accumulated. Furthermore a decrease in the chlorophyll level occurs in the treated cells, but there is a stronger loss of chlorophyll a, resulting in a lowering of the chlorophyll a/b ratio with time. Concerning the activity of substituted pyridazinones leading to inhibition of carotenoid biosynthesis this effect can be related to the chemical structure of these compounds: a trifluormethyl substitution of the phenyl ring and a mono- or dimethyl substitution of the amine (San 9789, San 6706) or a methoxy group instead of the substituted amine (BASF 44521) are required both for this effect. Other pyridazinone derivatives with either a trifluoromethyl substitition of the phenyl ring (San 9774) or a dimethyl subsittution of the amine (San 9785) or a methoxy group (BASF 13761) are without any effect on the pigment pattern of these algae.


On the mechanism of the acridine orange sensitized photodynamic inactivation of lysozyme. II. Kinetics in presence of N-acetylglucosamine. The photodynamic deactivation of lysozyme in presence of acridine orange is caused by a reaction between singlet oxygen formed via the dye triplet state and the protein. In order to identify the region where the singlet oxygen reacts with the protein we have investigated the kinetics of the deactivation in presence ofthe inhibitor of the enzymatic reaction N-acetylglucosamine (GlcNAc). The overall experimental rate constant becomes slower with increasing saccharide concentrations. As we can exclude experimentally that this kinetical effect is caused in presence of the saccharide by a physical quenching of singlet oxygen or of the dye triplet state it has to be assumed that GlcNAc protects the surrounding of its bindings place at subsite C of the enzymatic center sterically against an attack of singlet oxygen. In this region three tryptophan residues are located, which could be sensitive against singlet oxygen. Surprisingly, however, it has been found that only those species are protected, in which a second saccharide molecule is bound to the protein, probably at subsite E at the enzymatic center, where no sensitive amino acid side chains are located.


[Influence of DCMU on the formation of lipids and fatty acids, and on the ultrastructure of Euglena gracilis (author's transl)]. Euglena gracilis Klebs (strain Z) was grown heterotrophically in the dark for 6 days. Subsequently, the cells were grown photoautotrophically under white fluorescent light with varying amounts of 3-(3,4-dichlorophenyl)-1,1 dimethyl urea (DCMU) (1.7X10(-9)--1.0X10(-5)mol/l) added to the nutrient medium. Under non-photosynthetic conditions (addition of 10(-6)--10(-5)mol DCMU/l), the cells still produced chloroplast structures and a considerable percentage of compounds typical for chloroplasts, such as galactolipids (40-50%), chlorophylls (40%), and polyunsaturated C16 and C18 fatty acids (16:2, 16:3, 16:4, 18:2, 18:3) (65%). The results indicate that under these conditions the above compounds are synthesized from carbon sources outside the chloroplasts.


Formation of benzoic acid and p-hydroxybenzoic acid in the blue green alga Anacystis nidulans: a thylakoid-bound enzyme complex analogous to the chloroplast system. The photosynthetic procaryote Anacystis nidulans converts L-phenylalanine and L-tyrosine into benzoic acid and p-hydroxybenzoic acid, respectively. Results obtained with thylakoid fractions support the hypothesis that the reaction sequence is catalyzed by thylakoid-bound enzyme complexes consisting of phenylalanine ammonia-lyase and benzoate synthase of tyrosine ammonia-lyase and p-hydroxybenzoate synthase, respectively. Btoh complexes do not accept phenylacetic acids as substrates, and cinnamic acids only at a small extent. These properties suggest a striking similarity to a benzoic acid-synthesizing enzyme system from higher plants which is situated at the thylakoid membrane of chloroplasts. The respective complexes of Dunaliella marina and Porphyridium sp. were included in this comparison.


On the role of the cell coat glycoproteins in the permeability of the cell. The release of a part of the cell coat of Ehrlich ascites cells by chelation with ethylenediamine-tetraacetic acid modifies significatively the uptake of various radioactive molecules. This phenomenon seems to be related to a change in the permeabililty of the cell membrane. The chemical analyses of the released material appear to indicate that glycoproteins are involved in that change and that their release modifies the structural and physiological characteristics of the cell membrane.


Fusion of isolated sarcoplasmic reticulum membranes. Fragmented sarcoplasmic reticulum (FSR) vesicles from rabbit muscle were suspended in 1.5-5% glycerol solutions and were pelleted onto aluminum foil disks in a modified centrifuge tube. Examination of these pellets in the electron microscope after drying for 2--2.5, 4--5.5, and 21 hours revealed a progression of changes. First, distances between individual, round vesicles decreases. Next, somewhat flattened vesicles establish limited areas of contact with adjacent vesicles. Finally, vesicle fusion occurs and extended areas of double bilayers are formed. A water loss-time interaction appears to be needed for the fusion process. A Hg-phenyl azoferritin compound was used as a marker to identify intra- and extra-vesicular space in the fused samples. Quantitative measurements of birefringence during imbibition of pellet slices in a graded series (eta-1.41-1.43) is reached. The plateau seen in this part of the curve is again followed by steadily increasing birefringence at higher glycerol concentrations. This interruption in the birefringence curve is presumably due to a matching of the refractive indices of the glycerol solution and a lipid component in the membranes.


The effect of ethylene glycol and DMSO on fusion of isolated sarcoplasmic reticulum membranes. Fragmented sarcoplasmic reticulum (FSR) vesicles from rabbit skeletal muscle were suspended in 5-10% ethylene glycol (EG) or in 5, 10, or 15% dimethylsulfoxide (DMSO) and were pelleted onto flat aluminum foil disks. No vesicle fusion o-curs with either 5 or 10% EG treatment and 2-21/2 hours drying. After 4-5 hours drying, 5% EG-treated vesicles have established more areas of close contact and individual vesicles have begun to flatten when compared with the 10% EG vesicles remained round as in the 2-21/2 hour samples of all treatments. Overnight drying also causes extended sheets of bilayer pairs to form in the 5% DMSO-treated samples but, with 10 and 25% treated vesicles, destroys the double bilayers and only occasional dense regions of membrane whorls remain. Both EG and DMSO promote morerapid fusion of FSR vesicles than does glycerol but overnight drying after treatment with 10 or 25% DMSO DESTROYS THE FUSED MEMBRANE.


Indirect evidence for a very fast recovery kinetics of chlorophyll-aII in spinach chloroplasts. The 690 nm absorption change reflecting the turnover of the system-II-reaction center chlorophyll, Chl-aII (often referred to as P 680), has been investigated under different experimental conditions in spinach chloroplasts. A comparison was made with oxygen evolution and with absorption changes of Chl-aI measured at 703 nm, both indicating the number of electrons produced by system II. It was found: 1. The dependency on actinic flash intensity of the initial amplitudes of the measured 690 nm absorption change, deltaalpha0(Chl-aII) in Tris-washed chloroplasts is similar to that for the total amplutude of the 703 nm absorption change, deltaalpha0(Chl-aI) in normal chloroplasts, and can be described by an exponential function. On the other hand, deltaalphao(chl-aII) in normal chloroplasts exhibits a more complex biphasic dependency and much higher flash intensities are required for saturation. 3. Unver repetitive flash group excitation and in the presence of an ADRY(= acceleration of the deactivation reactions of the water-splitting enzyme system Y)-reagent the initial amplitude of the 690 nm absorption change oscillates in the same characteristic pattern as the oxygen evolution. 4. The initial amplitude of the 690 nm absorption change, deltaalpha0(Chl-aII), IN Tris-washed chloroplasts becomes significantly smaller (more than 50%) by the addition of system-II-electron donors (benzidine, p-phenylendiamine, tetraphenylboron), whereas the total amplitude of the 703 nm absorption change, detalalpha0)Chl-aI) increases 3-4-fold. In order to explain these results, the existance of a very fast reduction kinetics of Chl-aII+ is postulated, which is not detectable by our measuring equipment. The half time of this reaction is less than or equal to mus. Reaction centers with the very gast "undetected" Chl-aII+-reduction are photochemically transformed into slower one by double hit processes with a comparatively low quantum yield. Furthermore, it is inferred, that the dark recovery kinetics of Chl-aII is dependent on be charge accumulation state of the watersplitting enzyme system Y. This phenomenon is shown to explain also the oscillation pattern of delayed fluorescence. On the basis of the present results two alternative reaction schemes for the functional organization of the electron transport on the donor side of system II are discussed.


[Organ specific application of drugs by means of cellular capsule systems (author's transl)]. It is suggested to use living cells (red blood cells, lymphocytes and leucocytes) as drug delivery systems for temporal and spatial drug administration in human therapeutics and diagnosis. The effectiveness of drug loaded cells is demonstrated for the drug methotrexate which is used in cancer treatment. Red blood cells are loaded with methotrexate using the dielectric breakdown technique. Dielectric breakdown leads to a transient increase of permeability of the cell membrane. Red blood cells loaded with tritium-labelled methotrexate were injected into mice and the activity level was measured in several organs as a function of time. It is shown that with this drug delivery system more than 50% of the drug (after 10 min) can be accumulated in the liver and that a high activity level can be sustained in this or gan for more than 3 hours. On the other hand, administration of this drug by injecting solutions in the usual manner leads only to an 25% accumulation of methotrexate (after 10 min) in the liver. The drug is excreted completely after 1 to 2 hours. It is proposed to load red blood cells simultaneously with para- or ferromagnetic substances to obtain organ-specificity for any selected site of the body.


Labeling of animal cells with fluorescent dansyl cerebroside. A dansyl (diaminoaphthalenesulfonyl)-derivative of cerebroside was prepared which could be effectively incorporated into the plasma membranes of tissue culture cells and erythrocytes. The cells which had assimilated the glycolipid fluoreced intensely and could be observed under a fluorescent microscope. Cells were initially labeled rather homogeneously over the whole surface. With longer incubation time organization of the fluorescent glycolipid took place and patches of the lipid in the membrane were formed. The redistribution and organization of the membrane lipid could be demonstrated most clearly when cells labeled with this fluorescent glycolipid were infected with myxoviruses. After infection of MDBK and BHK cells with fowl plaque virus areas of dense fluorescence appeared at margines of neighboring cells. When BHK cells were infected with Newcastle disease virus fusion of the cells was accompanied by complete redistribution of the glycolipid. Erythrocytes could also easily incorporate dansyl cerebroside. Chicken erythrocytes which contain cytoplsmic and nuclear membranes incorporated the fluorescent glycolipid in both membranes.


Electron-beam induced conformation changes in polypeptide layers: an infrared study. Langmuir-Blodgett type polypeptide monolayers have been irradiated under conditions simulating the hazards of electron microscopic imaging. The damaging effect, i.e. the randomization of the alpha-helical layers, which occurs in the dose range between 50 and 200 e-/nm2, has been monitored by infrered dichroism.


[Reactivity and delayed neurotoxicity or organophosphates (author;s transl)]. Rate constants of the alkaline hydrolysis reaction were correlated with neurotoxic findings of some organophosphates using data published in the literature. This correlation shows upper and lower limits of reactivity comparable to those found with biological activities of some other xenobiotics.


On the reaction of methylmercuric hydroxide with methylbabalamin. The methylmercury-induced dealkylation of the corrinoid coenzyme methylcobalamin, yielding aquocobalamin and dimethylmercury as products, was studied spectrophotometrically at 350 nm using water as a solvent. Rate data were determined for the pH 7-9 region and also at pH 3.37. Evidence is provided which shows that CH3Hg+ serves as the species which accepts the methyl group and also that Hg2+ is methylated more rapidly than CH3Hg+ is.


[Experimental investigations on ultraweak photonemission form biological systems (author's transl)]. Measurements on untreated yeast cells, potato- and cucumber seedlings have confirmed the existence of photon emission from biological systems known as "ultraweak luminescence". The intensity is of the order of 10(2) counts per second, and the spectral distrubtion shows a maximum near 550 nm. The dependence of th photon emission on certain chemicals has been investigated. Some chemicals, as for instance acetone, intensify the photon emission from cucumber seedlings without essential change of the spectral distribution. On the other hand, NaCl leads to a shift to the red region of the spectrum. The treatment of EAT-cells by 4-Hydroperoxycyclofosfamide involves a nonlinear enhancement of the intensity with increasing concentration. There are some indications that collective interactions of the system are more appropriate than simple chemiluminescence reactions.


[Enzymatic formation of a cis,cis-muconic acid derivative using pyrazon-degrading bacteria (author's transl)]. The cis,cis-muconic acid derivative of pyrazon, which was formerly isolated from the medium of pyrazon-degrading bacteria, was formed enzymatically by incubation of the catechol derivative of pyrazon with partially purified ortho pyrocatechase from pyrazon-degrading bacteria.


[Enzymatic formationof 4-hydroxy-2-oxovalerate using pyrazon-degrading bacteria (author's transl)]. By treatment of 2-hydroxymuconic acid with a partially purified 4-oxalocrotonate decarboxylase 4-hydroxy-2-oxovalerate could be obtained. Both forms of 4-hydroxy-2-oxovalerate, the keto as well as the enol form could be isolated.


[The yolk nucleus in young oocytes of Neomacheilus barbatulus (L.) (Teleostei, Cobitidae) (author's tranls)]. The yolk nucleus in the young oocytes of the freshwater teleost Noemacheilus barbatulus (L.) was investigated by electron microscopy. Yolk nuclei are only found in stage I. They consist of nucleolar substance, mitochondria and partly of dictysomes. The nucleolar material leaves the nucleus through the pores of the nuclear membrane and gets into the juxtanuclear cytoplasm. It mainly consists of ribonucleic acid. The yolk nuclei of Noemacheilus doesn't have any relations to the formation of yolk.


Rhodopsin particles in the photoreceptor membrane of an insect. Electron-microscopic examination of freeze-fractured fly retinae has revealed the presence of particles, 80 to 100 A in diameter, on the photoreceptor membrane. Flies which were raised on a vitamin-A deficient diet show a substantial reduction in the density of such particles. The reduction in particle density is in agreement with the reduction in visual-pigment concentration as measured spectrophotometrically for these flies. These results suggest that the particles are identical with molecules of the visual pigment, rhodopsin.


The dorsal compound eye of simuliid flies: an eye specialized for the detection of small, rapidly moving objects. The highly specialized dorsal compound eye of male Simuliids is especially adapted to detect during flight the females which are very small animals (1X3 mm). At dawn, the eye functions close to the physical limit imposed by the quantum fluctuations of light. In birght illuminations, light-qauntum noise is not a limiting factor as can be shown by behavioural experiments.


[Surgical treatment of the Bland-White-Garland syndrome. Report of a successful treated case of adult type (author's transl)]. Report of a successful treated case of Bland-White-Garland syndrome of adult type in a 13 year old girl. A vena saphena bypass was implanted between the aorta and the ramus descendens anterior of the left coronary artery. The main stem of the left coronary artery was ligated near its origin from the pulmonary artery. Eight months after operation the patient is well and the bypass open.


[Chronic lower abdominal complaints in the woman - a postlaparoscopic analysis]. 2000 laparoscopies were performed between 1968 and 1975. 253 from 493 patients with unexplained pelvic pain were followed up a half till 5 years after laparoscopy concerning the pains. The discrepancy of clinical diagnosis and laparoscopie statement is compared and discussed. The most clinical diagnosis were: chronic pelvic pain (149 cases) and unexplained pelvic pain (32 cases). Postlaparoscopic findings were: inconspicuous statements (27,3%), pelvic adhesions (27,3%), chronic disease of the fallopian tubes (21,1%), chronic appendix diseases (10,3%), ovary cysts (9,8%), endometriosis (4,3%).52,9% of the patients were cured by specific treatment a half till 5 years after laparoscopy. The laparoscopy is considered to be a diagnostic and therapeutic acurate method. 14,2% of the patients with little or inconspicuous statements were cured after instruction. The laparoscopy may be the base for acurate diagnostic and team-work of several branches of knowledge.


Lytic patterns of Staphylococcus epidermidis type 1. In typing of Staphylococcus epidermidis higher concentrations of phages should be used in view of the danger of committing an error while typing at RTD only. Lytic patterns may be divided into long and short ones. The latter possess greater identification value. There are several phage types of Staphylococcus epidermidis type 1 which are more common. Phage type A 9c is chiefly encountered in hospital environments.


[Role of postural and vicarious muscular overloading in the formation of lumbo-ischialgic syndromes]. On the basis of neuro-orthopedical and tensoalgimetrical studies of 527 patients with sacral ostheochondrosis the authors elaborated a scheme of the distribution of overloading on the muscles of the legs and respective neurodystrophical and algic phenomena. These overloadings were expressed in fixed lordosis, kyphosis or skoliosis due to which there was a redestribution of these overloadings between the antagonists of legs in the sagittal and frontal plane. The overloadings occurred vicariously in some muscles while the others were in a paretic condition.


Studies on the pattern of circulating steroids in the normal menstrual cycle. Circadian variation in theperi-ovulatory period. Circadian variations of the plasma levels of dehydroepiandrosterone, 17-hydroxypregnenolone, pregnenolone and testosterone were investigated by radioimmunoassay in 10 normally menstruating women during the periovulatory period. In seven of the subjects it was also possible to estimate androstenedione and dihydrotestosterone levels. Blood was withdrawn continuously over a period of 48 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The circadian rhythm was studied during 13 3-hour sampling periods (36 h) which were identical in all subjects. Dehydroepiandrosterone, 17-hydroxypregnenolone and pregnenolone showed a marked circadian rhythm with highest mean levels in the morning between 06.00 and 0.900 h and lowest mean levels during the night between 21.00 and 24.00 h. The peak levels of individual subjects coincided completely with the highest mean levels in the case of dehydroepiandrosterone, in 9 out of 10 cases with regard to 17-hydroxypregnenolone and in 8 of 10 cases as far as pregnenolone levels were concerned. The lowest individual levels were more dispersed around the means than were the individual peaks. The difference between the highest (morning hours: 06.00-09.00) and lowest (evening hours: 21.00-24.00) geometeric mean values was 404% for 17-hydroxypregnenolone, 163% for dehydroepiandrosterone and 71% for pregnenolone. The mean testosterone levels also exhibited an elevation between 06.00 and 09.00 h which was significant (P less than 0.05). However, the individual peak values were scattered from 21.00 h of the first day to 18.00 h of the second day. The mean concentrations of androstendine showed a significant increase between 06.00 and 18.00 h. The individual peaks were widely dispersed. Hence a uniform circadian rhythm correlated to the levels of the 5-steroids mentioned above could not be demonstrated in the case of testosterone and androstenedione. An analysis of variance indicated no significant differences between sampling periods as far as dihydrotestosterone levels were concerned. The extent and regularity of the circadian variation in the plasma levels of the 5-steroids studied makes it mandatory to standardize very carefully the exact time of blood withdrawal in any longitudinal study. In view of the sharp changes in the plasma levels during the morning hours, it is suggested that sampling during the afternoon period may provide more constant values.


The influence of combined cyproterone acetate-ethinyl oestradiol therapy on serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women. Serum levels of dehydroepiandrosterone, androstenedione, and testosterone in hirsute women suffering from either idiopathic hirsutism or the polycystic ovary syndrome were determined before and during treatment with cyproterone acetate combined with ethinyl oestradiol. During this treatment the hirsutism decreased markedly. In untreated hirsute women serum dehydroepiandrosterone levels do not differ from those in normal women and do not change during therapy; androstenedione levels are higher than normal and decrease markedly during treatment, and the testosterone levels are elevated compared to normals, with a considerable overlap, and show only a tendency to decrease. There is no correlation between dehydroepiandrosterone and androstenedione levels or between androstenedione and testosterone levels in the serum of untreated hirsute women. After 12-14 months of cyproterone acetate-ethinyl oestradiol therapy a linear correlation is found between dehydroepiandrosterone and androstenedione levels. This can be explained by the relatively higher contribution of the peripheral conversion of dehydroepiandrosterone to androstenedione to the occurrence of lower androstenedione levels. The linear correlation between androstenedione and testosterone after treatment, also found in normal women, indicates the restoration of the role of androstenedione as the major peripheral precursor of testosterone.


Blinding and pinealectomy in male hamsters: Effects of pineal indoles and P-chlorophenylalanine on testes, seminal vesicles, pituitary and adrenal glands. No antigonadotrophic (AGT) activity was found after injecting 5 methoxytryptophol (5 MTPH) or both serotonin and melatonin simultaneously in normal male hamsters or hamsters subjected to blinding, pinealectomy, or both surgical procedures. Treatment with these indoles did not induce changes in weights of testes, seminal vesicles, pituitary or adrenal glands. Reproductive organs in hamsters blinded by enucleation atrophied in spite of daily consumption of the vasodilator, Apresoline. Feeding of p-Chlorophenylalanine (PCPA) revealed this antagonist to be mildly toxic. PCPA seemed to interfere in the hypophyseal-adrenal axis: these hamsters lowt the most weight, pituitary glands were enlarged and some hyperactivity occurred in the hamsters.


Thalamo-cortical systems regulating spindle bursts and recruiting responses. II. Effect of thalamic lesions. The effects of thalamic lesions on recruiting responses and spindle bursts have been studied in 12 cats immobilized with gallamine. Recruiting responses were elicited by stimulation of the midline thalamic nuclear complex. Spindle bursts were produced by lesions in the mesencephalic tegmentum. Recruiting responses and spindle bursts were recorded from the cortex and thalamus. The effect of thalamic lesions on such spontaneous and induced potentials was evaluated by making lesions anteriorly in the rostral pole of the thalamus, medially in the midline thalamic nuclear group, and laterally in the primary and association nuclei of the thalamus. 1. Small, anterior, thalamic lesions blocked spindle bursts and recruiting responses both at the cortex and in the thalamus. 2. Massive, medial, thalamic lesions blocked spindle bursts in the suprasylvian cortex, but did not affect either frontal cortex spindle bursts or frontal and thalamic recruiting responses induced by stimulation of N. ventralis anterior. 3. Massive, lateral, thalamic lesions including specific relay and association nuclei, failed to block spontaneous spindles and recruiting responses in frontal cortex and midline thalamic nuclei. It has been postulated that the rostral pole of the thalamus constitutes an important part of the thalamic portion of a thalamo-orbitocortical system which mediates and regulates electrocortical synchronization as manifested in spindle bursts, recruiting responses and synchronized wave-like potentials.


Alterations in the hippocampus of aged mice. The hippocampus of C57B1/6 mice was examined histologically and electron microscopically. Male and female mice at 3 and 8 months of age and female mice at 16 months of age were studied. PAS positive foci, containing particles 1-2 mu in diameter, were observed in the hippocampal region of 8 and 16 month old mice. These particles were diastase sensitive. Electron microscopically, in similar mice, a vacuolating change was observed in the cytoplasm of perithelial cells (pericytes) in the same area.


Cardiac haemangio-endotheliosarcoma. Review of the literature and report of a case. A case of primary haemangio-endotheliosarcoma of the right atrium is reported. A review of the literature is given and in all but four of the 56 cases, the tumour originates in the right atrium projecting into the cavity. This explains why these tumours present a rather uniform clinical picture characterized by superior vena caval syndrome combined with pericardial effusion, cardiomegaly, dyspnoea and chest pain. A male dominent sex distribution of 3 to 1 is found. The tumour is highly malignant and has caused death within an average of six months. We emphasize the possibility of early diagnosis particularly since eht clinical symptoms are rather typical and cases are reported where therapy apparently was successful.


Characterization of the glycolysis pathway and the plasma membrane of Lactobacillus and Bifidobacterium strains. The characteristics of the glycolytic pathway and the plasma membrane of Lactobacillus and Bifidobacterium were studied. The enzyme system of glycolysis (hexokinase, glucokinase and pyruvate kinase) which is the main source of energy in the anaerobic condition was localized in the cell soluble fraction (cytoplasma) of all species examined. Neither electron transfer chain components nor oxidase activities were found in anaerobically cultured Lactobacillus and Bifidobacterium. Adenosine triphosphatase (ATPase) activities were mainly localized in the plasma membrane, suggesting that membrane ATPase is playing a key role in membrane transport and ATP synthesis of anaerobic bacilla. SDS-polyacrylamide gel electrophoresis of membranes showed remarkable differences between the polypeptides patterns of B. adolescentis and B. bifidum. Such peculiarities in polypeptide patterns among the same genus may be useful in the identification of species.


Blastformation rate of peripheral blood lymphocytes before and after recurrence of cancer. Following curative resection for gastrointestinal cancer, it has been demonstrated that the blastformation rate rises slightly 3-4 months before the recurrence of cancer and that, during the two months prior to recurrence, the blastformation rate of peripheral blood lymphocytes to PHA decreases rapidly. The blastformation rate, therefore, if monitored routinely postoperatively, should be a significant improvement in predicting any recurrence of the cancer.


Fetal antigens associated with adenovirus 12 mouse tumors. The fetal antigen(s) of C3H/BfB/Ki mouse tumor cells induced by adenovirus type 12 was examined by transplantation resistance, local adoptive transfer and in vitro cell-mediated microcytotoxicity tests. Mice immunized with 8 to 9-day gestation fetal cells showed weak resistance to the challenge of small numbers of tumor cells, but immunization with 13 to 14-day gestation fetal cells did not confer transplantation immunity. Local adoptive transfer of multiparous pregnant mouse spleen cells mixed with tumor cells showed a small inhibition of tumor growth in all cases, but primiparous pregnant mouse spleen cells showed a protective effect in only one of three samples. In the cell-mediated microcytotoxicity test, spleen cells taken from the fetal tissue-immunized or multiparous pregnant mice showed a cytotoxic effect to MT-2 cells (adenovirus type 12 tumor cell line) and mouse fetal cells, but not to newborn mouse kidney cells. These results strongly suggest the presence of phase-specific tumor-associated fetal antigen(s) which can evoke transplantation immunity.


Cell proliferation stimulating factors in the supernatant of embryos and adult muscles of chickens of the same strain. Stimulating factors of cell proliferation were extracted from the supernatant of embryos and adult muscles of chickens of the same strain. The stimulating activity and physicochemical properties of these factors were altered after embryological development. The embryonic factors were about 3.5 times more effective than the muscular factors. These factors might be useful in analysis of the regulatory mechanisms of cell proliferation.


Down's syndrome: karyotypic stability of trisomy 21 in an established lympho-blastoid cell line. A trisomic lymphoblastoid cell line derived from the peripheral blood of a patient with Down's syndrome was sequentially analyzed for chromosome constitution for 16.5 months of continuous culture in vitro. The cell line was found to maintain a modal chromosome number of 47 with trisomy 21. Parallel studies of modal chromosomes before and after banding procedures revealed no structural abnormalities except trisomy 21.


Total parenteral nutrition after small intestinal bypass operation in rats. A jejuno-ileal bypass operation which excluded about 85% of the small intestine was conducted in two groups of rats to evaluate the effects of oral feeding versus total parental nutrition (TPN). One group received food orally while another group received TPN. Two other groups of nutritive control animals underwent laparotomy and suture markings on the intestine. Animals were sacrificed two weeks after the shunt or sham operation. The liver, kidneys, pancreas and spleen were weighed. The wet and dry weights and the villus height of small intestinal segments were also determined. The shunt-operated TPN rats showed a body weight gain of 28% over the initial body weight while the orally fed animals showed an increase of 3.2%. The TPN controls had a negative nitrogen balance only on the day of the sham operation, whereas the TPN shunt-operated animals changed to positive nitrogen balance on the second postoperative day. The wet weights of the liver, kidneys and spleen were significantly higher in TPN animals. The functioning region of the small intestine in the shunt-operated animals was hypertrophic in both the orally fed and the TPN animals, but there were greater quantitative changes in the orally fed animals. The experiments demonstrated the beneficial effect in rats of TPN over oral nutrition for the treatment of surgically induced malabsorption. The studies also showed that the small intestine is capable of developing compensatory mucosal action without intraluminal nutritive content, although the presence of food in the lumen appears to stimulate morphological changes to a greater extent after massive small bowel resection.