Factors affecting the frequency infection in renal transplant recipients.

A retrospective review of 149 patients receiving 162 renal transplants showed that 83% of these patients developed one or more infections during a follow-up period averaging one year. In 32 (73%) of 44 deaths, infection was an important contributing cause. In only four (9%) of the deaths were the patients free of infection at the time of death. The Klebsiella-Enterobacter group was the most common agent causing pneumonitis and sepsis. Cryptococcus neoformans caused seven of 11 cases of meningitis. Pseudomonas was the most frequent agent associated with infections documented during postmortem examinations. In a short-term controlled study comparing daily and alternate daily therapy with prednisone, the alternate daily group had significantly (P less than .05) more infections per patient, especially in patients who had no evidence of rejection (P less than .025).


Mating reaction in Saccharomyces cerevisiae. IX. Regulation of sexual cell agglutinability of a type cells by a sex factor produced by alpha type cells.

A diffusible sex-specific substance called alpha substance-I (alphaS-I) was isolated from culture filtrate of alpha type strains of the yeast Saccharomyces cerevisiae. The isolated alphaS-I, an oligopeptide, induced sexual cell agglutinability in inducible alpha type strains and enhanced the agglutinability in constitutive a type strains. The induction of sexual agglutinability was detected in 30 min and reached maximum in 90 min, when 0.2 mug/ml of alphaS-I was added to inducible a type cells. The a type-specific factor responsible for sexual cell agglutination, called a type agglutination factor (aAF), was shown to be produced during the induction or the enhancement of agglutinability of a type cells by alphaS-I. The aAF produced in response to alphaS-I was not different in the susceptibility to proteolytic enzymes and disulfide-cleaving agents from those produced constitutively in the absence of alphaS-I.


Promotion of sporulation by caffeine pretreatment in Saccharomyces cerevisiae. II. Changes in ribonuclease activity during sporulation.

Changes in RNase activity during sporulation of a homothallic diploid strain of Saccharomyces cerevisiae were measured in caffeine-treated and non-treated cells. 1. In caffeine-treated cells soon after the transfer to the sporulation medium a significant increase in RNase activity was observed; in control cells the rise of RNase activity was less and started after a lag period of 5 h. The final activity of RNase activity was about twice as high in caffeine-treated cells as in control cells. 2. Increase in RNase activity during sporulation was sensitive to cycloheximide in control cells, but insensitive in caffeine-treated cells. 3. RNases from vegetative cells and from sporulating ones are different in their Km values. Relation of the changes in RNase activity to premeiotic DNA synthesis is discussed.


Biosynthesis of sulphur amino acids in Saccharomyces cerevisiae II. Analysis of suplhite-producing strains.

A number of strains of Saccharomyces which produce sulphite by sulphate reduction were examined from an enzymatic and genetic point of view. There are a number of mechanisms that regulate this activity. All of these mechanisms involve the sulphite-reducing activity. In the strains examined, reduced function as a result of mutation in the Sr-locus (affecting H2S-NADP oxidoreductase EC 1.8.1.2), repression of biosynthesis of the enzyme because of a mutation below the specific locus, and inhibition of the enzyme by endogenous factors were found to be responsible. The production of sulphite can also be connected with a complex state of heterozygosity. It is probably this multiplicity of biochemical and genetic mechanisms that accounts for the frequency with which the production of sulphite is observed in wild strains in nature.


[Experimental infection of guinea pigs with Clamydia. 2. Fluorescent antibody examinations].

The direct fluorescent antibody technique was applied to blood smears and organ impression smears from guinea-pigs killed at various times during 13 weeks following nasal infection with a bovine strain of Chlamydia. Antigen inclusions were demonstrated one hour after infection in blood granulocytes, after 3 hours in most of the organs examined and after 6-12 hours in all the organs. Antigen was present throughout the period of observation in blood smears and samples from nasal mucosa, trachea, lung, small intestine, spleen and liver. It seemed that polymorphonuclear granulocytes played an important part in the pathogenesis of generalized chlamydial infection. In the case of intranasal inoculation, the nasal mucosa was evidently the site of the initial infection and proliferation of the agent, and the origin of primary chlamydaemia. For the initiation and maintenance of the secondary period of blood infection, the lungs and trachea were the principal site of multiplication of the agent; spleen, intestinal mucosa and CNS were also involved to a lesser extent. The antigen content of lung, trachea, nasal mucosa and spleen at each stage of infection was generally correlated with the extent and intensity of the inflammatory reaction.


Population shift in drug resistant and sensitive Escherichia coli during antibiotic treatment of children with diarrhea.

Changes in composition of Escherichia coli were followed during antibiotic therapy of nin children with acute diarrhea. In five cases enteropathogenic serotypes of E. coli were multiple-drug resistant, and in four other this feature characterized nonpathogenic E. coli strains. The results point to the importance of choice of the drugs effective not only against pathogenic serotypes, but also against nonpathogenic ones, and uselessness and even harmfulness of chemotherapy "in blindly".


Studies on the combined action of phosphonomycin with streptomycin, penicillin G and ampicillin.

Using the serial dilution method in solid media, sensitivity of isolated strains of S. aureus and E. coli to phosphonomycin, streptomycin, penicillin G and ampicillin, and the effect of combined action of phosphonomycin with these antibiotics were studied. Against S. aureus strains, phosphonomycin in combination with penicillin G showed synergistic action more often than in combination with streptomycin. On the other hand, against E. coli strains the combination of phosphonomycin with streptomycin and ampicillin was similarly synergistic. The findings suggest the possibility of clinical applications of combined therapy with phosphonomycin and antibiotics of the beta-lactam and aminoglycoside groups.


Studies on the immunosuppressive and anti-inflammatory action of L-asparaginase.

The influence of L-asparaginase (Crasnitin) on cellular reactions in the course of immunologically specific and nonspecific processes was studied. The preparation exerted particularly strong inhibitory action on the appearance of hemolysin-producing cells (Jerne's test) and on formation of rosette forms. A somewhat weaker effect on nonspecific inflammatory reactions, by the xylene and granulation tests, was noted. It was concluded that L-asparaginase depresses cellular reactions regardless of their immunologic component, but that immunologic reactions are more sensitive to this drug. It was established that L-asparaginase acts on bursal and thymus-dependent lymphocytes and, moreover, influences the hyperemic and proliferative reactions that accompany immunologically nonspecific processes.


Dantrolene sodium: long-term effects in patients with muscle spasticity.

Seventy-seven patients with muscle spasticity secondary to central nervous system pathology were treated with dantrolene sodium for periods of up to two years. The drug was effective in reducing muscle spasms, clonus, muscle tone, and the force of muscle contraction elicited by Achilles tendon tap and tibial nerve stimulation, but improvement of function was seen less often. The incidence of side-effects was considerable, and poses a problem regarding patient acceptance of drug treatment.


BCG immunotherapy in patients with malignant melanoma.

Twenty-one patients with malignant melanoma received immunotherapy with BCG. Thirteen patients had adjuvant immunotherapy on a monthly schedule. Of these, eight with regional lymph node metastases (stage III) had been treated by lymphadenectomy. Two of the stage III patients had tumor recurrences within one year, while six are alive and free of melanoma at a median interval of 22 months. The remaining five patients (stage I or II) had level 4 or 5 (Clark classification) primary lesions. Their average tumor-free survival has been 18 months, but there was one regional recurrence in six months. Eight patients received intralesional treatment with BCG. The extent of local response correlated inversely to the stage of their disease. Higher doses of BCG or multiple simultaneous injections into the same lesion did not produce complete resolution of nodules in patients with far-advanced melanoma. In none was the course altered by intralesional therapy.


[Several methodologic problems of evolutionary histology in light of the findings of molecular genetics].

The paper elucidates certain methodological problems of evolutionary histology. The principal attention is given to the necessary synthesis of modern molecular biology and genetics and evolutionary histology. Modern data on the levels of the organization of the living matter and their significance for the rightness of the A.A. Zavarzin's theory of parallel lines in the tissue evolution are presented. The hypothesis of an application of the theory of parallel lines in the hereditary variability by N.I. Vavilov to the analysis of regularities of the tissue evolution is set forth. The hypothesis is proposed that mutation changes of similar genes in representatives of different types of animals underlie the regularities of the tissue evolution discovered by A.A. Zavarzin, and epigenomic changes of regulation systems occurring most frequently in the process of ontogenesis of organisms lie in the basis of the divergent evolution of tissues after N.G. Chlopin.


[The evolutionary principle in histology].

The A.A. Zavarzin's law of parallel lines in tissue evolution showing the appearance of a common tissue organization pattern is the major regularity of the cellular development of animals in phylogenesis. It carries out the metabolism principally similar in all animals in their interaction with the environment. The A.A. Zavarzin's law of parallel lines is also the main regularity of the evolution of tissue interrelations bringing about the principal processes of metabolism. The tissue evolution as well as the evolution of the organism is under the influence of factors of heredity, variability and natural selection. These factors however have an influence mediated by the organism evolution. The precess of cephalization represents a fairly important manifestation of the evolution of animals. The theory of general histogenesis reflects the main regularity of the cellular development in ontogenesis of man and animals. Being a further development of the conception of the A.A. Zavarzin's tissue evolution this theory shows the development of the animal cellular structure as a single general process of histogenesis, beginning with a zigote and continuing till the end of the organism life. The integration, heterochronia and determination manifest themselves in this process of differentiation of cells, tissues and intertissue relations.


[The morphology of the endocrine portion of the amphibian pancreas].

It has been shown that the endocrinous part of the pancreas in amphibia is formed of A-, B- and D-cells. B-cells are always disposed around sinusoid capillaries, while A- and D-cells lie on the islet periphery and often have no contact with capillaries. In addition to islets in the pancreas there are remnants of the so-called "external" epithelium which is represented by solitary B-cells, located in the wall of small excretory ducts. In the periinsular zone there are numerous acino-islets of A-, B- and D-types among which B-cells are prevailing.


[An electron microscopic study of the interaction between salmonellae and the epithelium of rat ileum].

Electron-microscopy studies of the interaction between salmonellas and the epithelium of the ileum in rats showed that the microbes penetrated into enterocytes of rats in crypts. This is, apparently, associated with the absence of manifested glycocalix on the plasmatic membrane of microvilli of the crypt cells. Salmonellas penetrated into cells, as it seems, during the rupture of the apical plasmatic membrane. The salmonellas found in the prismatic cells showed no signs of degeneration nor digestion. Organells of the epithelial cells in the intraepithelial localization of salmonellas did not undergo any essential changes.


[Morphologic features of lymph and blood circulation in lymph nodes in leukemia].

In studies of the lymphatic microcirculation bed in 300 neck and mesenterian lymph nodes taken from 27 patients who had died of systemic diseases, its transformation into lymphatic channels histogenetically connected with various processes in the nodes, was established. The rearrangement of the lymphatic microcirculation bed of the node developed concomitantly with that of the blood circulation bed. In the process of their transformation it seems possible to single out three phases with characteristic stereomorphological (macro-microscopic) and pathomorphological changes - compensation, decompensation and reduction. In reduction of the lymphatic microcirculatory bed around the lymph nodes, as manifestation of compensation, there were formed collaterals. Due to chronic congestion of the lymph, non-affected lymph nodes drastically dilatated and in their walls developed secondary changes in the form, of hyperthophy, varicosis sclerosis and hyalinosis. In the affected lymphatic vessels infiltrative-destructive processes developed.


[Spot marking of photo-optic preparations intended for ultratomy].

The possibility of a highly precise spot marking of those areas of the tissue which are of interest for the investigator of the group and individual cells revealed during the photo-optic investigation of preparations, is of particular importance for their subsequent ultrastructural studies. However, the markers used new for marking photo-optic preparations, whose effect is based on the principle of delineation and of the area concerned, suffer a number of shortcomings, one of them being the impossibility to variate while marking the geometrical form of the mark on the preparation and to apply to it simultaneously more than one mark. In combined photo-optic and electron-microscopy studies of preparations it would be invaluable to apply a highly precise spot marker capable of applying simultaneously to the preparation two marks differing from each other by their geometrical form. In this case, the process of formation of "pyramid" would have been considerably easier for the investigator during the preparation of the specimen for ultratomy. Exactly this kind of a highly precise spot universal marker based on the principle of stamping has been designed and used by the author.


[New classification of tumor lesions of the hematopoietic and lymphatic tissues and use of these classifications in prosector practice].

The author presents a review of the world medical literature reports on the latest classifications of tumours of the hemopoietic and lymphatic tissues, based on new concepts of the hemopoiesis system. Changes in the interpretation of the meaning of such terms as "reticular cell", "reticulosis", reticulosarcoma", "hemocytoblastosis", and others are discussed. A contraversial nature of many new concepts and incompleatness of the discussion concerning the problem are emphasized. The author is one of the opinion that it would be better to abstain from the use of new classifications and from alterations in terms in practical work of pathologists before the appearance of a unified international classification of the tumours in question. Further studies of new theoretical aspects of the problem and continuation of detailed morphological, including histochemical, immunomorphological and other investigations of the substrate of tumour lesions of the hemopoietic and lymphatic tissues are recommended.


[Reeducation and spontaneous recovery of motor function in lesions of the nervous central system].

A review is made of the current concepts on the several techniques (kinesitherapy programs) used with the purpose of recovering motor impairments caused by damage of the central nervous system. In this way data are gathered for the discussion and explanation of the intricate mechanisms involved in reeducation and recovery of the motor ability.


[Pyrrolidine acetamide as an auxiliary drug in the treatment of cerebral palsy].

Twenty children, with the diagnosis of cerebral palsy (CP) and under classical, physiotherapeutical and pedagogical, treatment, received piracetam (pyrrolidine acetamide) as an auxiliary drug. The goal was to better spasticity, learning and nervous instability problems aiming at better results of over-all treatment of CP. The group that received the drug has been compared to a control group of 20 children treated by the customary treatment only. The comparison showed favourable results for the medicated group. The drug was administered in the dose of 80 mg/kg/day during 10 weeks. The criteria for evaluation have been psychological, clinical, physiotherapeutical and pedagogical. The drug has been given in a new form of presentation: 6% solution for oral use.


Baseball implant. A method of secondary insertion of an intraorbital implant.

A surgical technique for secondary emplacement of an orbital implant is described in which a spherical implant encased in a scleral homograft is placed in the orbit through a transconjuctival incision and sutured to the superior part of the periosteum.


Herpes simplex of the epiglottis.

Herpes simplex commonly affects only the lips and oral cavity. We report a case of a herpetic lesion that appeared to be a carcinoma localized to the epiglottis. The lesion resolved spontaneously within a month. The diagnostic value of viral culture, serological testing, and immunofluorescence, as well as histopathological evaluation is assessed, and a brief review of upper-respiratory tract herpetic disease is presented.


Paravertebral lumbar myelomeningocele: a report of three cases.

Three cases of lateral myelomeningocele in the lumbar region are reported because of their rarity. It is stressed that in these laterally placed cystic swellings spinal dysplastic conditions should be also considered. The literature is briefly reviewed.


[Functional significance of the columnar structure of the stratum corneum and its occurrence on free autologous skin grafts].

The morphological presentation of the stratum corneum and simultaneously measurements of the alkali resistance and alkali neutralization time of the skin have been carried out in 26 guinea pigs. Whereas we could not demonstrate any association between the alkali neutralization time and the structure of the stratum corneum, a significantly better alkali resistance of the skin could be found when the columnar structure of the stratum corneum was most pronounced. The structure of the stratum corneum on full thickness skin autografts was also compared to that of normal skin in 26 animals. The columnar structure can be just as well pronounced on grafts as on normal skin. Significant differences between graft and normal skin could not be demonstrated but random samples showed that a disturbance in the columnar structure occurred more often in the grafts.


Hormonal control of Luteal 20alpha-Hydroxy steroid dehydrogenase and delta5-3beta-hydroxy steroid dehydrogenase during luteolysis in the pregnant rat.

Treatment of pregnant rats with human chorionic gonadotrophin, luteotrophin (luteinizing hormone), luteotrophin-releasing hormone, prostaglandin F2alpha, aminoglutethimide, or by foetoplacental removal or hysterectomy achieved a common multiple-response pattern, namely increased activity of luteal 20alpha-hydroxy steroid dehydrogenase with decreased activity of delta5-3beta-hydroxy steriod dehydrogenase and release of delta4-3-oxo steroids in vitro. 2. Similar effects of foetoplacental removal are noted in pregnant mice. 3. Gonadotrophin induced lower activities of 20alpha-hydroxy steroid dehydrogenase, except at the very end of pregnancy, and partly inhibited the induction caused by foetoplacental removal. 4. The results suggest that existence of a placental factor that restrains these changes until the end of normal pregnancy, which is produced in amounts proportional to the number of placentae and is conveyed to the ovary via the blood. 5. This factor was not replaced by prolactin. 6. It is argued that neither placental lactogen nor pituitary luteotrophin participate in the induction of 20alpha-hydroxy steroid dehydrogenase at late pregnancy in the rat. 7. Aminoglutethimide induced 20alpha-hydroxy steroid dehydrogenase only in late pregnancy. This was partly reversed by progesterone, wholly reversed by progesterone plus oestrogen, and did not involve the pituitary.


The pentose cycle and insulin release in isolated mouse pancreatic islets during starvation.

When islets from mice were incubated with 16.7 mM-glucose, previous starvation for 48 h decreased the rate of insulin release by approx. 50% and glucose utilization was decreased by approx. 35%. The maximally extractable activity of glucose 6-phosphate dehydrogenase was diminished by 28% after starvation. The formation of 14CO2 from both [1-14C]glucose was, however, higher than the rate of oxidation of [6-14C]-glucose in islets from both fed and starved mice. The fraction of glucose utilized that was oxidized (specific 14CO2 yield) ranged from one-fifth to one-third and was higher in islets from starved mice with both [1-14C]glucose and [6-14C]glucose as substrate. The contribution of pentose-cycle oxidation to total glucose metabolism was small (3% in the fed state and 4% in the starved state). The absolute rates of glucose carbon metabolism via the pentose-cycle oxidation to total glucose metabolism was small (3% in the fed state and 4% in the starved state). The absolute rates of glucose carbon metabolism via the pentose cycle and the turnover of NADPH in this pathway were identical in islets from fed and starved animals. After incubation at 16.7 mM-glucose for 30 min the contents of glucose (6-phosphate and 6-phosphogluconate were both unchanged by starvation. It is concluded that there is no correlation between the decreased sensitivity of the insulin secretory mechanism during starvation and the metabolism of glucose via the pentose cycle, the islet content of glucose 6-phosphate or 6-phosphogluconate.


Functional anaerobic electron transport linked to the reduction of nitrate and fumarate in membranes from Escherichia coli as demonstrated by quenching of atebrin fluorescence.

Measurements were made of energy-dependent quenching of atebrin fluorescence in membrane particles prepared from Escherichia coli grown anaerobically with glycerol as carbon source in the presence of either nitrate or fumarate. It is concluded that this technique can be used to study the functional organization of the anaerobic proton-translocating electron-transport chains that use nitrate or fumarate as terminal electron acceptor.


The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies.

The rate of oxidation of 14C-labelled fatty acids and of ketone bodies was measured in isolated pancreatic islets of obese-hyperglycaemic mice (ob/ob). The following main observations were made. 1. Octanoate, palmitate and oleate were all converted into CO2 by the pancreatic islets. Octanoate was oxidized with the highest rate followed by palmitate and oleate. 2. The rate of oxidation of 0.7 mM-palmitate was 3.1 pmol/h per mug drug weight. This was decreased by 50% in the presence of 16.7 mM-glucose. The rate of palmitate oxidation was also inhibited by 2-bromostearate. The palmitate oxidation showed a concentration-dependent increase, which was most marked between 0.25 and 1.0 mM. 3. Octanoate (5 mM) had no effect on the rate of oxidation of 3.3 mM- glucose. 4. Acetoacetate (5 mM) and D-3-hydroxybutyrate (5 mM) were oxidized at rates of 5.9 and 5.4 pmol/h per mug dry weight respectively. These rates were less than 10% of those found in kidney-cortex slices. The magnitude of the oxidation rates found for fatty acids and for ketone bodies suggest that these substrates represent important metabolic fuels for the pancreatic B-cells.


The association of yeast phosphoglycerate kinase (EC 2.7.2.3).

1. A mol.wt. of 40030 +/- 830 has been estimated for phosphoglycerate kinase in concentrations less than 0.1 g/100 cm3 comparing favourably with expected values from X-ray diffraction measurements by 10% lower than the previously reported molecular weights made at higher concentrations. 2. The so20w, was estimated to be 3.12(+/-0.02)x10(-13)s and the coefficient had a low concentration dependency giving a g value (concentration-dependency) of 2.3 +/- 1.6cm3 .g-1. This agrees with previous qualitative observations. 3. By using fluctuation-intensity spectroscopy, the D20,w was estimated to be 7.4(+/-0.2)x10(-11)m2.s-1, and this was indistinguishable from the D20,w calculated from ultracentrifuge results. The water of hydration was estimated to be 0.46 g/g of protein. 4. It is inferred from the estimates that phosphoglycerate kinase associates with an interaction coefficient at 20 degrees C for monomer/dimer of between 10 and 12 cm3.g-1. 5. The ratio of molecular asymmetry (a/b) was estimated to be 2.5+/-0.2 from the values of D20,w and water of hydration. This compares favourably with the ratio from the overall dimensions estimated from X-ray diffraction measurements.


The extraction and purification of a cysteine transfer ribonucleic acid from baker's yeast.

1. A modification of the RPC 1 system of A.D. Kelmers, G.D. Novelli & M.P. Stulberg (1965) (J. Biol. Chem. 240, 3979-3983) is described in which the support medium is a Celite of narrow range particle size treated with dichlorodimethylsilane. 2. By using this system an apparently pure preparation of tRNA Cys was isolated from baker's yeast tRNA. 3. This preparation accepted at least 60% of the theoretical quantity of [3-14C]cysteine in a conventional assay and failed to accept isoleucine, phenylalanine, proline, serine or tyrosine. 4. A theoretical countercurrent-distribution curve calculated by assuming a distribution coefficient K of 2.03 was in excellent agreement with the profiles of E260 and cysteine-acceptor ability after 537 transfers in the 1.85 M-phosphate/formamide/propan-2-ol system of C.M. Connelly & B.P. Doctor (1965) (J. Biol. Chem. 241, 715-719). 5. Chromatography of tRNA Cys on Bio-Gel P100 polyacrylamide beads afforded two components one of which was far less efficient than the other in accepting cysteine. The base compositions of the two were similar.


Acrolein, an irreversible active-site-directed inhibitor of deoxyribose 5-phosphate aldolase?

The enzyme deoxyribose 5-phosphate aldolase was irreversibly inactivated by the substrate analogue acrolein with a pseudo-first-order rate constant of 0.324 min-1 and a Ki (apparent) of 2.7 x 10(-4) m. No inactivation was observed after prolonged incubation with the epoxide analogues glycidol phosphate and glycidaldehyde. It is suggested that the acrolein is first activated by forming a Schiff base with the enzyme active-site lysine residue and it is the activated inhibitor that reacts with a suitable-active-site nucleophile.


A rapid immunological procedure for the isolation of hormonally sensitive rat fat-cell plasma membrane.

1. A rapid method for the isolation of hormonally sensitive rat fat-cell plasma membranes was developed by using immunological techniques. 2. Rabbit anti-(rat erythrocyte) sera were raised and shown to cross-react with isolated rat fat-cells. 3. Isolated rat fat-cells were coated with rabbit anti-(rat erythrocyte) antibodies, homogenized and the homogenate made to react with an immunoadsorbent prepared by covalently coupling donkey anti-(rabbit globulin) antibodies to aminocellulose. Uptake of plasma membrane on to the immunoadsorbent was monitored by assaying the enzymes adenylate cyclase and 5'-nucleotidase and an immunological marker consisting of a 125I-labelled anti-(immunoglobulin G)-anti-cell antibody complex bound to the cells before fractionation. Contamination of the plasma-membrane preparation by other subcellular fractions was also investigated. 4. By using this technique, a method was developed allowing 25-40% recovery of plasma membrane from fat-cell homogenates within 30 min of homogenization. 5. Adenylate cyclase in the isolated plasma-membrane preparation was stimulated by 5 mum-adrenaline.


Membrane attachment of folded chromosome of Escherichia coli.

By fractionation of the envelope part of membrane-associated folded chromosomes it is shown that only the outer membrane is bound to the DNA. Experiments with the M-band technique suggest the presence of attachment points for the membrane also in membrane-released folded chromosomes.


Serial 3 orthogonal lead electrocardiographic abnormalities after pulmonary embolism. Computer assisted study.

The 3 orthogonal lead electrocardiogram has been evaluated with computer assisted interpretation in 20 patients with acute pulmonary embolism confirmed by pulmonary angiography. Initial 3-lead electrocardiographic abnormalities were found to be at least as helpful as the 12-lead electrocardiogram in supporting the clinical diagnosis. In addition, however, sequential changes in both the maximum QRS and T vector orientations in frontal and transverse planes were more often apparent than any sequential changes in the 12-lead electrocardiogram. While no specific 3 lead electrocardiographic criterion for pulmonary embolism could be determined, this technique was more helpful than conventional methods in following serial electrocardiographic changes in patients with this condition.


Prolonged recovery after diazepam sedation: the influence of food, charcoal ingestion and injection rate on the effects of intravenous diazepam.

Thirteen subjects received diazepam 0.3 mg/kg i.v. twice with a 2-week interval between the doses. In seven subjects who had eaten at 3 h after the injection, reactive skills in a choice reaction test were impaired significantly (P less than 0.05) and there was a 20% increase in the serum diazepam concentrations at 5 h. When the meal was eaten at 7 h, a 50% increase (P less than 0.01) in the serum diazepam concentration was not associated with a significant impairment in psychomotor skills. In a second group of six subjects charcoal ingestion failed to hasten the clearance of diazepam from serum, and did not affect recovery of co-ordinative skills. In a third group of 12 subjects receiving diazepam 0.15 mg/kg i.v. twice at an interval of 2 weeks, the rapid injection of diazepam resulted in a significantly greater (P less than 0.05) degree of drooping of the upper eyelid and in a greater incidence of amnesia to abdominal pinching. The subjects also experienced more pain in the arm during the faster injection (P less than 0.01). Late effects on psychomotor skills were similar with both rates of injection. The results suggest that the remobilization of diazepam from its storage site after food intake induces a late impairment of psychomotor skills, especially if the food is eaten within less than 5 h after the injection. A rapid i.v. injection of diazepam induces greater sedative and amnesic effects than a slow injection of the same dose, but the slow injection of a greater dose is preferable because of the possibility of thrombophlebitis after rapid injection.


Intradermal study of a new local anaesthetic agent aptocaine.

In  a double-blind trial in 28 human volunteers, a new local anaesthetic agent, aptocaine, was compared intradermally at 1, 2 and 3% concentrations with lignocaine 2% and bupivacaine 0.5%. In a second trial in 27 subjects, 1% aptocaine was compared with mepivacaine and prilocaine, both 1, 2 and 3%. In terms of activity as determined by area of anaesthesia, and of duration of action, aptocaine was similar to mepivacaine and more active and long-lasting than lignocaine and prilocaine. By this route aptocaine also appeared longer-lasting than bupivacaine. Duration of action was unaffected by concentration. Aptocaine had marked vasoconstrictor activity, which was maximal at 1%. These local anaesthetic properties suggest that aptocaine merits clinical trials, especially in dentistry.


The adrenergic response to surgery involving cardiopulmonary bypass, as measured by plasma and urinary catecholamine concentrations.

Plasma and urinary catecholamine concentrations have been measured in 13 patients undergoing cardiac surgery involving cardiopulmonary bypass. The large and progressive increase in plasma catecholamines during bypass reported in previous studies has not been confirmed, and this may be a result of improvements in surgical, anaesthetic and perfusion techniques. The interpretation of urinary findings was complicated by the finding of a positive correlation between catecholamine excretion and urine flow-rate. The findings suggest the need to modify current concepts of the adrenergic response to cardiac surgery and bypass, and question the validity of measuring the urinary catecholamine concentration as an index of stress in these circumstances.


Ligation of patent ductus arteriosus in premature infants.

Twenty-four neonates at 25-34 weeks' gestation with a weight range of 570-1530 g underwent ligation of patent ductus arteriosus (PDA). The infants had mild to severe respiratory distress syndrome at birth and later developed signs of heart failure as a result of left-to-right shunting through a PDA. Surgical closure of the PDA was performed within 2-31 days after birth. In the period before operation the heart rate was monitored constantly and the arterial blood-gases were assessed frequently. The trachea was intubated and respiration was controlled with a ventilator. Surgery was performed under controlled ventilation and no anaesthesia was used. Care was taken not to overventilate the lungs. Nine infants died. Death was associated with higher peak inspiratory ventilator pressures at the time of operation and with complications occurring during or after the operation. The most common complication was tension pneumomediastinum which appears to be related to excessive ventilator pressures during surgery.


Subanaesthetic dosage of Althesin as a sedative for conservative dentistry. A controlled trial.

A randomized partial cross-over clinical trial of two intravenous techniques for outpatient conservative dentistry was performed in 61 patients. Subanaesthetic incremental doses of Althesin were used at 52 sessions and a single sedative dose of diazepam at 45 sessions. Each technique produced similar cardiovascular and respiratory changes. With Althesin, recovery after operation was more rapid and there was some evidence of a stronger anxiolytic effect and of less frequent and less severe thrombophlebitis. In contrast, Althesin was sometimes associated with jaw tremor or shivering and was less frequently mentioned by those patients who expressed a strong preference for one of the two techniques.


Neutrophil function in lymphoreticular malignancy.

Neutrophil function has been assessed in 62 patients with lymphoreticular malignancy by means of the NBT test and an in vitro micro-organism killing technique. Normal or enhanced phagocytosis was found, the greatest enhancement being found in patients with disseminated disease (in the absence of infections). Candicidal capacity alone was depressed in 7 patients but 4 of these showed depressed cell-mediated immunity to Candida antigen. Splenectomy, radiotherapy and chemotherapy did not alter phagocytic function.


Severe hereditary haemolytic anaemica in dogs treated by marrow trasplantation.

Severe hereditary haemolytic anaemia related to pyruvate kinase deficiency occurs in Basenji dogs homozygous for this autosomal recessive defect. In the current study, three anaemic dogs were treated by total body irradiation and marrow transplantation from non-anaemic histocompatible littermates with resultant complete correction of their haemolytic anaemia. The possible use of marrow transplantation for life-threatening haemolytic anaemias in man is discussed.


The clinical diagnosis of major congenital abnormalities of the fetal central nervous system.

During the ten years between 1965 and 1974, 207 infants with a major congenital abnormality of the central nervous system were born at Mill Road Maternity Hospital, Liverpool; open neural tube defects occurred in 92 per cent of cases. Only cases of anencephaly were frequently diagnosed clinically before labour and this was rarely so for spina bifida alone. Only 11 patients (5-3 per cent) had previously been delivered of an affected infant. The routine screening of pregnant patients is briefly discussed.


Hormonal patterns in conceptual cycles and early pregnancy.

Androstenedione, testosterone, progesterone and human chorionic gonadotrophin (HCG) in plasma and total oestrogens, luteinizing hormone (LH) and HCG in urine were measured in five women during conceptual cycles and in early pregnancy. There were increased levels in plasma and urine of all the hormones measured between 12 to 48 days after ovulation except progesterone. The concentration of this hormone in plasma decreased during this time. The possible sources of these hormones in early pregnancy are discussed.


Single extra-amniotic injection of prostaglandins in viscous gel to induce abortion.

A single extra-amniotic injection of prostaglandin (PG) E2 or F2alpha in a highly viscous gel was administered to 230 patients to induce abortion between 9 and 24 weeks gestation. PGE2 doses of 1-0, 1-5, 2-0 or 3-0 mg induced abortion within 24 hours in 30 per cent, 75 per cent, 76 per cent and 70 per cent of patients respectively. The incidence of gastrointestinal side-effects was dose dependent, being 20 per cent, 35 per cent, 45 per cent and 70 per cent in the respective groups. A 10-0 Pmg dose of PGF2alpha induced abortion within 24 hours in 66 per cent of patients and 45 per cent had gastrointestinal side-effects. Abortion was more often complete with PGE2 (76 per cent) than with PGF2alpha (36 per cent). Immediate withdrawal of the catheter following PG administration did not influence induction-abortion intervals or 24-hour abortion success rates. This technique significantly reduced individual patient care and minimized the potential risk of intrauterine sepsis associated with extra-amniotic techniques requiring repeated or continuous PG administration.


Surgical correction of trachomatous cicatricial entropion.

A modified version of Wies's operation for the correction of cicatricial entropion is described, the most important modification being a different plane for the incision through the eyelid. The possible complications and their prevention are discussed.


Fitting contact lenses after keratoplasty.

Even when a clear corneal graft results from keratoplasty spectacles or contact lenses may still be needed for reasonable vision. In a series of patients treated at the contact lens department, Moorfields Eye Hospital, a transparent graft and functional improvement resulted in about 90 per cent of cases. One hundred of these successful cases are reviewed and the problems of achieving a reasonable visual acuity for the patients discussed. Of those who are needed a visual aid 41 preferred a corneal contact lens. The particular difficulties of fitting these are reviewed and the need for a flexible procedure to meet the varying circumstances emphasized. The methods adopted in the cases under review are described. In the 100 eyes visual acuities of 6/6 were attained in 29, 6/9 in 36, and 6/12 in 17.


Interaction specificity of the anthracyclines with deoxyribonucleic acid.

The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.


Control of ribonucleic acid synthesis in eukaryotes. 2. The effect of protein synthesis on the activities of nuclear and total DNA-dependent RNA polymerase in yeast.

A thermosensitive conditional yeast mutant (ts-187) which suppresses protein synthesis at the nonpermissive temperature (36 degrees C) also suppresses RNA synthesis. The effect of temperature on the mutant is similar to the addition of cycloheximide--it inhibits the incorporation of labeled precursors into RNA in both whole cells and isolated nuclei. The effect of temperature is selective for the RNA polymerases bound to the nuclear template but not for the total RNA polymerases. Thus, the specific activities and total amounts of RNA polymerase species extracted and assayed with exogenous DNA template are similar in the ts-187 cultured at 23 degrees C and at 36 degrees C. On the contrary, the nuclear polymerases, i.e., RNA synthesis in isolated nuclei, are dramatically inhibited in cells cultured at 36 degrees C. When amino acid starved ts-187 cells are transferred to 36 degrees C, release from the inhibtion of RNA synthesis is observed. As with the addition of cycloheximide, this relaxation is observed in cells but not in isolated nuclei. The parental strain, A364A, which responds by stimulating instead of inhibiting protein synthesis when the temperature is increased to 36 degrees C, also exhibits an inhibition in the incorporation of labeled precursor into RNA as well as reducing RNA synthesis in isolated nuclei. However, these are transitory inhibitions and afterward there is reinitiation of both processes. Reinitiation of RNA synthesis in isolated nuclei is similar to the relaxed phenomenon and it is called "nuclear relaxation". This relaxation can only be obtained if protein synthesis is not inhibited; however, cellular relaxation occurs in the absence of protein synthesis. The repression of the nuclear RNA polymerase activities which starvation and inhibition of protein synthesis produce appears to be due to a restriction in the nuclear DNA template. This notion is supported by the fact that a net diminution of these nuclear enzyme activities is observed in spheroplasts cultured under starving conditions. Studies of the four main ribonucleotide pools indicate that stringency and inhibition of protein synthesis (ts-187 cultured at 36 degrees C) produce an increase in UTP and CTP pools. This is consistent with the concept that stringency and inhibition of protein synthesis affect the rate of utilization rather than the synthesis of these ribonucleotide residues. In the A364A and ts-187 yeast strains, the conversion of uracil but not of uridine into the UTP and CTP is inhibited when there is inhibition of the nuclear RNA polymerases. This indicates that the uracil phosphoribosyltransferase but not the uridine-cytidine kinase is allosterically inhibited by UTP and CTP in yeast. The feedback inhibition in the metabolic pathway of the base explains why relaxation cannot be detected when uracil instead of uridine is used as the labeled RNA precursor.


Control of ribonucleic acid synthesis in eukaryotes. 3. The effect of cycloheximide and edeine on rna synthesis in yeast.

The addition of cycloheximide to a thermosensitive conditional yeast mutant (ts-187) before and after transfer to the nonpermissive temperature (36 degrees C) for initiation of protein synthesis produces the uncoupling of the RNA and protein synthetic machineries. Since the drug can produce this relaxation in the presence and absence of protein synthesis, it is concluded that the coupling of protein and RNA synthesis, which a temperature shift produces, is not exclusively related to the inhibition of protein synthesis. Support for this assumption has been obtained using the parental (A364A) strain. Transferring this strain to 36 degrees C produces inhibition of RNA synthesis in the presence of stimulation of protein synthesis. Furthermore, cycloheximide and edeine prevent this inhibtion of RNA synthesis that temperature shift produces. It is, therefore, postulated that this inhibition of RNA synthesis results from the synthesis or activation of a factor(s) elicited by the increase in temperature whose function is to repress the transcriptional apparatus. Cycloheximide or edeine can prevent the function of this repressor-like factor by binding to the factor or by preventing its synthesis. The fact that inhibition of protein synthesis either by cycloheximide action or temperature shift in ts-187 produces inhibition of RNA synthesis in isolated nuclei indicates that, in addition to the aforementioned repressor, other factor(s) having a promoter function may exist. Since a slight inhibition of protein synthesis produces nuclear template restrictions, it is postulated that the promoter-like factor(s) is a polypeptide different from the RNA polymerase and, at least in yeast, has a high turnover.


Affinity labeling of Escherichia coli DNA-dependent RNA polymerase with 5-formyl-l-(alpha-D-ribofuranosyl)uracil 5'-triphosphate.

5-Formyl-1-(alpha-D-ribofuranosyl)uracil 5'=triphosphate has been used to affinity label E. coli DNA-dependent RNA polymerase. It is a noncompetitive inhibitor of the enzyme with Ki=0.54 mM. A short preincubation of the enzyme and alpha-fo5UTP is required to achieve maximum inhibition, and the entent of the inhibition is dependent upon the alpha-fo5UTP concentration. When a preincubation mixture of alpha-fo5UTP/enzyme is diluted, the enzyme regains activity with time showing that the inhibition is reversible, presumably occurring by Schiff base formation between an amino group on the enzyme and the formyl group. Upon sodium borohydride reduction of an enzyme/alpha-fo5UTP preincubation mixture the enzyme is irreversibly inhibited. alpha-fo5UTP is more effective in inhibiting the enzyme than alpha-fo5U, and the inhibition is decreased by the presence of ATP, UTP, or GTP in the preincubation mixture, suggesting that inhibition is occurring at a triphosphate binding site. The stoichiometry of binding of alpha-fo5UTP to the enzyme was determined using the gamma-32P-labeled derivative. After a 20-s preincubation of enzyme/alpha-fo5UTP followed by NaBH4 reduction the stoichiometry of binding was 1.1:1 (alpha-fo5UTP bound: inactivated enzyme), and this rose to 2.42:1 after a 10-min preincubation. After a 20-s preincubation the [gamma-32P]-alpha-fo5UTP was shown to be located on the beta subunit of RNA polymerase by cellulose acetate electrophoresis in 6 M urea.


4-Thiouridine, a built-in probe for structural changes in transfer RNA.

The luminescence of an aqueous solution of 4-thiouridine was compared with its emission when forming part of the polynucleotide chain of tRNA. In both cases excitation into the last absorption band at 335 nm yields a weak emission in the 520--550 nm region. However, while in aqueous solution this emission has a lifetime of approximately 240 ns, it increases in native tRNA to tau congruent to 6.6 mus. Oxygen and Cl- ions quench the thiouridine emission efficiently in aqueous solution while Na+ and Mg2+ ions have no influence on it. On the other hand thiouridine which forms part of a tRNA molecule is quite insensitive to Cl- ions and to O2 while its emission is greatly enhanced by Na+ and Mg2+ ions. From these salt effects as well as from data on the temperature dependence of the emission yield and the decay curve, it is concluded that the site of the thiouridine residue is very well protected within the tertiary structure of tRNA. Both permanent changes in the secondary and in the tertiary structures of the polynucleotide as well as dynamic conformation changes can be observed by following the emission characteristics of its thiouridine residue.


Spatial relationship of the sigma subunit and the rifampicin binding site in RNA polymerase of Escherichia coli.

sigma subunit of Escherichia coli RNA polymerase is known to stimulate specific RNA chain initiation. Rifampicin, an inhibitor of RNA chain initiation, binds to a single site on the beta subunit of RNA polymerase. We have used the fluorescence energy transfer technique to deduce proximity relationships of sigma subunit and rifampicin binding site on the enzyme. Isolated sigma subunit was covalently labeled with fluorescent donors in two ways: specific labeling of a single sulfhydryl residue with N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonate (1,5-I-AENS) and nonspecific labeling on the surface of the protein with dansyl chloride (Dns-Cl) adsorbed on Celite. The labeled sigma subunits were biologically active and formed a stoichiometric complex with core polymerase. The efficiency of energy transfer was obtained from the fluorescence intensity and the excited-state lifetime of the sigma-labeled holoenzyme in the presence and absence of rifampicin, which served as an energy acceptor. The transfer efficiency (2%) from AENS to rifampicin placed AENS somewhere between 42 and 85 A away from the rifampicin binding site. The rotational mobility of the donor was determined by nanosecond fluorescence depolarization spectroscopy, while the acceptor orientation was assumed to be fixed at some unknown angle. The efficiency measured for energy transfer from Dns to rifampicin was 10% in the presence of 0.2 M KCl. The distance from the surface of sigma subunit to the rifampicin binding site was calculated to be 27--38 A for a model having a randomly distributed and oriented array of donors on the surface of a spherical sigma subunit of 31-A radius. Our results indicate that rifampicin does not inhibit the initiation of transcription by RNA polymerase through a direct interaction with sigma subunit. In addition, energy transfer measurements under low salt conditions suggest that in RNA polymerase dimer the two rifampicin binding sites are symmetric with respect to each sigma subunit.


Physicochemical and kinetic properties of iodinated yeast 3-phosphoglycerate kinase.

The present studies have established that there is a critical tyrosyl residue in yeast 3-phosphoglycerate kinase. The iodination of this enzyme results in an inactivation following first-order kinetics. The extent of the modification is limited to only one tyrosyl residue. The monoiodotyrosine formation which leads to inactivation of the enzyme does not induce any significant conformational change as evidenced by hydrogen exchange and optical rotatory dispersion. The role of this tyrosine in the action of the yeast 3-phosphoglycerate kinase is studied. An effective protection against inactivation is observed with 3-phosphoglycerate, and the characteristic spectral effect of 3-phosphoglycerate binding cannot be detected in the modified enzyme. It is concluded that the essential tyrosyl residue may play a role in substrate binding.


Fructose 1,6-bisphosphate: isomeric composition, kinetics, and substrate specificity for the aldolases.

13C NMR shows fructose 6-phosphate and fructose 1,6-bisphosphate to contain respectively 4.1 and 2.0% keto isomer at room temperature. The lower value for fructose 1,6-bisphosphate can be attributed to the electron-withdrawing effect of the C-1 phosphate. Measurements of the ring-opening rates of the alpha and beta anomers of fructose, 1,6-bisphosphate by an NMR line-broadening technique show them to be about 8 and 35 S-1, respectively, at pH 7.2, and 25degreesC. The value for the predominant beta anomer is threefold greater than the turnover rate of muscle aldolase so that, if the kinetic properties of the keto form were favorable, the reaction could proceed entirely through the keto form in solution. The kinetic properties of a fructose 1,6-bisphosphate(keto) analogue, 5-deoxyfructose, 1,6-bisphosphate, in the muscle aldolase reaction are more favorable (Vmax = 2.6, Km = 0.11 X 10(-6) M) than those of fructose 1,6-bisphosphate total (Vmax = 1, Km = 2.3 X 10(-6)M), giving a value of Vmax/Km that is 56 times greater for the 5-deoxy analogue. At the 2.0% concentration of the keto form this is sufficient to account for the steady-state rate and requires that the beta form, present at 40 times greater concentration, contributes little to the cleavage rate. With yeast aldolase the cleavage rate can be explained by the rapid spontaneous ring opening and reaction of the keto form with the enzyme. In view of the high rate of ring opening and the excellent properties of the keto form, previous rapid kinetic studies favoring action of cyclic forms may require reevaluation.


Properties of a major protein released from Escherichia coli by osmotic shock.

A large fraction of a constitutively synthesized polypeptide, comprising 5% of the total Escherichia coli protein, is released when plasmolysed cells are subjected to osmotic shock into ice-cold water. Since the protein is not liberated by the conversion of cells to spheroplasts, it is not a typical periplasmic protein. A complex pattern of association with the cell envelope indicates that it is bound to this structure in vivo. Its susceptibility to trypsin and its interaction with specific antibodies vary with the type of preparations used. Based on these observations, we postulate a peripheral location at the inner surface of the plasma membrane. The protein has been purified to homogeneity from osmotic shock fluid. It has a mass of 44 000 daltons. Some of its physical and chemical properties have been investigated. Most remarkable are its strongly aggregating and adhesive characteristics and its precipitation by vinblastine and calcium ions. These unusual properties, its presumed location, and the observation that it is present in large amounts (approximately 70 000 molecules per cell) suggest a structural role for this protein.


Codon-dependent rearrangement of the three-dimensional structure of phenylalanine tRNA, exposing the T-psi-C-G sequence for binding to the 50S ribosomal subunit.

Codon-anticodon interaction induces an allosteric rearrangement of the three-dimensional structure of Phe-tRNAPhe that exposes the T-psi-C-G sequence for binding to the C-G-A-A sequence of the 5S rRNA within the 50S ribosomal subunit. The conformational change in the tRNAPhe structure was followed by the binding of C-G-[3H]A-[3H]A to the T-psi-C-G sequence, as measured by equilibrium dialysis at 10 mM Mg2+. C-G-A-A (14 pmol) was bound to tRNAPhe in the complete system containing elongation factor Tu-GTP-Phe-tRNA-(uridylyl-3',5')7-uridine-30S ribosomes (100 pmol). At a Mg2+ concentration lower than 5 mM the rearrangement was dependent on elongation factor-Tu, whereas GTP could be replaced by guanylyl imidodiphosphonate. In the absence of elongation factor-Tu-GTP a sigmoidal C-G-A-A binding curve with respect to Mg2+ concentration was obtained, showing half-saturation at 6 mM Mg2+. To achieve the change in the tRNAPhe structure in the absence of 30S ribosomes, a twofold higher concentration of (uridylyl-3',5')7-uridine had to be used. A sigmoidal curve was obtained again when the Mg2+ dependence of the C-G-A-A binding was followed, with 12 pmol of C-G-A-A being bound to 200 pmol of Phe-tRNA. Since T-psi-C-G exposure should influence the binding of Phe-tRNA to 70S ribosomes, Phe-tRNA binding to 70S ribosomes was examined. In the "nonenzymatic" binding (i.e., no elongation factor-Tu-GTP) of Phe-tRNA a sigmoidal Mg2+ dependence was found, whereas the "enzymatic" binding (elongation factor-Tu-GTP present) showed a hyperbolic curve. With 30S ribosomes as controls, only hyperbolic binding curves were found. The Mg2+ dependence of AA-tRNA binding thus reflects the rearrangement of the tRNA structure.


Biosynthesis of yeast mannan. Independent formation of two carbohydrate moieties in the mannoprotein molecule.

The formation of two distinct types of carbohydrates moieties, beta-elminable saccharides attached to serine and/or threonine and of the polysaccharide portion of yeast mannan-protein was investigated using the particulate mannan synthetase from Saccharomcyes cerevisiae and GDP-[U-14C]mannose as mannosyl donor. The accumulated evidence obtained by following the kinetics of mannose incorporation into the different carbohydrate portions of mannoprotein, kinetics of thermal denaturation of enzymes responsible for their synthesis and by "pulse-chase" experiment where the change in the distribution of incorporated radioactivity was followed between the two carbohydrate moieties strongly suggests that the two carbohydrate portions in yeast mannoprotein are being synthesized independently, most probably by different sets of enzymes. At the same time, the obtained data show the beta-eliminable saccharides attached to serine and threonine in the peptide do not serve as precursors in the formation of polysaccharide part of mannoprotein.


Ascorbate-independent carotenoid de-epoxidation in intact spinach chloroplasts.

Slow (greater 1 s) light-induced absorbance changes in the 475-5300 nm spectral region were examined in Type A chloroplasts from spinach. The most prominent absorption change occurred at 505 nm. The difference spectrum for this light-induced increase, its absence in osmotically shocked chloroplasts and restoration by ascorbate, and its sensitivity to dithiothreitol indicate that the absorption change is due to carotenoid de-epoxidatiion. The reaction in intact chloroplasts is characterized by its independence of exogenous ascorbate and a rate constant 3- to 8-fold higher than that reported previously for chloroplasts supplemented with ascorbate. The relevance of carotenoid de-epoxidation to other photosynthetic processes was examined by comparing their sensitivities to dithiothreitol. Levels of dithiothreitol that eliminate the 505 nm shift are without effect on saturated rates of CO2 fixation and do not appreciably inhibit fluorescence quenching. We conclude that carotenoid de-epoxidation is not directly involved in the reactions of photosynthesis or in the regulation of excitation allocation between the photosystems.


Sugar transport and potassium permeability in yeast plasma membrane vesicles.

Plasma membrane vesicles were isolated from homogenised yeast cells by filtration, differential centrifugation and aggregation of the mitochondrial vesicles at pH 4. As judged by biochemical, cell electrophoretic and electron microscopic criteria a pure plasma membrane vesicle preparation was obtained. The surface charge density of the plasma membrane vesicles is similar to that of intact yeast cells with an isoelectric point below pH 3. The mitochondrial vesicles have a higher negative surface charge density in the alkaline pH range. Their isoelectric point is near pH 4.5, where aggregation is maximal. The yield of vesicles sealed to K+ was maximal at pH 4 and accounted for about one third of the total vesicle volume. The plasma membrane vesicles demonstrate osmotic behaviour, they shrink in NaCl solutions when loosing K+. As in intact yeast cells the entry and exit of sugars like glucose or galactose in plasma membrane vesicles is inhibited by UO22+. Counter transport in plasma membrane vesicles with glucose and mannose and iso-counter transport with glucose suggests that a mobile carrier for sugar transport exists in the plasma membrane. After galactose pathway induction in the yeast cells and subsequent preparation of plasma membrane vesicles the uptake of galactose into the vesicles increased by almost 100% over the control value without galactose induction. This increase is explained by the formation of a specific galactose carrier in the plasma membrane.


tRNA methyltransferases from rat liver. Differences in response of partially purified enzymes to polyamines and inorganic salts.

Three tRNA methyltransferases, purified from rat liver, have been compared for their activity in the presence of various amines and Mg2+. The enzymes differ with respect to the ion which permits maximal activity; they also differ with respect to the concentration of a given ion necessary for maximal activity. The methyltransferase which forms N2-methylguanine in the region between the dihydrouridine loop and the acceptor stem (2mG I), when assayed using purified tRNA as substrate, shows high activity with 3--5 mM sperimidine or 20 mM putrescine and significantly lower rates of methylation with 200--350 mM ammonium acetate or 1--10 mM magnesium acetate. The enzyme responsible for forming N2-methylguanine between the dihydrouridine and anticodon loops (2mG II) works well in the presence of 0.2--0.5 mM spermidine, 10 mM putrescine or 200--300 mM ammonium acetate and shows slightly lower activity with 1 mM magnesium acetate. The optimal conditions for assaying 1-adenine methyltransferase (1mA) with purified tRNAs are either 200--300 mM ammonium acetate or 30 mM putrescine; spermidine is slightly less effective and magnesium acetate permits less than 25% of maximal activity. The addition of 10 mM Mg2+, in combination with polyamines or NH4+, depresses slightly the activity of the guanine methyltransferases but completely abolishes the polyamine or ammonium-stimulated activity of the adenine methyltransferase. When unfractionated (Escherichia coli) tRNA is used as substrate, the concentrations of polyamines required for optimal methyltransferase activity are increased but the patterns of response of the three enzymes do not differ significantly from those obtained with purified tRNA substrates. Based on the studies with these three enzymes, unfractionated tRNA and 40 mM putrescine should provide the most reliable system for detecting methylating activity if the nature of the tRNA methyltransferase is unknown.


Reversible envelope effects during and after killing of Escherichia coli w by a highly-purified rabbit polymorpho-nuclear leukocyte fraction.

The effects of a highly-purified, potently bactericidal fraction from rabbit polymorphonuclear leukocytes on the envelope of Escherichia coli (W) have been examined. This leukocyte fraction has equally enriched bactericidal, permeability-increasing and phospholipase A2 activities, and is essentially devoid of lysozyme, myeloperoxidase and protease activities (Weiss, J., Franson, R.C., Beckerdite, S., Schmeidler, K. and Elsbach, P. (1975) J. Clin. Invest. 55, 33-42). Rapid killing of E. coli by this fraction is accompanied by two almost immediate alterations in the bacterial envelope: (1) a discrete increase in envelope permeability (measured by inhibition of bacterial leucine incorporation by normally impermeant actinomycin D), and, (2) hydrolysis of 14C-labeled fatty acid-prelabeled E. coli phospholipids. Both envelope effects are promptly reversed during further incubation at 37 degrees C, But not at 0 degrees C, with 40 mM Mg2+. Reversal is also produced by Ca2+ (40 mM) and trypsin (200 mug/ml), but 200 mM K+ causes only partial recovery and Na+ and hyperosmolar sucrose are ineffective. Upon addition of Mg2+, phospholipid degradation ceases abruptly and the labeled products of hydrolysis (free fatty acids and lysocompounds) disappear with a corresponding reaccumulation of radioactive diacylphosphatides. The time course of resynthesis of phospholipids coincides with that of restoration of the permeability barrier. Higher concentrations of the leukocyte fraction and prolonged incubation increase both the extent of phospholipid degradation and the time required for reversal of both envelope effects. These findings suggest that both the initiation of the increased permeability and its reversal are linked to respectively the breakdown and resynthesis of major E. coli membrane phospholipids, and thus depend on the fact that the biochemical apparatus of E. coli remains capable of biosynthesis despite loss of viability. Treatment of E. coli, exposed to the leukocyte fraction, with albumin results in extracellular sequestration of the products of hydrolysis and also restores the permeability barrier to actinomycin D, suggesting that the accumulation of lytic products of lipid hydrolysis within the bacterial envelope, rather than the loss of phospholipids per se, causes increased permeability Whereas the effects on the envelope are reversible as long as 2 h after nearly complete loss of ability to multiply by E. coli, the effect on bacterial multiplication is irreversible within 5 min.


Relationship between efflux of ionic calcium and phosphorus during excitation of pancreatic islets with glucose.

Simultaneous rates of [32P]orthophosphate and 45Ca2+ efflux from prelabeled rat pancreatic islets have been evaluated to assess whether these ions move in concert throughout all phases of "stimulus-secretion coupling". Perifusion with stimulatory concentrations of glucose elicited immediate but transitory increases in 32P outflow accompanied by initial retardations and subsequent augmentations in net 45Ca2+ outflows. These monophasic 32P and biphasic 45Ca2+ responses to secretory stimulation were abolished completely by membrane stabilization with tetracaine. However, certain manipulations enabled individual components to be modified separately. During stimulation with glucose, inhibition of insulin release by Ni2+ abolished the late increases in 45Ca2+ outflow without affecting the initial retentions of 45Ca2+ or the increased releases of 32P. Under basal conditions, the ionophore A23187 "triggered" increased releases of 45Ca2+ and insulin without prior retentions of 45Ca2+ or enhancements of 32P efflux. Thus, the immediate retardations of 45Ca2+ outflow and heightened efflux of 32P may reflect early events in stimulus-secretion coupling which can be dissociated from the augmented release of 45Ca2+ accompanying activated emiocytosis.


Effect of the lipid composition of Mycoplasma mycoides subspecies capri and phosphatidylcholine vesicles upon the action of polyene antibiotics.

(1) The effects of filipin and amphotericin methyl ester upon the K+ efflux from Mycoplasma mycoides subsp. capri and egg lecithin sonicated vesicles were investigated. Both the nature of the sterol and the composition of the membranes affected the sensitivity to each polyene antibiotic. (2) M. mycoides subsp. capri containing ergosterol was much more sensitive to amphotericin methyl ester than cells containing cholesterol. Cholesterol-containing cells were about twice as sensitive to filipin as the ergosterol-containing cells. These results were confirmed with phosphatidylcholine vesicles. (3) At 2 degrees C the filipin sensitivity of M. mycoides subsp. capri was independent of the membrane cholesterol content and the sensitivity towards amphotericin methyl ester decreased when the membrane cholesterol content was increased, in contrast to the results at 20 degrees C. (4) At 2 degrees C, sterol-free egg lecithin vesicles became very sensitive to both filipin and amphotericin methyl ester and the presence of cholesterol in the vesicles did not increase the sensitivity further. At high concentrations of cholesterol (greater than 30 mol%), the polyene antibiotic sensitivity, particularly towards amphotericin methyl ester, was greatly reduced.


Complete amino acid sequence of the heme-binding core in bakers' yeast cytochrome b2 (L-(+)-lactate dehydrogenase).

We are reporting here an analysis of the chymotryptic peptides obtained from the tryptic heme-binding fragment of flavocytochrome b2 (cytochrome b2 core). These results completely establish the sequence of the 96 residue-long fragment, for which preliminary evidence has been published before [24]. We also report full experimental details concerning the automatic degradation, the specific cleavages at the unique arginine and methionine residues, and the analysis of the tryptic peptides. In addition, it is shown that the main heme-binding fragment resulting from cytochrome b2 proteolysis by yeast proteases has an additional glutamic acid residue at the C-terminal end relative to the main tryptic heme-binding fragment. The slight sequence modifications presented here (amide groups and insertion of a lysine residue after position 71) do not substantially modify the comparison with liver microsomal cytochrome b5. A new sequence alignment is proposed for the two proteins, and a few structural considerations are presented, based on the inspection of calf liver cytochrome b5 three-dimensional model [50,51].


[Structure of a pepsin fragment containing the functionally important aspartic acid residue].

The structure of B-5 fragment obtained under degradation of pig pepsin by cyanogen bromide is determined. B-5 fragment is a central part of pepsin molecule and it contains 46 amino acids, including a functionally important aspartic residue of the active site of the enzyme. Amino acid sequence of B-5 fragment was established by means of sequenator analysis and of studying the structure of peptides isolated from B-5 fragments.


[Functions of bacteriophage T4 rII genes. Preparatory isolation and several properties of rIIB protein].

A method of preparative isolation of membrane rIIB protein from bacteriophage T4 is worked out. Conditions are found to maximal rIIB protein accumulation in membranes of E. coli cells infected with bacteriophage T4. The membrane isolation by ultracentrifugation is substituted with their sedimentation from polyethyleneglycol solutions by low-speed centrifugation. A fraction, enriched with rIIB protein, is obtained using the treatment of cell walls with detergents. Preparative polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate was used for further rIIB protein purification. The method described can be applied for the purification and preparative isolation of memorane and poor-soluble proteins. The problem on location and ufunctioning of rIIB protein is discussed.


[Trypsin peptides of the polyhedral protein from the B. mori virus of nuclear polyhedrosis].

Amino acid composition, partial or complete sequence of 43 tryptic peptides of pelyhedral protein of nuclear polyhedrosis virus is investigated. These peptides include 327 amino acid residues. There are 28 peptides with unique sequences containing 240 amino acid residues. It conforms to polypeptide chain molecular weight ca. 28000 and coincides with earlier reported data on polyacrylamide gel electrophoresis.


[Biospecific chromatography of chymosin].

Chromatography of commercial rennet was studied on biospecific sorbents obtained by means of coupling of activated Sepharose 4B with epsilon-aminocapronyl-D-phenylalanine methyl ester and amide, epsilon-aminocapronyl-L-phenylalanyl-D-phenylalanine methyl ester, gramicidin S and N-2,4-dinitrophenylhexamethylenediamine. A mixture of two similar on their specificity enzymes chymosin and bovine pepsin was isolated from rennet by the chromatography on these sorbents. The individual enzymes might be isolated by chromatography on immobilized ribonuclease at pH 3,0, or by means of electrofocusing in pH gradient 4-6. Coloured inhibitor of acid proteases, N-diazoacetyl-N'-2,4-dinitrophenyl-ethylenediamine (DDE) is found to inactivate chymosin at pH 5,6 in the presence of Cu2+,one residue of the inhibitor being attached to the enzyme molecule. Unlike pig pepsin, chymosin is not inhibited with DDE at pH 4,7 and at the enzyme:DDE:Cu2+ ratio being 1:40:40. a synthesis of peptide sorbents is described.


[Modification of the method of extracting DNA-polymerase from E. coli].

Described earlier method of isolation of E. coli DNA-polymerase is modified. In order to decrease the possible effect of proteases on DNA-polymerase, the time of autolysis was shortened. An additional stage of precipitation by ammonium sulfate of 65-80% of saturation was introduced. Chromatography on DEAE-Sephadex A-25 revealed 4 fractions exhibiting DNA-polymerase activity. It is established that combination of certain DNA-polymerase fractions, belonging to different peaks, significantly intensifies the enzyme activity. It may be due to the formation of enzymic complexes.


[Inhibition of bacterial agmatinase by several aliphatic diamines].

About 10 amino derivatives, capable to inhibit agmatinase of Proteus vulgaris, are found. Hexamethylenediamine was found to possess the highest inhibitory effect among diamines, the inhibitory constant being 2.5 mM. The substitution of an amino group for methyl one in a diamine increased its inhibitory effect. The presence of carboxyl group in the molecule of a reagent resulted in a complete elimination of the inhibitory effect (putrescine-ornithine and cadaverine-lysine pairs were tested). The degree of inhibition was found to be pH-dependent. A supposition is made on hydrophobic character of substrate binding by the enzyme.


Immune rejection of tumor cells: in vivo significance of anti-tumor in vitro immune reactions.

The mechanism of immune tumor rejection remains poorly understood. The respective roles of antibodies, macrophages, cytolytic T cells (CTL) and that of "K" cells or any other cell which could be involved in antibody dependant cell mediated cytotoxicity are still unknown. It is probable that the CTL play some role in tumor rejection but the "in vivo" relevance of the other, "in vitro" detected phenomena, is less clear. The correlations between "in vivo" tumor rejection and "in vitro" detected reactions are very difficult to establish, specially for the following two reasons: a) the different methods used in vitro do not explore identical phenomena ; b) some of them provide both specific and non-specific reactions.


[Diastolic reinforecement by intra-aortic balloon. Critical review of temorary mechanical ventricular assistance technic].

The treatment of the cardiogenic shock complicating acute myocardial infarction has been drastically improved by the progress in temporary mechanical cardiovascular support. The improvement of the synchronous assist device, such as the intra aortic balloon, associated with the progress in the monitoring of the patients, in the surgical treatment of myocardial insufficiency and ventricular abnormalities such as ventricular septal defect and mitral insufficiency, has changed the seroius prognosis in patients. A review of some theretical, physiological and clinical problems are discussed in this paper.


[Influence of allogeneic thymocytes on radioleukemogenesis in AKR-T1ALD mice].

When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrow cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S. : (i) early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and (ii) late L.S from donor cells. The present experiments were investigate the potential influence of normal allogenic thymic cells, with or without syngeneic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occurr significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differentiation of haemopoietic precursors at the expense of the lymphoid cells. Alternatively the thymic cells may co-operate with exogenic B.M., and stimulate their differentiation thus triggering them out of a stage whereby they could become a selective target for the Gross virus.


Evaluation of carrageenan as an immunosuppressive agent and mediator of intravascular coagulation.

Carrageenan suppressed antibody responses to SRBC in mice and rats, measured in terms of splenic IgM PFC production. The effect, in mice, was dependent on dose and on the temporal relationship between treatment and antigen administration. Carrageenan was found to alter the time course of the PFC response and also to produce disseminated intravascular coagulation. Some correlation between the observed effects and the use of chemically distinct carrageenans was found. The possible mode of action of carrageenan is discussed in the light of these, and other findings.


Relationship between Hassall's corpuscles and thymocytes fate in guinea-pig foetus.

The development and structure of the Hassall's corpuscles are studied with the light and electron microscope in 53 guinea-pig foetuses from 30 to 58 days gestation. The different stages of their life cycle are described. Prior to the appearance of Hassall's corpuscles, no medullary lymphocytes can be found in the early medulla. Hassall's corpuscles are seen initially between 35-42 days gestation. They are surrounded by large and medium-size lymphocytes, while medullary lymphocytes are in close contact with the "external cells" which exhibit cytoplasmic characteristics of a secretory function. The data reported in this paper suggest that Hassall's corpuscles are not the only sites of lymphoid cells destruction but are also "privileged" areas for maturation of medullary lymphocytes at least for the guinea-pig.


Assessment of ophthalmologic, endocrinologic and genetic findings in the Bardet-Biedl syndrome.

There is a great degree of heterogeneity of ophthalmologic and endocrinologic manifestations among patients with the Bardet-Biedl syndrome. The similarity of the atypical forms of retinitis pigmentosa and cone-rod degeneration indicates that definitive functional and electrophysical retinal work-ups should be performed on young patients with this syndrome. Since many cases of delayed puberty occur, the diagnosis of hypogonadism should be deferred until age 15. Segregation analysis on a large study of Bardet-Biedl syndrome in Switzerland differs from that expected with simple autosomal recessive inheritance. Excess affected males and deficient consanguinity are also documented. The occurrence of other family members with incomplete forms of the syndrome is noted in many reports in the literature. The authors propose that consideration be given to the hypothesis that the Bardet-Biedl syndrome may be transmitted by polygenic inheritance, since this would be compatible with features of the syndrome mentioned above.


Clinical and radiographic variations in hemifacial microsomia.

Variations expressed clinically and radiographically in hemifacial microsomia preclude classifying all the abnormalities as coming from the first and second branchial arches. Anatomic structures arising from the branchial arches are directly involved but the final expression results from the combined impact of the primary anatomic defect and the secondary effects on contiguous structures. The deformities resulting from the latter are probably due to abnormal neuromuscular function.


[Restoration of the osteogenic properties of bone marrow following irradiation according to the findings of heterotopic transplantation].

It was found that bone marrow obtained from the tibium or the femur (locally irradiated with 2000 R) and transplanted subcapsularly into the kidney of mice of the same strain 0-4 months after the irradiation was always resorpted. As to the bone marrow from the nonirradiated bones of the same donors--it always possessed osteogenic potencies. Stroma of the irradiated limb was defective ang failed to regenerate at the expense of repopulation of the stroma elements from the nonirradiated sections. Analogous conclusions were drawn on the basis of the experimental results with repeated irradiation of mice with the shielded extremity. In difference to the hemopoietic, stromal elements were incapable of repopulation (according to the data of heterotopic transplantation).


[Study of the dynamics of lymphocyte receptor affinity for hapten in the process of the primary immune response].

The affinity of the lymphocyte receptors for DNP-determinants was studied by free hapten inhibition of rosette-forming cells. The avidity of the antigen-binding lymphoid cells was found to increase with the advance of time after the immunization. The results suggest that an increase in the cellular avidity during the immune response depended on both the affinity of the gamma-globulin receptors and their concentration on the cell surface.


[Correlation between cytotoxic lymphocytes and cells that synthesize the macrophage migration inhibitory factor in the H-2 system].

High immunological specificity of the direct and indirect macrophage migration inhibition tests was demonstrated in the H-2 system. The capacity of immune lymphocytes for the MIF production was revealed under their incubation with splenic cells of the congenic or recombinant strains of mice sharing particular private or public H-2 specificities with the donor strains. Selective removal of cytotoxic fraction of lymphocytes resulting from their absorption on the corresponding target cells failed to reduce the capacity of the non-adherent cell population for the MIF production. A fraction of the MIF-producing lymphocytes was found to adhere to the target cells and thereafter to be eluated with the cytotoxic lymphocytes. MIF-producing and target-destroying T-lymphocyte populations are supposed to have antigen-binding receptors differing in their affinity and structural arrangement on the cell surface.


[Quantitative analysis of the ultrastructure of tumor tissue cell cultures].

Morphometry was applied to the study of the fine structure of the mitochondria, ergastoplasma and polyribosomal apparatus of the cells of the primary and continuous cultures of the tumour tissues. Both among the primary and among the continuous cultures there can be found marked differences in the fine structure of the cells of individual strains. However, as a whole these groups displayed a significant difference by organization of the cytoplasmic protein-synthesizing apparatus. Of the continuous cultures characteristic is a more reduced ergastoplasm and more marked polyribosomal apparatus. It can be supposed that for the tumour cells cultivation on glass served as a factor promoting a further reconstruction of the protein-synthesizing apparatus on the synthesis of the substrates necessary for the growth and multiplication of the cell mass.


[Morphofunctional changes in the cat pancreas after resection of the jejunum].

Experiments with resection of the jejunum were carried out in male cats. Changes in the structure of the exocrine and endocrine portion of the organ were studied histologically. Amylase and lipase activity and sugar content were determined in the blood. Hypertrophy and hyperplasia were discovered in the acinar portion of the gland in the course of 1 to 14 days of the experiment; in the endocrine portion it was present for 7 to 30 days. On the 21st, 30th and 180th days of the experiment an atrophic process was observed in the acinar cells; in the island cells it was seen on the 180th day only. The function of the exocrine portion of the pancreas was disturbed on the 2nd-21st days of the experiment, while that of the endocrine portion-on the 7th day only.


[Localization of antigens in common (cross-reacting) with Neisseria perflava and Klebsiella pneumoniae in the tissues of the human bronchopulmonary tract].

An attempt was made of detecting antigenic similarity beyween the fraction of microsomes of the tissues of human broncho-pulmonary apparatus and the cells of microbes of human respiratory tract. Cross reactions of antimocrosomal sera were studied in the complement fixation test with Neisseria perflava and Klebsiella pneumoniae. Fixation of antibacterial antibodies and antibodies against the microsomal fraction of the lung tissues was studied on the sections of the lung tissues ahd human bronchi. The presence in the microsomal fraction of tissues of human bronchopulmonary apparatus of the antigens cross reacting with antimicrobial sera was demonstrated.


[Distribution of a cross-reacting antigen common to epithelium and group A streptococci in human and animal tissues].

With the aid of pure antibodies to polysaccharide of streptococcus, of group A, there was revealed by the method of indirect immunofluorescence with the use of pure antibodies to rabbit immunoglobulins (labeled with fluoresceine isothiocianate) localization of the cross-reacting antigen common for streptococcus and tissues of man and animals in the cells of surface epithelium of the ectodermal origin (the skin, salivary ducts, oral mucosa, esophagus, inferior portion of the rectum, uterine cervix, and the elements of the thymus epithelium). Detection of the cross-reacting antigen was of interest in connection with the study of the mechanisms of development of chronic pathological processes in man associated with streptococcus infection and investigation of the structure, function and pathology of the thymus.


[The relationship between hemopoiesis and osteogenesis in several species of rodents].

Differentiation of the bone marrow transplants of rats, guinea pigs and dwarf hamsters placed under renal capsule of irradiated mice was studied. Active osteogenesis occurred in the transplants of rats and guinea pigs; as to hemopoiesis-it was irregular in rats and was arrested in guinea pigs. On the contrary, in the transplants of dwarf hamsters an intensive hemopoiesis was maintained and osteogenic capacity of the stroma was poor. It is supposed that the bone tissue in some rodent species was not a prerequisite for normal maintenance of myeloid hemopoiesis, while in others-primary bone stroma formation was necessary for the subsequent functioning of hemopoietic tissue.


[Mechanism of changes in lymphocyte dehydrogenase activity during heart transplantation].

A study was made of the activity of succinic dehydrogenase (SDH) and of the alpha-glycerophosphoric dehydrogenase (alpha-GPDH) in the peripheral blood lymphocytes and the transplant myocardium in the CBA mice in transplantation to them of the heart of newborn C57BL/6 mice into the pinna, subcutaneously. It appeared that the (see article) ratio in the myocardium and the lymphocytes of intact animals and also in the recipients of the isolinear transplant of the heart was greater than 1, but in allogenous transplantation this ratio became less than 1 on account of alpha-GPDH activation in the blood lymphocytes, which preceded the inversion in the transplant myocardium. It is supposed that the mentioned phenomenon was associated with the development of the immunological conflict.


[Nature and mechanism of plaque formation (vesiculocytosis)].

According to N. N. Klemparskaya the process of plaque formation in the peripheral blood was the result of erythrocyte hemolysis by autohemolysins released by immunocompetent mononuclears--lymphocytes and plasma cells. However, such interpretation was not confirmed in investigation of the mentioned process. Plaque staining, cinemicrography and other methods showed plaque formation to occur on account of drawing apart the erythrocytes, not their hemolysis, by the substances which was released from the cells as a result of destructive processes with vesicle formation (vesiculocytosis). No vital activity or division of these cells was observed in the blood preparations. Polynuclears -- chiefly neutrophils, not mononuclears, served as the plaque-forming cells.


[Growth inhibition of embryonic tissues transplanted to syngeneic newborn recipients].

Skin grafts of embryos and teratomas formed after the transplantation of ground tissues of embryos (18-20 day and 12-14-day) to neonatal syngeneic recipients were studied; it appeared that their growth was considerably delayed in comparison with analogous transplants in adult recipients. It is supposed that the organism of embryos and neonates has factors controlling the growth of embryonic tissues.


[Functional anatomy of the superfical temporal blood vessels].

Functional study on superficial temporal vessels. These vessels appear to have a board territory on--the horizontal part of the scalp--the superior lateral face--the anterior and superior half of the external ear The terminal part of these vessels and the rich anastomotic system is particularly studied. This system passes the middle line; the anastomoses are in the fascia superficilialis. Secondly there is a sub-dermal plexual formation which is in a parallel direction to the vessels. Practical consequences can be found--in neuro-surgery--in plastic-surgery--and in the new surgery of cutaneous transfer with micro-anastomoses of the vessels.


An experiment in teaching MEDLINE.

The design and implementation of an experimental MEDLINE module at Case Western Reserve University School of Library Science is described. The module places MEDLINE within the context of multiple data bases and networking operations andis embedded in a course in health science communications. The module consists of eight weeks of lectures, demonstrations, videotapes, and exercises on terminals.


Ilse Bry--a tribute.

The late Ilse Bry made numerous contributions to health science librarianship in the roles of scholar and librarian. Her professional interests lay in the literature and bibliography of the behavioral sciences; she served as Librarian of the New York Psychoanalytic Institute and later became the library associate in charge of the New York University Psychiatric Library. Upon leaving active librarianship Ilse Bry continued to work as a meticulous bibliographer and as Editor of the Mental Health Book Review Index.


Clinical application study of externally powered upper-limb prosthetics systems: the VA elbow, the VA hand, and the VA/NU myoelectric hand systems.

The results have been presented of a 2-year survey designed to determine whether external power systems offer a significant contribution to the needs of the upper-limb amputee or whether they represent novelties duplicating the functions of conventional mechanical components. The following conclusions have been drawn: 1. External power does offer advantages to the arm amputee. Myoelectric control, especially combined with a self-suspending socket, offers an otherwise normal partial forearm amputee better function without the necessity of a harness. External power, especially for the short partial or total arm amputee and others with limited excursion, brings increased function with less effort. For these patients the advantages of such components as the electric elbow outweigh the recent disadvantages. 2. The components evaluated in this Study are not without limitations. Maintenance requirements of the VA Elbow were excessive. The VA Elbow should not be prescribed for patients who do heavy work with their prostheses because the flexspline may break. Regarding such concerns as lack of sensory feedback, noise, weight, and flexion/extension speed, the advantages of each unit must be weighed against the disadvantages with preference to the individual amputee. 3. The endoskeletal forearm with soft cover is an advantage because of its lightness and cosmesis. 4. Because of the many malfunctions attributed to prosthetist errors, the need is evident for thorough specialized education in the field of external power. A few centralized fabrication facilities may be desirable as opposed to fabrication by many facilities with limited experience. Modular components that are interchangeable and field repairable would be desirable. The systems should be fitted, installed and repaired only by trained prosthetists who have successfully completed a course in externally powered upper-limb prostheses. All members of the Clinic Team should be thoroughly educated in external power as it is related to prosthetics. 5. Many malfunctions were due to patient misuse. Patients, too, after careful selection must be given thorough training in the care and use of externally powered components, including the limitations and capabilities of these devices. 6. Finally, and most important, the Clinic Team must be recognized as the focal point for the selection of patients and prescription of devices. Each patient must be carefully screened for information such as occupation, motivation, prosthesis use (as opposed to wear), ability to learn and follow through with instructions (charging batteries, etc.), and most importantly, the benefits that external power can offer.


The indirect deltopectoral flap.

A method of indirect transfer of the deltopectoral flap is described to repair craniofacial defects out of reach of the conventional direct flap.


Improved repairs in 100 cases of penile hypospadias.

A technique of hypospadias repair is detailed which combines the most desirable features of the methods of Byars and Cloutier. In 100 consecutive repairs performed personally the occurrence of fistulas was only 5 per cent.


Unlined repairs of defects following oral cancer ablation.

A technique is described in which unlined skin flaps are used after excision of malignant oral lesions. Mucosal defects are sealed with a rubber diaphragm. The method can be used when the defect is confined to the mucosa or when full-thickness cheek is involved. In the latter case, the forehead flap is preferred because of its good blood supply. Trismus has not been a problem so long as physiotherapy is carried out immediately after reconstruction.


Reconstruction of the central mandible with a single block of iliac bone.

A reconstruction of the central mandible is described using a single carved segment of iliac bone. The design of the graft takes into account the forces acting upon the remaining mandibular remnants and the need to provide absolutely rigid fixation until bony union is achieved.


A controlled trial of phenothiazine withdrawal in chronic schizophrenic patients.

Phenothiazine drugs were withdrawn from 17 chronic schizophrenic in-patients, with a control group of 14 patients remaining on active medication. The trial was conducted under double blind conditions over a period of 42 weeks with weekly assessment of the patients by ward nurses. Of the placebo group 35% relapsed, relapse being related to the level of previous active medication.


A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders.

A double-blind prospective study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders. The average Affective Morbidity Index was lower, but not significantly so, in patients treated with lithium. A further analysis, based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study, demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives. A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report. A highly significant negative correlation (r=-0-97; p less than 0-001) was found between plasma maprotiline concentration and body weight. Although the results showed lithium carbonate to be superior to maprotiline in the study, it should be emphasized that the plasma levels of lithium were constantly monitored and maintained at what is considered to be its optimum concentration, whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels.


Efficacy and side effects of nitrazepam and thioridazine as sleeping aids in psychogeriatric in-patients.

The efficacy and side effects of 10 mg of nitrazepam and 25 mg of thioridazine as sleeping aids were measured in 20 psychogeriatric in-patients during the 14th night and morning of drug administration. The trial used a double blind, cross-over design. The effect of nitrazepam was slightly faster than that of thioridazine. After thioridazine, but not after nitrazepam, the patients slept significantly longer than after placebo. Nitrazepam, but not thioridazine, significantly impaired patients' abilities to move and to conduct everyday activities. It is concluded that thioridazine is a suitable sleeping aid for psychogeriatric patients, but that nitrazepam should be avoided.


Developmental defects in the cranial vault.

The parietal bone seems to be the target for a number of different developmental conditions of the calvaria some of which are congenital whilst others develop in later life. The characteristic radiological patterns of a number of these lesions are described and illustrated, and an attempt is made to correlate the pathology with alterations in bone growth.