FITC-labelled antibody staining of tropomyosin-containing fibrils in smooth, cardiac and skeletal muscle cells, prefusion myoblasts, fibroblasts, endothelial cells and 3T3 cells in culture. FITC-labelled antibodies to purified chicken gizzard smooth muscle tropomyosin were prepared and used to stain muscle and non-muscle cells in culture. Skeletal muscle myoblasts stained both diffusely throughout the cytoplasm and in fine filamentous structures. Once myotubes developed the staining was localized exclusively in the I-band region of the myofibrils. Similarly, cardiac muscle cells stained in the I-band alone. Primary and subcultured smooth muscle cells, irrespective of their state of differentiation, stained exclusively in long, straight fibrils. The staining of the fibrils was interrupted with stained regions 1-2 micrometer long and unstained spacings 0.5 micrometer. Interrupted fibrils were also observed in fibroblasts and endothelial cells, however their staining reaction was very weak (almost indistinguishable from that with pre-immune serum) and they were few in number. 3T3 cells demonstrated moderate staining in interrupted fibrils. Sheaths of very fine fibrils staining with a similar intensity were also found throught the cytoplasm. Interruptions in these fine fibrils were often aligned to give the whole cell a striated appearance. Sheaths of fibrils were not found in the other cell types studied.


Immunofluorescence-microscopic demonstration of myosin and actin in salivary glands and exocrine pancreas of the rat. Actin and myosin were localized in various salivary glands (parotid, submandibular, sublingual, lingual and Harderian gland) and the exocrine pancrease of rats by indirect immunofluorescence microscopy using specific rabbit antibodies against chicken gizzard myosin and actin. A bright immunofluorescent staining with both antibodies were observed at three main sites: (1) In myoepithelial cells of all salivary glands, (2) in secretory gland cells underneath the cell membrane bordering the acinar lumen (except Harderian and mucous lingual gland), and (3) in epithelial cells of the various secretory ducts (of all glands) in similar distribution as in acinar cells. The present immunohistochemical findings in acinar cells could lend further support to a concept suggesting that myosin and actin are involved in the process of transport and exocytosis of secretory granules.


Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus. The human hypothalamic-neurohypophysial hormone-producing nuclei were investigated with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. The  size, shape and location of the supraoptic, paraventricular, accessory supraoptic and suprachiasmatic nuclei were determined. It was demonstrated in the human hypothalamus, as well as in the hypothalamus of other mammals, that vasopressin and oxytocin are synthesized in separate neurons. In each of the nuclei of the magnocellular neurosecretory system, the distribution, ratios and structural features of the vasopressinergic and oxytocinergic neurons were determined. It was shown that the human suprachiasmatic nuclei contain numerous neurophysin-vasopressin-producing neurons.


Immunohistochemical identification of gastrointestinal neurotensin cells in human embryos. The endocrine gastro-entero-pancreatic (GEP) system of 10 human embryos was studied with special reference to neurotensin-immunoreactive cells. These cells are first present in the ileal and jejunal mucosa of 12 to 13 week old embryos. Thereafter the neurotensin-immunoreactive cells are found regularly in these segments of the gut with an increasing number towards the terminal ileum. At about the twentieth week of gestation, the neurotensin cells are detected also in the lower duodenum, i.e. the distribution pattern is more extensive in this age than in younger embryos or in adults.


The prolactin and growth-hormone producing cells of the guinea-pig pituitary. Electron microscopic study using immunocytochemical means. Different immunohistochemical techniques were used to identify the prolactin and growth hormone producing cells (STH cells) in the pituitary of normal guinea pigs at the ultrastructural level. Prolactin cells revealed two main aspects: 1. Cells with granules from 2500 to 3500 A in diameter some of which are irregularly shaped. These granulations are scattered throughout the whole cytoplasm. The rough endoplasmic reticulum is well developed and organized in parallel lamellae. 2. In cells of the second type the granules are less numerous and smaller in diameter (1800 to 2500 A) and the rough endoplasmic reticulum is less well developed. The cytoplasm of the STH cells contains many more round granules (generally grouped) which also range from 2500 to 3500 A in diameter. The prolactin molecules and the STH molecules are essentially confined to the granules but with the immunocytochemical technique before embedding a slightly diffuse reaction appeared in the entire cytoplasm. These results are discussed.


On the occurrence of nucleosome phasing in chromatin. We have found that DNAase I digestion of yeast, HeLa and chicken erythrocyte nuclei produces a pattern of DNA fragments spaced 10 bases apart and extending to at least 300 bases. This "extended ladder" of DNA fragments is most clearly seen with yeast, and least clearly with chicken erythrocytes. The appearance of regular and discrete bands at sizes much larger than the repeat size shows that the core particles (140 bp of DNA + H2A, H2B, H3 H4) in at least some fraction of chromatin are spaced in a particular fashion, by discrete lengths of spacer DNA, and not randomly. Based on the abundance of small repeats in yeast and from experiments with nucleosome oligomers, we conclude that the extended ladder and nucleosomal phasing probably arise mainly from regions in the chromatin in which nucleosome cores are closely packed or closely spaced (140-160 bp X n). Contributions from less closely packed but still accurately phased nucleosomes, however, cannot be entirely excluded.


Mutagenesis by 4-nitrobenzofurazans and furoxans. 15 nitrobenzofurazans and 10 nitrobenzofuroxans synthesized primarily for testing as potential anti-rheumatic drugs were also tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100. The method used involved placing each compound in a "well" cut out of a plate of selective medium previously seeded with the appropriate tester strain, and then adding a rat liver microsome/cofactor mixture to one of the two wells on each plate. This method is considerably cheaper and more convenient than the conventional agar overlay technique, but in the present series of experiments failed to detect 4 compounds which could be detected by the overlay technique. Using a combination of the two techniques, 21 of the 25 compounds tested were found to be mutagenic. All 10 benzofuroxans and 9 of the 15 benzofurazans were detected as direct-acting mutagens with at least one of the two tester strains. Two of the benzofurazans gave positive results only in the presence of rat liver microsomes, and hence are pro-mutagens. One of the 4 benzofurazans which gave negative results for mutagenicity in these tests was found to be an efficient inhibitor of a neutral protease activity found in rheumatic synovial fluid, and may therefore have some potential as an anti-rheumatic drug.


[Problems in perfusion and preservation of the rat kidney isolated for the purpose of transplantation]. AA. performed an experimental trial on rats in order to demonstrate damages derived from organ perfusion (kidney) with endo- and extracellular electrolitic solutions. M/E values of structural alterations of the cells allowed the standardisation of renal perfusion methods for transplantation.


Reticuloendothelial phagocytic response to bacterial challenge after traumatic shock. Resistance to intravenous (IV) and intraperitoneal (IP) bacterial challenge during periods of reticuloendothelial (RE) depression following trauma as well as the influence of bacteremia on RE phagocytosis were studied. The experimental shock model utilized was the anesthetized (2 mg/100 g sodium pentobarbital) male rat subjected to nonlethal Noble-Collip drum trauma. During post-traumatic RE depression (60 min after injury) rats were challenged IV or IP with Escherichia coli (1.02 X 10(10)). The clearance half-time of the bacterial load injected intravenously in controls was 1.23 +/- 0.10 min. In contrast, the half-time was 3.62 +/- 0.69 min after sublethal trauma (p less than 0.005) and associated with prolonged blood bacterial retention. Pulmonary localization of E. coli administered either IV or IP was elevated in traumatized rats. Comparison of routes of bacterial challenge with respect to blood levels of viable bacteria suggested lower host bacterial resistance to the IP injection as opposed to the IV route of administration. Production of experimental bacteremia in normal rats resulted in a 39% depression (p less than 0.01) of RE test colloid clearance rate accompanied by a 49% increase (p less than 0.01) in pulmonary colloid localization. The data suggest that depressed systemic RE clearance capacity following trauma may decrease systemic resistance to septicemia, and that severe bacteremia may further undermine the functional state of the reticuloendothelial system.


In vitro effects of E. coli endotoxin on fatty acid and lactate oxidation in canine myocardium. We studied the in vitro effect of E. coli endotoxin on the oxidation of palmitate, palmitoyl CoA, and lactate by canine heart homogenate. Heart homogenates were incubated in calcium-free Krebs-Ringer-phosphate buffer in the presence of a 14C-labeled substrate. Oxidation of the individual substrate was calculated from the rate of 14CO2 production. The rate of oxidation of palmitate, palmitoyl CoA, and lactate was proportionally inhibited by increasing amounts (80-800 microgram) of endotoxin. The decrease in substrate oxidation could be mimicked by adding calcium chloride to the tissue preparation, and could be effectively prevented by the chelating agent, EDTA. Ionic calcium was released from tissue stores during incubation of the tissue preparation with endotoxin. These findings demonstrate that E. coli endotoxin inhibits substrate oxidation by heart homogenates when incubated under in vitro conditions. The data also suggest that the inhibition may be mediated by ionic calcium released from the tissue in response to the action of endotoxin.


Leukocyte response and hypoglycemia in superlethal endotoxic shock. This laboratory has documented a progressively developing hypoglycemia associated with systemic hypotension, hepatosplanchnic pathology, and death in endotoxin-shocked dogs. Recent data documented accelerated uptake of glucose in blood following endotoxin, with certain components of the buffy coat responsible for the increased uptake. The present study utilizing the awake dog assayed a possible protective role of leukocytes against the lethal effects of endotoxin. Animals were divided into paired groups: saline controls (Group I) and endotoxin experimentals (Group II). Group II animals were injected intravenously with sublethal doses of E. coli endotoxin on 2 successive days (Days 1 and 2), LD100 on the third day, and 2 X LD100 on Day 4. The control group received equal volumes of saline on Days 1, 2, and 3, but on Day 4 received a superlethal dose of endotoxin identical to the experimental group. The awake dog became febrile and exhibited initial leukopenia with subsequent marked leukocytosis in response to endotoxin. Lethal hypoglycemia was not seen in animals demonstrating initial leukocytosis (zero time) on the day of superlethal endotoxin challenge, while animals with initial normal leukocyte counts died with low glucose concentrations (mean, 40 mg%). Results suggest that an initial leukocytosis and sustained gluconeogenic function are important factors in survivability to endotoxin shock.


Protection against endotoxin shock and impaired glucose homeostasis with ATP. ATP-Mg++ (10 mumoles/100 g, iv) increased the LD50 for Salmonella enteritidis lipopolysaccharide (endotoxin) in male Holtzman rats (300 +/- 10 g) from 1.3 to 6.0 mg/rat. While endotoxin at 3 mg/rat iv 5 hr previously induced hypoglycemia to 12 +/- 4 mg/dl, ATP cotreatment blunted the hypoglycemia; i.e., plasma glucose values were 78 +/- 6 mg/dl. ATP treatment prevented the depression in gluconeogenesis induced by endotoxin as evaluated in vivo by the conversion of 14C-alanine to 14C-glucose. ATP treatment also reduced the hypercatabolism of U-14 C-glucose to 14CO2 in vivo and by epididymal fat pads in vitro. A role for ATP in preventing disruption of glucose homeostasis and development of endotoxin shock via counteracting insulin is suggested.


Discrete membranous subaortic stenosis. Report of 31 patients, review of the literature, and delineation of management. The presentation, management, and follow-up of 31 patients with discrete membranous subaortic stenosis (DMSS) is presented. DMSS comprised 16% of 185 patients with congenital left ventricular (LV) obstruction. Only one patient was older than 40 years. The rarity of DMSS in older patients in both our population and in the literature is noted, and possible explanations are discussed. One-quarter of these patients had dyspnea, chest pain, or syncope combined with electrocardiographic left ventricular hypertrophy (LVH) and strain, and these all had peak LV outflow gradients (PSG) greater than 85 mm Hg. One-quarter had neither symptoms nor electrocardiographic abnormalities and all had PSG less than 90 mm Hg. Bacterial endocarditis was found in 13%, and in 13% an immediate family member also had congenital LV obstruction. Following surgical resection (25 patients), 18 were asymptomatic, two had residual fibromuscular obstruction, and four developed new fibromuscular obstruction after from one to six years (leading in one to late sudden death). Thus, even after resection, these patients require continued re-evaluation for residual or new LV obstruction.


Migratory traumatic cardiovascular foreign bodies. Six cases of cardiovascular foreign bodies secondary to trauma are presented. The various modes of entry and travel within the vascular are reviewed. Routine radiographic examination and angiography are shown to be the most useful techniques in defining the location and subsequent course of the foreign body in the vascular system.


A comprehensive classification of kinetic methods of analysis used in clinical chemistry. This paper presents a comprehensive classification of kinetic methods of analysis used in clinical chemistry. Objectives of the presentation are to place kinetic methods into perspective with other analytical appraoches, to identify concisely what is and is not a kinetic method, to group different kinetic methods into categories that identify important differences in operational and performance characteristics, and to suggest terminology that can identify the different approaches without ambiguity. In addition to these major objectives, the paper includes a brief historical development of the kinetic approach that covers the period from 1881 to the present, and discusses some current terminology that is believed to be ambiguous and misleading. I suggest that the detection step in analytical methods can be divided into two general categories, called equilibrium and kinetic methods. The kinetic methods are then subdivided into two general categories called fixed sensor-signal and variable sensor-signal methods. Each of these groups is then subdivided into one-point, two-point, and multi-point methods, which are then further subdivided according to what types of blanks are used, what variables are measured, and how the measured data are used to compute enzyme activity or analyte concentration. The paper identifies some commercial instruments that represent different approaches and briefly discusses relative merits of different approaches.


Measurement of carbamazepine and its epoxide metabolite by high-performance liquid chromatography, and a comparison of assay techniques for the analysis of carbamazepine. We describe a modified high-performance liquid-chromatographic method for the simultaneous analysis of carbamazepine andits biologically active metabolite, carbamazepine-10, 11-epoxide. Concentrations of both these compounds in the plasma of 35 epileptic patients receiving chronic carbamazepine therapy are presented. Concentrations of carbamazepine in plasma were related to those of carbamazepine-10, 11-epoxide (r - 0.495, P less than 0.05). Total daily doses of carbamazepine were better correlated with plasma concentrations of carbamazepine-10, 11-epoxide (r = 0.714, P less than 0.001) than of carbamazepine (r = 0.269, P greater than 0.05). Close correlations were found between results of the three assay procedures we used to measure plasma carbamazepine concentrations: high-performance liquid chromatography, gas-liquid chromatography, and enzyme immunoassay. Correlation coefficients exceeded 0.97 and regression slopes were near unity, indicating that all three procedures were individually specific for the quantification of plasma carbamazepine.


Enzyme immunoassay for hepatitis B and its comparison to other methods. A solid-phase enzyme immunoassay for the qualitative detection of hepatitis B surface antigenemia is presented and the results compared to the counter-immunoelectrophoresis and radioimmunoassay methods for detection of the same antigen. The enzyme-antibody conjugate was prepared from horseradish peroxidase coupled with antibodies to three sub-types of hepatitis B virus. Polystyrene plastic tubes were used as the solid-phase support. The results of the enzyme immunoassay compare favorably with radioimmunoassay and exceed counterimmunoelectrophoresis in sensitivity.


Bromocriptine suppression of plasma growth hormone in acromegaly. Twelve acromegalic patients were studied in one or more of three protocols to establish the response of plasma growth hormone (hGH) concentraions to (a) a single oral test dose of bromocriptine, (b) incremental dose therapy from 10 mg/day to 40 mg/day over 4 weeks, and (c) sustained therapy with 20 mg/day over a 3 month period. Ten of the patients studied had previously been treated by yttrium implantation, external pituitary irradiation or surgical hypophysectomy. A high incidence of side effects including postural hypotension, hallucinations and peripheral vasospasm was noted reducing the numbers of patients completing the three protocols. Suppression of hGH concentrations was disappointing; significant reductions in hGH concentraions occurred in five of eleven patients in response to a single test dose of bromocriptine, and in only one of seven patients treated with the drug over a sustained period. An impression of clinical improvement was gained in one patient, but there was no associated reduction in plasma hGH concentrations. It seems likely that acromegalic patients who have failed to respond to conventional treatment may be more resistant to bromocriptine therapy.


A self-adjusting randomization plan for allocation of patients into two treatment groups. This paper presents a self-adjusting randomization plan which is thought to be useful in controlled stratified randomized clinical trials. The method assures an optimal balance of treatments within each subgroup of patients. An imbalance caused by a high number of dropouts in one treatment group will be counteracted by the self-adjusting nature of the method. The method has been tested in computer-simulated trials and has been shown to produce better results than conventional plans for stratified randomized clinical trials. The method does not involve any complicated calculations and its use in a running clinical trial has shown that it is easy to handle.


Metabolism of l-bunolol.

Metabolism of l-bunolol. The metabolism of l-bunolol, a new beta-blocking drug, was studied in man after single oral 3-mg doses of 3H-labeled compound. Absorption from the gut was rapid and virtually complete. Peak levels of bunolol and of dihydrobunolol, an active metabolite, were observed at 1 hr. Excretion of the administered radioactivity was mainly into the urine (78% in 4 days), with only 3% appearing in the feces. Bunolol, bunolol glucuronide, bunolol sulfate, dihydrobunolol, and dihydrobunolol glucuronide were identified and quantified in the plasma. These compounds represented 82% of the radioactivity in plasma at 30 min and 55% at 24 hr. Plasma half-lives (+/-S.D.) were estimated to be 6.1 +/- 0.3 hr for bunolol, 9.1 +/- 1.9 hr for bunolol glucuronide, 17.4 +/- 2.5 hr for bunolol sulfate, 7.1 +/- 0.5 hr for dihydrobunolol, and 7.7 +/- 0.8 hr for dihydrobunolol glucuronide.


Guanabenz and methyldopa on hypertension and cardiac performance. In previous placebo-controlled studies, guanabenz was shown to be a safe and effective antihypertensive drug without acute effects on cardiac function. In view of its therapeutic advantages, a double-blind comparison of guanabenz with methyldopa was performed in a group of 36 patients over 6 mo. Both drugs produced statistically and clinically significant decreases in blood pressure with similar side effects. No laboratory or electrocardiographic abnormalities were found other than positive Coombs' tests which developed in 3 patients during methyldopa therapy. Cardiac performance in 26 of the patients, as measured by noninvasive techniques, showed no significant changes from either drug except for a progressive and statistically significant increase in systolic time interval (QS2) and the ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) during methyldopa therapy. For an additional 6 mo, continued efficacy and safety were shown under open conditions in those patients who had received guanabenz. The study suggests that guanabenz may be an important new antihypertensive drug because of effectiveness, absence of adverse cardiac effects, and paucity of side effects.


Physiologic consequences of mechanical ventilation. Mechanical ventilatory support with a variety of devices and techniques has saved many lives; however, it remains the responsibility of those charged with the care of patients suffering from respiratory failure to be thoroughly familiar with these techniques and their complications.


[Robert Schumann as a patient in Bonn-Endenich]. Although there exists a voluminous biographic literature on Robert Schumann, there are only few informations on the last 2 years of his life, which he spent in the sanatorium Endenich near Bonn/Rh. Schumann, suffering from a recurring psychosis since 1833 at least, had been received there after a suicidal attempt on March 4th, 1854. His physical and psychical state deteriorated permanently and Schumann died on July 29th, 1856, somatically and mentally disordered. Up to now there exists no clear diagnosis, but there is every reason to believe that Schumann was suffering from a schizophrenic psychosis, combined with a cardiac and circulatory disease.


Psychiatry and history: aspects of history of psychiatry. Psychiatry has asked and has been helped from many sides. As far as history is concerned, it was interested, almost exclusively, as long as it was history of psychiatry. In this paper an attempt has been made to show that history and, especially, philosophy of history could offer substantial help, particularly as teachers of methodology and hermeneutics.


[Elaboration of the psychosomatic phenomenon: observations on the biography of Blaise Pascal]. The paper aims to take a closer look at some of the problems surrounding the 'psychosomatic phenomenon'. The origin, development and effects of the phenomenon, as well as the way in which one individual managed to overcome it, are illustrated in the example of the French philosopher and physicist, Blaise Pascal. The authors hold the view that the psychosomatic phenomenon is rooted in disturbances in the early identification processes of the infant. Somatic symptoms flare up whenever the individual, in a phase of disorganization, becomes dominated by his psychosomatic phenomenon. If, however, the person concerned has the ability to go through with the suffering involved in experiencing and elaborating these early defects, thus giving them a psychic dimension, he may be able to overcome them and in this way even attain to creativity. The genius Pascal is an extreme example of one who had this ability and so gained access to his own truth, which he found in God.


The electroencephalogram in dementia.

The electroencephalogram in dementia. The EEG in normal aging and in dementia due to a variety of diseases has been described. In dementia due to degenerative diseases, metabolic disorders, normal pressure hydrocephalus, and deficiency states, the diffuseness of the abnormalities observed has been emphasized; whereas with cerebrovascular disease and with intracranial massess, the focal nature of the changes has been stressed. Although a normal EEG does not rule out the diagnosis of dementia especially in its early stages, the EECG can nevertheless be a significant instrument in the identification or organic processes when the diagnosis is uncertain, in differentiating diffuse from focal cerebral lesions, and in following the course of the disease. Because electroencephalography is easily performed, is safe, and can be frequently repeated, it should be considered one of the more useful tools in the clinical evaluation of patients with dementia.


Choline acetyltransferase.

Choline acetyltransferase. Acetylcholine is essential to neural function. It synthesis is catalyzed by choline acetyltransferase, the enzyme responsible for the acetylation of choline by acetyl coenzye A, a reaction favored slightly thermodymodynamically and not at all kinetically. An analytically pure enzyme still has not been obtained; however, method of purification have been greatly improved recently. Numerous inhibitors of the enzyme have been synthesized and their structure-action relationships examained. Evidence has been accumulated showing the essential involvement of an imidazole group in the active site of choline acetyltransferase. The literature regarding the controversial role to thiol groups in choline acetyltransferase is reviewed. Recently, derivatives of coenzyme A have been introduced as inhibitors of this enzyme and the specificity of coenzyme A binding has been examined. Possible mechanisms responsible for the control fo acetylcholine synthesis are discussed.


Dynamic light scattering of biopolymers and biocolloids. Widespread applications of dynamic light scattering techniques to the study of macromolecular Brownian motion have yielded not only a valuable store of factual information concerning solution conformations and conformational changes, but have also provided an important window through which to view the dynamics of internal modes of motion. These techniques have coincided with a resurgence of interest in the solution physical chemistry of macromolecules, including hydrodynamic properties, and the profound effect of intermolecular interactions on both the disposition and dynamics of macromolecules in solution.


The pathogenesis of immune thrombocytopenic purpura. Chronic idiopathic thrombocytopenic purpura (ITP)  is a human disease manifested by destructive thrombocytopenia due to a circulating antiplatelet antibody. The antibody is of IgG type and is produced primarily in the spleen and bone marrow. After binding of the antibody to a platelet-associated antigen, phagocytosis is triggered either via the Fc portion of the attached antibody or as a consequence of fixation of the third component of complement (C3). The spleen is the prime area of platelet destruction due to its unique milieu. The large intrasplenic platelet pool is subjected to high local antiplatelet antibody concentrations in an environment teeming with phagocytic cells. In addition, the stagnant blood-flow characteristics of the spleen allow ample time for antibody sensitization and phagocytosis. Similar circumstances may occur in the bone marrow. In patients with "severe" disease and high antibody titers, the liver also becomes an important area of platelet destruction. The nature of the platelet-associated antigen is presently unknown but may differ from patient to patient. A pathogenetic model is proposed on the basis of presently available data.


Psychophysical and psychometric approaches to sensory evaluation. Sensory evaluation has recently utilized the methods developed by psychophysicists and psychometricians, who week to represent data in terms of various scales and mathematical formulations. This review covers the development of ratio scaling to develop relations between sensory and instrumental measures of food, the use of multivariate psychophysical procedures which relate a variety of physical variables to a single sensory response, and the use of multidimensional scaling to relate different sensory percepts to each other. Each of these approaches is nascent in applications to sensory evaluation, although the mathematics and formulations are very developed. Each approach gives the experimenter insights into subjective and objective correlations and the manner in which the panelist perceives relations among stimuli. The treatment of the reported literature for each approach follows the same course: necessary conditions for its application to sensory evaluation, experiences with model systems and real foods, and potential uses and limitations in sensory evaluation.


Toxicants in plants and plant products.

Toxicants in plants and plant products. Toxicants are widely distributed in plants and plant products, including intentionally added, incidentally added, and naturally occurring food toxicants. This review covers the toxicity of some food additives: the distribution, residues, toxicity, and methods of removal of some pesticides and toxic metals; and the presence of naturally occurring toxicants in plants and plant products. Extensive review has been done, particularly on natural toxicants. However, there are still extensive gaps in our knowledge pertaining to effect upon the health of many of the substances known to be present in natural plant food products, as well as even the identity of many natural chemical components of plant foods and their potential toxicological significance. An understanding of their presence, formation, and toxicity is important as far as public health is concerned.


The analysis of essential oils and extracts (oleoresins) from seasonings--a critical review. A critical review of the analytical methods employed for the determination of the relevant components of seasonings is presented. Where the available methods were inadequate, new ones have been devised. Particular emphasis has been placed on those methods of analysis that provide a rapid and sufficiently accurate appraisal of seasoning extracts and essential oils from seasonings under routine control laboratory conditions. At the same time, the margin of error of these methods has been determined. The individual seasoning extracts were assessed according to the following criteria: (1) essential oil--cardamom, laurel leaves, cloves, origanum (marjoram), sage, and thyme; (2) essential oil and nonvolatile lipids--dillseed, coriander, caraway, mace, nutmeg, pimento (allspice), and celery seed; (3) essential oil and/or pungent ingredients--capsicum, ginger, and pepper; (4) essential oil and/or coloring matter--turmeric (curcuma) and paprika; (5) essential oil and other components--garlic, onion, and cinnamon.


Determination of vitamin A in foods--a review. Formerly, few foods were routinely analyzed for vitamin A, but recent emphasis on nutrient requirements, nutrient labeling, and use of dietary convenience foods has created need for determining vitamin A in a variety of foods. There are many vitamin A methods--some suitable for certain products only. For regulatory purposes, the FDA specifies the AOAC method where it is applicable. However, some food analysts and organizations continue with their own vitamin A methods. If possible, a single, widely applicable general method should be used for vitamin A in foods. Vitamin A may be determined by spectrophotometric, colorimetric, and fluorometric procedures. Sometimes chromatography is required as an important part of the method. Colorimetric procedures with SbCl3 are now most widely used to measure vitamin A (retinol) in foods. If vitamin A content is high enough and extracts sufficiently free of interfering substances, spectrophotometric or flurometric methods are satisfactory. Methods in various stages of development for determining vitamin A in foods are based on flurospectrophotometry, gas-liquid chromatography, high-performance liquid chromatography, and automation. To estimate total vitamin A nutritional value of certain foods may also require determination of vitamin A isomerization and contents of carotenes, cryptoxanthin, reinaldehyde, and apo-carotenal.


Organic food.

Organic food. "Organic" or "organically grown" foods are commonly represented as "food grown without pesticides; grown without artificial fertilizers; grown in soil whose humus content is increased by the additions of organic matter; grown in soil whose mineral content is increased with applications of natural mineral fertilizers; has not been treated with preservatives, hormones, antibiotics etc." The substitution of "organic" for "chemical" fertilizers during the growth of plants produces no change in the nutritional or chemical properties of foods. All foods are made of "chemicals." Traces of pesticides have been reported to be present in about 20 to 30% of both "organic" and conventional foods. These traces are usually within the official tolerance levels. Such levels are set low enough to protect consumers adequately. Indeed, there is no record of a single case of injury to a consumer resulting from the application of pesticides to food crops at permitted levels.


Biopsy in vesicobullous disorders.

Biopsy in vesicobullous disorders. Through actual case illustration, I have tried to present the way biopsy of a vesicobullous lesion would be approached by the dermatopathologist. I did not intend this article to be a comprehensive review and, because of the limitation of space, have ommited the more unusual bullous dermatoses. Comprehensive reviews of the role of immunofluorescence in vesicobullous disorders can be found in the Archives of Dermatology and Progress in Dermatology.


Comparative bronchodilator responses to atropine and terbutaline in asthma and chronic bronchitis. We have compared bronchodilator responses to atropine and terbutaline in 39 chronic bronchitics and 16 stable asthmatics. Fasting subjects were given either 1.05 mg atropine of 5.0 mg terbutaline orally. Pulmonary function was assessed using the peak responses, namely: three 60-minute intervals for terbutaline and three 30-minute intervals for atropine. A subgroup of five reactive bronchitis patients was given a placebo with no response. Areas under the percent response-time interval curve were compared. Both patient groups responded to the same degree to atropine and terbutaline with respect to reduction of airway resistance. However, the FEV1 and V50 responses to terbutaline were markedly enhanced compared to atropine in the asthmatics while equal to the atropine response in the bronchitis patients. Thus, atropine appears to exert its effect upon both large and small airways in bronchitis, but predominantly on large airways in asthma. The results are consistent with a state of enhanced vagal tone in small airways in bronchitis compared to asthma, but other explanations are conceivable.


Comparison of the bronchodilator effects of aerosol fenoterol and isoproterenol. Aerosolized fenoterol in a dosage of 400 microgram was compared to isoproterenol 150 microgram in 31 asthmatic subjects during the course of a double-blind parallel 90-day study. Bronchodilator activities of the two drugs were evaluated for up to 6 hours on days 1, 45 and 90. Analysis of the data revealed that fenoterol consistently produced a significantly greater increase in FEV1, FEF25-75% and Gaw/VL. Specific airway conductance increased on each test day 25 percent or more above baseline for over three hours after use of fenoterol and for only one hour after use of isoproterenol. Fenoterol has less effect upon the cardiovascular and central nervous systems, but produced a greater incidence of shaking compared to isoproterenol. Patients used fenoterol less frequently than isoproterenol which can be attributed to the former having a greater peak effect and time course of bronchodilation. The therapeutic efficacy of fenoterol was sustained throughout this three-month study, and suggests that this relatively selective beta2 adrenergic drug will provide a well tolerated, alternative aerosol for chronic use in asthma.


Aerosol administration of fenoterol hydrobromide (Th 1165a) in subjects with reversible obstructive airway disease. Bronchodilatory and side effects of fenoterol hydrobromide (Th1165a; hydroxyphenylorciprenaline; Berotec) and isoproterenol given by inhalation were compared in a double-blind crossover study involving 20 volunteer subjects with reversible obstructive disease of the airways. Subjects inhaled medications from aerosol canisters containing fenoterol hydrobromide (0.1 mg, 0.2 mg, or 0.4 mg) or isoproterenol (0.15 mg) or an inert placebo propellant in a random sequence of five testing days. All active drugs substantially increased the forced expiratory volume in one second, the mean forced expiratory flow during the middle half of the forced vital capacity, and the specific conductance. The onset of bronchodilation after both fenoterol and isoproterenol was rapid, but the effect from fenoterol lasted much longer, up to eight hours. None of the medications cuased significant tachycardia or hypertension. After inhalation of 0.1 mg of fenoterol hydrobromide, none of the subjects reported nervousness, headache, tremor, or nausea, incontrast with results reported for isoproterenol, higher aerosol doses fo fenoterol, or oral administration of fenoterol. No additional therapeutic benefit was found in the administration of higher doses of fenoterol.


Neuropsychologic effects of continuous oxygen therapy in the aged. This study investigated the effects of continuous therapy with oxygen on the neuropsychologic functioning of aged subjects professing problems with their memory. Nineteen men (mean age, 71 years) were evaluated on eight neuropsychologic measures during three different periods of time. Subjects were tested before any treatment, after a month of continuous therapy with oxygen, and after a period of sham treatment. The results indicated statistically significant improvement in the Wechsler Memory Quotient and, with one exception, improvement in all other measurements in favor of the treatment with oxygen. Differences between the results of this investigation and those of other studies are discussed, along with the factors possibly accounting for these differences.


New tests for the detection of obstructive pulmonary disease. Abnormalities in small airways appear to be important in the evolution of chronic obstructive pulmonary disease. Patients with these pathologic lesions may have normal values for airway resistance and forced expiratory volume in one second. Two new tests, the closing volume (CV) and the dependence of maximal flow on density, are believed to be sensitive to abnormalities in the peripheral airways. The CV test detects an increased nonuniformity of changes in volume of pulmonary units. Reduced dependence of flow on density is believed to result from an increase in the peripheral component of the losses of driving pressure which determine maximal expiratory flow. Both tests differentiate smokers with normal conventional spirometric data from age-matched nonsmokers. Although this evidence suggests that these tests can be used to detect abnormalities in small airways, there is very little pathologic confirmation of this belief. The clinical significance of abnormalities in the results of either of these tests in an otherwise normal person has not yet been determined.


[Management of ureteral stenoses and urinary fistulas following kidney transplantation]. The treatment of strictures and fistulas at the lower ureter after kidney transplantation was simple and could be achieved by reimplantation into the bladder. Proximal urinary fistulas caused early abdominal symptoms. The i.v. urogram showed a dilated renal pelvis without drainage into the ureter. The anatomical findings were in all cases strictures or total obstruction of the ureter beneath the pelvic junction and a rupture of the renal pelvis or calix. Adequate therapy consisted of ureteroureterostomy with the recipient ureter and nephrostomy splintage.


Indications and contra-indications for perforation keratoplasty. Thirty years' experience with perforating keratoplasty has shown us new indications for this technique, but certainly also new contra-indications. At first the prognosis of perforating keratoplasty improved because of better surgical techniques, so that the number of indications increased. Recently a better prognosis for heavily vascularized eyes has become possible thanks to HLA-matched donor material.


First experiences with HLA-matched corneal grafts in high risk cases. In highly vascularized corneas the number of graft failures caused by irreversible rejections is higher than in non-or slightly vascularized corneas. The importance of antigen compatibility is demonstrated, especially in these 'high risk' cases. Ten highly vascularized corneas were grafted with HLA-matched donor material; only one reversible rejection was seen in this group. Nine non-or slightly vascularized corneas were grafted with donor material chosen a random. Retrospective HLA matching was performed. Three irreversible rejections were seen in this group. The number of HLA incompatibilities was high.


[MK-231 (Sulindac) in the treatment of rheumatoid arthritis (author's transl)]. MK-231 (Sulindac), 200-400 mg daily, was given to 25 patients with rheumatoid arthritis. The therapeutic response was good and there were no side effects at all. The drug should be used more frequently than heretofore in the drug treatment of symptoms of rheumatoid arthritis.


[Scientific theoretical models in dentistry]. Developments leading to modern medicine only began about 150 years ago. The foundation of this progress was laid by the introduction of scientific working methods into practical and theoretical medicine. The principal methodical procedures are described in the present work, defined and examined as to its scientific basis. Examples from dental, oral, and maxillo-facial surgery are given as proof that the models used in the definition of present day biological research are helpful not only give accuracy to content recognized by scientific method but also to assure transition from theoretical to practical science.


[Free autologous skin implantations in plastic periodontal surgery]. From 1972 to 1974, 25 autologous skin transplantations were carried out within the framework of complex periodontal therapy. Prior to the operation, ischemia and mobility of the marginal gingiva were found in all patients in the region of the lower incisors. After the operation, the gingiva had broadened by 5.6 to 6.6 mm. The grafts shrank after the operation. In two cases the graft failed and was rejected. The transplanted skin does not change in color, although keratinization of the transplanted skin is considerably reduced.


A female case of Kallmann's syndrome.

A female case of Kallmann's syndrome. A case of 20-year-old woman with hypogonadotropic hypogonadism and anosmia is reported, since very few female cases of Kallmann's syndrome have been reported so far in Japan. Three uncles on the father's side had no children. Height was 168 cm, and arm span 165 cm. The olfactory test revealed complete anosmia. Bone age was 13 year. Chromosome was 46 XX and normal karyotype. Basal levels of serum FSH, LH and estrogens (E1, E2 and E3) were low. Serum FSH and LH levels rose slightly only after LH-RH administration, and did not increase in clomiphene test. Plasma estrogens did not increase after daily injection of 150 IU of HMG for 3 successive days. The response of serum GH to arginine infusion was normal, while that to insulin-induced hypoglycemia was poor.


Chemistry and physiology of inhibin--a review. Several reports have appeared on the presence of inhibin, the second testicular hormone postulated by McCullagh, in such sources as testicular extracts, seminal plasma, rete testis fluid, spermatozoa as well as ovarian follicular fluid. The resurgence, in recent years, of interest in the physiology of inhibin is reviewed in the historical perspective of earlier work. This survey presents an outline of the general findings on the nature and characterization of this substance. Studies relating to its exact site of production as well as its site of action are briefly described and discussed.


A critical review of current methods for induction of parturition in the mare. The efficacy and safety of oxytocin, dexamethasone and prostaglandin, used alone or in combination as inducing agents, are discussed. It is contended that insufficient evidence exists to support the routine application of any of these methods in practice. Oxytocin has been the most widely used and it is claimed by some to be free from side effects. However, the synthetic prostaglandin analogue, fluprostenol, seems to pose the least risk to the foetus and dexamethasone appears to be either ineffective, or too dangerous to use at all. The main indications for induced foaling are managerial convenience or for research and teaching purposes. There are few clinical indications, although ventral rupture and cases of prolonged gestation have been mentioned by various workers. It is considered that foetal maturity is the pre-requisite before a decision to induce should be made in practice, and 3 criteria are essential: 1) a gestational length of greater than 320 days, 2) substantial mammary development, 3) the presence of colostrum in the mammae.


Circular dichroism studies of the binding of o-nitrophenyl-beta-D-fucoside and o-nitrophenyl-beta-D-galactoside to lac repressor. The binding of o-nitrophenyl-beta-D-fucoside and o-nitrophenyl-beta-D-galactoside to Escherichia coli lac repressor was investigated by circular dichroism in the wavelength range 300--400 nm corresponding to the o-nitrophenyl chromophores. The CD signal of both ligands drastically changed when they bound to lac repressor due to the asymmetric interaction of the o-nitrophenyl ring with chemical groups of protein. The CD spectra of bound ligands indicate close similarity between the environment of o-nitrophenyl-beta-D-fucoside and o-nitrophenyl-beta-D-galactoside on lac repressor. The CD signal is used to calculate the binding parameters (K and n) to lac repressor. It is demonstrated that the limited proteolytic digestion of lac repressor which gives a 'core protein' does not affect the environment of both ligands on the protein.


Studies on the transcription complex of Escherichia coli RNA polymerase. To study the chain elongation phase of enzymatic RNA synthesis ternary transcription complexes with T7 DNA or poly[dA) - (dT)] as template were isolated by gel exclusion chromatography. The DNA in these complexes contains single-stranded regions which are recognized by a single-strand-specific nuclease from Neurospora crassa. The non-codogenic DNA strand in the poly[(dA) - (dT)] ternary complex is preferentially hydrolysed by the nuclease. The polymerase protects predominantly the codogenic strand in this complex from digestion by DNAse I. In the T7 DNA ternary complex a DNA fragment with a chain length of approximately 26 nucleotides and an RNA fragment of about 22 nucleotides are protected by polymerase from digestion by DNAse and RNAse.


Interrelation between transfer RNA and amino-acid-activating sites of methionyl transfer RNA synthetase from Escherichia coli. Binding of tRNA(Met/f) to the monomeric trypsin-modified methionyl-tRNA synthetase turns off the methionine-dependent isotopic ATP--PPi exchange. In the case of the dimeric native methionyltRNA synthetase, one anticooperatively bound tRNA(Met/f) inhibits the exchange by only 50%. These behaviours of tRNA do not require the integrity of the 3'-terminal adenosine. Esterification by methionine of the 3' end of tRNA reinforces the affinity of tRNA(Met/f)for the enzymes. In the case of the native enzyme, due to this effect, a second binding mode for methionyl-tRNA may be demonstrated through the isotopic exchange. This additional binding of tRNA corresponds to the expression of the anticooperatively blocked tRNA binding site. Methionine reverses competitively the reinforcing effect of the esterified methionyl moiety on tRNA binding. It is concluded that after esterification of tRNA, the aminoacyl residue still binds the enzyme, probably within the methionine activating site. The latter behaviour may account for the observation that excess methionine accelerates the aminoacylation turnover rate of tRNA(Met/f).


The involvement of protein L16 on ribosomal peptidyl transferase activity. Radioactive ribosomes from Escherichia coli were treated with increasing concentrations of NH4Cl in the presence of 50% ethanol. The resulting particles were tested for peptidyl transferase activity as well as for the binding of (U)C-A-C-C-A-Leu-Ac, (U)C-A-C-C-A-Leu, chloramphenicol, lincomycin and erythromycin. At the same time the proteins present in the particles were quantitatively estimated and the amount of each related to the residual activity displayed by the treated ribosomes. It was found that the loss of protein L16 closely paralleled the inactivation of the particles implying an important role for this protein in the structure of the peptidyl transferase center.


On the distribution and packing of RNA and protein ribosomes. From the analysis of the measured radii of gyration of the RNA (Rg = 6.6 +/- 0.3 nm) and protein (Rg = 10.2 +/- 0.5 nm) components of the 50-S subparticle of Escherichia coli ribosomes it is concluded that proteins containing a large amount of hydrodynamically bound water are located on the periphery of the tightly packed RNA. We found that the common features of the measured X-ray scattering curves of the E. coli 70-S ribosome, its 30-S and 50-S subparticles and wheat 80-S ribosomes in the region of scattering angles corresponding to scattering vectors mu from 1 to 5 nm-1 reflect features of the RNA compact packing. A hypothesis is proposed that the compact packing of RNA helices in the range of Bragg distances of 4.5--2.0 nm is a general structural feature of all ribosomal particles.


The effect of modification of cytosines in Escherichia coli 16-S rRNA on reconstitution and function of 30-S ribosomes. O-Methylhydroxylamine (methoxyamine) was used for selective modification of cytosine residues in Escherichia coli 16-S rRNA. It was shown that cytosines accessible for methoxyamination are randomly distributed along the 16-S rRNA chain. Preparations of methoxyaminated 16-S rRNA, containing 2--130 modified cytosines/chain, still retained the ability to bind 30-S proteins, but the physical assembly of reconstituted particles was incorrect. The protein compositions of the reconstituted and native particles did not differ qualitatively from each other. However, the amount of protein in reconstituted particles decreased with an increasing number of methoxyaminated cytosines in 16-S rRNA. The particles obtained sedimented slower than native 30-S subunits, lost their ability to associate with 50-S ribosomes and to bind native phage f2 RNA. In contrast, modification of 16-S rRNA did not affect binding of poly(U) by reconstituted particles.


The palmityl binding sites of fatty acid synthetase from yeast. Fatty acid synthetase was covalently labelled with [14C]palmitic acid from [14C]palmityl-CoA. Tryptic and peptic digestion of the [14C]palmityl enzyme resulted in the formation of radioactive palmityl peptides carrying the long-chain acyl residue both in oxygen-ester and thio-ester linkage. The lipophilic palmityl peptides were purified by column and thin-layer chromatography using organic lolvent systems. Peptides arising from the acyl carrier protein, the condensing enzyme and the palmityl transferase were identified and characterized. The amino acid sequence of a 4'-phosphopant-etheine-containing peptide was established. It comprises 13 residues and shows a high degree of homology with the acyl carrier protein from Escherichia coli. A heptapeptide and an octapeptide from the palmityl transferase active site were partially sequenced. The identical amino acid composition of palmityl transferase and malonyl transferase core peptides is briefly discussed.


Topography of Escherichia coli ribosomal protein L12 in situ. The ionization constants of each individual free amino group of Escherichia coli ribosomal protein L12 as it exists on the native intact 50-S subunit has been determined. All these amino groups are exposed and have pK values varying from 9.7 to 11.0. The amino terminus, on the other hand, is unreactive and therefore appears to be buried. In addition, the reactivities indicate that the aminoterminal region of residues 1--59 undergoes a pH-dependent conformational change on the 50-S subunit.


Endonucleolytic cleavage of parental DNA and T4 late-gene expression: distribution analysis of single-strand and double-strand breaks. In order to investigate the dependency of late transcription on concurrent DNA replication during bacteriophage T4 development, we analyzed the endonucleolytic cleavage kinetics of the DNA of a T4 mutant lacking DNA polymerase, DNA ligase and exonuclease by using the sucrose gradient sedimentation technique. Our results can be summarized as follows. 1. The single-strand endonucleolytic cleavage of the T4 mutant DNA is not a random process. 2. The number of single-strand nicks reaches a plateau level of 10--12 nicks/molecule. 3. The occurrence of a double-strand break is delayed and their number is at any time lower than the number of single-strand nicks. 4. The circular permutation T4 genome, as computer-simulated by the Monte Carlo method, produces a smoothing of the discrete distribution which would be expected if nicks were localized in the promoter sites of late transcription units. We conclude that our findings support the model which relates single-strand DNA nicks to the late transcription initiation sites.


Synthesis of transfer RNA during the synchronous nuclear division cycle in Physarum polycephalum. 1. The synthesis of tRNA during the synchronous nuclear division cycle in plasmodia of Physarum polycephalum has been investigated using an isotope dilution procedure and compared to the pattern of synthesis of rRNA. 2. The synthesis of both tRNA stops during mitosis. As the genes for the two types of RNA are not linked, this finding suggests that cessation of synthesis during nuclear division is a common characteristic of all types of transcription, supporting earlier work using pulse labelling and autoradiography to investigate the same problem.


beta-D-Galactoside transport in Escherichia coli: substrate recognition. 1. A number of galactosides and other sugar compounds were examined as inhibitors of facilitated or active transport by the lactose permease system of Escherichia coli. Efficient inhibition required an alpha- or beta-anomeric galactopyranosyl ring of D-configuration, a free 6-hydroxyl group, and a certain aglycone size which was reached, for example, by monosaccharide or nitrophenyl substituents. 2. Aromatic alpha-D-galactopyranosides acted as high-affinity inhibitors (Ki, below 50 micrometer). At least two of them were not transported, in contrast to alpha-galactoside disaccharides and to aromatic beta-D-galactopyranosides. 3. beta-D-Galactoside transport was not significantly inhibited by specific inhibitors and transitionstate analogues of beta-galactosidase (D-galactal, D-galactonolascone). 4. The beta-D-galactopyranoside, lactitol, and alpha-D-galactopyranoside, galactinol, were not efficiently bound by the lactose permease system, although the maximal rate of uptake of lacitol was similar to that of lactose. By comparison with several structurally related D-galactopyranosides, the decreased affinity was attributed to an effect of the membrane/water interface. A model for substrate recognition by the lactose permease system is presented.


Immunological properties of a high molecular weight component from yeast cell autolysate in dogs and evaluation of its potential role in human dextran reactions. A high molecular weight component (HMC) of autolysate from Saccharomyces cerevisiae yeast cells was prepared. HMC was found to be immunogenic in dogs, inducing hemagglutinating antibody formation. Upon HMC challenge of immunized dogs, systemic anaphylactoid reactions were observed in 4/5 animals. The most prominent symptom was decreased cardiac output. Decrease in mean arterial pressure and increase in pulmonary arterial pressure were also observed. Consumption of total serum complement activity amounted to 22% of initial values. HMC also exhibited mitogenic activity in lymphocyte cultures from nonimmunized and immunized dogs. Since yeast autolysate is used as nitrogen source for Leuconostoc mesenteroides in the production of clinical B 512 dextran it is a theoretically possible trace contaminant of such solutions. Therefore, dogs hyperimmunized with HMC were also challenged with clinical dextran. No anaphylactoid signs were observed. These data suggest a negligible causal role of macromolecular contaminants derived from yeast cell autolysate in rare human anaphylactoid reactions following infusion of clinical dextran.


Disposition of valproic acid in man.

Disposition of valproic acid in man. The pharmacokinetics of valproic acid (VPA) have been studied in 6 healthy subjects following a single 600 mg dose, and after multiple doses over 12 days (1200 mg daily) of enteric-coated sodium valproate. A time lag before absorption of 1 to 2 h was observed in each subject, and then absorption was rapid, peak concentrations being recorded 3 to 4 h after administration of the dose. The plasma level decline was biphasic with a terminal half-life of 15.9 +/- 2.6 h in the single dose and 17.3 +/- 3.0 h in the multiple dose experiments. There was no evidence of dose dependent kinetics or autoinduction. Total plasma clearance was 0.0064 +/- 0.0011 l/kg X h. The apparent volume of distribution was small at 0.15 +/- 0.2 l/kg. The mean steady state plasma concentration (Css) reached after 4 days was 81.3 +/- 13.0 microgram/ml. Css observed was lower than Css predicted (99.2 +/- 14.7 microgram/ml) from single dose kinetics (p less than 0.001). The difference was probably due to a reduction in plasma protein binding at higher concentrations. VPA concentration in saliva was between 0.4 and 4.5% of the total plasma concentration and was not equal to the concentration of unbound drug in plasma (6.7 +/- 0.8% unbound). 3.2% of the dose was excreted in urine as the parent drug and 21.2% as conjugated metabolites.


Controlled trial of acebutolol in hypertension. Acebutolol, a new cardioselective beta-adrenoceptor blocking agent, has been evaluated for the treatment of hypertension. Thirty eight previously untreated male patients with essential hypertension received placebo treatment during a 4-week run-in period, and then they were randomly (double-bind) allocated either to continued placebo treatment for three 4-week periods or to treatment with acebutolol 400, 600, and 1200 mg daily, respectively, for three 4-week periods. Blood pressure and heart rate were recorded at the end of each 4-week period. Treatment with acebutolol produced statistically significant reductions in blood pressure and heart rate as compared to the placebo regimen.


Long term effect of timolol and hydrochlorothiazide, or hydrochlorothiazide and amiloride, in essential hypertension. Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.


The regional localisation of a new potent centrally acting antihypertensive agent R 28935 and its less active threo-isomer R29814 in the cat brain. Systemic administration of the centrally acting antihypertensive agent R 28935 to cats resulted in a long lasting decrease of mean arterial pressure (+/-30%) whereas the same dose of the threo-isomer R 29814 was ineffective. The antihypertensive activity was due to the unaltered drug. In spite of an identical log P, pKa, dose and a comparable plasma level, the concentration of R 28935 in all the brain areas tested was about twice that of the threo-isomer, suggesting a stereoselective uptake and/or binding of R 28935.


Prostacyclin (PGI2) is a weak contractor of coronary arteries of the pig. The actions of prostacyclin (PGI2), prostaglandin E2 (PGE2), prostaglandin H2 (PGH2) and arachidonic acid have been examined on isolated coronary arteries from pigs. Arachidonate metabolites contracted this tissue, the order of potency being PGH2 greater than PGE2 greater than PGI2 suggesting that the coronary vasoconstrictor effects of PGH2 are limited by metabolism to PGI2. Sodium arachidonate and linoleate weakly relaxed porcine coronary arteries, but the former induced a secondary prolonged contraction: only the contraction was abolished by indomethacin. Thus the relaxation induced by fatty acids does not depend on metabolism to prostaglandin-like substances.


Effects of methylxanthine drugs on pyrogen-induced hyperthermia. The hyperthermic response to pyrogen was not potentiated by caffeine or theophylline administered i.p. into cats or rabbit. Injection of these drugs into the anterior hypothalamus or into the third cerebral ventricle in cats was also without effect on pyrexia. These results support the hypothesis that cyclic AMP in the anterior hypothalamus does not mediate pyrogen-induced hyperthermia in cats.


Stimulation of cell division in ectopic liver tissue following partial removal of the lung. Autografts of liver were implanted into the left lung (Xenopus laevis). Subsequent removal of the right lung stimulated increased mitotic activity in the lung and in the liver graft.


A procedure for the rapid freezing of whole embryos. A procedure for the rapid freezing of whole chick embryos for histochemical treatment is described. The problems of deformation during preparation for quenching and orientation for sectioning have been largely overcome by placing embryos inside lengths of chicken trachea. The subsequent disorientation of tissues that follows cracking and shattering due to the rapid freezing of whole embryos is avoided. The method permitted a more precise identification of the position and time of appearance of formaldehyde-induced fluorescence and myosin antibody immunofluorescence in serially sectioned embryos.


[Pharmacological pecularities of natural and synthetic alpha-adrenomimetic substances II]. The comparative examination of noradrenaline, octopamine, Privin and 2-phenylethylamine on the isolated rat vas deferens made under controlled conditions (1) has been extended by introducing more complex experimental conditions. Pretreatment of the animal with reserpine does not change the response to Privin, while the response to the maximal doses of noradrenaline is reduced; the response to octopamine remains unchanged while that of 2-phenyl-ethylamine is abolished.


Microsurgical reconstruction of the uterin tube in sterilized patients. Increasing requests for reversal of sterilization prompt a re-evaluation of guidelines for sterilization and for methods of reconstruction. The method of nonmicroscopic (gross) reconstruction is examined, and its frequent failures are felt to be in consequence of surgically induced distortion and damage to physiologic function. Microsurgery minimizes these failings and results in a doubled pregnancy rate. Microsurgical procedures are described and illustrated, and criteria are given for selection of candidates.


Comparison of two techniques of suturing in microsurgical anastomosis of the rabbit oviduct. Microsurgical reconstruction of the rabbit oviduct was undertaken utilizing either through-and-through sutures including the mucosa, or sutures penetrating the serosa and myosalpinx but not the mucosa. Patency and pregnancy rates did not seem to vary with the suturing technique. However, scanning electron microscopic observation revealed abnormal mucosal fold patterns at 3 weeks after surgery. Fibrinous exudates over the surface of the intraluminal sutures increased with time until the entire surface was thickly veiled by 9 weeks. The observation also revealed regeneration of epithelial cells along the suture. These cells included many abnormal forms such as giant cells and misshapen cells. The majority of these were nonciliated. In theory, the intraluminal suture could form a nidus for epithelial hyperplasia which might cause future tubal obstruction. However, the patency and pregnancy rates obtained with through-and-through suturing were similar to those obtained when the endosalpinx was excluded, both in this study and in previous studies from these laboratories.


Immunodetection of a human chorionic gonadotropin-like substance in human sperm. The presence of a human chorionic gonadotropin (hCG)-like substance in human spermatozoa is reported. A highly sensitive immunocytochemical procedure was utilized (double-antibody immunofluorescence technique). Rabbit anti-hCG or rabbit anti-hCG beta-subunit was used as the first antibody. A positive fluorescence reaction was found in all human specimens analyzed and in positive controls (choriocarcinoma cells). No fluorescence was detected in other species studied (sheep, pig, goat, horse, bull, and guinea pig), nor in the negative controls. These findings open a new research area on the physiologic role of this hCG-like substance in human reproduction.


[Effect of monoamine levels on gonadotropin releasing hormone concentration in the hypothalamus, pituitary gonadotropic fuction and ovarian ovulatory and hormonal function]. Daily administration of 0.25 mg reserpine during 14 days reduces the noradrenaline and dopamine level in the hypothalamus by 21--47 per cent and the LH level in the blood. The amount of Gn-RH in the supra-and retrochiasmatic portions of the hypothalamus is significantly increased thereby indicating an inhibition of the RH release into the blood of portal vein. The same course of 0.5--0.75 mg reserpine reduces the level of catecholamines by 51--82 per cent, the Gn-Rh content decreasing in the preoptic, supra-and retrochiasmatic areas along with further decrease of LH level in the blood. This is due, probably, to disturbance of both synthesis and release of Gn-RH. Consequently, the catecholamines activate primarily the release and then the synthesis of Gn-RH. The level of gonadotropins in hypophysis undergoes no essential alterations under the influence of reserpine, the animals develop a constant diestrus, great major yellow bodies appearing in the ovaires while the number of folliculi reduces. The hormonal activity of ovaries at that (secretion of estrogens and progesterone) decreases.


The role of passenger lymphocytes in rat skin allografts. Alloantibody formation (as measured by the haemagglutination assay) and graft rejection time were measured in HO rats receiving skin grafts from the Ag-B incompatible DA or (HO X DA)F1 strain. Pretreatment of the graft donor with irradiation (1 000 R) or thoracic duct drainage for 5 days, though reducing the level of circulating lymphocytes in these rats drastically, did not impair the host immune responses. Irradiation of graft donors with 1 500 rads did reduce the alloantibody response in the DA leads to HO combination, but this dose also impaired proper graft healing. Lymphocytes injected subcutaneously in small doses (0.3 and 3 X 10(6)) cells) immunized the recipients efficiently for a haemagglutinin response; however, the response developed in a much quicker tempo than the response after skin grafting. Skin grafts varying in size by a factor of approx. 4 evoked alloantibody formation of identical magnitude. On the basis of this and other recent evidence, it is suggested that the antigenicity of rat skin is not critically dependent on the presence of passenger lymphocytes in it.


[Significance of iontophoresis in dermatology. With special reference to the management of lymphedemas]. The development of modern medicine has very often pushed older methods of treatment to the background. It will be tried to represent the importance of iontophoresis as a special form of electrotherapy for dermatology according to studies of literature and own observations. Iontophoresis is for most of the 40 to 50 dermatologic indications named in literature without any importance for the present. This is also to be said for their diagnostic and experimental application. Because of the synergistic effect of the galvanic current and the medicament sluiced in, iontophoresis is said to be recommended following literature, for the treatment of the rest of therapeutically only with difficulty to be influenced idiopathic hyperhidrosis manuum et pedum, constitutional hypertrichosis, the lymphedema and also the induratio penis plastica and of thrombophlebitis. It will be reported about own experiences in the treatment of lymphedema.


Papular dermatitis herpetiformis. Report of a case with localized, facial lesions. A male patient with unusual clinical features of dermatitis herpetiformis is reported. The eruption consisting mainly of erythematous papules developed symmetrically around the mouth and later around the eyes, and has been circumscribed within these areas for 4 years. The dermatitis herpetiformis nature of the lesion was confirmed by direct immunofluorescent testing.


[The heterotopic heart transplantation: first clinical experiences (author's transl)]. Ten patients, all men, have been operated of heterotopic heart transplantation since the end of 1974. Ages ranged from 59 to 24 years with an average of 38 years. Six of them suffered from ischaemic heart disease, two from cardiomiopathy and two from rheumatic heart disease. All of them presented end stage cardiac disease. The first two patients underwent to left ventricular bypass only, in the remaining eight a right and left bypass was performed. At the present time, June 1977, 6 of the original 10 patients are alive all of them in functional class I. Five of them have resumed a full time job, the sixth will be soon able to do so. Four patients died. There were no deaths from acute rejection, but three died from infection, and the fourth one from a pulmonary embolus, 4 months after transplantation. There has been only one episode of acute rejection which has responded well to the treatment. The advantages of the heterotopic versus the orthotopic cardiac transplantation are discussed.


[The effects of tolamolol on excito-conduction in men (author's transl)]. The electrophysiologic effects of tolamolol (UK-6558-01), a new beta-adrenergic blocking agent, were studied using the endocavitarian electrocardiography and the extrastimulus method. The drug was infused intravenously in the dose of 20 mg (0,23-0,36 mg per kilogram). Tolamolol resulted in: -- prolongation of sinus cycle length in 17 patients (P less than 0.001); -- prolongation of correct sinus node recovery time in 16 patients (P less than 0.001); -- there was no significant modification in intra-atrial conduction (P less than 0.3), while atrail effective refractory period was slightly lengthened (P less than 0.03); -- in A-V node conduction was prolonged in 17 patients (P less than 0.001) and the effective functional refractory periods were prolonged in all patients (P less than 0.001); -- a A-V block of 2 degrees grade appears in 17 patients at a more prolonged cycle length (P less than 0.001). Tolamolol had no effect on His-Purkinje system conduction time as well as the relative refractory period, measured before and after the drug in 2 patients. In 6 patients, during the induction of extrastimuli an "echo zone" appeared; after tolamolol its duration was reduced in 4 patients, in one unchanged and in one abolished. The therapeutical properties of this drug are discussed on the basis of such experimental data.


Specific inhibition of human group I pepsins by two pepsin inhibitiors. Two pepsin-inhibitors, a peptide produced by Streptomyces EF-44-201 and a peptide produced by Actinomycetes have been found to inactivate completely the human group I pepsin, but to have little activity against the group II pepsins.


Tolerance to lactose among lactase-deficient American Indians. To determine the amount of lactose that could be tolerated in a meal, 59 lactase-deficient American Indians, ranging in age from 5 to 62, were given graded doses of lactose. The diagnosis of lactase deficiency had beeen documented previously by showing increased breath hydrogen after an oral lactose load (2 g per kg, maximum 50 g). With this load, 88% of the subjects had symptoms. On 6 consecutive mornings, each subject was given a breakfast that contained graded doses of lactose ranging from 0 to 18 g. The order of the breakfasts was randomized and the contents were double-blinded. Symptoms, which were assessed by a "blinded" observer, were present after 9% of the breakfasts at all dosage levels, including the lactose-free breakfast. Thus, under the conditions of this study, a modest amount of lactose, equivalent to that present in 1 to 1 1/2 glasses of milk, when taken with a meal, is well tolerated by the lactase-deficient American Indian.


Gastrointestinal and systemic toxicity of fecal extracts from hamsters with clindamycin-induced colitis. The production of toxic substances by intestinal bacteria is one pathogenic mechanism proposed for antibiotic-associated colitis. We demonstrated the presence of a toxic substance(s) in the feces of hamsters developing clindamycin-induced enterocolitis. Suspensions derived from cecal contents of clindamycin-treated animals induced a hemorrhagic ileocecitis and death within 2 to 4 days after being given orogastrically to hamsters. Intraperitoneal injection of sterile filtrates of these suspensions produced an exudative peritonitis, intraabdominal hemorrhages, and death of 80 to 100% of hamsters within 1 day. These effects were not seen with intraperitoneal injection of clindamycin or endotoxin, only small amounts of which were present in the filtrate. Incubation of the filtrate in vitro with polyvalent clostridial antitoxin neuralized its toxicity. In vitro incubation of the filtrate with normal equine serum did not reduce its in vivo toxicity. The toxic substance(s) contained in the filtrate was heat-labile and produced morphological changes in Y-1 adrenal cell cultures characteristic of heat-labile enterotoxins. Cecal filtrates obtained from saline-treated animals produced none of these effects. These preliminary studies suggest that enterotoxin-like substances, possibly produced by clostridia, may play an important role in the pathogenesis of clindamycin-induced colitis in the hamster.


Evaluation of carbenoxolone sodium in the treatment of duodenal ulcer. A double blind trial involving 21 patients on carbenoxolone and 23 patients on placebo was conducted under endoscopic control to assess the healing of duodenal ulcers over a period of 6 weeks. The two groups were adequately matched with the exception that larger ulcers predominated in the carbenoxolone group. Relief of symptoms showed poor correlation with ulcer healing. Fourteen of the 21 patients in the carbenoxolone group and 7 of the 23 in the placebo group showed endoscopic evidence of complete healing. The result is highly significant (P less than 0.016) and confirms the therapeutic efficacy of carbenoxolone sodium positioned-release capsules in the treatment of duodenal ulcers. Side effects of carbenoxolone therapy in the form of weight gain, rise in diastolic blood pressure and hypokalaemia were observed, but with adequate monitoring and appropriate countermeasures, no patient suffered any ill effects.


[The effect of therapeutic doses of gamma radiation on candida albicans cells in vitro (author's transl)]. The problem of side effects of radiotherapy in genital carcinomas on a concomitant vaginal yeast infection was investigated by subjecting candida albicans cells in vitro to the effects of gamma radiation. Agar plates with a defined number of candida albicans cells were irradiated with the conventional gynaecological sources of radium applicators and tele-cobalt. The experimental incubation of the agar plates showed that the number and growth of the yeast colonies were either completely inhibited or stunted by the effect of the radiation. There were also mutations in the cell morphology, animal pathogenecity and sensitivity to antimycotic drugs. The clinical implications of these results are discussed.


Recombination pathway specificity of Chi. Chi in phage lambda is a genetic element increasing the rate of recombination in its vicinity. Chi activity requires the wild-type functions of both the recA and the recB genes of E. coli. In terms of the pathway concept for recombination, Chi is active in the RecBC pathway and inactive in the Red, RecE., and RecF pathways.


The timing of UV mutagenesis in yeast: a pedigree analysis of induced recessive mutation. The mechanism of UV-induced mutation in eukaryotes was studied in individual yeast cells by a procedure that combined pedigree analysis and tetrad analysis. The technique involved the induction of recessive lethals and semilethals in G1 diploid cells. Induced frequencies were 25 and 61 percent at survival levels of 90 and 77 percent, respectively. No evidence of gross chromosome aberrations was detected. Recessive mutations that affect only one strand or that affect both strands of the DNA molecule are induced much at random among a population of cells, and both types can occur within the same cell. However, the data confirm that two-strand mutations are in the majority after a low level of irradiation. The simplest explanation involves a mechanism whereby most mutations are fixed in both strands prior to the first round of post-irradiation DNA replication. The recessive mutational consequences of irradiation are exhausted at the conclusion of the first post-irradiation cell division, although dominant-lethal sectoring continues at a high level through the second post-irradiation division. It is concluded that pyrimidine dimers that persist to the second round of DNA replication are rare or ineffective.


[Effects of pretreatment with carteolol on metabolic changes induced by coronary artery ligation in dog left ventricular wall (author's transl)]. Effects of coronary artery ligation on myocardial glycogenolysis were studied in the endo- and epicardial layers of the left ventricular wall in dogs pretreated with 10 or 100 microgram/kg (i.v.) of carteolol, a potent beta-adrenergic blocking agent. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. In control (saline-pretreated) dogs, an increase in phosphorylase alpha activity and an increase in breakdown of glycogen were observed in both endo- and epicardial layers after coronary artery ligation. In the presence of 10 or 100 microgram/kg of carteolol, however, increases in phosphorylase alpha activity and increase in breakdown of glycogen were not observed in either the endo or epicardial layers. These results indicate that pretreatment of the dog with carteolol inhibits the increase in glycogenolysis caused by coronary artery ligation. Nevertheless, carteolol did not completely inhibit the coronary artery ligation-induced increase in glucose-6-phosphate and lactate levels, and the coronary artery ligation-induced decrease in phosphocreatine level, particularly in the endocardial layers.


Transforming activity of plasmid and chromosomal DNA in Escherichia coli. An auxotrophic strain of Escherichia coli with the recB recC sbcB genotype was transformed by chromosomal DNA of the prototrophic strain and by plasmid DNA carrying genes for antibiotic resistance (R1 drd19). The donor plasmid DNA obtained by cell lysis in the presence of Triton X-100 and subsequent centrifugation in a caesium chloride-ethidium bromide gradient was shown to have a circular molecule and to retain its completeness after penetration into the recipient. Experiments with mixtures or plasmid and chromosomal DNA indicate a competition between these two DNA types during the transformation reaction in the given system.


Specificity of trans-inhibition of amino acid transport in baker's yeast. The trans-inhibition potency of intracellular amino acids on the transport of various amino acids follows the same sequence, viz. Pro(Lys), Phe, Glu, Ala, Gly, Leu, and alpha-aminoisobutyric acid. The same sequence was found for the reciprocal of trans-inhibition constants. It appears that the intracellular amino acid itself or a derivative thereof acts on a component that is common to all amino acid transport systems of baker's yeast.


Effect of phosphate on ergot alkaloid synthesis in Aspergillus fumigatus. High concentration of inorganic phosphate in the culture medium of Aspergillus fumigatus inhibited ergot alkaloid synthesis. Addition of L-tryptophan but not mevalonate or 5-methyltryptophan to the above culture restored the alkaloid synthesis to the level found in normal cultures. The decrease in alkaloid synthesis in the fungus accompanies an increase in cell mass, cellular protein and sterol content. Aspartate aminotransferase and alanine aminotransferase activities were significantly increased in the high-phosphate culture.


[Tertiary malaria with acute lung edema in a Turkish child]. In the past 10-15 years there has been a continuous increase of imported cases of malaria in the Federal Republic of Germany. The case of a two-year-old child of a Turkish foreign worker with severe tertian malaria complicated by pulmonary edema is described. In general tertian malaria is rarely fatal to adults, but in children the primary attack can be life threatening.


[Covering of skin defect wounds with a synthetic skin substitute. Conditioning of defect wounds of various origins with a synthetic skin substitute as a preparation for skin transplantation]. Treatment of large skin defects with a synthetic substitute for homograft skin is described. Defect wounds of different genesis, particularly with heavy infections, were treated with the synthetic skin substitute Epigard (Parke-Davis). An advantage is an easy wound dressing and good condition of the wound ground with development of a sufficient vascularization and cleaning of the wound bed for the reconstructive procedures keeping the wound ready for autotransplantation.


[Analgesia with mild side effects].

[Analgesia with mild side effects]. The efficacy of nefopam, a novel analgesic agent, was compared to pentazocine in a double blind study in 40 cancer patients with chronic pain. Both drugs were administered orally for 10 days. Pain relief after nefopam was at least as good as after pentazocine. Side efftects after nefopam were different in nature and less frequent than after pentazocine; respiratory depression or sedation were no observed.


[Cytopherometry in neurologic diseases (author's transl)]. Cytopherometry in neurologic diseases is discussed with regard to antigenic reactivity, the formation of cytokines and the direct changes of electrophoretic mobility of immune-competent cells. The Macrophage-Electrophoresis-Mobility (MEM) test, the variants of the method and additional techniques produced some results of diagnostic and immunpathologic value. A general and unspecific sensitization during cellular immune reaction in lesions of the nervous parenchyma was detectable. Using adequate antigens and extended methods of characterisation in the test system, differentiated reactivity, mainly of the inflammatory diseases and in some pathogenetic processes - including a defect of cell-membrane - was found. Typical findings were shown with the MEM-LAD (linoleic acid depression) test in M.S. This technique led to novel pathogenetic, family-genetic and therapeutic aspects. Similar diagnostic progress in various types of brain tumors was shown by using tumorassociated antigens. Analysis of specific factors of cellular immunity was extented by developing a thymosine assay and direct assessment of cytokines, especially fo the MSF (macrophage slowing factor) in the MSF assay. The thymosine assay may prove valuable for the cellular basis of immunologic processes (in particular myasthenia and therapeutic thymectomy). With the direct MSF assay a differentiated high MSF activity in the CSF in chronic neuroimmunologic processes and particularly in M.S. was shown which led to novel aspects of the immunology of the CSF. The characteristics of the MSF, found after column-chromatographic fractionation, showed identical zytokine activity in CSF and the supernatants of lymphocyte-antigen-incubation which lay in the lower range of molecular weight of migration inhibitory lymphokines.


Insulin and glucagon: plasma levels and pancreatic release in the genetically obese Zucker rat. Circulating levels of insulin and glucagon, as well as their release from isolated pancreatic islets, have been measured in Zucker rats to examine the effect of genotype, sex and diet. The obese animals had higher plasma insulin levels and enhanced release from islets when compared to lean controls. Conversely, obese animals, despite no significant differences in fed plasma levels of glucagon, showed substantially reduced release from islets. Diet had no main effect on any of these parameters.


Calcium antagonists and islet function. XI. Effect of nifedipine. Nifedipine inhibits calcium-45 net uptake and glucose-induced insulin release in rat pancreatic islets, without affecting glucose oxidation and calcium-45 efflux. These findings are compatible with the view that nifedipine inhibits the entry of calcium in the B cell, by interfering with the plasma membrane ionophoretic channels.


Sequence determination of protein S9 from the Escherichia coli ribosome. The complete amino acid sequence of ribosomal protein S9 of Escherichia coli has been established. The protein was digested with trypsin and Staphylococcus aureus protease and the resulting peptides were separated by ion exchange chromatography on a new Dowex 50W-X7 microcolumn or a small phosphocellulose column. If necessary, they were rechromatographed on purified cellulose thin-layer plates on a preparative scale. The sequences of the peptides were determined by the micro dansyl-Edman technique, whereas the alignments of the tryptic peptides were mainly established from large cyanogen bromide fragments which were sequenced by the automatic Edman degradation process. Protein S9 is 128 amino acids long and has the following composition: Asx7, Thr5, Ser7, Glx16, Pro3, Gly13, Ala10, Val10, Met3, Ile7, Leu9, Tyr5, Phe4, His1, Lys10, Arg18. The molecular weight as calculated from the amino acid composition is 14 569. A total of 92.6 mg of the lyophilized protein was used for the determination of the primary structure of S9. Most of the material was needed to isolate sufficient amounts of the CNBr-fragments for the automatic degradation in the sequenator.


Secondary structures of proteins from the 30S subunit of the Escherichia coli ribosome. The secondary structures of the proteins S4, S6, S8, S9, S12, S13, S15, S16, S18, S20 and S21 from the subunit of the E. coli ribosome were predicted according to four different methods. From the resultant diagrams indicating regions of helix, turn, extended structure and random coil, average values for the respective secondary structures could be calculated for each protein. Using the known relative distances for residues in the helical, turn and sheet or allowed random conformations, estimates are made of the maximum possible lengths of the proteins in order to correlate these with results obtained from antibody binding studies to the 30S subunit as determined by electron microscopy. The influence of amino acid changes on the predicted secondary structures of proteins from a few selected mutants was studied. The altered residues tend to be structurally conservative or to induce only minimal local changes.


Preparation of (S)2-methylsuccinate and (2S,3S) [2,3-2H]2-methylsuccinate by biohydrogenation of 2-methylfumarate. 2-Methylfumarate can be hydrogenated by resting cells of Proteus mirabilis under an atmosphere of hydrogen gas. Optically pure (S)2-methylsuccinate is formed in a yield greater than 95%. The hydrogen addition, presumably catalyzed by the fumarate reductase, occurs in a trans fashion, as with succinate dehydrogenase of mammalian systems. Only one reactive enzyme-substrate complex with 2-methylfumarate seems to be possible.


The complete amino acid sequence of protein S16 from Escherichia coli. This paper presents the experimental details which led to the elucidation of the complete primary structure of S16, a protein which belongs to the small subunit of E. coli ribosomes. Protein S16 was digested with trypsin, alpha-chymotrypsin, and the staphylococcal protease. The resulting peptides were purified on paper and their amino acid composition and sequence were determined. Automatic Edman degradation with a modified sequenator on the complete protein yielded information from the 56N-terminal residues. The combination of all these results led to the following complete amino acid sequence: Met-Val-Thr-Ile-Arg-Leu-Ala-Arg-His-Gly-Ala-Lys-Lys-Arg-Pro-Phe-Tyr-Gln-Val-Val-Val-Ala-Asp-Ser-Arg--Asn-Ala-Arg-Asn-Gly-Arg-Phe-Ile-Glu-Arg-Val-Gly-Phe-Phe-Asn-Pro-Ile-Ala-Ser-Glu-Lys-Glu-Glu-Gly-Thr-Arg-Leu-Asp-Leu-Asp-Arg-Ile-Ala-His-Trp-Val-Gly-Gln-Gly-Ala-Thr-Ile-Ser-Asp-Arg-Val-Ala-Ala-Leu-Ile-Lys-Glu-Val-Asn-Lys-Ala-Ala. The molecular weight derived from the sequence amounts to 9 162.


Anorexia nervosa and the hypothalamus.

Anorexia nervosa and the hypothalamus. A new name, "puberal starvation-amenorrhea", is proposed as more descriptive of the syndrome and less committal concerning its etiology. Though the etiology remains uncertain, a growing body of evidence--deranged hormonal secretory patterns, deficient thermal and water regulation, and other physiologic abnormalities--indicates that a specific hypothalamic dysfunction is responsible for this bizarre, sometimes lethal disease.


Dental problems in the elderly.

Dental problems in the elderly. Since the personal physician is likely to see the elderly patient far more often than the dentist does, he may be the first to spot signs of ill-fitting dentures, poor chewing ability, drug effects on the mouth, leukoplakia, and other oral problems described here.


The adoptive secondary response to human serum albumin under conditions of high antigen pressure. The response of high and low avidity B cell subsets. Thoracic duct lymphocytes (TDL) from (AS2 x AS)F1 rats previously injected with human serum albumin (HSA) were transferred to 900 r irradiated syngeneic recipients which were challenged with various doses of soluble HSA (s-HSA). TDL from partially tolerant rats, which were deficient in high avidity B cells, produced a maximum PFC response to the largest challenge dose (1 g s-HSA). In contrast, high avidity B cells from primed donors were optimally stimulated by 1 microgram and maximally inhibited by 1 mg s-HSA (day 7 PFC). An additional increase in antigen concentration by 1000 fold failed to diminish the PFC numbers further. Plaque inhibition profiles indicated that these antibody forming cells resisting inhibition were of the same high avidity as those triggered by low doses of antigen. The inability of s-HSA to completely inhibit antibody synthesis is discussed with regard to current views on B cell inactivation. Evidence is also presented which indicates that the standard haemolysis-in-gel test may fail to detect many low avidity antibody forming cells to proteins.


IgG anti-hapten antibody secretion in vitro commences after extensive precursor proliferation. We have investigated whether the intermediate cells that arise in primed mice after boosting require further cycles of division in culture before maturation into IgG antibody secreting cells. Killing of dividing cells between days 1--4 in culture, by exposure to BUdR-uv irradiation ablated the high IgG response observed on day 5 in control cultures. After T cell removal and replacement by a soluble factor (TRF) similar results were obtained. Thus B cell division over an extended period occurs prior to the appearance of IgG secreting cells. Furthermore, autoradiography of plaques from cultures briefly exposed to [3H]thymidine before harvest showed that some antibody secreting cells were synthesizing DNA at the time of assay.


Protection of mice against malaria by a killed vaccine: differences in effectiveness against P. yoelii and P. berghei. (C57BI x Balb/c)F1 mice are normally killed by a strain of the malaria P. yoelii, but they can be fully protected by a killed vaccine. The best results were obtained with saponin-lysed parasitized cells subsequently fixed with 0-06% formalin and injected intravenously with the adjuvant B. pertussis, though good protection was also obtained without the adjuvant. The protection was specific and at least partly mediated by a serum factor. A similar regime gives little or no protection against P. berghei. Possible reasons for this difference are considered and the mechanisms by which vaccination works against P. yoelii are discussed.


The immunodepressive effect of Friend virus III. Effects on spleen T cells. We have examined various T lymphocyte functions in the spleens of mice infected 4 days previously with Friend viurs (FV) in order to analyse its effect on the antibody response. We have found (a) that infection does not reduce the percentage of T lymphocytes in the spleen, nor their ability to respond to PHA, (b) that infected spleen cells mediate allogeneic augmentation of the primary response to SRBC in vitro, even though their own depressed response cannot be restored via the allogeneic effect, and (c) that infected spleen cells restore responses to SRBC by both allogeneic and syngeneic spleen cell cultures depleted of T lymphocytes. These results suggest that FV does not affect spleen T lymphocyte proliferation of helper function. Since macrophages from infected spleens cooperate normally in the response to SRBC in vitro, we conclude that the immune defect resides in the B lymphocytes.


Appearance of non-specific suppressor T cells during in vitro culture. It was found that when normal mouse spleen cells were cultured for 4 days they were capable of non-specifically suppressing the in vitro antibody response of non-precultured spleen. The suppression was mediated by a subpopulation of viable, non-adherent, T lymphocytes with the surface phenotype Ly-1+, Ly-2- and Ia-. Furthermore, it appeared that the suppressor cells were responding to foetal calf serum antigens present in the tissue culture medium and were subsequently inactivating either B lymphocytes or accessory cells required for antibody formation, which had passively absorbed these antigens.


Liability to hydrophobic and charge interaction of smooth Salmonella typhimurium 395 MS sensitized with anti-MS immunoglobulin G and complement. Sensitization of smooth Salmonella typhimurium 395 MS bacteria with hyper-immune anti-MS immunoglobulin G (IgG) antibodies increased the liability to hydrophobic interaction as assessed by the affinity for a column of Octyl-Sepharose. After sensitization, the material originally eluted with 1 M (NH4)SO4 in a 0.01 M phosphate buffer (pH 6.8) was not desorbed until the ionic strength was reduced to nil, and 0.1% (vol/vol) Triton X-100 in the 0.01 M phosphate buffer was used as eluant. Furthermore, by including positively charged bis-trimethylamino-polyethylene glycol (PEG) or negatively charged bis-sulfoamino-PEG in an aqueous two-phase system of dextran T500 and PEG 6000, the partition of the IgG-sensitized bacteria was affected by either of the polymers, whereas that of the parent bacteria was not. The hydrophobic effect of IgG binding was enhanced by complement. With heat-inactivated complement, the effect of IgG was diminished. The F(ab')2 fragment showed a much lower capacity to promote a hydrophobic interaction than the complete IgG molecule.


Effect of some R factors on the sensitivity of rough Enterobacteriaceae to human serum. Eight plasmids out of 26 tested confer partial serum resistance to Escherichia coli K-12 strains (Bhs character). Four Bhs+ plasmids were tested in a rough Salmonella typhimurium host, and three conferred partial serum resistance to this host as well. Plasmids representative of 19 different incompatibility groups were examined; the Bhs+ property was found in some (but not all) representatives of groups N, O, S, T, W, and F'lac (FI), and there was no apparent association between other plasmid markers and Bhs. It is likely that more than one mechanism can promote the Bhs+ phenotype and that Bhs genes are responsible for modifications of the surface structures involved in serum sensitivity.


Cellular source of interferons in the circulation of mice with delayed hypersensitivity. The cellular origins of type I and type II interferons released into the circulation of mice with delayed hypersensitivity were investigated. We determined the effect of treatment with various immunosuppressive agents, including cyclophosphamide, cycloheximide, antithymocyte serum, and whole-body X-irradiation, on the release of interferons after intravenous injection of specific (old tuberculin) or nonspecific (lipopolysaccharide) stimuli. The results suggest that (i) a heterogeneous population of lymphocytes (T and B cells) produces type II interferon, (ii) type I interferon is produced by a different cell population, and (iii) type II interferon is produced de novo after challenge with old tuberculin of mice sensitized with Mycobacterium bovis BCG.