Cerebrovasodilatation through selective inhibition of the enzyme carbonic anhydrase. 1. Substituted benzenedisulfonamides. A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal diuretic effect. 19 selectively increased cerebral blood flow in animals and man without producing an unacceptable level of metabolic acidosis.


Design of potent antagonists of the vasopressor response to arginine-vasopressin. As part of a program in which we are attempting to design and synthesize antagonists of the vasopressor response to arginine-vasopressin (AVP), [1-deaminopenicillamine]arginine-vasopressin (dPAVP), [2-O-methyl)tyrosine]-arginine-vasopressin [Tyr(Me)AVP], and [1-deaminopenicillamine,2-(O-methyl)tyrosine]arginine-vasopressin [dPTyr(Me)AVP] were synthesized by the solid-phase method and assayed for vasopressor, antidiuretic, and oxytocic activities. Tyr(Me)AVP has a vasopressor potency of 9.7 +/- 0.5 units/mg and an antidiuretic potency of 386 +/- 36 units/mg. These values are 2.5 and 120%, respectively, of the corresponding potencies of AVP. The analogue is an antagonist of the in vitro response to oxytocin (pA2 = 7.44 +/- 0.12). dPAVP has an antivasopressor pA2 of 7.45 +/- 0.11. Its antidiuretic potency is 42.2 +/- 2 units/mg, 2.5% that of its parent, 1-[deamino]arginine-vasopressin (dAVP). It is an antagonist of the in vitro response to oxytocin (pA2  value = 6.93 +/- 0.10). dPTyr(Me)AVP has an antivasopressor pA2 of 7.96 +/- 0.05 and an antidiuretic potency of 3.5 +/- 0.5 units/mg. It is also an antagonist of the in vitro oxytocic response to oxytocin (pA2 value = 7.61 +/- 0.14). It is thus one of the most potent vasopressor antagonists reported to date.


Structure-activity relationships of aminoalkyl and -aryl glycosides having insulin-like activity. A number of alkyl, aryl, and aralkyl glycosides (mono- and disaccharides) substituted in the aglycon with a primary amino group have been found to exert insulin-like activity on rat adipocytes in vitro. Systematic variations in the saccharide configuration, glycosidic linkage, aglycon moiety, and sugar substitution pattern were investigated to delineate structure-activity relationships. A high degree of structural specificity was observed. Maximal insulin mimicking activity was obtained with the 6-aminohexyl 1-thio-D-mannopyranosides; the beta anomer was more active than the alpha anomer. Modification of the sugar hydroxyl groups resulted, in most cases, in partial or complete loss of biological activity at the levels tested; however, in a few instances, sugar-modified derivatives did show enhanced insulin-like effects. Specific structural types evaluated are discussed in greater detail. 6-Aminohexyl 1-thio-beta-D-mannopyramoside also exhibited in vivo insulin-like effects on both diaphragm muscle and omental adipose tissues. The specificities for the sugar as well as the aglycon portions of these carbohydrate derivatives suggest that both parts of the molecule are involved in the expression of the full biological activity observed; their respective roles in the mechanism of the insulin-like activity are discussed.


Pivaloyl esters of N,N-dialkylated dopamine congeners. Central dopamine-receptor stimulating activity. In order to test for dopamine-receptor stimulating activity a new, sensitive biochemical screening method was designed. For behavioral studies and for determination of the duration of action on the compounds, motor activity measurements were used. O,O'-Dipivaloyl-N,N-dipropyldopamine (4) was the only derivative of a series of dipivaloyl-N,N-dialkyldopamines studied that showed any significant activity. However, the monopivaloyl ester 2-(3-pivaloyloxyphenyl)-N,N-dipropylethylamine (8) seemed to be more potent. The same relationship was found for the corresponding phenols, N,N-dipropyldopamine (3) and 2-(3-hydroxyphenyl)-N,N-dipropylethylamine (7), although both were more active than their pivaloyl esters.


Diacridines, bifunctional intercalators. Chemistry and antitumor activity. The synthesis and the characterization of a number of diacridines connected through the 9-amino position of the acridine rings by alkyl chains of varying lengths and with various substituents on the acridine ring are described. An interesting chemical property has been noted; whereas the 3-amino monoacridines cannot form stable dihydrochloride salts, the corresponding diacridines can form stable trihydrochloride salts. The biological activity of the diacridines encompasses a broad spectrum of action. Their antitumor activity (% ILS) and their toxicity have been correlated with their biological actions. The % ILS, as measured by inhibition of growth of P-388 ascites cells in BDF/1 mice, shows no significant correlation with their ability to inhibit the growth of P-388 cells in culture (I50). The toxicity of the diacridines does not correlate with the inhibition of DNA or RNA synthesis, the uptake of the diacridines by P-388 cells, or with % ILS. The only significant correlation that has been found to date between the antitumor effectiveness of the diacridines and their effects on intact cells occurs between % ILS and cell agglutination. These results emphasize that caution should be used in attributing the "antitumor activity" of a single compound or  of a small number of congeners of a given chemical structure to a particular site of biological inhibition. Furthermore, the results suggest that effective antitumor drugs are those that affect the host-tumor interaction and that the toxicity of the drugs may not be essential to their antitumor properties.


Antiviral activity of some beta-diketones. 4. Benzyl diketones. In vitro activity against both RNA and DNA viruses. The synthesis and in vitro antiviral evaluation of a series of substituted benzyl beta-diketones are described. The introduction of a styryl group onto the phenyl ring enhanced activity against herpesvirus type 2. The 4-methoxystyryl homologue 8 was evaluated extensively in vitro and was found to be effective against both RNA and DNA viruses. Compound 8 was evaluated in the mouse vagina against herpes simplex type 1 and produced a significant increase in survival rate as well as in survival time.


Analgesic activity of novel spiro heterocycles. 2-Amino-7-oxa-3-thia-1-azaspiro[5,5]undec-1-enes and related compounds. (+/-)-2-Amino-7-oxa-3-thia-1-azaspiro[5,5]undec-1-ene (1a) and many of its derivatives exhibit significant activity in the phenylquinone writhing and yeast inflamed foot assays. In order to develop structure-activity relationships, the related spiroheterocycles, (+/-)-2-amino-7-oxa-3-thia-1-azaspiro[5,4]dec-1-ene (2), (+/-)-2-amino-3-thia-1-azaspiro[5,5]undec-1-ene (3), and (+/-)-2-amino-7-oxa-1-azaspiro[5,5]undec-1-ene (4), were examined. Of these, only 4 failed to show activity indicating that the analgetic properties displayed by compounds 1--3 are associated, mainly, with the 2-amino-1,3-thiazine ring system. In the 2-acylimino series, evidence is presented suggesting a contribution to the observed activity on the part of the spiroannulated ether ring as well. Both 1a and its p-fluorobenzoyl derivative 33 exhibit analgesic activity in the rat tail-flick assay.


Synthesis and antiinflammatory evaluation of substituted isophthalonitriles, trimesonitriles, benzonitriles, and terephthalonitriles. In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.8% reduction at 100 mg/kg), six compounds, dosed at 50 mg/kg, produced reductions in inflammation comparable to this standard. However, the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further study was not warranted. Fifteen compounds possessed activity in excess of 20% reduction at 200 mg/kg and also possessed LD50 values greater than 300 mg/kg. Of these cyanobenzenes, trimesonitrile (16), 4-chlorobenzonitrile, 2-chloroterephthalonitrile, and 2-fluoroterephthalonitrile with reductions in edema of 32, 30, 46, and 49%, respectively, represent the best candidates for subsequent study.


Structure-activity correlations for a series of antiallergy agents. Oxanilic, quinaldic, and benzopyran-2-carboxylic acids. Ab initio Hartree-Fock SCF calculations with the molecular fragment technique have been performed on several drugs which exhibit activity in the rat passive cutaneous anaphylaxis (PCA) assay. Representative molecules of the following types were included in the series: oxanilic acids, 1,4-dihydro-4-oxoquinaldic acids, and 4-oxo-4H-1-benzopyran-2-carboxylic acids. A quantitative relationship has been established between the observed biological activity and an electronic index obtained from the calculations. The correlation is rationalized in terms of charge-transfer stabilization of the drug-receptor complex.


Reactions of chloropromazine cation radical with physiologically occurring nucleophiles. The reactions between chlorpromazine cation radical and a variety of physiologically occurring nucleophiles, which involve formation of a covalent, yet reversible bond, have been examined. As reported earlier, this reaction does not involve disproportionation of the radical but, rather, direct reaction between radical and nucleophile. The resulting adduct further reacts to form chlorpromazine sulfoxide or hydroxylated derivatives, and the original nucleophile is regenerated. The products and kinetics of the reaction depend strongly on the identity of the nucleophile, with the sulfhydryl group being the fastest and water being the slowest of the nucleophiles studied. The likely involvement of these reactions in the metabolism of chlorpromazine is discussed. In addition, it is proposed that the radical/nucleophile interaction is a reasonable model reaction for the effects of chlorpromazine radical on neuronal enzymes and receptor sites.


N7-Substituted 7-aminoactinomycin D analogues. Synthesis and biological properties. A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) in vitro. Against the P388 mouse leukemia in vivo, most of the analogues had activity comparable to actinomycin D and one was significantly more active. The results show that substitutions of this kind do not interfere with the antitumor activity of actinomycin D and may be useful for the design of modified actinomycin D analogues with greater selectivity.


Semisynthetic cephalosporins. Synthesis and structure-activity relationships of 7-(1-pyrryl)- and 7-(1-indolyl)acetamidocephalosporin derivatives. A series of 1-pyrrole- and 1-indoleacetamido derivatives of 3-heteroaryl-substituted cephalosporins was prepared. The most active compound in the series was 7-[[2-(1-pyrryl)acetyl]amino]-3-[[(1-methyltetrazol-5-yl)thio]-methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (6), which showed comparable potency in vitro and in vivo to that of cefazolin, and, in addition, was more potent than cefazolin against Enterobacter sp. and Providencia stuartii.


Effects of thiophene analogues of chloroamphetamines on central serotonergic mechanisms. Ring-chlorinated thienylisopropylamines, thiophene analogues of chloroamphetamines, have been synthesized and their effects on serotonergic mechanisms in the rat brain have been evaluated. With 4,5-dichlorothienylisopropylamine (3e), a pharmacological profile similar to that of p-chloroamphetamine, consisting in a marked and long-lasting serotonin depletion and a rather strong and prolonged inhibition of synaptosomal uptake of serotonin, was found. Chloro substitution in position C3 of the thiophene ring did not determine brain serotonin depletion nor serotonin uptake inhibition but enhanced brain MAO inhibitory activity present in all these compounds. 3,5-Dichlorothienylisopropylamine (3g) was the only compound of the series in which the inhibition of serotonin uptake was more marked than the serotonin depleting property.


Antiallergic activity of tetracyclic derivatives of quinoline-2-carboxylic acids. 1. Substitution of 1,4-dihydro-4-oxoquinoline-2-carboxylic acid by acetyl, benzoyl, and phenylsulfonyl substituents was found to enhance activity in the rat passive cutaneous anaphylaxis assay. A further increase in activity, to equipotency with DSCG, was achieved by incorporation of the 8-benzoyl moiety into a tetracyclic structure to give 1,4-dihydro-4,11(1H,11H)-dioxoindeno[1,2-h]quinoline-2-carboxylic acid (20). In contrast, the reverse isomer 19 was found to have little activity.


Synthesis and xanthine oxidase inhibitory analysis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) and two of its derivatives. The synthesis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) (1), 5-methyl-1H-pyrrolo-[3,2-c]pyridine-4,6(5H,7H)-dione (1-methyl-3,7-dideazaxanthine) (2), and 1,7-dihydropyrano[4,3-b]pyrrole-4,6-dione (1-oxa-1,3,7-trideazaxanthine) (3) has been accomplished from 3-alkoxycarbonylpyrrole-2-acetates (4, 11, and 12 for 1 and 2) and from 3-carboxypyrrole-2-acetic acid (6 for 3). Compounds 1 and 2 have been found to be weak inhibitors of the noncompetitive type for xanthine oxidase while 3 showed no inhibitory properties toward this enzyme.


Diseases of the curriculum.

Diseases of the curriculum. During the past 20 years the author has visited almost half of all the American medical schools, usually as a consultant in matters of curriculum and instruction. Certain recurring curriculum problems have emerged and have been described as "diseases of the curriculum." To be exact, this article includes nine such entities. In addition to the naming of these nine curriculum conditions, there is ample illustrative material to ensure that each curriculum disease is fully explained--although the basic sciences supporting the study of education as a discipline are not advanced enough to allow fuller understanding of the disease processes. There is speculation, however, that even being able to name and describe these disturbances of normal curriculum development might be of help in solving some of our more serious curriculum problems.


The effect of timing on the validity of student ratings. Student ratings of a course are usually administered during the last days of class, on the day of the final examination, or following receipt of grades. Bias may be introduced simply by choosing a "convenient" time. In this study equivalent random groups of medical students rated an anatomy course at one of three times: immediately before or after the final examination or by mail after receiving grades. The effects of course achievement and timing on favorableness of rating were examined using analysis of variance. Results indicated a significant achievement effect but no difference in rating means due to timing. Students responding to the mail survey represented an academic cross-section of the class. Students present on the last two days of class were higher achievers and on subsequent evaluations gave higher ratings than did absentees, indicating that ratings administered on the last days would have produced a favorably biased response. Thus, comparative analyses among courses may be invalidated by including the ratings of both biased and representative student groups.


A faculty and house-staff group practice: report of an operational model. The internal medicine group practice at Colorado General Hospital was formed in 1974 to improve patient care and educational experience for residents. Six residents, two faculty members, a nurse practitioner, a dietitian, and a group practice coordinator provide 24 hour-a-day, seven day-a-week care for 666 patients. The program features: a balanced degree of faculty and house staff involvement in direct patient care, a high level of accountability provided by the coordinator, and small group size. The first 19 months of operation are reviewed, and the program is contrasted with other group practices reported in the literature.


Resident education in primary care: how residents learn. The process of resident education in an internal medicine practice was examined through interviews with 14 residents, who discussed their educational experience while caring for 10 patients. These retrospective evaluations provided insights about how the residents learned when caring for their patients. The study results suggest that resident education in this setting depends upon feedback provided through residents' use of educational resources or through their participation in elements of patient care. These essential elements of resident education were identified: treating and following patients, having cases reviewed by consultants and supervisors, encountering and recognizing diseases, and reading about problems. The study results provide a conceptual model of resident education upon which to base future research projects that should focus on patient selection and organizational aspects of the residents' practice.


Introduction to patient care: a basic science course for medical students. Basic science education of physicians has been almost exclusively in the biological fields. Although in recent years many schools have added behavioral sciences to the preclinical curriculum, there has been no agreement as to content or method in this area. An understanding of human behavior is essential for all physicians and is the goal of the course described here. This course, entitled "Introduction to Patient Care," utilizes readings, group presentations, site visits, small-group seminars, and specifically stated educational objectives to present the following topics: health problems of the United States, physicians and other healers, humanistic values--the sick role, and the doctor-patient relationship. The small-group seminars, with behavioral science and clinical faculty, help to guide the student's learning experience toward a scientific analysis of the art of medicine.


Immunological response to a strain of Staphylococcus epidermidis in the rabbit: production of protective antibody. A rabbit was immunised with a heat-killed vaccine prepared from strain 1142 of Staphylococcus epidermidis. The HA titres of the antisera against a surface-polysaccharide antigen extracted from the homologous strain were highest in the 2nd-4th weeks after immunisation and subsequently declined. Only a minor amount of 2-ME-resistant antibody was formed, and this at a late state of the reaction. After a booster injection of the vaccine at the 10th week, there was a significantly greater HA-antibody response and a greater amount of 2-ME-resistant antibody was formed. The relative passive-protective activity of the sera in mice corresponded to their content of 2-ME-sensitive HA antibody. The protective activity of the sera was 2-ME sensitive and was not removed by absorption with anti-rabbit IgG goat serum. Further, 280 microgram of IgM-rich serum fraction obtained by sucrose-density-gradient ultracentrifugation passively protected against homologous challenge infection in mice, but even 910 microgram of IgG-rich fraction did not. These results indicated that the protective antibody was of the IgM class.


The antibodies involved in the human immune response to leptospiral infection. Antibody responses were studied in human patients from whom leptospiral serovars--mainly  pomona or hardjo--had been isolated and identified. The antibody to the polysaccharide F4 antigen belonged exclusively to the IgM class, even as late as 10 months after infection. Human sera cross-reacted widely with F4 antigen from heterologous serovars. The antibodies involved in leptospiral agglutination were mainly IgM, but some patients also produced IgG agglutinins. The titres of IgM agglutinins were higher than those of IgG agglutinins and persisted for many months, regardless of the presence or absence of IgG agglutinins. Both types of immunoglobulin from patients with serovar pomona infection protected hamsters against lethal infections with homologous leptospires. The hamster-protective capacity of human sera correlated well with agglutinin titres. Sera from patients infected with serovars other than pomona protected hamsters against challenge with pomona only if they contained agglutinins to that organism.


Serological and protective-antibody responses of rabbits to leptospiral antigens. The rabbit antibody response to leptospiral F4 antigen extracted from serovar pomona depended on the method of immunisation. Intravenous injection of whole leptospires stimulated F4 antibodies that were confined to the IgM class, but leptospires injected intramuscularly with adjuvant stimulated F4 antibodies in both the IgM and the IgM and the IgG classes. Both methods of immunisation stimulated agglutinins in both the IgM and IgG classes. F4 antigen in soluble form was immunogenci when injected intradermally with adjuvant, but not when given alone. The F4 antibodies were distinct from the agglutinins in that they did not protect hamsters from acute infection with homologous leptospires, nor did they kill leptospires in vitro although they reacted with leptospires. The hamster-protective capacity of rabbit sera depended on the level of agglutinin.


Effects of intestinal micro-organisms on fluid and electrolyte transport in the jejunum of the rat. Culture filtrates of micro-organisms isolated from the upper intestinal secretions of malnourished children and grown in pure culture were shown to impair the intestinal absorption of water and electrolytes in live rats. Decreased net movement out of the intestinal lumen, or actual secretion of water, sodium or potassium into the intestinal lumen, was found with culture filtrates of single isolates of Staphylococcus epidermidis, Escherichia coli 055, Escherichia coli B7A, Shigella sonnei, Klebsiella pneumoniae, Candida albicans and Candida tropicalis. These organisms have been found to contaminate upper intestinal secretions in malnourished children and it is suggested that the effects observed in these experiments might be relevant to the production of the diarrhoea that is a dominant clinical feature of childhood malnutrition.


The anatomy of the reproductive system in male Dutch rabbits (Oryctolagus cuniculus) with special emphasis on the accessory sex glands. The morphology and microscopic anatomy of the reproductive organs and colliculus seminalis of the male rabbit are described and illustrated. Special attention is given to the accessory sex glands, because not all have been accurately identified previously. The terminology suggested for the accessory glands (with other terms commonly used in the literature in parentheses) follows: glandula vesicularis (glandula seminalis, vesicular seminalis), proprostata (glandula vesicularis, coagulating gland, prostata), prostata, paraprostata (glandula Cowperi superior), glandula bulbourethralis (glandula Cowperi inferior). The English equivalents are vesicular, proprostate, prostate, paraprostate and bulbourethral glands. Organs were obtained from 39 adult Dutch-belted rabbits that averaged 2,023 g in bodyweight. Organ weights (means and standard deviations) were as follows: testis, 2.035 +/- 0.529 g; caput epididymidis, 0.264 +/- 0.087 g; corpus epididymidis, 0.046 +/- 0.019 g; cauda epididymidis, 0.398 +/- 0.123 g; proximal part of the ductus deferens, 0.098 +/- 0.026 g; ampulla of the ductus deferens, 0.177 +/- 0.069 g; vesicular gland, 0.529 +/- 1.169 g; proprostate gland, 0.633 +/- 0.304 g; prostate gland, 0.411 +/- 0.181 g; paraprostate gland, 0.040 +/- 0.019 g; bulbourethral gland, 0.390 +/- 0.133 g; and epididymal fat pad, 0.545 +/- 0.339 g. Correlations among organ weights were calculated and interrelationships among them and bodyweight are discussed.


Histological study of muscular hypoplasia in the crooked neck dwarf mutant (cn/cn) chick embryo. Tibiotarsal segments of 12-day chick embryos homozygous for the crooked neck dwarf gene (cn/cn) were examined histologically following routine methods of preparation. The myogenic mass fails to divide into separate muscle bundles during the early stages of differentiation. Myoblasts and myotubes are observed, although the proportion favors the mononucleate cell population. Multinucleate myotubes are often wavy in appearance and many contain eosinophilic cytoplasmic inclusions. The entire tissue mass of mutants appears more compacted than in control limbs. Poor organization of muscle appears related to the lack of a suitable connective tissue system. Epimysia, perimysia, and subcutaneous connective tissue fail to develop properly. Tendons are poorly developed or absent. Comparisons between mutant and control embryos show no differences in peripheral innervation. Nerve fascicles penetrate deeply into the developing muscle of both species. The distribution of vascular elements is seemingly normal also. Skeletal muscle of cn/cn embryos is capable of differentiating to the myotube stage, after which it undergoes cellular degeneration without achieving a functional state. Comparisons of this mutant with alleged chemical phenocopies show important differences.


Forebrain projections of the pigeon olfactory bulb. The olfactory system of the pigeon (Columba livia) was examined. Our electrophysiological and experimental neuroanatomical (Fink-Heimer technique) data showed that axons from the olfactory bulb terminated in both sides of the forebrain. The cortex prepiriformis (olfactory cortex), the hyperstriatum ventrale and the lobus parolfactorius comprised the uncrossed terminal field. The crossed field included the paleostriatum primitivum and the caudal portion of the lobus parolfactorius, areas which were reached through the anterior commissure. In this report the relationships between areas that receive olfactory information and the possible roles that olfaction plays in the birds' behavior are discussed.


Seasonal ultrastructural variations in pinealocytes of the woodchuck, Marmota monax. The ultrastructure of the pinealocyte in the woodchuck, Marmota monax, was studied during the four seasons of the year. Fall cells have a fairly uniform cytoplasmic density, organelles consistent with synthetic and/or secretory activity and rather extensive pericapillary and intercellular spaces. Many winter pinealocytes are nearly devoid of ribosomes and granular endoplasmic reticulum but contain lipid droplets associated with mitochondria. Pericapillary and intercellular spaces are minimal. Spring glands have the greatest variation in cytoplasmic density with intercellular and pericapillary spaces similar to that seen in fall glands. Cells containing electron dense cytoplasm have Golgi zone associated, secretory granules, free ribosomes, short sections of granular endoplasmic reticulum and dense bodies. Cells with a more electron lucent cytoplasm are similar to the most frequently observed summer pinealocytes which have numerous Golgi zones but few associated secretory granules. Microtubules are prominent in the cytoplasm of these cells, the plasma membranes are smooth and intercellular and pericapillary spaces are minimal. A yearly rhythm or cyclic activity of the pinealocyte is suggested.


Structural relatedness of kappa-casein and fibrinogen gamma-chain. kappa-Caseins, involved in the milk clotting process, and human fibrinogen gamma-chain, involved in the blood clotting process, show structural similarities. Several long kappa-casein sections, together corresponding to 80% of the whole protein molecule, have their counterparts in the gamma-chain of fibrinogen, in that 31--42% of the amino acid residues occupy identical positions. The section of kappa-casein which contains the chymosin-sensitive bond has a counterpart not only in the gamma but also in the Bbeta-chain of fibrinogen. Furthermore, the secondary structures of the kappa-caseins and of the gamma-chain predicted according to the method of Chou and Fasman present several common features.


Cyanamide mediated syntheses under plausible primitive earth conditions. V. The synthesis of phosphatidic acids. A mixture of ammonium palmitate, 14C-sn-glycero-1(3)-phosphate, cyanimide and imidazole when heated for several hours formed significant quantities of phospholipids. These reaction products were shown by chromatographic, chemical and enzymatic procedures to be monopalmitoylglycerophosphate (MPGP), dipalmitoylglycerophosphate (DPGP) and monopalmitoyl cyclic glycerophosphate (cMPGP). A portion of the MPGP and DPGP possessed the same steric configuration as naturally occurring lysophosphatidic acid and phosphatidic acid. The yield of total phospholipid was maximal at temperatures between 60 degrees and 90 degrees after 8 h. When ratios of reactants were varied, up to 45% of radioactive glycerophosphate was converted into phospholipids. The average proportions of individual phosphatidic acids were: 60% MPGP, 27% DPGP and 13% cMPGP. Evidence was obtained for a synergistic relationship between cyanamide and imidazole in promoting the formation of phosphatidic acids. These results suggest that phosphatidic acids, which are essential precursors for the biochemical synthesis of more complex membrane phospholipids, could have been produced on the primitive Earth.


The asymmetry of life.

The asymmetry of life. Stereoselective physical phenomena and their possible importance for the prevalence of D-sugars and L-aminoacids in living matter are reviewed. A classification is presented according to which a selective force provides a microscopic or macroscopic selection depending on its generality when taken over a macrosystem (a 'unitary biosphere' such as the Earth). The microscopic 'selections' are not genuine selections because the final sense of asymmetry is here determined by chance, in other words the initial choice is 'random', while it is 'directed' in the macroscopic selection. Two macroscopic selections appear possible: 1. selection due to an intrinsic energy difference between enantiomorph configurations, 2. selection accomplished by elliptically polarised radiation.


Nonrandom amino acid substitution and estimation of the number of nucleotide substitutions in evolution. A method of estimating the number of nucleotide substitutions from amino acid sequence data is developed by using Dayhoff's mutation probability matrix. This method takes into account the effect of nonrandom amino acid substitutions and gives an estimate which is similar to the value obtained by Fitch's counting method, but larger than the estimate obtained under the assumption of random substitutions (Jukes and Cantor's formula). Computer simulations based on Dayhoff's mutation probability matrix have suggested that Jukes and Holmquist's method of estimating the number of nucleotide substitutions gives an overestimate when amino acid substitution is not random and the variance of the estimate is generally very large. It is also shown that when the number of nucleotide substitutions is small, this method tends to give an overestimate even when amino acid substitution is purely at random.


Evaluation of compositional nonrandomness in proteins. Cornish-Bowden and Marson have recently suggested that the finite sampling component of Q, a measure of nonrandomness in the amino acid composition of proteins, may have been underestimated because it was calculated on the basis of the genetic code table frequencies rather than on the basis of the average natural abundance with which the twenty amino acids actually occur in proteins. This underestimate would lead to an overestimate of Qc a measure of selective effects above and beyond those imposed by the average natural abundance of the amino acids. In this paper the finite sampling component of Q is quantitatively estimated on the basis of these natural abundances and found to reduce Qc from its previous average value of 24.3 to the lower value of 9.7, with the standard deviation of the population of Qc values being 12.5. Individual Qc values are given for 81 protein families of mean composition per 61 codons of Ala5.3Arg2.4Asn3.0Asp3.6Cys1.5Gln2.6Glu3.5Gly4.7His1.3Ile3.4Leu4.5Lys4.2Met1.0Phe2.3Pro2.3Ser4.2Thr3.6Trp0.8Tyr2.6Val4.2. The mean Qc value of 9.7 is notably small, and indicates that quantitatively minimal adjustments away from the average protein composition are necessary to maintain many different biological functions. This small value, however, is shown to differ significantly from the value of zero expected were the natural abundances of the amino acids the only selective constraint. These small deviations from the natural abundances are thus effectively selected for in the Darwinian sense.


Psychosexual counseling of the mastectomy patient. A pilot research study is described, aimed at investigating the hypotheses that psychosexual factors are of central importance in the psychological recovery of the mastectomy patient and that counseling would prove beneficial. Forty-one women were interviewed. Results indicated (1) that sexual self-concept superseded mortality as the primary concern of most recovery mastectomy patients, (2) that the attitude of the partner--husband or lover--was crucial to that self-concept, (3) that most partners were eager to help, and (4) that psychosexual counseling was welcomed and found to be appropriate. Resistances to the execution of the study are also described.


A conceptual framework for the study of anomalous erotic preferences. Operational definitions are given for the terms "erotic" or "sexual" and "erotic arousal level." Measurement of erotic arousal level is discussed as well as "scales of erotic value." A reference system for the analysis of the progression of sexual interaction is expounded, and the analysis of anomalies from the norm of such a progression briefly discussed.


Truth and consequences in sex and marital therapy: the revelation of secrets in the therapeutic setting. This paper describes the development by the author and his colleagues of a policy of full revelation of secrets between spouses as a prerequisite to offering sex and marital therapy. This stand is controversial, for it directly contradicts the advice and practice of many sex and marital therapists. The exploration of this therapeutic position by therapists who are firmly convinced of the need for sexual and emotional commitment, but who will not themselves betray confidences, has offered crucial new opportunities to couples. For example, many couples have been able to confront the self-serving aspects of the wish to "protect" the other partner from knowledge that would in reality subject both partners to risk and a sense of vulnerability. Remarkably, there has not been one casually in the series of more than 30 cases. Marital and sexual case illustrations, alternate methods of handling such secrets, and a discussion of the course of subsequent treatment are considered.


Arousal, personality, and assortative mating in marriage: generalizability and cross-cultural factors. The significant assortative mating for the sensation-seeking motive in (married) American students reported by Farley and Davis was significantly cross validated on American (N = 160) and German (N = 160) samples randomly selected from two comparable cities in the Federal German Republic and the United States. A control condition of age-matched unmarried pairs was included. Spouses were found to have 19% and 29% of sensation-seeking variance in common in the American and German samples, respectively. The later figure is exceptionally high for the literature on assortative mating (exceeding or approximating some of the relationships found for intellectual measures). No significant variance was in common for the unmarried pairs. When a simple and easily measured construct with such wide implications as the sensation-seeking motive can be shown to be so significantly involved in marital partner similarity, then its consequences for successful and unsuccessful marriage should be pursued with vigor. Such a program in research and therapy is recommended and a theoretical model suggested.


Effects of a marriage enrichment program: an outcome study. This study investigated the impact of a marriage enrichment program. Fourteen couples were randomly assigned to one of two experimental groups or to a no-treatment control group. One experimental group received fair-fight training for 3 weeks followed by a sexual enhancement format for 3 additional weeks. The second experimental groups received the opposite treatment sequence. The same counselor team used the same exercises in both groups. The sequence of treatment did not differentially affect outcome. The immediate and longer term treatment effects that were found generally favored the treatment groups over the no-treatment control group on spouses' separate reports of marital and personal functioning. Using larger and more homogeneous samples, future studies should examine the relationship of individual partner changes to couple changes, conduct a follow-up evaluation of at least 3 months, and obtain behavioral assessments of couples' interactions before and after treatment.


The erotic factor as a complication in the dual-sex therapy team's effective functioning. One of the most traditional modes of sex treatment involves the dual-sex therapy team. A team must face all the usual interpersonal hindrances to smooth therapeutic functioning; however, in sex treatment the erotic factor, due to the case content, becomes particularly significant. The tendency for cotherapists to view each other a "supersexed," as well as the communication difficulties intrinsic to the subject of sex, further complicates the cotherapists' interaction. This paper discusses some of the complex problems related to these issues and suggests procedures for resolution.


Resistance in the behavioral treatment of sexual dysfunctions. Although there has been a rapid burgeoning of interest in the treatment of sexual problems in recent years, particularly in treatments that include or rely heavily upon learning-based behavioral intervention strategies, little has been written about the patient "resistances" during this form of treatment. This report describes five categories of resistance: Type I resistance results from the patient not understanding what he is supposed to do, Type II resistance from a deficit in the patient's skills, Type III resistance from lack of motivation or expectation of success, Type IV resistance from anxiety or gulit elicited or mobilized by the treatment situation, and Type V resistance from positive reinforcement (secondary gain). Treatment strategies differ depending on the type of resistance.


Treatment for premature ejaculation through male-only groups. A report on the treatment of premature ejaculation in a group format is provided. In this format only males attended group therapy sessions, but they were expected to relay all information on the group meetings to their regular sexual partners. The women then participated in structured retraining exercises with their male partners. This approach was both cost effective and successful for most couples. It is argued, though, that group treatments are not likely to be as effective as the Masters and Johnson strategy and that clinics should, therfore, remain flexible enough to provide more individualized treatment for those couples who do not succeed with group approaches. Therapists are also encouraged to ensure that treatment gains are well established before terminating therapy.


Personality correlates of the marital sexual compatibility of professional men. The relationship between personality and sexual compatibility in 60 married men in their early 30s was studied as part of a longitudinal study of maturing. Sexual compatibility was assessed by the men's ratings of their own and spouses' sexual pleasure, of the similarity of their sexual values, of their mutual faithfulness, and of the consideration by the spouse of the men's sexual needs. The measure was independently validated by the judgments of the men's wives of the men's excellence as sexual partners and lovers. Extensive psychological test, questionnaire, and judge ratings from the men's wives, closest male friends, and colleagues were secured. Sexual compatibility was significantly related to 39% of the more than 400 measures of adult personality and interpersonal relationships. Sexual compatibility was moderately related to sexual pleasure and satisfaction, but not to marital coital frequency. Increasing sexual compatibility was consistently related to increasing psychological maturity, interpersonal maturity, and the mutuality of the marital relationship, to effectiveness in fulfilling various adult roles, and to marital happiness.


A sexual intimacy survey of former nuns and priests. Men and women who have lived in a celibate religious community experience a unique set of sexual, social, and psychological problems upon resuming a secular life style. In many instances the personality factors and circumstances which led both to a decision to enter and then to leave a celibate religious community are not easily appreciated by the nonreligious professional counselor and do not readily lend themselves to extrapolation from other population groups. This article reports the findings of a preliminary study to identify the sexual experiences and problems of persons who have left religious communities. Data is based on responses to a mailed, anonymous questionnaire by 126 former nuns and priests living in all parts of the country. Information is reported on the following areas: (1) sexual behavior and enjoyment prior to, while living in, and after leaving a religious community; (2) current sexual behavior, satisfaction and problems; (3) sexual counseling experience; and (4) general problems and concerns with integrating sexual intimacy into present life styles. Comparisons are made with similar data published in the literature and data obtained from persons attending Sexual Attitude Reassessment (SAR) Workshops. The findings of this study suggest that persons who have left celibate religious communities have had limited sexual experience in adolescence and early adulthood compared to nonreligious persons. Further, there are special sexual problems and needs in readjusting to a secular life style. Implications for specific counseling are discussed.


A sexual enhancement program for elderly couples. This study was designed to examine the effects of a group sexual enhancement program for elderly couples. Ten marital couples whose ages ranged from 51 to 71 were placed in one of three sexual enhancement groups based on their scheduling preferences. All groups followed the same format, but each was conducted by a different pair of group leaders. The sexual enhancement program was divided into three 2-week phases: (1) a pretreatment period in which there was no contact with the therapists, (2) an education phase in which subjects were provided with information on human sexual functioning in aging people in particular, and (3) a communication exercises-sexual techniques phase in which subjects were instructed on methods to improve communication and increase enjoyment of sexual contact. Following an initial interview in which the purpose of the study was explained, subjects were administered a questionnaire assessing satisfaction and frequency of sexual activities and perception of partner's sexual satisfaction. The questionnaire was readministered after the pretreatment phase, after the education phase, and 4 weeks following the end of the program. In general, significant increases in sexual satisfaction, frequency of certain sexual activities, and positive attitudes about marital and life satisfaction were found to occur over the course of the sexual enhancement program. These significant increases occurred either during the pretreatment period or during some combination of phases.


Changes in marital sexual relationship following treatment for sexual dysfunctioning. Ten couples treated for sexual dysfunctional problems were administered the Sexual Compatibility Test before and after treatment. Significant changes between before-and-after testing were found on all subscales, on the major scales, and on dysfunctional scores. Changes occurred in amount of sexual communication, amount of sexual activity, level of sexual pleasure, and the ability to perceive accurately a mate's sexual preferences and pleasures. The group means of test scores for before-and-after testing were computed and the significance of the differences presented. No significant differences were found for a control group. Group profiles of the treatment group were presented. The impact of the observed changes upon the lives of the treatment couples was discussed.


Coping with homosexual expression within heterosexual marriages: five case studies. The general consensus of previous studies dealing with heterosexually married homosexuals is that the outcome is a rather poor and unhappy marriage, or divorce. The subjects in previous studies, for the most part, had not disclosed their sexual orientation to their marriage partner or were divorced at the time of the study. Presented are five case studies of heterosexual marriages where disclosure to the spouse is evident. Examined are the coping mechanisms involved when such marriages do not end in divorce. A three-phase heuristic model is offered for understanding and aiding individuals in such marriages.


Congenital duodenal web in an adult.

Congenital duodenal web in an adult. Congenital duodenal webs, as a cause of duodenal obstruction in adults, are rare. Demonstration of the web prior to operation is even rarer. A case is presented showing diagnostic findings on a gastrointestinal (GI) series.


Expectoration of bronchogenic carcinoma. A case of expectoration of primary squamous cell bronchogenic carcinoma is reported. Only two previous cases of expectoration of grossly visible fragments of primary bronchogenic carcinoma have been reported. Interestingly enough these were also squamous cell carcinomas. Patients suspected of having pulmonary neoplasm should be instructed to save any grossly visible expectorated tissue fragments.


Schneiderian inverted papilloma: report of a case. A case of Schneiderian inverted papilloma is presented. Etiology, gross and microscopic pathology, and clinical course are discussed along with a plan of treatment.


Mammary malignancy in the male.

Mammary malignancy in the male. Mammary carcinoma in the male, a relatively uncommon disease, represents about 0.9 to 1.5 percent of all breast cancers. (1,2) The authors reviewed 16 cases of male breast cancer seen in a 30-year period at the State University of New York, Kings County Hospital Medical Center in Brooklyn, and the North Shore University Hospital in Manhasset. Epidemiology, etiology, demography, signs and symptoms, management, and prognosis are discussed. A review of pertinent literature is presented.


A response to history: a review of one medical school's efforts to graduate minority physicians. The number of minority physician graduates depends upon both the recruitment and retention of physician manpower. Numbers cannot be increased until the problems of recruiting and retaining minority students are minimized. This paper describes the process by which one medical school initiated changes to overcome barriers to recruiting, admitting, and graduating more minority students for medical practice.


Primary myxedema heart disease.

Primary myxedema heart disease. A case of primary myxedema heart disease in an 84-year-old man is presented. His history and physical examination were typical of myxedema. Electrocardiographic changes showing generalized low voltage, nonspecific S-T segment and T-wave changes, and nodal rhythm are characteristic of the disease. The patient showed remarkable improvement after oral liothyronine (Cytomel) therapy.


Metastases to bones of the hands and feet. Although metastases to bones from solid tumors are very common, involvement of small bones of the hands and feet is extremely rare. One half of the cases reported in literature resulted from a primary tumor in the lung. Four cases seen over the last four years with metastases to bones of the hand and one case with metastases to foot bones are discussed. None of these patients had a lung primary tumor. Three of the four patients who had metastases to hand bones had the disease on the right side.


Compound incomplete dislocation of the trapezium and compound fractured hamate hook. A wringer injury with a compound "fracture" dislocation of the trapezium treated with single Kirschner-wire axial-fixation to the proximal second metacarpal is discussed. Full return of function was present at one year with minimal traumatic arthritis. A hamate hook fracture also healed without complications and without excision.


Rudimentary horn pregnancy with neonatal and maternal survival. Pregnancy in a rudimentary uterine horn is an unusual event that often terminates early in gestation with catastrophic hemorrhage. Under rare circumstances an intact rudimentary horn or a secondary abdominal pregnancy from a ruptured horn continues to term.These cases present with pain or anemia, an uncertain or abnormal fetal lie, and may be complicated by symptoms of preeclampsia. Physical examination, and ultrasonic and radiographic studies lead to the correct diagnosis. Rapid surgical intervention can result in fetal and maternal survival with preservation of fertility.


[Anatomy of the anterior male perineum]. The central nucleus of the perineum. Having carefully studied the anatomy of the central nucleus of the perineum on 27 male pelvises, the authors discuss the fibromuscular nature of this structure which extends from the peritoneal cul-de-sac to the perineal fascia, between urogenital pathways in front and digestive pathways in back. The connections to all the pelvic-perineal organs are discussed. The middle perineal adoneurosis. A personal conception. The study of twenty seven male perineums has permitted the authors to formulate a personal conception of the anatomy of the middle perineal aponeurosis. It is made up of adjoining structures organized in front and in back of the urethrae; above all it includes a smooth fibromuscular part in back of this canal, whereas in front, it behaves as a vessel-carrying sheath, where the dorsal pack of the penis and the Santorini plexus pass.


[Coralliform urolithiasis. A report of 56 case histories (author's transl)]. Analysis of 56 cases of coralliform urolithiasis has shown, among other things, the normally poor symptomology. This is in contrast to the poor prognosis which, in the absence of treatment, almost always ends in the destruction of the kidney. Besides ten immediate nephrectomies, 52 conservative operations were performed on forty patients. These conservative operations are difficult, long and meticulous. They are greatly facilitated by using an endocavitary lighting source of cold light. The use of contact X-ray is indispensable. Removal of stones must be absolutely complete. The number and extent of the nephrotomies must be reduced to a strict minimum. One must avoid the big, destructive nephrotomies--except, perhaps, in children. With the help of all these precautions, the results are encouraging; no secondary nephrectomies until present time, only two real relapses, and three small previously-undetected calculi. Yet, thanks to the systemic use of the cold light and of the contact X-rays, there were no more "undetected" calculi for the last 4 1/2 years.


[An unusual appearance of ureteric bilharzia (author's transl)]. The authors report a case of bilharzia localised to one of the ureters in a case of double renal pelvis and ureter. The parasitic infection was identified only at the time of exploratory surgery (laboratory investigations and preoperative endoscopy negative). The "providential" double ureter made it possible to combine excision of the pathological ureter with a termino-lateral anastomosis between the lower renal pelvis and the ureter of the upper renal pelvis. The result remains very satisfactory with a follow-up of 13 months.


Nucleotide sequences at the 5' termini of reovirus mRNA's. During in vitro synthesis of reovirus mRNA by viral cores, methyl groups from S-adenosylmethionine are incorporated only into 5'-terminal cap structures, i.e., m7GpppGmCp.... Thus, mRNA synthesized in the presence of S-adenosyl-[methyl-3H]methionine is 3H labeled specifically at the 5' terminus. This circumstance was exploited in the determination of 5'-terminal nucleotide sequences. Seven 5'-terminal fragments derived by complete RNase T1, digestion of methyl-3Hlabeled mRNA were partially degraded with RNase T2, and the products were separated by electrophoresis-homochromatography. From the patterns formed by the methyl-3H-labeled RNase T2 products, the sequences of the seven RNase T1-generated fragments were deduced. All seven fragments started with the sequence m7GpppGmCUA, after which the sequences diverged, with a tendency to be either U-rich or A-rich. Their chain lengths ranged from 7 to 10 nucleotides (excluding the m7G residue), and none of them contained an initiator AUG triplet. The sequences obtained support the hypothesis that virion-associated oligonucleotides arise through abortive transcription of the viral genome. There is no apparent 5'-terminal sequence feature distinctive of early versus late mRNA species within the small-mRNA size class.


Transcriptional mapping of rabies virus in vivo. Synthesis of the proteins of rabies virus was studied in hamster cells infected with UV-irradiated virus. The UV target size of genes L, N, M1, and M2 was measured during primary transcription. Except for N, the target size of the remaining genes was considerably larger than that of their physical sizes. The data fit the hypothesis that four genes occupy a single transcriptional unit and that transcription of rabies virus proceeds in the order N, M1, M2, and L.


Electron microscopic study of measles virus infection: cell fusion and hemadsorption. Virus-induced cell fusion has been studied after infection of Vero cells with measles virus. Scanning and transmission electron microscopy were combined with immunoperoxidase labeling of measles antigens to correlate viral production and distribution of virus-induced erythrocyte binding sites with progress of fusion. Release of infectious virus started before syncytia were detected and decreased while the number and size of syncytia were increasing. Most virions were seen budding from mononucleated cells or from the periphery of syncytia where cells were being recruited. Moving inward, the surfaces of syncytia where cells were being recruited. Moving inward, the surfaces of syncytia were covered with numerous ridges containing viral antigen, but few viral buds were seen, suggesting that syncytia might be sites of defective viral formation. Hemadsorption occurred predominantly within the confines of syncytia. Erythrocytes were scattered sparsely over immature syncytia but were densely packed in the center of mature syncytia. Active binding sites for erythrocytes were located on cell villi and ridges covered with measles antigens. Hemadsorption was completely inhibited in measles virus-infected cultures pretreated with virus-specific immunoglobulin G for 1 h at 4 degrees C. However, when these cultures were shifted to 37 degrees C, hemadsorbing sites were recovered at the periphery of enlarging syncytia. Virus-induced sites for erythrocyte adsorption were found to move centripetally on syncytium membranes as fusion progressed.


Hexagonal glycoprotein arrays from Sindbis virus membranes. Freeze-etch electron microscopy of Sindbis virus and of glycoprotein arrays derived from Sindbis membranes by nonionic detergent treatment shows that the local geometry of glycoprotein-glycoprotein interaction does not depend on the presence of the nucleocapsid.


Electrical and mechanical activities in the denervated semitendinosus muscle of the frog. Denervated frog's semitendinosus muscles were studied. No differences in resting potential were found between denervated and control fibres. Spontaneous discharges of fibrillation potentials were recorded from random points along the length of denervated fibres. The frequency of the potentials varied between 2 and 30/sec; the duration of the discharges varied between 5 and 120 sec. Each potential originated from a prepotential, reversed the sign of the membrane potential between 10--20 mV, and was followed by a transient hyperpolarization. The time course of the spontaneous potential produced by a fibre was slower than that of a spike elicited by an electrical pulse applied to the same fibre. After the cessation of a train the fibrillation potentials were replaced by small rhythmic potentials 10--15 mV in amplitude; this activity lasted for periods as long as 7 min. Some reduction of the resting potential was usually observed during the discharge of a train of fibrillation potentials, however, repolarization occurred after the end of electrical activity and a second discharge of full size fibrillation potentials could be observed in most of the fibres. Mechanical activity was not always present. When observed, it was reduced to light movements unable to eject the microelectrode. In general, no one-to-one correlation could be observed between fibrillation potentials and mechanical activity. In those fibres in which the correlation was present, the tension developed by a single fibrillation was less than 0.2/kg/cm2. Some denervated fibres developed tetanus-like contractions, the maximal tension developed by these fibres was less than 1.0 kg/cm2. The data are discussed according to the current ideas on generation of fibrillation potentials.


A reflexogenic area for controlling the blood pressure in toad (Bufo vulgaris formosa). In the toad, Bufo vulgaris, the pulmocutaneous artery, which is innervated by a fine branch of the laryngeal nerve, was shown to be a reflexogenic area affecting the systemic blood pressure. Distension of the vascularly isolated pulmocutaneous artery evoked falls in systemic blood pressure. Impulses in bursts, synchronous with the systolic rise of the blood pressure, were recorded from the peripheral cut end of the laryngeal nerve when all branches, save the one innervating the pulmocutaneous artery, had been divided. Differing from mammalian baroreceptors, those in toads occurred with a marked latency in response to rises in blood pressure. A hyperbolic relation was obtained between the pressure and the latency. Existence of these baroreceptors in pulmocutaneous artery was confirmed in preparations in vitro. Punctate stimulation was used to localize the baroreceptive site.


Neuronal mechanisms of the late N-wave induced in vitro in thin sections of the olfactory cortex of rats. Experiments were done to elucidate properties of the late N-wave which was induced in vitro in thin sections of the olfactory cortex of the rat in response to stimulation of the lateral olfactory tract. The late N-wave decreased in size at a stimulation rate of more than once every 90 sec or at temperatures higher than 27 degrees C. The late N-wave was suppressed in the presence of GABA, picrotoxin or bicuculline or in the Cl-free medium. Penicillin or pentylenetetrazol, which blocked actions of GABA on the presynaptic potential, also suppressed the late N-wave. The late N-wave first appeared at postnatal ages of 18--25 days. The late N-wave reversed in polarity when recorded from the deep layers of the sections or from the cut surface of the sections. Single cells in the deep portions of the sections discharged during the late N-wave. Cells in the superficial layers fired just before or after the late N-wave. In order to explain these observations, a neuronal model for generation of the late N-wave was presented.


Selective inhibition of potassium contracture in guinea pig taenia coli by ruthenium red. Effects of ruthenium red on isotonic KCl induced contracture (K-contracture), cellular 45Ca uptake and 45 Ca binding to surface membranes were examined in the smooth muscle cells of guinea pig taenia coli. These results were compared with those using lanthanum (La3+). The tonic component of the K-contracture was selectively inhibited by 1 mM ruthenium red. In contrast, 1 mM La3+ inhibited the phasic component of the K-contracture to a large extent. Use of 1 mM ruthenium red selectively inhibited the tonic component of K-contracture and caused a marked decrease in cellular 45Ca uptake in that component of K-contracture. In contrast, 1 mM La3+ largely inhibited the phasic component and caused a significant decrease in cellular 45Ca in that component. According to Scatchard plot analysis, there are two kinds of Ca2+ binding sites of high and low affinity, respectively, on the surface membrane of the taenia coli. One mM ruthenium red suppressed those of low affinity more strongly than those of high affinity. In contrast, 1 mM La3+ suppressed high affinity sites more markedly than low affinity sites. Based on these results, it seems possible to conclude that ruthenium red mainly blocks the initial binding sites linked with Ca2+ influx which is related to the production of the tonic component while La3+ blocks those sites related to the phasic component of the K-contracture of guinea pig taenia coli.


Effects of electro-acupuncture on rat jaw opening refelx elicited by tooth pulp stimulation. Effect of electro-acupuncture (EA) on the jaw opening reflex induced by tooth pulp stimulation was investigated in Wistar albino rats. The amplitude of the digastric muscle EMG (dEMG) evoked by stimulation of the lower incisor tooth pulp was measured as the magnitude of the reflex and estimated as an indicator of the EA effect. Acupuncture needling was given at one meridian point of Ho-Ku and two other nonmeridian points in one forepaw. Compound action potentials of ulnar, median and radial nerves elicited by 15 min EA stimulation at 45 Hz through the needling points were recorded from the brachial plexus innervating the same acupunctured forepaw. Of the above-mentioned three nerves, the afferent volleys in the radial nerve were found to be the most effective to suppress the dEMG during EA stimulation. The EA stimulation of the Ho-Ku point showed a greater effect than that of nonmeridian points. There was a significant correlation between the amplitude of Abeta fibers in the compound action potentials elicited by EA stimulation and the dEMG suppression. To confirm the so-called morphine-like action of EA that has recently been proposed, levallorphan (LORFAN), antagonist of morphine, was administered before and after EA stimulation. In the premedicated case, no suppression of the dEMG occurred. In the postmedicated case, on the contrary, the dEMG responses which were reduced during 15 min EA stimulation recovered more rapidly than in the case without LORFAN. These results suggest that the afferent impulses conducted along Abeta fibers mainly in the radial nerve cause the release of endogeneous morphine-like substances in specific central nervous areas for suppressing the dEMG activity.


Reflex activation of extrinsic tongue muscles by jaw closing muscle proprioceptors. Depression of the mandible in the decerebrate cat induced retraction of the tongue. The mechanism of this jaw-tongue reflex was analyzed by recording electromyographic activity from the temporal and styloglossal muscles as representative masticatory and extrinsic tongue muscles, respectively. Tongue muscle activity was elicited when the mouth was opened beyond 10 degrees while the threshold for the masticatory muscle activities was around 2 degrees. Neither sectioning of the masseteric nerve nor anesthetization of the temporomandibular joint capsule affected the tongue muscle activities. In contrast, exfoliation of the temporal muscle from the temporal bone greatly reduced the effects of jaw depression. When the isolated coronoid process of the mandible was stretched downwards, activities were evoked in the tongue muscle. Repetitive electrical stimulation at a frequency of 100 Hz to the temporal nerve activated the tongue muscle, and the threshold of reflex activation was between 1.3 and 1.7 times threshold of the temporal nerve. Vibratory stimuli applied to the mandible at frequencies below 130 Hz were also effective in evoking tongue muscle activity. However, when the frequency was above 135Hz, tongue muscle activity was not induced although activity was still observed in the masticatory muscles. These results indicate that the jaw-tongue reflex is elicited mainly by proprioceptors in the temporal muscle, and that they may probably be the Golgi tendon organs and the secondary endings rather than the primary endings of the muscle spindle.


Differences in characteristics between glycine and glycylglycine transport in guinea pig small intestine. The properties of glycylglycine and glycine transport across the mucosal border of the epithelium were studied in isolated guinea pig ileum. The initial influxes of both substances obeyed simple Michaelis-Menten kinetics, but the values of the kinetic parameters were greatly different between two substances; Jmax and Kt for glycine were 290 nmol.cm-2.min-1 and 27 mM, and those for glycylglycine were 57.4 nmol.cm-2.min-1 and 3.4 mM, respectively. Total replacement of Na+ in the incubation medium with mannitol completely suppressed the cellular uptake of glycine, while it reduced glycylglycine uptake only slightly. The omission of Na+ caused a slight increase in Kt for glycylglycine (from 3.4 mM at 100 mM Na+ t0 5.2 mM at 0 mM Na+) without changing the value of Jmax. Glycylglycine taken up by the epithelial cells had been completely hydrolysed into glycine within 2-min incubation period. The results of the present study seem to indicate that there are entirely distinct transport systems for glycine and its dimer and that the membrane digestion and subsequent transport as the monomer may not be involved in the absorption of glycylglycine.


Contribution of an electrogenic sodium pump to the membrane potential in the intestinal epithelial cell. The transmural potential difference of isolated rat duodenum and the membrane potential of its epithelial cell were examined during changes of the ionic medium at both warm (31--35 degrees C) and cold temperatures (2--5 degrees C). In the range of low external K+ concentrations, cooling produced an immediate and reversible depolarization of the membrane potential (around -10 mV) greater than that estimated from a simple thermodynamic temperature effect (RT/F). Such a temperature sensitive component of the membrane potential at 31 degrees C was completely abolished by anoxia and serosal ouabain. Readmission of K+ to the bathing fluid of duodenum previously deprived of K+ and loaded by Na+ caused a remarkable transient hyperpolarization of the epithelial membrane, which was abolished by serosal ouabain. Decreases in the value of transmural potential difference were also produced by cooling, anoxia and serosal ouabain, but these were so small that concurrent changes in the membrane potential could be regarded as chiefly reflecting changes in the effective emf of the cell. Thus, an electrogenic Na+-K+ exchange pump located on the serosal membrane of the duodenal epithelial cells was shown to contribute significantly to the membrane potential under normal conditions (up to around -7 mV). The coupling ratio of Na+-efflux and K+-influx associated with this pump was estimated by the Mullins-Noda equation (1963) to be approximately 4:3 under the physiological steady-state conditions.


Rat liver aldehyde dehydrogenases: strain differences in the response of the enzymes to phenobarbital treatment. The effect of phenobarbital on activities of aldehyde dehydrogenases in the subcellular fractions was studied in vivo in rats of three strains. Regarding the responses of the mitochondrial and microsomal enzymes to phenobarbital treatment no difference among the strains was observed. Regarding the responses of the supernatant enzyme remarkable strain differences were observed. In rats of the Long-Evans strain the high Km-enzyme activity increased as much as 15-fold above control levels by phenobarbital treatment. By contrast, in rats of the Wistar strain the high Km-enzyme activity was unchanged in all rats by treatment with phenobarbital. In rats of the Sprague-Dawley strain the high Km-enzyme activity remained unchanged in 52% of all rats treated with phenobarbital and was increased approximately 4-fold over control levels in 48% of treated rats.


Relationship between excitation of vagal inhibitory neurons and nucleoside release: estimation by paper chromatography. Experiments were carried out to determine whether ATP or its metabolites are increased in vascular perfusate from the guinea pig stomach in response to stimulation of vagal non-adrenergic innervation. Compounds in the perfusate were identified by paper chromatography and by determination of the absorption maximum in ultraviolet rays. The following compounds were detected in the perfusate from the resting preparation; hypoxanthine, inosine and uridine, a small amount of xanthine and adenosine and two other non-adenine compounds. When the nutrient medium containing ATP was recycled, hypoxanthine and inosine, and a small amount of adenosine and AMP increased. On the other hand, stimulation of the non-adrenergic inhibitory nerve did not produce any appreciable increase in these compounds in the perfusate. These findings do not support the idea that the transmitter substance responsible for relaxation of the guinea pig stomach in response to stimulation of the vagus nerve is ATP or its related compounds.


Glutathione depletion by aniline analogs in vitro associated with liver microsomal cytochrome P-450. Enzymic depletion of glutathione (GSH) in vitro by aniline analogs was mostly dependent on the cytochrome P-450 level in liver microsomes. In a case of acetaminophen (AAP), active metabolite of AAP formed through liver microsomal drug metabolizing enzymes consumed GSH. The active metabolite formed binds, at least in part, covalently to liver microsomal proteins. In addition, species differences in the extent of GSH depletion by AAP in vitro was related to the amounts of the active metabolite of AAP bound covalently to liver microsomal protein(s) by experiments using 14C-AAP. Similar depletion of GSH was also seen with other aniline analogs such as aniline itself and p-chloroaniline, but not with acetanilide, in four animal species. These in vitro results obtained here strongly support the well-known findings concerning both GSH depletion and covalent binding in vivo of the active metabolite after AAP treatment.


Pharmacological studies on experimental nephritic rats. (4) Improvement of hyperlipemic models in rats utilizing anti-rat kidney rabbit serum and effects of anti-hyperlipemic agents on serum lipid levels. Three hyperlipemic models in rats were compared regarding serum lipid levels and known anti-hyperlipemic agents were tested for their effects on the hyperlipemia. In rats fed a cholesterol diet (group A), only serum cholesterol level resulted in a marked increase as compared with normal level. In animals given a large dose (0.7 ml/100 g body weight, i.v.) of anti-kidney serum (group B), extremely high elevations of serum total lipid, phospholipid, triglyceride and cholesterol levels were observed. In animals given a small dose (0.3 ml/100 g body weight, i.v.) of anti-kidney serum and fed the cholesterol diet (group C), elevations of these serum lipids except for triglyceride were not only greater than in group B, but also synergistic. On the contrary, serum triglyceride level and proteinuria were less in group C than in group B. Furazabol, clofibrate the beta-sitosterol given orally for 7 days at doses of 1,100 and 500 mg/kg/day, respectively were clearly effective on the hyperlipemia of group C, without affecting the proteinuria. Furthermore, this model was more sensitive to these anti-hyperlipemic agents than groups A and B. From the above results, group C would seem to be an adequate and effective experimental hyperlipemic model.


Potassium contracture of smooth muscle in the presence of dextran. The apparent diffusion coefficient of Ca ions in the extracellular space of guinea pig taenia coli was estimated from model experiments to be 3.2 x 10(-6) cm2 sec -1, while the relationship between Ca concentration in the medium and tonic tension in 40 mM K-contracture was measured in the same muscle both in the presence and absence of dextran 10. On the basis of these experiments and certain assumptions, the time course of tension decline by Ca withdrawal during K-contracture was calculated. Under all dextran concentrations tested (0--15%) the calculated time course of tension decline was in good agreement with one actually observed except in a short period of time immediately after Ca withdrawal. The results suggested that Ca distribution in the extracellular space during the loss of Ca is in good agreement with the diffusion theory in cylinder, and that each muscle fiber shows its tension without delay in response to the change in Ca concentration in the vicinity of the fiber according to the tonic tension-Ca relationship mentioned above. The discrepancy between calculation and observation was partially explained on an experimental basis.


Site of emetic action of oral copper sulfate in dogs. (I) Thresholds of various portions of gastrointestinal tract to locally applied copper sulfate. Emetic thresholds to copper sulfate administered into the Pavlov pouch, Forrest pouch, Thiry fistulas of the jejunum and ileum, and duodenal, jejunal and ileal catheters were measured in dogs to conjecture the site of emetic action of copper sulfate. The oral emetic threshold had been measured preoperatively. In the stomach, the pyloric antrum had a high sensitivity, while the corpus had a low sensitivity to the topically applied copper sulfate. In the intestine, the sensitivity was high in the duodenum, whereas a low sensitivity was noted in the jejunum. Almost no sensitivity was observed in the ileum. Thus it would appear that the site of the emetic action of copper sulfate was the pyloric antrum and/or duodenum.


Echo guided percutaneous transhepatic cholangiography with puncture transducer. Conventional percutaneous transhepatic cholangiography (PTC) has some disadvantages because it is customarily performed blindly. If the bile duct is made visible, these disadvantages are eliminated. The biliary tree, if dilated, can be clearly delineated by ultrasound technique. By combining the B-mode examination of the biliary tract with the ultrasonic puncture transducer, percutaneous transhepatic cholangiography was performed successfully in 16 examinations on 12 patients. PTC needle could be inserted directly into the lumen of the bile duct without appreciable difficulty. The echo guided PTC was found to be an easier, safer, and more reliable method than the conventional blind technique.


Ventricular fibrillation during cardiopulmonary bypass. Changes in ultrastructure after induced ventricular fibrillation were studied in the normothermic and nonhypertrophic canine heart using a transmural myocardial biopsy method. Comparisons were made between subendocardial and subepicardial layers by the quantitative evaluation of ultrastructural changes in mitochondria and glycogen granules. Slight abnormalities characterized by interstitial edema, mitochondrial derangement, contraction bands, swelling of capillary endothelium were demonstrated throughout the myocardium following ventricular fibrillation. The myocardium following ventricular fibrillation did not demonstrate differences in ultrastructure between the subendocardial and subepicardial layers. These pathologic fine structural changes were at least in part reversible. Quantification of ultrastructure showed that mitochondria and glycogen granules were well preserved. It was suggested that the myocardium following ventricular fibrillation may be less affected by the no-reflow phenomenon after restoring normal coronary circulation.


Left ventricular function studies in constrictive pericarditis. Left ventricular function studies were performed on five patients with constrictive pericarditis. Functional data were obtained from intracardiac pressure measurements and cineangiocardiographic films. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), ejection fraction (EF), stroke work index (SWI), circumferential fiber shortening, and percent circumferencial shortening were significantly below normal values in the five cases. These changes are reflected mainly in the degree of pericardial restriction. Reduction in mean Vcf was also observed. Theoretically, the velocity of ventricular internal circumferential shortening is also affected by changes in ventricular volume or resting myocardial fiber length, however, in patients with constrictive pericarditis, reduction in mean Vcf suggests left ventricular dysfunction. Our clinical studies indicate that evaluation of mean Vcf is valuable in the assessment of postoperative prognoses.


The effect of blood oxygen content and the no-reflow phenomenon on the subendocardial ultrastructural reversibility following anoxic arrest using hemodilution variables in the experimental model. Hemodilution is an accepted modality for the conduct of cardiopulmonary bypass. The degree of hemodilution clinically employed has been in the range of 20 per cent of the initial hematocrit levels. This study was designed to evaluate the effects of hemoglobin levels and oxygen content on the reversibility of the damaged or altered ultrastructure of the endocardial layer of the ventricle and the possible role of the no-reflow phenomenon. Two series of mongrel dogs were subjected to cardiopulmonary bypass at normothermic levels and a standard period of ischemic arrest. One series was with hemoglobin levels between 5 and 10 grams (mean 7.25 grams) designated as moderate hemodilution (MH). The second series was of hemodilution with less than 5 grams of hemoglobin (mean 4.8 grams) designated as severe hemodilution (SH). The ultrastructural alteration gradient (UAG) between the epicardium and endocardium was studied with its relationship to reversibility of myocardial function and animal survival. The study demonstrated a definitive relationship between oxygen content and the reversibility of myocardial damage under normothermic conditions and anoxic arrest. The poor survival results in the SH group; two of 12 are attributed to the low oxygen availability possibly triggering the no-reflow phenomenon which prevents reversibility of the myocardial ultrastructural damage and ultimately the functional integrity of the ventricle.


A new surgical approach to extensive arterial occlusion of lower extremity--femoro-popliteal open endarterectomy with arteriovenous shunt. A revascularized surgery for extensive arterial occlusive lesions of the lower extremities, namely open endarterectomy of the occluded femoro-popliteal artery with arteriovenous shunt, was devised. The procedure is specially indicated to the extensive arterial occlusion of the lower extremity for which the conventional reconstructive vascular surgery is not applicable. The patency of the reconstructed femoro-popliteal arteries are ensured by virture of an arteriovenous shunt and newly developed collaterals from the reopened genicular network is expected to provide effective blood flow to peripheral parts. From 1967 to 1975, this procedure was applied to 59 extremities in 53 patients, all of whom had extensive arterial occlusion from the femoral artery to the periphery with impending ulcer and severe rest pain. Fourty-five out of 59 extremities had remarkable improvement of the ischemic symptoms and signs at the time of discharge. Long-term effectiveness was shown in 34 out of 59 extremities or 58 per cent.


Bilateral popliteal artery entrapment syndrome--report of a case. A 15-year old female presented with bilateral popliteal artery entrapment syndrome. The left popliteal artery was completely occluded and thromboendarterectomy was performed. Angiography on passive dorsiflexion revealed compression of the right popliteal artery, although it was free of symptoms and of normal caliber. End-to-end anastomosis in the normal anatomical position without division of the medial head of the gastrocnemius muscle was performed on both sides.


Degree of bowel distension on plain-radiographs--a surgical-radiological study of new criteria in mechanical intestinal obstruction. Three hundred sixty clinical cases which presented with or without mechanical intestinal obstruction were evaluated in order to discover reliable quantitative and qualitative criteria for pre-surgical x-ray diagnoses. It was discovered that small bowel distension of above 1.0 (ratio) together with obvious gas fluid level is usually indicative of small bowel obstruction, while large bowel distension of above 1.5 (ratio) together with obvious gas fluid level is usually indicative of large bowel obstruction. Subsequent surgery confirmed that there exists a correlation between the degree of small bowel distension seen on radiographs prior to surgery and the actual small bowel distension secondary to small bowel obstruction measured during surgery. The present results may be diagnostically useful in the radiological differentiation of mechanical intestinal obstructions from other abdominal conditions.


Primary volvulus of the small intestine in infants. Primary small bowel volvulus which no definite cause can be detected surgically is rare. In this paper, we present five cases of primary small bowel volvulus and discuss the clinical features including etiology.


Cellular hypersensitivity to autologous tumor extract in patients with breast carcinoma. The indirect macrophage migration inhibition technique was used to study cellular hypersensitivity to autologous tumor extract in relation to the progress and prognosis of breast carcinoma. Cellular immune response, evidenced by production of a macrophage migration inhibitory factor (MIF), was noted preoperatively in 21 of 63 patients (33 per cent). This reactivity was used at the time of surgery to determine the grade of the primary tumor, lymph node involvement and the stage of the disease according to the TNM system. The five-year survival rate was 76 per cent for patients whose lymphocytes responded preoperatively and 54 per cent for patients whose lymphocytes did not respond, indicating that this assay may be valuable in detecting cellular immune response to breast carcinoma and in evaluating the immunological status of patients.


The preventive effect of cimetidine on producing stress ulcer in rats. Stress ulcers were formed by a standard method after fasting and restraining each rat in a performed conduit tube and placing them in a cold room head inverted at 4 degrees C for three hours. The severity of the ulcer was graded into four groups; Grade 0: no ulcer, Grade 1: 1-10 ulcers, Grade 2: 11-20 ulcers, Grade 3: more than 21 ulcers. The animals were divided into six groups: Group I: no stress, no treatment; Group II: stressed but not treatment; Group III: pretreated with saline and stressed; Group IV: pretreated with antacid and stressed; Group V: pretreated with Cimetidine and stressed; Group VI: stressed and then post-treated with Cimetidine. In group II 47 out of 49 (96 per cent) developed ulcers compared to no ulcers in group I. In group V, 13 out of 38 (34 per cent) and in group IV, 13 out of 20 (65 per cent) developed ulcers. In group V, not only the incidence was reduced markedly but also the severity of ulcer was significantly less. However, post-treatment with cimetidine was not as effective as pre-treatment. Cimetidine, therefore, seems to be very effective in preventing stress induced ulcers in rat when instilled in the stomach before the stress.


Thayer lecture. Diabetes mellitus: a brief overview. Thus to summarize, there are a number of experimental and critical observations which all tend to support the contention that the hyperglycemia and perhaps to a lesser degree, the insulin deficiency, contribute significantly to the atherosclerosis and more directly initiate and expidite the microangiopathy and neurological abnormalities noted in diabetes. There is little evidence to suggest that the microangiopathy has any direct genetic relationship except via the beta cell and the resulting insulin deficiency.


Misleading noninvasive signs of Bjork--Shiley mitral valve dysfunction. Three months after receiving a Bjork--Shiley mitral valve prosthesis, a patient experienced acute gastronintestinal bleeding associated with heavy alcohol intake and poor compliance with oral anticoagulation therapy. As a result of the gastrointestinal bleeding, treatment with warfarin was discontinued. Ten months later, the patient presented with symptoms of transient cerebral ischemia. Despite demonstrated loss by phonocardiography of the previously well-recorded opening click and echocardiographic suggestion of a thrombosed prosthetic mitral valve, no thrombosis or dysfunction of the prosthetic mitral valve was revealed at reoperation.


Acute mental status changes caused by propranolol. A 74-year-old woman with mild dementia became disoriented and developed paranoid delusions when treated with low-dose propranolol. There was no evidence of cardiovascular instability, and the symptoms resolved within a week. Rechallenge with propranolol led to a recurrence of mental status changes.


[Determination of dehydrogenase and acid phosphatase activity in the lymphocytes in hypertension and vasorenal hypertension]. The activity of succinate dehydrogenase, alpha-glycerophosphate dehydrogenase and acid phosphatase in the lymphocytes of peripheral blood was studied in 28 patients with hypertensive disease and vasorenal hypertension (the diagnosis was made on the basis of the findings of angiographic examination) by the method of quantitative cytochemical analysis suggested by R.P. Nartsissov. It was revealed that alpha-glycerophosphate dehydrogenase activity was significantly lower in vasorenal hypertension than in hypertensive disease. The calculation of the difference between the value of succinate dehydrogenase activity and that of alpha-glycerophosphate dehydrogenase activity in these groups was also significant. It is concluded that a complex of cytochemical analysis may be used in differential diagnosis of vasorenal hypertension and hypertensive disease.


[Quantitative shifts in acid phosphatase isoenzymes in the blood in myocardial infarct]. The spectrum of acid phosphatase isoenzymes was studied by means of disk electrophoresis in polyacrylamide gel. Seven isofractions were detected of this enzyme in blood plasma. In patients with the acute stage of myocardial infarction the amount of isofraction 3 was increased, its electrophoretic mobility was 0.479 +/- 0.059. It is suggested to use the test for acid phosphatase fraction 3 in blood plasma as an auxiliary method in the diagnosis of pathological conditions of the myocardium.


[Kidney reaction to an increase in the volume of extracellular fluid in rabbits with ischemic cerebral hypertension]. The excretion of water, electrolytes and osmotically active substances and the blood plasma natriuretic activity were studied following isotonic dilation of the extracellular space in experiments on rabbits with ischemic cerebral hypertension. Rabbits with hypertension were marked by the phenomenon of exaggerated natriuresis and increased excretion of water and osmotically active substances after volumetric stimulation, which was due to a greater inhibition of processes of tubular reabsorption than in intact animals. The increase in the content of the natriuretic factor in the blood plasma of rabbits with ischemic cerebral hypertension after an increase in the volume of extracellular fluid could not be identified as one of the possible causes of inhibition of sodium reabsorption.


[Importance of determining the renin activity in the blood plasma of the renal veins in symptomatic hypertension]. In patients with vasorenal hypertension blood plasma renin activity was always higher on the side of the lesion than on the contralateral side, whereas in patients with nephrogenic hypertension and coarctation of the aorta this value was within physiological norm. After reconstructive operations in vasorenal hypertension (in an unilateral lesion) a hypotensive effect was produced when the ratio of blood plasma renin activity on the side of the lesion to that on the healthy side was 1.4 and more. The ratio of renin activity in plasma of blood in the renal veins is an important diagnostic and prognostic criterion.


[Renin activity in the blood plasma in healthy persons and in hypertension patients of different ages and sexes]. Examination of 248 persons, among whom 64 were healthy (35 males and 29 females from 17 to 40 years old), and 184 (139 males and 54 females from 17 to 50 years old) suffering from hypertensive disease was conducted. Blood plasma renin activity in healthy males was 1 1/2 times higher than that in healthy females. Similar differences were revealed in the group of patients with a labile form of hypertensive disease. No significant difference in renin activity was revealed between males and females with a stable form of the disease. A significant decrease in renin activity was revealed in males and females over 40 years of age with labile and stable forms of hypertensive disease.


[Vascular reactivity and catecholamine excretion in hypertension]. Increased vascular reactivity to noradrenaline was revealed in patients with Stages I and II hypertensive disease; the reaction to the sympathomimetic agent of indirect action ephedrine remained at the control level. A salt load increased the discrepancy between the level of the reactions to these two agents. It is suggested that processes of catecholamine storage and excretion in the tissues are disturbed in hypertensive disease and that sodium ions probably take part in this process. The daily excretion of noradrenaline was in negative relation with the reactivity to noradrenaline and correlated positively with the reactivity to angiotensin.


[Combination of a hormonally active adrenal tumor with hypertensive disease of the kidneys]. The author observed 230 patients with hormone-active tumor of the adrenal attended with arterial hypertension. In 90 patients there were concomitant hypertensive diseases of the kidneys. The diagnosis of the concomitant disease was verified during roentgenography, aortography included. In 66 of 90 patients (73.3%) arterial hypertension followed a malignant course. The presence of adrenal tumor was verified morphologically after the operation in 208 patients and during autopsy in 22. The concomitant renal disease was confirmed histologically on autopsy in 7 fatal cases and by kidney biopsy in 36. The clinical characteristics of the variants of combined lesions of the kidneys and adrenals and the methods of their diagnosis are discussed. The author recommends examining the adrenals in all patients suffering from malignant arterial hypertension.


[Comprehensive study of central and regional hemodynamics in hypertension using bloodless research methods]. Tetrapolar chest rheography is a convenient, noninvasive method for determining the stroke and minute blood volumes. Its application made it possible to reveal various types of hemodynamics in patients with hypertensive disease and apply differentiated treatment with due account for these peculiarities. Study of regional hemodynamics showed a significant increase in the tonus of the arteries of the brain and crura and diminished tonus of the veins. The method is most valuable in a follow-up during treatment and particularly for recording rapid shifts in hemodynamics in functional loads. Assessment of the reactions of patients with hypertensive disease during the orthostatic test revealed various degrees of disorders of the circulatory system adaptation mechanisms; with the progression of the disease these disorders become more intense.


[Hemodynamic types of hypertensive disease according to echocardiographic data]. Central hemodynamics was studied by means of echocardiography in 7 patients suffering from neurocirculatory dystonia with a high cardiac index but normal arterial pressure, and in 41 patients with essential hypertension prior to, and after treatment. Two groups of patients suffering from essential hypertension were distinguished: with a hyperkinetic type of circulation and with a normal cardiac index. In the first group there was a statistically significant increase in the stroke index and the index of diastolic left ventricular diameter with a normal ejection fraction. The increase in the cardiac index in the hyperkinetic type of essential hypertension is caused by an increase in the stroke output according to the Frank--Starling law. The authors believe that the increase in peripheral resistance is the principal pathogenetic mechanism of hypertension with any level of the minute volume.


[Central and renal hemodynamic indices under physical load in hypertension]. The article shows the results of studying the functional condition of the cardiovascular system in hypertensive disease. Under physical load healthy individuals demonstrated an increase in arterial pressure, rate of cardiac contractions, cardiac and stroke output, arteriovenous difference in oxygen, and diminution in the circulation volume, total peripheral resistance, renal blood flow and renal fraction of the minute blood volume. In patients with hypertensive disease there was a tendency to a lesser decrease in the cardiac output under load, the difference with the indices of healthy individuals increased with each stage of the disease. In hypertensive disease of stage IIB there were significantly smaller cardiac output, diminution of stroke volume under load, and a sharper rise than in the control group of arteriovenous difference in oxygen. The diminution of renal blood flow in response to the load was more marked in hypertensive disease.


[Reactivity of the hemostatic system depending on the model of the behavior and personality characteristics of hypertensive patients under emotional stress]. The results of investigating the effect of emotional stress on the blood coagulation and anticoagulation systems are discussed. It was found that similar conditions of emotional stress cause three types of reactions in different people: functional hypercoagulation, functional hypocoagulation and the absence of any noticeable reaction according to the findings of thrombelastography. The degree of activation of the blood fibrinolytic system depends on the extent of involvement of the patients in interpersonality relationships. Patients with hypertensive disease are characterized by neuroticism, heightened level of anxiety and dependence, and increased emotional aggressiveness. Signs of introversion also prevailed in these patients, which was attributed to the forced formation of new behavior models due to the disease.


[Detection and treatment of arterial hypertension at a district polyclinic]. Arterial hypertension was revealed in 65 of 210 (30.9%) males 40 to 59 years of age living on the territory of one doctors' locality of a district out-patient clinic. Among patients with increased arterial pressure 32.3% received hypotensive treatment which proved effective in 10.7%. The results of six-month treatment of 30 patients are analyzed. The most significant decrease in diastolic arterial pressure was encountered in the group of persons who were given regular treatment.


Resistance to parathyroid hormone in renal failure: role of vitamin D metabolites. Resistance to the calcemic action of parathyroid extract (PTE) was shown in thyroparathyroidectomized rats after 5 hr of renal failure that was induced by either bilateral nephrectomy (NPX) or ureter ligation (UL). Studies were carried out to investigate the relationship of parathyroid resistance to the vitamin D status of the animal. Concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) were similar in pooled sera samples from rats either UL or sham-operated and treated with PTE. Pretreatment with oral 25-hydroxycholecalciferol or with a combination of i.v. 24,25(OH)2D3 and 1,25(OH)2D3 prior to UL failed to alter the resistance. Resistance was also present in a group in vitamin-D-deficient rats. A similar group given 1 microgram of vitamin D2 showed more parathyroid resistance than did the group not given vitamin D2. In chronic renal failure of 28 day's duration, parathyroid resistance was again demonstrated, but, in contrast to the acute renal failure models, this was partly corrected by prior 1,25(OH)2D3 administration. These studies show that parathyroid resistance is not caused by an abnormality of vitamin D metabolism in the acute renal failure model, and we suggest that the phenomenon is due to the accumulation of one or more uremic factors.


[Immunoreactive parathyroid hormone in samples from thyroid veins (author's transl)]. Blood samples were obtained from 16 patients with primary or secondary hyperparathyroidism by selectively catheterising cervical and thyroid veins. Immunoreactive parathyroid hormone was measured with two aminoterminal (anti-N)- and three carboxyl-terminal (anti-C)-specific antisera. Two anti-C sera and one anti-N serum were useful in localising the parathyroid tumors. In addition, the parathyroid hormone fragments were separated by gelfiltration and the immunoreactivity in the effluent was estimated with anti-N and anti-C sera. The results suggest that the usefulness of antisera for parathyroid tissue localisation is determined by their affinity for the intact hormone, regardless of their anti-N or anti-C qualities.