Geographic and host-related variation among species of Fessisentis (Acanthocephala) and confirmation of the Fessisentis fessus life cycle.

Specimens of the 4 known species of Fessisentis, acquired through new collections in 6 states and laboratory infections, were compared with existing descriptions and collections. It was concluded that the number od longitudinal rows of proboscis hooks and lengths of proboscis receptacles, largest proboscis hooks, and reproductive systems are not useful in distinguishing the species. Egg size is of limited usefulness. Regardless of host or geographical locality, proboscis shape and length, the number of proboscis hooks in each longitudinal row, hook shape and size distribution, number of testes, number of cement glands, and female genital pore position are consistent differences. Cystacanths of Fessisentis fessus occurred in aquatic isopods, Asellus forbesi and Lirceus lineatus, in Jackson County, Illinois, where Siren intermedia is the usual definitive host. Laboratory infections confirmed the life cycle of this species.


Observations on the subgenus Argas (Ixodoidea: argasidae: Argas). 17. Argas (A.) polonicus sp. n. parasitizing domestic pigeons in Krakow, Poland.

Argas (A.) polonicus sp. n. is described from males, females, nymphs, and larvae from the steeple tower of St. Mary's Church, Karkow, Poland, where it feeds on domestic rock pigeons, Columba livia Gmelin. This species is related to the widely distributed Eurasian A. (A.) vulgaris Filippova and to certain other species of the eastern area of the Palearctic Faunal Region; it differs distinctly from A. (A.) reflexus (Fabricius) of western Europe. Comparative study under the light microscope. and especially under the scanning electron microscope, reveals numerous structural differences in adult and immature stages of these species, chiefly in the Haller's organ roof of each stage, adult body shape and integumental formations, dental formulae, and setal lengths and numbers on the larval dorsum.


Effect of mebendazole on the larval development of three Hymenolepidid cestodes.

Mebendazole or Telmin (which contains 16.7% mebendazole) markedly retarded the development of Hymenolepis diminuta and H. nana when their intermediate hosts Tribolium confusum were fed on flour mixed with it from day 1 to day 10 p.i. Though retardation also occurred with H. microstoma, the effect of the drug on this parasite was noticeably less pronounced than with the other 2 species of this genus.


Studies on encystment of Echinostoma revolutum cercariae.

Cercariae of Echinostoma revolutum encysted in the kidney of the snail Physa heterostropha within 1 hr and on mucus trails from Helisoma trivolvis, P. heterostropha and Lymnaea sp. within 2 hr. Significantly, more normal cysts were formed in mucus of Helisoma than in mucus of Physa or Lymnaea. Optimal, in vitro encystment occurred within 24 h in either Locke's  1 : 1 or Locke's 1 : 1 + 1% glucose. Significantly more normal cysts occurred in the Locke's 1 : 1 medium. Both normal and abnormal cysts from Lock's media and snail mucus excysted in an alkaline bile trypsin medium. Cercariae did not encyst in Lock'e media supplemented with casein hydrolysate or in agar cultures containing various chemicals.


Behavioral responses of Schistosoma mansoni miracidia in concentration gradients of snail-conditioned water.

Movement patterns of Schistosoma mansoni miracidia were examined in several concentrations and gradients of snail-conditioned water (SCW). Miracidia surrounded by uniform concentrations of SCW swam at the same speed and exhibited the same rate of turning (angular velocity) as did control miracidia swimming in spring water. However, miracidia in gradients of SCW exhibited a 3-fold increase in their angular velocity without altering their swimming speed. Miracidia ascending gradients of SCW did not increase their angular velocity and failed to orient to the gradient of the stimulant. In contrast, miracidia which encountered sufficiently abrupt decreases in SCW concentration, while descending the gradient, sharply increased their angular velocity. This behavior caused miracidia to remain in regions of high concentration of stimulant. The magnitude of decrease in SCW concentration needed to evoke this response depended on the absolute concentration of SCW. Thus, the miracidial response is a "boundary reaction", a form of chemoklinokinesis, and not a chemotaxis.


Effect of duration and intensity of infection with Echinostoma audyi on survival of Lymnaea rubiginosa exposed to copper sulfate.

Lymnaea rubiginosa infected with 1 to 5 miracidia of Echinostoma audyi for 1, 2, 3, and 5 weeks, and snails infected with up to 10 or 20 miracidia for 3 weeks, were exposed to copper (Cu) as CuSO4 2 hr and allowed to recover 48 hr. In general, snails ininfected with up to 5 miracidia of E. audyi were no more susceptible to Cu than noninfected snails. Snails infected with up to 10 miracidia for 3 weeks were 1.3 times more susceptible to Cu than noninfected snails. However, snails infected with up to 20 miracidia for 3 weeks were not more susceptible to Cu, possibly because infection with such a large number of parasites eliminated the most susceptible snails from the population prior to exposure to Cu.


Solubilization of antigens of Fasciola hepatica which react with antibodies to Schistosoma mansoni.

Extracts of Fasciola hepatica adult worms contain antigens reactive with antisera prepared against Schistosoma mansoni adult worms. These antigens are poorly solubilized when homogenized in a phosphate buffered saline (PBS) solution and pellet readily when subjected to high speed centrifugation. Solubilization is improved greatly by the addition of sodium dodecyl sulfate (0.03%) to the PBS. When this is done, one obtains approximately the same total amount of crude Lowry reactive material as with PBS extraction followed by high speed centrifugation but antigenic reactivity to an anti-S. mansoni antiserum increases enormously. The antigens liberated from F. hepatica SDS extraction are largely materials under 200,000 MW and over 60,000 MW.


Hymenolepis nana: intestinal tissue phase in actively immunized mice.

We investigated the fate of the intestinal cestode Hymenolepis nana in immunized mice. Immunity was induced by infection with the parasite eggs. These immunized animals and unimmunized controls were then challenged with 50,000 H. nana eggs. The mice were killed 4 to 90 hr after challenge, and H. nana in the intestinal tissue were counted. At 4 hr after challenge the unimmunized and immunized animals had approximately equal numbers of oncospheres. By 12 hr there were fewer parasites in the immunized than in the unimmunized animals. At 90 hr, no H. nana were seen in the immunized mice, whereas in the unimmunized animals the median number of cysticercoids was more than 1,000. It appears, therefore, that in mice well immunized to H. nana by infection, challenge oncospheres can burrow into the intestinal tissue before they are killed. The reduced number of oncospheres in the immunized mice 12 hr after challenge, and the accumulation of eosinophils near individual oncospheres still present, indicate that an immune response to the parasite was taking place. Absence of a lymphocyte infiltration near any of the oncospheres suggests that the mechanism of immunity was not lymphocyte mediated; thus, the histopathology of the reaction is consistent with that of humoral immunity.


Initiation of development in vitro of third-stage Nippostrongylus brasiliensis.

Third-stage larvae of Nippostrongylus brasiliensis were maintained in vitro in 5 different culture systems at 25 C and 37 C, and initiation of development to the parasitic phase was evaluated at the morphological and biochemical levels. A few larvae grown in Krebs-Ringer-Tris solution at 25 C showed minimal development of the anterior region and intestinal cells. The amount of development was enhanced with an increase in medium complexity. At 25 C the greatest development was obtained in NCTC-135 : calf serum (8 : 2/v : v). Temperature elevation from 25 C to 37 C had a more significant effect on development than increasing the complexity of the culture medium. The number of L3 showing development in Krebs-Ringer-Tris at 37 C was significantly greater than the number maintained at 25 C in NCTC-135 : calf serum. Likewise, RNA biosynthesis was greatest in those larvae grown in NCTC-135 : calf serum at 37 C. These results support the idea that an elevation of temperature and certain nutritional components stimulate the transcription of that portion of the genome coding for development into the parasitic phase of the life-history.


Carbohydrate transport in Moniliformis dubius (Acanthocephala). III. Post-absorptive fate of fructose, mannose, and galactose.

The initial metabolism of fructose, mannose, and galactose in Moniliformis dubius (M. moniliformis; Acanthocephala) was examined following brief aerobic incubations in 14C-labeled substrate. The pattern of incorporation of radioactivity from 14C-fructose and 14C-mannose into intermediates of hexose metabolism was indistinguishable from that reported elsewhere for the initial post-absorptive metabolism of 14C-glucose under comparable conditions; these hexoses were phosphorylated rapidly following their absorption, and much of the radioactivity absorbed as mannose or fructose was recovered in the nonreducing disaccharide trehalose [alpha-D-glucopyranosyl-(1 leads to 1)-alpha-D-glucopyranoside]. 14C-Galactose was phosphorylated less readily than the other hexoses. More than half of the radioactivity absorbed as galactose was incorporated into disaccharide; some of the galactose-derived disaccharide had properties suggesting the presence of a galactosyl moiety. Incorporation of radioactivity from any of the hexoses into glycogen was minimal. The extensive incorporation of hexose moieties into trehalose or a trehalose-like disaccharide rather than glycogen underscores the probable importance of trehalose metabolism to carbohydrate assimilation in Moniliformis. Physiological factors which might favor trehalose biosynthesis over glycogenesis are considered.


Experimental life cycle of Ascaridia columbae in intravenously infected pigeons, Columba livia.

The fate and routes of migration of infective larvae of Ascaridia columbae were studied in intravenously (i.v.) infected pigeons. Larvae were able to complete a trachael migration, and arrived at the small intestine where they established a patent infection. Granulomas were observed and histopathologically described in the lungs of i.v. infected birds.


Morphology of the advanced-stage larva of Eustrongylides wenrichi Canavan 1929, occurring encapsulated in the tissues of Amphiuma in Louisiana.

Larval nematodes identified as Eustrongylides wenrichi Canavan 1929, from cysts in the tissues of Amphiuma means tridactylum Cuvier in Louisana were redescribed. The extent of differentiation of the sex organs was found to be greater than that of 3rd-stage Dioctophyma renale, or of the infective stage of Trichinella spiralis, and comparable with the late 4th-stage larva of secernentean (phasmid) nematodes.


Lipids of Leishmania promastigotes.

A chromatographic analysis of lipids of cultured promastigotes of Leishmania donovani, L. braziliensis, L. mexicana, L. tropica, L. enriettii, L. hertigi, L. adleri, and L. tarentolae showed that total lipids were 2--15% of dry wt, and neutral and polar lipids were 14--55% and 45--86% of total lipids. Major lipid classes were as follows: sterol ester, triacylglycerol, sterol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine. Predominant fatty acids were 18:2 (n - 6) greater than 18:3 (n - 3) greater than 18:1 (n - 9) greater than 18:0 greater than 22:6 (n - 3) greater than 22:5 (n - 6) greater than 16:0 greater than 14:0 greater than 18:4 (n - 3) greater than 20:3 (n - 3). Some remarkable distributions of fatty acids among the phospholipid fractions were observed, as follows: diphosphatidylglycerol 18--33% 22:6 (n - 3); phosphatidylinositol 31--68% 18:1 (n - 9); phosphatidylcholine 13--41% 18:3 (n - 3). Alk-l-enyldiacyl glycerols, and alk-l-enylacyl and alkylacyl forms of phosphatidylethanolamine and of phosphatidylinositol were found, and their glyceryl ethers and fatty adehydes analyzed. Notable in the phosphatidylethanolamine of some leishmanias was a cyclopropane fatty acid (4--11%), identified as cis-9,10-methylene octadecanoic acid by chromatographic, and by mass and proton resonance spectrometric analyses. The comparative biochemistry of the cyclopropane fatty acid, characteristic of many prokaryotes, and of alpha-linolenic acid, characteristic of photosynthetic plants, are commented upon.


Eimeria dispersa, E. adenoeides, and E. meleagrimitis: intestinal mucosal disruption in turkeys as seen with scanning electron microscopy.

Tissues from the digestive tract of turkeys infected with Eimeria dispersa, E. adenoeides, or E. meleagrimitis were compared with tissues from uninfected controls as seen with light microscopy (LM) and scanning electron microscopy (SEM). Six regions were examined--duodenum, jejunum, ileum, cecal neck, cecal pouch, and large intestine. Although LM showed large numbers of E. dispersa in the epithelial cells, SEM usually showed little mucosal disruption. Occasionally the surface of duodenum and jejunum, as seen with SEM, was convoluted and disrupted. In one bird, some parasite-induced damage was found with either LM or SEM in the duodenum and jejunum of turkeys given E. adenoeides oocysts. Although LM showed parasites in the rest of the digestive tract of all E. adenoeides infected birds, SEM showed only a localized sloughing of the mucosa in the cecal pouch. The most extensive damage to the villar surface was caused by E. meleagrimitis. Infections often disrupted the villar tips, especially in the small intestine and cecal neck. Localized areas of pitting were often found on individual villi. All 3 species produced oocyst extrusion sites, especially in the ileum and the ceca.


Thin-layer chromatographic analysis of phospholipids in Echinostoma revolutum (Trematoda) adults.

Thin-layer chromatographic analyses were made of phospholipids extracted from adult Echinostoma revolutum (Trematoda) and from the nonnutrient medium in which worms were maintained. Identity of phospholipids was based on comparison with authentic lipid standards and on specific chemical detection tests. The most abundant phospholipids in the extract were phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl serine; lesser amounts of cerebrosides and lysophosphatidyl choline were detected also. Phospholipids detected in the incubation medium were essentially as described for extracts.


Two new species of coccidia, Eimeria leucuri and E. oreoecetes (Protozoa: Eimeriidae), in grouse from Colorado.

Eimeria leucuri is described from white-tailed ptarmigan (Lagopus leucurus), and E. oreoecetes from white-tailed ptarmigan and blue grouse (Dendragapus obscurus) from Colorado. Oocysts of E. leucuri are ellipsoidal, 26.6 by 17.7 micron, each bearing a micropyle, micropyle cap, up to 4 polar granules, but no oocyst residuum. The lemon-shaped sporocysts are 15.4 by 6.7 micron, and have Stieda bodies and large amounts of sporocyst residuum. The sporocyst contents are enclosed in a membrane. Oocysts of E. oreoecetes are subspherical, 26.0 by 22.6 micron, and have up to 4 polar granules. The lemon-shaped sporocysts are 14.6 by 8.8 micron, and have both Stieda bodies and substiedal bodies and a large amount of sporocyst residuum. The sporocyst contents are enclosed in a membrane. These are the first coccidia to be described from these tetraonids.


Leishmania herreri sp. n. from sloths and sandflies of Costa Rica.

Leishmania herreri sp. n. is described after isolation in pure culture from blood, viscera and skin of two-toed (Choloepus hoffmanni) and three-toed (Bradypus griseus) sloths from Costa Rica. Also, it was isolated from the following sandflies: Lutzomyia trapidoi, L. ylephiletor and L. shannoni. The amastigote forms were not seen in the final hosts but they were obtained in tissue culture at 33 C. Both promastigotes and amastigotes failed to infect hamsters. The new parasite is isolated frequently in culture, mixed with other hemoflagellates such as L. braziliensis, Endotrypanum sp. and Trypanosoma rangeli.


Apteragia pursglovei sp. n. (Trichostrongyloidea: trichostrongylidae) from the white-tailed deer, Odocoileus virginianus.

Two species of Apteragia were found in white-tailed deer (Odocoileus virginianus) from 152 counties in 13 southeastern states. Specimens previously reported as Skrjabinagia odocoilei were reidentified as belonging to 2 similar species of the genus Apteragia, A. odocoilei, and A. pursglovei sp. n. Apteragia pursglovei sp. n. is differentiated primarily by the length, conformation, and degree of sclerotization of the spicules. Of the 824 deer, A. odocoilei occurred in 76.5%, A. pursglovei in 13.8%, both species in 5.0%, and neither in 4.7%. Reassessment of distribution data revealed that only A. odocoilei was present in deer from 99 counties, only A. pursglovei in deer from 25 counties, and both species in deer from 28 counties. Both A. odocoilei and A. pursglovei were found in Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, and Virginia. Apteragia odocoilei also occurred in Maryland, Tennessee, West Virginia, Texas, Oklahoma, New Jersey, and the Virgin Islands.


Effects of some factors on the susceptibility of Peromyscus leucopus to infestation by larvae of cuterebra fontinella (Diptera: Cuterebridae).

Two levels of 3 factors, (1) host age, (2) host dietary state in regard to vitamin A, and (3) previous infestation history, were tested individually and in combinations for their effects on the susceptibility of Peromyscus leucopus to infestation by larvae of the rodent bot fly, Cuterebra fontinella. Previous infestation was the only significant single factor. Previously uninfested (Pu) mice usually were more susceptible to infestation than previously infested (Pi) mice. Interactions of age and state of vitamin A had the following effects: 1) Young Pu mice that had been denied vitamin A were much less susceptible to infestation than equivalent mice that had been fed diets containing the vitamin; and 2) when Pu mice were deficient in vitamin A, old mice were more susceptible than young mice but when Pu mice were not deficient in the vitamin, young mice were more susceptible. These findings may have significance for natural infestations of P. leucopus.


The limiting effect of host availability for the immature stages on population growth in economically important ixodid ticks.

Of 12 southern African species of ixodid ticks in which the adults are commonly parasitc on cattle, only 4 exhibited massive increases in abundance in the absence of dipping. It is suggested that host availability for the immature stages is the major factor limiting population growth in a given environment. The species showing large increases in abundance are those in which the immature stages are predominantly parasitic on cattle, whereas the species showing small to moderate increases in abundance are those in which the immature stages are parasitic on specific nonungulate hosts.


Effects of exogenous changes in heart rate on facilitation of thought and resistance to persuasion.

Two experiments were conducted to examine the effects of an accelerated heart rate on information processing and resistance to persuasion. Experiment 1 addressed the effects on cognitive performance of manipulating heart rate exogenously for brief periods of time. Fourteen subjects wearing implanted demand-type cardiac pacemakers performed reading comprehension and sentence generation tasks while their heart rate was either accelerated or not accelerated. Results revealed that performance was better when heart rate was accelerated than when it was not accelerated. Experiment 2 addressed the effects on counterargumentation and resistance to persuasion of manipulating heart rate using the cardiac-pacing technique employed in Experiment 1. Subjects read highly involving counterattitudinal communications while their heart rate was either ostensibly or actually accelerated. Accelerated heart rate resulted in the generation of more total thoughts and counterarguments than did basal heart rate; resistance to persuasion was related significantly to the number of counterarguments generated. The methodology used provides a means by which social psychologists can study the effects on social processes of actual but unperceived changes in physiological processes.


Effects of paced respiration and expectations on physiological and psychological responses to threat.

While waiting to receive electric shocks, 105 males either (a) regulated their breathing at one half the normal rate, (b) regulated their breathing at the normal rate, or (c) did not regulate their breathing rate. Half of the subjects in each breathing condition were told that their breathing task would aid them in relaxing, whereas the other half were not given that expectation. Subjects in a no threat condition were not threatened with shocks, did not regulate their breathing, and were not provided with expectations. The results indicated that slowing respiration rate reduced physiological arousal as measured by skin resistance and finger pulse volume (but not heart rate) and reduced self-reports of anxiety. Expectations did not influence arousal. These data provide evidence for the effectiveness of paced respiration as a coping strategy, and they resolve the conflicting findings of previous investigations.


Blood donation and the foot-in-the-door technique: a limiting case.

Three experiments testing the effectiveness of the foot-in-the-door technique for recruiting blood donors consistently failed to demonstrate that this procedure influences either verbal or behavioral compliance, suggesting that the generality of the foot-in-the-door phenomenon is limited. Experiment 1 attempted to demonstrate that an earlier failure of this technique was due to poor operationalization rather than to the magnitude of the critical request or to the invalidity of the phenomenon, but it failed to do so. Experiment 2, designed to more closely resemble other foot-in-the-door studies by using telephone contacts and an initial request for persons to answer questions, was conducted to examine other possible explanations for the two previous failures. This experiment also failed to show any foot-in-the-door effect. Experiment 3 was a conceptual replication of Experiment 2 but used personal contacts. One apparent foot-in-the-door effect emerged in this case, but it was more likely due to a factor other than the experimental treatment. It is concluded that although the foot-in-the-door procedure may indeed influence verbal compliance with requests for minimal forms of aid, it probably will not significantly affect people's willingness to comply with more substantial requests involving behaviors that are psychologically costly to perform.


Disruptive effects of disconfirmed expectancies about crowding.

The experiment utilized a 2 (high vs. low room density) X 2 (forewarning of a crowded room vs. no forewarning) X 2 (simple vs. complex task) design to examine the effects of anticipation of crowding on task performance. More tasks were attempted and efficiency was higher when expectancies about the crowd were confirmed. Subjects not told to anticipate a crowd who actually worked under high density and subjects warned about a crowd that did not materialize performed most poorly. These differences were largest for the complex task. Baum and Greenberg's results were replicated with the performance data. Perceptions of the experimental room also differed as a function of anticipation, but failure to obtain a Crowding X Anticipation interaction did not support their hypothesis that anticipating a crowd induces identical perceptions to those obtained under actual crowding. The results are discussed in terms of disconfirmed expectancies being disruptive of performance, particularly complex task performance.


Effects of preparatory information about sensations, threat of pain, and attention on cold pressor distress.

Pain experience is conceptualized as a combination of stimulus sensations (e.g., aching) and emotional distress. In Experiment 1, less distress was reported to cold pressor stimulation by subjects first told about stimulus sensations than by subjects who were uninformed or were told about symptoms of bodily arousal (e.g., tension). Adding a pain warning to sensation information blocked distress reduction, presumably by eliciting an emotional interpretation of the stimulus. In Experiment 2, subjects attending only to hand sensations reported less distress than subjects attending to their bodies. This decrease in the power of the stimulus to provoke emotion is presumably mediated by a schema of hand sensations formed by attention. In Experiment 3, subjects attending to hand sensations early in the immersion and distracting themselves later reported the same low levels of distress as did subjects who attended to hand sensations throughout. Subjects distracted throughout and subjects attending to hand sensations later showed no distress reduction. Therefore, stimulus schematization must precede distress reduction. Implications for distress control are discussed.


Blockade by saralasin of adrenergic potentiation induced by renin-angiotensin system.

Participation of the renin-angiotensin system in the potentiation of responses to adrenergic nerve stimulation in the pump-perfused dog paw was studied during suprarenal aortic constriction. Vasoconstrictor responses in the paw were elicited by norepinephrine injected intra-arterially and by sympathetic nerve stimulation in a control session and during suprarenal aortic constriction (cephalad to the origin of one or two renal arteries). Aortic constriction decreased renal blood flow by approximately 50% and increased systemic blood pressure and plasma renin activity. The vasoconstrictor responses to norepinephrine and nerve stimulation were not significantly affected when the constriction was cephalad to only one renal artery, but there was a 31% increase in the response to stimulation at 5 Hz during aortic constriction above two renal arteries. There was an approximate 2-fold greater increase in plasma renin activity during the latter than in the former case. Saralasin administered intra-arterially to the paw reversed the adrenergic potentiating effect of aortic constriction. These results indicate that when the renin-angiotensin system is activated by restricting renal blood flow, sufficient circulating endogenous angiotensin is formed to cause a moderate adrenergic potentiating effect in the canine cutaneous circulation of the paw.


Arrest of cultured cells in the G1 phase of the cell cycle by indomethacin.

Indomethacin reversibly inhibited growth of rat hepatoma cells (HTC) and human diploid fibroblasts in the G1 phase of the cell cycle. Cytophotometric measurements showed that greater than 90% of cells incubated for 48 hr with indomethacin had a DNA content that corresponded to the G1 state. Synchronous growth of both the HTC and fibroblast cultures occurred after removal of drug as indicated by the sequence of changes in [3H]thymidine incorporation into DNA, cellular DNA content, mitotic index and cell number. Autoradiographs of HTC cell cultures incubated with [3H]thymidine indicated that all (98%) of the cells engaged in DNA synthesis following the removal of indomethacin. Since viability of the cells was not impaired, even by prolonged exposure to indomethacin, this drug provides a means of synchronizing growth. Suppression of cell proliferation could contribute to the therapeutic and/or toxic effects of indomethacin in vivo.


Isolation of the sino-atrial node with veratramine.

The effects of veratramine on transmembrane potentials of the isolated right atrial preparation of the cat were examined. Veratramine slowed spontaneous rate and precipitated a characteristic rhythm consisting of alternating periods of asystole and normal atrial rhythm (periodic rhythm). After large doses or continued exposure to low doses of veratramine electrical and mechanical activity of the atria ceased; subsequently activity resumed only in a discrete area within which action potentials were consistent with pacemaker characteristics. This discrete pacemaker area, easily located by sight, greatly facilitates study of the sino-atrial node. A gradation of veratramine effect in cells lying between the quiescent common atrial cells and the active pacemaker suggests the existence of "transitional" cells with electrophysiological responses intermediate between common atrial cells and pacemaker cells.


Pharmacological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes. Effects on isolated hearts and coronary vessels.

The 2-n-propyl and 2-n-butyl aminoindene hydrochlorides were previously reported to interfere with excitation-contraction coupling in uterine and intestinal smooth muscle, and with stimulus-secretion coupling in the adrenal medulla, by interfering with the action of calcium at an intracellular site. The present investigation was designed to apply this knowledge to the potential coronary and cardiac effects of such a pharmacological action. The 2-n-propyl and 2-n-butyl aminoindenes (5 X 10(-6)-10(-4) M) produced a concentration-dependent relaxation of potassium-contracted strips of bovine extramural coronary vessels, which was reversible upon elevation of the calcium concentration in the medium. In the nonstimulated isolated perfused rabbit heart, the 2-n-propyl aminoindene (3 X 10(-5) M) and the 2-n-butyl aminoindene (3 X 10(-5) and 10(-4) M) increased coronary flow without affecting cardiac chronotropic activity. However, the 2-n-propyl aminoindene (3 X 10(-5) and 10(-4)M) and the 2-n-butyl aminoindene (10(-4) M) produced a negative inotropic action in this preparation. The combination of coronary dilation and decreased force of cardiac contraction may represent desirable properties for drugs useful in the treatment of ischemic heart disease.


Characteristics of hepatic excretory function during development.

The purpose of this investigation was to characterize the development of hepatic excretory function in rats. Cumulative (40 min) intestinal ouabain content was lower and plasma ouabain concentrations were higher in 15-day-old rats than in 21-, 25-, 35- and 45-day-old animals and reached adult levels when rats were 35 days old. Impaired transport of ouabain in rat neonates correlated to low initial ouabain concentration in liver, which suggested that the inability of young rats to accumulate ouabain in liver may be the most important determinant for functional insufficiency. Bile duct ligation and bile salt infusion, treatments that primarily depress and enhance (respectively) excretion of sulfobromophthalein from liver into bile, markedly altered the disappearance of sulfobromophthalein from plasma of adult rats but did not appreciably affect sulfobromophthalein disappearance from blood of 15-day-old rats. The effect of bile duct ligation on ouabain transport in 15-day-old rats was also not as dramatic as the effect produced in adult rats. Hepatic uptake is rapid in adult rats and overall excretion is limited by a slower rate of transport from liver into bile. The lower rate of uptake in 15-day-old rats may limit overall transport function in young animals.


Ethanol-induced spontaneous norepinephrine release from the rat vas deferens.

Acute ethanol exposure increases norepinephrine (NE) turnover both centrally and peripherally. One of the mechanisms by which ethanol could increase NE turnover is by increasing spontaneous NE release. The effect of ethanol on spontaneous NE release was investigated using tritium release from l-[3H]NE-labeled vasa deferentia as an index of NE release. Ethanol, 65 mM, increased spontaneous tritium release by 8% and pargyline, 100 mg/kg b.wt., pretreatment increased the ethanol effect by 63%. Ethanol alone (22 mM) had no effect on tritium release; however, with pargyline pretreatment tritium release increased by 13%. Combined reserpine, 5 mg/kg, and pargyline, 100 mg/kg, abolished these ethanol effects.  Preincubation with tyramine, 1.8 microM, and omitting calcium from Krebs-bicarbonate buffer also abolished the ethanol effect. Butanol and propanol were more potent and methanol less potent than ethanol in increasing spontaneous tritium release. The mechanism consistent with all the above observations is that ethanol increases spontaneous exocytosis due to a nonspecific effect on presynaptic and vesicular membranes.


A model of cardiac arrhythmias and sudden death: cantharidin-induced toxic cardiomyopathy.

Toxic cardiomyopathy may result in fatal arrhythmias. To develop a model to study ventricular fibrillation and asystole, we investigated the effect of cantharidin in the production of cardiac arrhythmias and myocardial damage. Conscious albino rabbits, weighing between 1.8 to 2.8 kg received an intravenous bolus injection of cantharidin ranging from 0.6 to 1.9 mg/kg or a control injection of solvent. The electrocardiogram was continuously monitored on tape before and after injection for extended periods of time. Dose-related effects were observed with the following: 1) presence, magnitude and duration of ST depression after injection; 2) occurrence of fatal arrhythmias; 3) survival time (high doses were usually fatal within 3 hr); and 4) electron microscopic evidence of mitochondrial swelling, intramitochondrial granules and myofibrillar degeneration. The most common arrhythmias associated with the high doses of cantharidin were frequent ventricular ectopics, ventricular tachycardia, ventricular fibrillation or asytole. The arrhythmias could not be explained by alterations in blood pressure, electrolytes or blood gases. These findings show the cardiotoxic properties of cantharidin and its ability to produce fatal cardiac arrhythmias. Thus, it may serve as a model to study sudden death and the efficacy of antiarrhythmic drugs.


A new platelet aggregation inhibitor which possesses hypolipemic and uricosuric properties, 2-[3-(2-thiazolylthio)phenyl]propionic acid (TPA).

In vitro, 2-[3-(2-thiazolylthio)phenyl]propionic acid (TPA) at plasma concentrations ranging from 0.02 to 1.0 microgram/ml prevents aggregation of human platelets induced by various aggregating agents. Oral administration of TPA to guinea pigs inhibits platelet aggregation; the estimated dose to reduce aggregation by 50% is 0.3 mg/kg. TPA protects rabbits against arachidonate-induced thromboembolic death (50% protection at 0.79 mg/kg i.p.). TPA is a potent hypotriglyceridemic agent in rats when present in the diet in concentrations as low as 0.003%. In chimpanzees, TPA is uricosuric at oral doses of 0.625 and 2.5 mg/kg. This rare combination of pharmacological properties suggests that TPA is a potentially useful antithrombotic agent.


Variation in contractile response characteristics of rabbit aorta strips with surface of drug entry.

Contractile responses of rabbit aorta strips to norepinephrine in the presence of cocaine, histamine and serotonin entering through the intima have been compared with those when these drugs enter via the adventitia. The responses to entry through the inner compared with the outer surface occur after a shorter latency, rise at a greater initial velocity and reach a high steady state. Differences persist after removal of the tunica adventitia. Responses of strips to intimal entry appear identical to those of the intact strip. These results suggest an asymmetry of vascular smooth muscle cell characteristics across the thickness of the tunica media of the rabbit thoracic aorta.


Interaction of lidocaine and calcium on the electrical characteristics of rabbit atria.

The interactions of lidocaine (1-5 X 10(-5) M) and calcium ions (1.25-5.0 mM) on electrical characteristics of atrial potentials were determined with standard microelectrode techniques with major reference to the maximum rate of rise of the action potential (Vmax of AP), the time constant of recovery of the rapid sodium carrier (gamma) and repetitive firing due to early extra stimuli (arrhythmia). Lowering Ca caused depolarization and decreased Vmax and gamma; high Ca caused changes in the opposite direction. The relation of gamma to membrane potential was downward concave when membrane potential was changed by Ca but upward concave when equivalent changes in membrane potential were induced by changing the external potassium concentration. Lidocaine (1 X 10(-5) M) had no significant effect at 2.5 mM Ca but significantly decreased the overshoot and Vmax of AP, increased gamma and effective refractory period and was antiarrhythmic at 1.25 mM Ca. These changes were closely similar to the effects of lidocaine (5 X 10(-5) M) at 2.5 mM Ca. The effects of this high concentration were decreased when Ca was changed to 5.0 mM. The effect of lidocaine most clearly predictive of efficacy for the type of arrhythmia was that on Vmax, with changes in gamma in particular not being related to antiarrhythmic activity.


Adrenergic mechanisms in postvagal tachycardia.

The adrenergic mechanisms involved in the sinus tachycardia which follows the termination of vagal stimulation ("postvagal tachycardia") were studied in the anesthetized dog. The following results were obtained. Postvagal tachycardia: 1) is not affected by ventricular or atrial drive; 2) is enhanced by the application of either norepinephrine or dopamine on the sinus node area; 3) is increased in magnitude and duration by the catecholamine uptake blockers desipramine and phenoxybenzamine; 4) is significantly reduced by beta blockade with propranolol; 5) is not affected by alpha blockade with phentolamine or dopaminergic blockade with haloperidol; 6) is not affected by Disulfiram, a drug which inhibits dopamine beta-hydroxylase and thereby increases endogenous dopamine; 7) rises more slowly to a smaller peak after bretylium; and 8) is enhanced by phenoxybenzamine, but not by desipramine, after destruction of sympathetic nerves by 6-hydroxydopamine. It is concluded that release of catecholamines by vagally liberated acetylcholine is involved in postvagal tachycardia. The released catecholamine acts on beta but not alpha or dopamine receptors. Catecholamines released from sympathetic nerves may account for an initial component in postvagal tachycardia, but catecholamine(s) released from extraneuronal stores account for most of postvagal tachycardia.


Cholinergic mechanisms in heart: interactions with 4-aminopyridine.

Acetylcholine (ACh) hyperpolarized the guinea-pig atrium and increased the maximum rate of rise of the spike and ionic conductance. There was a dose-dependent decrease in action potential duration in most preparations. However, some atrial showed a contractility decrease without a concomitant change in action potential duration. This was not related to acetylcholinesterase activity. Reduction in contractility by ACh resulted from doses 10 times lower than were required for action potential shortening. Small quantitative differences in electrical response were seen between the left and right atria. 4-Aminopyridine lengthened the action potential and increased spike amplitude. These effects were not frequency-dependent but were potentiated by low Ko+. This drug antagonized both the electrical and contractile effects of ACh, suggesting that they are mediated by an increase in KO+ permeability. Modification of excitation-contraction coupling by ACh is discussed and a role for cyclic guanosine 3':5'-monophosphate suggested.


Studies on the behavioral and biochemical effects of hemicholinium in vivo.

Hemicholinium (HC-3) causes a behavioral reactivity in rats which is correlated with the depletion of brain acetylcholine (ACh). The decrease in ACh levels and behavioral effects caused by HC-3 are correlated in a dose-dependent manner, maximal effects being achieved at an intraventricular (i.vt.) dose of 1 microgram. The HC-3 concentration in the brain 2 hr after i.vt. injection does not increase further with doses greater than 10 microgram. HC-3 (i.vt.) does not affect the uptake of choline (Ch) into subcellular fractions prepared from treated animals. ACh depletion in the brain areas studied closely parallels the HC-3 distribution. HC-3 pretreatment results in greater effects on newly synthesized than on stored ACh. Utilizing a concentration equal to that found in brain after an in vivo dose, HC-3 does not inhibit the uptake of Ch in synaptosomal preparations in which the neuronal membrane was disrupted with ether. The commonly accepted mechanism of action of HC-3, i.e., an inhibition of high affinity Ch uptake at the cholinergic nerve terminal, appears to provide a satisfactory explanation of its effects in vivo.


Effect of cephaloridine on respiration by renal cortical mitochondria.

The effects of the nephrotoxic antibiotic, cephaloridine, were studied in rabbit renal cortical mitochondria. Mitochondria from animals which received a toxic dose of 200 mg/kg of the drug 2 hr before sacrifice (in vivo exposure) had significantly decreased rates of respiration compared with those of mitochondria from untreated control animals. In vitro exposure of normal mitochondria to cephaloridine resulted in a qualitatively similar decrease of respiration. With both in vivo and in vitro exposure, inhibition was greatest with ADP-dependent respiration using succinate as substrate. The severity of in vitro inhibition of respiration showed some correlation to the degree of in situ cytotoxicity at different cephaloridine concentrations. The results are in agreement with the finding of a reduction of rates of respiration in renal tubule suspensions after similar in vivo and in vitro exposure to cephaloridine. These studies provide preliminary evidence that cephaloridine nephrotoxicity may be mediated through an inhibitory effect on mitochondrial respiration.


The exceptional potential in each primary care consultation.

A four-point framework is described which has been found to be helpful for general practitioners who try to achieve greater breadth in each consultation. The framework has also provided a useful stimulus in undergraduate and postgraduate teaching, because it provides a nomenclature to identify four major components of clinical practice which are particularly relevant to primary care.


Common sense and consulting.

Three hundred and forty-two general practitioners in Scotland presented their views on content and training in relation to consulting with patients. Differences in responses from trainers, non-trainers, and trainees are examined and possible reasons for the divergences are discussed.


Cigarette smoking and associated disease.

I report an undergraduate medical student project in which a questionnaire was used to try to assess the present level of public knowledge about the harmful effects of cigarette smoking on health. Patients attending a health centre were selected for the study, and a total of 410 questionnaires were completed and analysed. Non-smokers appeared to be better informed about hazards than smokers. The general level of awareness was not as high as might be predicted in view of continual propaganda.


High blood pressure: public views and knowledge.

After completing a screening for hypertension among patients aged between 45 and 54 in a group practice, a sample of both responders and non-responders to screening were surveyed to determine their attitude to screening and knowledge of hypertension.The reasons for non-response were various, and 18 per cent felt screening to be unnecessary. There was little difference between responders (both hypertensive and non-hypertensive) and non-responders in their knowledge of hypertension, and they were well informed about related conditions and illnesses caused by hypertension. The majority were aware of some likelihood of the disease being symptomless, and 38 per cent thought no symptoms were likely to be caused by hypotensive drugs. They seemed aware that the treatment was long term, but only 14 per cent thought it would be life-long.


Lecturing to general practitioners.

We describe the findings of a telephone interview survey among those who have recently been paid through the Department of Health and Social Security (DHSS) to lecture to general practitioners in the North-Western Region. We report the way the lectures are planned and the lecturers' attitudes and motivation. The findings have implications for both future research and policy.


Electronic structures of cephalosporins and penicillins. 9. Departure of a leaving group in cephalosporins.

Molecular orbital calculations by the CNDO/2 method are used to study the potential energy surface for the stretching and rupturing of the CH2-OAc bond in a model cephalosporin structure, 7-amino-3-(acetoxymethyl)-3-cephem. The bond is easier to stretch and break when a nucleophilic group is in the vicinity of or attached to the beta-lactam carbonyl carbon (C8). The rate of acylation by a beta-lactam antibiotic at the receptor sites in bacterial cell-wall enzymes will be enhanced by a suitable leaving group at the 3' position. An orientational specificity is predicted for the direction of departure of the leaving group. Regardless of the direction the nucleophile approaches C8, the CH2-OAc bond is easiest to break when the acetate group departs from the alpha face of the molecule.


Computer assisted structure-activity studies of chemical carcinogens. An N-nitroso compound data set.

N-nitroso compounds, consisting of nitrosamines and nitrosamides, are potentially important in the etiology of human cancer. An attempt to study the molecular structure-carcinogenicity relations of these compounds is reported. A pattern-recognition approach was used to develop predictive ability for carcinogenic potential. A set of 15 calculated molecular structure descriptors that supported a linear discriminant function able to successfully separate 116 carcinogens from 28 noncarcinogens was identified. Predictive ability of an overall of 91%--93% for carcinogens and 85% for noncarcinogens--was obtained in the randomized testing. This relatively high predictability demonstrates that pattern-recognition methods can be useful in analyzing these compounds for carcinogenic activity. The inclusion of two electronic descriptors implicitly supports the alpha-hydroxylation hypothesis. The relations of descriptors used and possible mechanism of action are discussed.


Actinomycin D oxazinones as improved antitumor agents.

1,4-Oxazinone derivatives of the phenoxazinone chromophore in actinomycin D (AMD) have been synthesized by condensation of AMD with alpha-keto acids. By varying the starting alpha-keto acid, the substitutions on the oxazinone ring and, consequently, the lipophilicity of the molecule could be altered. These oxazinone derivatives revert to AMD in physiological media and it appears that these oxazinones are "depot" forms of AMD and possess physicochemical and DNA-binding properties which are significantly different from those of AMD. The oxazinones, which have bulky and lipophilic substituents at position 3, demonstrate more pronounced antitumor activity against P388 mouse leukemia and are less toxic than AMD.


Synthesis, base-catalyzed hydrolytic reactivity, and anticancer evaluation of O-aryl phosphorodiamidates as a novel class of pro(phosphorodiamidic acid mustards).

Bis(2-chloroethyl)phosphoramidic dichloride [MP(O)Cl2, M = N(CH2CH2Cl)2] has been used as the starting material for the synthesis of O-aryl phosphorodiamidates having the general structure MP(O)(NHR)OAr: 9, R = H, Ar = 4-NO2C6H4; 10, R = H, Ar = C6F5; 11, R = C6H5, Ar = C6F5; 12, R = 4-MeC6H4, Ar = C6F5; and 13, R = 4-EtOC6H4, Ar = C6F5. The phosphorodiamidic chloride precursor to 13 (14) was also isolated. Kinetics for the base-catalyzed hydrolysis of compounds 9--13 were investigated by UV and NMR methods and are considered in connection with service of these compounds as pro(phosphorodiamidic acid mustards) [MP(O)(NHR)OAr leads to MP(O)(NHR)OH] via an E1cB mechanism involving the intermediacy of a mustard-bearing metaphosphorodiimide [MP(O)=NR]. Anticancer screening tests against L1210 lymphoid leukemia in mice indicated that 9--14 are inactive; similar negative results were obtained with the KB cell culture, except in the case of 14 which was marginally active.


Alkylating nucleosides. 2. Synthesis and cytostatic activity of bromomethylpyrazole and pyrazole nitrogen mustard nucleosides.

Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucleosides 5 and 7, respectively. In some cases, the positional isomers 6 and 8 were also obtained. Treatment of 5 and 7 with methanolic ammonia gave the deprotected 3-(aminomethyl)pyrazole-5-carboxamide nucleosides 9. Reaction of 3--5 and 7 with bis(2-chloroethyl)amine led to the corresponding pyrazole nitrogen mustards 10--13. All the bromomethylpyrazole nucleosides described showed significant cytostatic activity against HeLa cell cultures.


Acute effects of alkylating agents on canine renal function. 1. [4-(2-Bromoalkanoyl)phenoxy]acetic acids.

A group of [4-(2-bromoalkanoyl)phenoxy]acetic acids was studied to determine if there was an association between the alkylating ability and the diuretic activity of its members. Acute studies in dogs revealed that there is not a consistent correlation in the alkylating potential of these alpha-bromo ketones and their ability to induce a diuretic response. In addition, pretreatment of dogs with the various alpha-bromo ketones did not alter the diuretic activity normally observed with ethacrynic acid (EA). The role of chemical-induced renal tissue alkylation in the initiation of a diuresis or a nephrotoxic response is discussed.


Synthesis and analgesic activity of some spiro[dibenz[b,f]oxepin-10,4'-piperidine] derivatives.

A series of 10,11-dihydro-11-oxospiro[dibenz[b,f]oxepin-10,4'-piperdine] derivatives (II) was synthesized and evaluated for analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Preliminary structure-activity correlations indicate that optimum activity is associated with a short-chain (R less than or equal to C2) N substituent and a nuclear fluorine function, as exemplified by 9b. This compound, when administered orally, was equipotent to morphine in protecting against mouse writhing. The observation that the PQW activity of 9b remained relatively unchanged after naloxone challenge seems to favor a nonnarcotic profile.


Synthesis and hypoglycemic activity of pyridyl alcohols.

The potent hypoglycemic activity of 3-(3-methyl-2-pyridyl)propan-1-ol (1) prompted us to synthesize and study related structures. Some of the variables studied were the position of the methyl and alcohol side chains, the distance between the heterocyclic ring and the hydroxyl group, the effect of additional nuclear substitution, and the effects of branching and substitution on the alcohol side chain. The compounds were tested in 48-h fasted rats, usually at a dose of 150 mg/kg po. 1, the corresponding propionic acid 12, the acetate and methyl ether of 1 (22 and 23), and the 5-methyl analogue of 1 (29) were of comparable hypoglycemic potency. However, these compounds all caused a concomitant elevation of hepatic triglycerides and/or death in the test animals when observations were continued for 4--24 h.


Synthesis and biological activity of cocaine analogues. 2. 6H-[2]Benzopyrano[4,3-c]pyridin-6-ones.

1,2,3,4-Tetrahydro-2-methyl-6H-[2]benzopyrano[4,3-c]pyridin-6-one (20) and cis- and trans-1,2,3,4,4a,10b-hexahydro-2-methyl-6H-[2]benzopyrano[4,3-c]pyridin-6-one (3a and 3b) were synthesized. The design of 3b was based on the proposal that the active conformation of cocaine is one in which the phenyl and amino groups are arranged in a manner that will superimpose upon a beta-phenethylamine in a trans-staggered conformation. The compounds were compared with cocaine and tropacocaine for their ability to inhibit uptake of [3H]norepinephrine by rat brain synaptosomal preparations. The test compounds (IC50 = 3.2 X 10(-4) M, 20; 6.5 X 10(-4) M, 3a; and 3.2 X 10(-4) M, 3b; respectively) were considerably weaker than cocaine (IC50 = 5.8 X 10(-7) M) and tropacocaine (IC50 = 5.6 X 10(-6) M). Compound 3b showed selectivity at 1 X 10(-5) M for inhibiting the uptake of norepinephrine (36%). It inhibited dopamine (3%) and serotonin (0%) uptake to a much lesser extent, if at all, at this concentration.


Analogues of methotrexate.

Analogues of methotrexate (MTX) were prepared by alkylation of side-chain precursors with 6-(bromomethyl)-2,4-pteridinediamine followed, where necessary, by saponification of the intermediate esters and, in two cases, by electrophilic substitution reactions in the pyridine ring portion of 3-deazamethotrexate. Effects of the various modifications on their ability to inhibit dihydrofolate reductase, cytotoxicity, and activity against L1210 leukemia in mice were examined in light of recent findings concerning active transport of MTX and related compounds and the binding features of the MTX-dihydrofolate reductase complex.


Some 9-hydroxycannabinoid-like compounds. Synthesis and evaluation of analgesic and behavioral properties.

A series of 9-hydroxylated cannabinoid-like compounds was prepared and tested for analgesic properties in mice and behavioral properties in dogs. Although the prototype compound, 9-nor-9-hydroxyhexahydrocannabinol, has potent antinociceptive activity in laboratory animals, the new analogues were relatively inactive. All of the compounds produced an alteration of behavior in unanesthetized dogs. Two of the compounds produced cannabinoid-like effects and the other two produced general CNS depression.


Some 11-substituted tetrahydrocannabinols. Synthesis and comparison with the potent cannabinoid metabolites 11-hydroxytetrahydrocannabinols.

A series of compounds was prepared in which the 11-hydroxyl of 11-hydroxy-delta8-THC, the potent metabolite of delta8-THC, was replaced by a methyl, methyoxy, amino, or acetamido group. All of the compounds tested produced behavioral changes in dogs, but only the methoxy compound has analgesic properties in mice. An isosteric oxime was inactive in mice.


2',3'-Bis(2-chloroethyl)aminophosphoryl-3'-amino-3'-deoxyadenosine: a cyclic nucleotide with antitumor activity.

The synthesis of the title compound from 3'-amino-3'-deoxyadenosine in 40% yield is reported. 3'-Amino-3'-deoxyadenosine was made by an improved synthesis in 12 steps from inexpensive D-xylose in 15% overall yield. Both isomers of the title compound, separated by column chromatography, possess confirmed activity against KB tumor cell cultures.


Active-site studies of neurohypophyseal hormones: synthesis and pharmacological properties of [5-(N4,N4-dimethylasparagine)]oxytocin.

Synthesis and biological properties of [5-(N4,N4-dimethylasparagine)]oxytocin are reported. In this analogue, the hydrogens of the primary carboxamide moiety in the side chain of the asparagine residue in position 5 of the posterior pituitary hormone oxytocin have been replaced by two methyl groups. The protected nonapeptide intermediate was prepared by a stepwise procedure using solution techniques. The analogue possesses 4.60 +/- 0.03 units/mg (mean +/- SEM) uterotonic activity on the isolated rat uterine horn and 9.14 +/- 0.03 units/mg of avian vasodepressor activity. Moreover, it displays an identical intrinsic activity in the in vitro rat uterotonic assay as oxytocin, when tested in the presence of either 0.5 mM Ca2+ (standard assay conditions) or at reduced levels of Ca2+ (0.3, 0.15, and 0.05 mM). This result is significant in view of the proposed biologically active model of oxytocin, in which the side chain of the 5 position residue was assigned to contain an "active element" responsible for the intrinsic activity of the hormone when bound to the uterine receptor.


Correlates of clinical performance during medical school.

Many efforts have been made to define the complex factors related to successful clinical performance and to determine relationships among them. This study was an attempt to increase the understanding of cognitive and noncognitive attributes of clinical performance. Intercorrelations among overall clinical performance ratings, quarterly comprehensive examination scores, total scores on the Part II examination of the National Board of Medical Examiners, and overall grade-point average were computed for a graduating class of medical students. Aspects of clinical performance pertaining to information, concepts, skills, ingenuity, and conscientiousness were found to correlate with academic achievement as measured by grades and cognitive tests; however, such a correlation was not found for other aspects pertaining to attitude, peer relations, maturity, patient rapport, and integrity.


Report on a survey of program directors regarding selection factors in graduate medical education.

A national random sample of 25 percent of the graduate education program directors in internal medicine, family medicine, surgery, and pediatrics was sent a questionnaire; subjects were asked to judge the importance of 31 variables in the selection of house staff. A rank-ordering of variables for all respondents placed interpersonal skills demonstrated in the interview as number one. When rank order correlations were calculated for all possible pairs of program specializations, strong positive relationships were revealed. A two-way analysis of covariance was also undertaken to assess how selected program characteristics, such as size of program, type of program, and affiliation or nonaffiliation with a medical school, affected the judgment of the importance of the variables. The results have implications for further studies in several areas.


A national survey of undergraduate teaching in obstetrics and gynecology.

Representatives of 114 academic departments of obstetrics and gynecology in North America completed a written questionnaire in 1977 designed to assess undergraduate educational programs. Respondents reported increases in numbers of departments and faculty per department and decreases in the length and number of students per clerkship in comparison with a 1968 survey. Small-group discussion, lecture, and professional patients were preferred instructional modalities of faculty and students. Evaluation procedures and faculty development activities are reported and discussed in relation to prior surveys of departments of obstetrics and gynecology.


On the professional socialization of black residents in psychiatry.

Residents in psychiatry, in addition to acquiring technical knowledge and skills, undergo the process of professional socialization during which they assimilate the values, attitudes, and normative behavior of their professional group. The socialization of any group of trainees is fostered by the clarity and precision of a socialization structure and by the visibility and contribution of certain specific agents of socialization. The authors outline the areas of this process that create problems for black residents in psychiatry and suggest alternatives to the present experience encountered in most training programs.


Development of departmental promotion guidelines.

In making optimum use of its faculty, a medical school department should ensure that each faculty member has a clear understanding of what is expected of him and what will be evaluated when he is considered for reappointment or promotion. A set of departmental promotion guidelines which are available to all faculty can serve both these ends. In addition to defining the nature of the work which will be evaluated and stressing that performance quality is important, such guidelines should make explicit the various ways in which the work will benefit the department, the medical school, and the discipline. The guidelines can be used at the time of promotion, but they should also contribute to an ongoing evaluation of faculty work by the administration and by the faculty themselves.


Continuing medical education: linking the community hospital and the medical school.

Community hospitals and medical schools have different but complementary resources to carry out continuing medical education. To strengthen the educational capabilities of both, a group of community hospitals has been linked to a medical school in a continuing medical education network. A peripatetic educational development team based at the medical school completes the link by helping community hospital physicians identify educational needs and develop educational responses, using both local and medical school experts as faculty. The educational development team provides skills and staffing which no small or moderate-sized community hospital could afford alone. The program is financially feasible for community hospitals and the medical school, does not consume the resources of either, and conserves the time of the community physician and medical school faculty.


Comparison of faculty and resident expectations for residency training in hypertension.

Faculty and residents in family medicine rated the degree of importance for a resident to have mastered each of 123 performance objectives by the end of residency training. The performance objectives, developed at the national level, describe the diagnosis, treatment, and management of clinic patients with hypertension. While faculty members' ratings of the objectives were in moderate agreement, the ratings of the residents by level of training were in low agreement. A comparison of faculty and resident ratings resulted in very low agreement. An analysis of the type and nature of the performance objectives and topic areas where disagreement occurred was also conducted. The results indicate that while disagreement was widespread, no pattern for the disagreement was evident. Implications for the use of performance objectives developed outside a local residency program are discussed.


Introduction of ambulatory medical training in a Veterans Administration hospital.

Planners of postgraduate medical education in the United States have mandated that training programs include experience in continuing patient care in the ambulatory setting. Idiosyncratic administrative features and limitation of resources present relatively unique problems for the development of such programs in Veterans Administration teaching hospitals. The authors describe the implementation of a continuity of care clinic in a highly subspecialized large VA internal medicine training program. Crucially, all residents attend the clinic on the same day. The internal medicine educational program was altered to prevent conflict of the new clinic with other teaching activities. The program has been well received by the involved house staff members and has achieved some of the intended goals.


Can continuity of medical care be taught?

The health sciences literature indicates that although continuity often has been shown to be associated with a number of favorable outcomes, the concept is as yet poorly conceptualized and difficult to quantify. In this paper the authors describe an approach to teaching continuity developed at the University of Washington. Beginning in 1973--74 second-year students in an elective family medicine preceptorship were placed with practicing family physicians one-half day per week for a complete academic year. The medical care of a few families was closely followed by each student throughout the period. Required written reports of each student's longitudinal-care experiences were analyzed to identify student-perceived benefits of extended patient contact. Three-fourths of the students over a two-year period were judged to have experienced important aspects of continuity. Results suggest that the teaching program described is a viable means for teaching students to recognize, appreciate, and employ approaches to patient care available only in settings characterized by continuity.


Mental health of medical school applicants: the role of the admissions committee.

This study was of the role of admissions committees as it relates to the mental health of applicants. Two-part questionnaires were sent to 115 medical schools. The first part explored the composition of the committee. In most schools the dean selected the members, attempting to obtain equal representation from clinical and basic science departments; most of the schools had one or more psychiatrists on the committee. The second part focused on the policy for applicants with former mental health problems. Over one-third of the committees asked about previous or present mental illness or therapy. Ninety percent of the schools had no policy or guidelines for using such information; instead, most relied on psychiatric interview or outside reports in making admissions decisions. The impact of federal legislation regarding the handicapped on admissions procedures is discussed. Since more students with previous or current psychiatric problems may be admitted, schools must be prepared to respond to their needs as fully as they now respond to other medical problems.


An evaluation of income incentives and board-certification trends.

In this paper the author examines income differentials between board-certified and non-board-certified physicians to determine whether the trend toward board certification is consistent with economic incentives. Although simple income comparisons indicate substantial differentials by certification status, after adjustments are made for specialty-mix, age distribution, and hours worked, the remaining differential is small. However, results by specialty indicate that physicians are most likely to become certified in specialties with the largest income differentials.


Time trends in the association of a rural or urban background with physician location.

The association of rural or urban background with choice of practice location was investigated in two time periods, 1950--1955 and 1963--1968, using the alumni of Marquette School of Medicine (now the Medical College of Wisconsin) in Milwaukee, Wisconsin. Background included size of communities of birth, high school, college, and internship. Small communities were screened to distinguish suburban from rural settings. It was found that in the 1950s the percentage of physicians from rural schools who chose to practice in rural areas was 2.2 times as great as this percentage for physicians from nonrural high schools (26 percent versus 12 percent). In the 1960s the ratio increased to 3.5, (35 percent versus 10 percent). This time trend was reversed for physicians more than 28 years old at the time of graduation from medical school. Place of birth and place of internship also were significantly associated with practice location; place of college showed a significant association with practice location only in the 1950s; and class rank was not associated with place of practice.


Medical student instructional costs in a primary care clerkship.

Using a variety of techniques, such as logs kept daily by the faculty, direct observation, and on-site interviews, the authors determined the instructional costs of a required third-year primary care clerkship based in an ambulatory care setting. Included in the analysis were labor costs of both faculty members and nonfaculty personnel, space and materials, and general university overhead. Total instructional costs were $54.20/student/day. If other third-year clinical clerkships generate equivalent costs, the direct instructional costs of clerkships for third-year medical students would be in excess of $11,500/student/year. The study results imply that ambulatory-based teaching of medical students generates considerable costs and thus requires support from student tuition, federal or state government, or other sources.


A 'firm' system for graduate training in general internal medicine.

The faculty of the Department of Medicine at Cleveland Metropolitan General Hospital has responded to the challenge of fostering general internal medicine in a graduate training program by organizing a "firm" system of medical care which has appealed to academic internists with broad interests in clinical medicine. This firm system consists of four medical teams which care for distinct patient populations, closely integrating their outpatient and inpatient care. The firms are made up of all the house staff in training in internal medicine together with senior and junior faculty members who are directors for the firms. Medical students in general medicine are also assigned to firms. This firm system is relatively simple to understand and establish and is readily applicable to other academic departments with general medical responsibilities.


A multidisciplinary clerkship in emergency medicine.

An obligatory, multidisciplinary, fourth-year emergency medicine clerkship is described and the particular problems of multidisciplinary courses discussed. The course is designed to produce medical students who adequately demonstrate: knowledge of emergency care and facility in specified skills, familiarity with the appropriate use of an emergency room, and conversance with treatment of nonemergency cases. Students are required to complete successfully an advanced cardiac life support providers course, serve on ambulance duty, rotate through a community hospital emergency room, and participate in the more traditional clinical experiences. The course offers the fourth-year student an opportunity to synthesize prior knowledge within the context of a multidisciplinary patient care experience.


Functions of a family medicine preceptorship.

The preceptorship in family medicine, a required four-week experience for fourth-year medical students at the University of North Carolina, was studied during academic year 1976--77. Analysis of narrative comments and closed-ended scales indicated that the preceptorship was a "synthesis" experience valued by both students and preceptors, regardless of the students' choice of graduate specialty training. From these same data seven functions of the preceptorship, many of which are not official program goals, were identified. The authors recommend that preceptorships be designed and evaluated with these, often latent, functions in mind.


Isolation of an abnormally phosphorylated erythrocyte membrane band 3 glycoprotein from patients with myotonic muscular dystrophy.

A fraction of erythrocyte Band 3 (Mr, 93,000) glycoprotein that demonstrates decreased autophosphorylation in membranes from myotonic muscular dystrophy patients is demonstrated. Sequential affinity chromatography of Triton X-100 solubilized erythrocyte membrane proteins separated three specifically retained glycoprotein fractions on a Ricin Communis I-Sepharose 4B column. One fraction contains a portion of the major sialoglycoprotein (apparent Mr, 78,000) and is specifically eluted from the column by 10 mM NaCl and 100 mM D-galactose (10/100). The two other glycoprotein fractions are eluted by 100 mM NaCl, 10 mM D-galactose (100/10) and 100 mM NaCl, 100 mM D-galactose (100/100). The composition of both fractions contains greater than 95% Band 3 (apparent Mr, 93,000 glycoprotein. The quantities of glycoprotein in each fraction obtained from erythrocytes of myotonic dystrophy patients did not differ from the quantities obtained from control erythrocytes. Following endogenous protein kinase incubations of ghosts with [gamma-32P]ATP, the specific [32P] phosphorylation of the 10/100 and 100/10 fractions are identical. The 100/100 fraction, which makes up approximately 3% of the total erythrocyte membrane protein, demonstrates a different pattern for myotonic dystrophy patients; specific phosphorylation was reduced by 50% relative to activity in control experiments. These findings are consistent with previous experiments that demonstrated decreased autophosphorylation of the glycoprotein portion of Band 3 (Roses & Appel, 1975, J. Membrane Biol 20:51) and are consistent with the autosomal dominant mode of inheritance in this disease.


Structural simplicity of the zonula occludens in the electrolyte secreting epithelium of the avian salt gland.

The structure of the zonula occludens in the secretory epithelium of the salt gland of the domestic duck was determined by thin section and freeze-fracture electron microscopy. These glands secrete an effluent with a NaCl concentration four times that of plasma, and thus maintain a steep ionic gradient across their secretory epithelium. Freeze-fracture replicas from salt stressed ducks demonstrate that the zonula occludens is surprisingly shallow in depth (20-25 nm) and generally consists of two parallel junctional strands which are juxaposed along their entire length. In addition to the simplicity of the junction separating mucosal and serosal compartments, the ratio of junctional length to apical surface area is large since luminal surfaces of secretory cells are narrow and intermesh with one another. The zonula occludens in nonsecreting fresh water-adapted birds is similar to the salt stressed group except that two sets of double strand junctions are seen in addition to junctions consisting of a single set. Based on previous ultrastructural, cytochemical and physiological studies in salt glands and in other epithelia, a model for salt secretion was suggested in which intercellular space Na+, generated by basolateral ouabain-sensitive Na+ pumps, reaches the lumen via a paracellular route (Ernst & Mills, 1977, J. Cell Biol. 75:74). The simplicity of the morphological appearance of the zonula occludens in the salt gland, which resembles that described for several epithelia known to be leaky to ions, is consistent with this hypothesis.


K+ conduction phenomena applicable to the low frequency impedance of squid axon.

The observation of peaking in power spectra of K current noise in squid axon (Fishman, H.M, Moore, L.E., Poussart, D.J.M. 1975, J. Membrane Biol. 24:305) led to the calculation of low frequency K conduction feature in the impedance (admittance) which was confirmed (Fishman, H.M., Poussart, D.J.M., Moore, L.E. & Siebenga, E., 1977, J. Membrane Biol. 32:255). This paper analyzes two physical phenomena, one within and the other outside of the excitable membrane, that might account for the low frequency impedance (admittance) feature. The accumulation of potassium ions in a space outside the axon in conjunction with diffusion through the Schwann cell layer produces a low-frequency mode that is similar in some respects to that observed experimentally. Alternatively, a hypothetical inactivation process, with a voltage-dependent time constant, associated with conduction in potassium channels gives a better account of the data. Either or both of these phenomena could be involved in producing the low-frequency impedance behavior in the squid axon.


Effects of bicarbonate on fluid and electrolyte transport by the guinea pig gallbladder: a bicarbonate-chloride exchange.

Fluid transport and net fluxes of Na, K, Cl and HCO3 by guinea pig gallbladder were investigated in vitro. A perfused gallbladder preparation was devised to simultaneously study unidirectional fluxes of 22Na and 36Cl. The net Cl flux exceeded the net Na flux during fluid absorption in the presence of HCO3. This Cl excess was counterbalanced by a net HCO3 secretion: a HCO3-Cl exchange. PGE1 reversed the direction of fluid transport and abolished the net Cl flux. The magnitude of the HCO3 secretion remained unchanged, but shifted from a HCO3-Cl exchange to a net secretion of NaHCO3 and KHCO3. Furosemide inhibited both the HCO3-Cl exchange and HCO3 secretion after PGE1 without influencing fluid absorption. Ouabain inhibited the HCO3-Cl exchange as well as fluid absorption; only the effect on the HCO3 secretion was entirely reversible. Secreted HCO3 appeared not to be derived from metabolic sources since HCO3 secretion was abolished in a HCO3-free bathing medium. HCO3 secretion was also dependent on the Na concentration of the bathing fluid. Three lines of evidence are presented in favor of an active HCO3 secretion in guinea pig gallbladder. HCO3 is secreted against: (i) a chemical gradient, (ii) an electrical gradient and (iii) the direction of fluid movement under control conditions.


Active and passive properties of rabbit descending colon: a microelectrode and nystatin study.

The electrical properties of the basolateral membrane of rabbit descending colon were studied with microelectrode methods in conjunction with the polyene antibiotic nystatin. Two problems were examined: (i) the relative distribution of tight junctional, apical membrane and basolateral membrane resistances, and (ii) the ionic basis of the basolateral membrane potential. Intracellular K+ activity (K+) was measured using liquid ion exchanger microelectrodes ((K+) = 76 +/- 2 MM) and was found not to be in equilibrium with the basolateral membrane potential. In order to measure membrane resistances and to estimate the selective permeability of the basolateral membrane, the apical membrane was treated with nystatin and bathed with a K2SO4 Ringer's solution which was designed to mimic intracellular K+ composition. This procedure virtually eliminated the resistance and electromotive force of the apical membrane. Shunt resistance was calculated by two independent methods based on microelectrode and transepithelial measurements. Both methods produced similar results (Rs = 691 +/- 63 omega cm2 and 770 +/- 247 omega cm2, respectively). These findings indicate that the shunt has no significant selectivity, contrary to previous reports. Native apical membrane resistance was estimated as 705 +/- 123 V cm2 and basolateral membrane resistance was 95 +/- 14 V cm2. To estimate basolateral membrane selectivity, the serosa was bathed in a NaCl Ringer's solution followed by a series of changes in which all or part of the Na+ was replaced by equimolar amounts of K+. From measures of bi-ionic potentials and conductance during these replacements, we calculated potassium permeability and selectivity ratios for the nystatin-treated colon by fitting these results to the constant field equations. By correcting for shunt conductance, it was then possible to estimate the selective permeability of the basolateral membrane alone. Selectivity estimates were as follows: PNa/PK = .08 and PCl/ PK = .07 (uncorrected for shunt) and PNa/PK = .04 and PCl/PK = .06 (basolateral membrane alone). In a second set of experiments, evidence for an electrogenic Na+ pump in the basolateral membrane is presented. A small ouabain-sensitive potential could be generated in the nystatin-treated colon in the absence of chemical or electrical gradients by mucosal, but not serosal, addition of NaCl. We conclude that this electrogenic pump may contribute to the basolateral membrane potential; however, the primary source of this potential is "passive": specifically, a potassium gradient which is maintained by an "active" transport process. An appendix compares the results of nystatin experiments to amiloride experiments which were conducted separately on the same tissues. The purpose of this comparison was to develop a comprehensive model of colonic transport. The analysis reveals a leak conductance in the apical membrane and the presence of an amiloride-insensitive conductance pathway.


Interaction of tritium-labeled H2DIDS (4,4'-diisothiocyano-1,2,diphenyl ethane-2,2'disulfonic acid) with the Ehrlich mouse ascites tumor cell.

The experiments reported in this paper were undertaken to explore the interaction of tritiated H2DIDS (4,4'-diisothiocyano-1,2,diphenyl ethane-2,2'-disulfonic acid) with Ehrlich ascites tumor cells. Addition of (3H)H2DIDS to tumor cell suspension at 21 degrees C, pH 7.3, resulted in: (i) rapid reversible binding which increased with time and (ii) inhibition of sulfate transport. Tightly bound H2DIDS i.e., reagent not removed by cell washing, also increased with time. Binding of 0.02 nmol H2DIDS/mg dry mass or less did not affect sulfate transport, but, at greater than 0.02 nmol and up to 0.15 nmol the relationship between tight binding and inhibition of transport is linear. The fact that H2DIDS could bind to the cell and yet not affect anion transport suggests that binding sites exist unrelated to those concerned with the regulation of anion permeability. Support for this is the observation that H2DIDS is spontaneously released from cells even after extensive washings by a temperature-sensitive process. The most important source of released H2DIDS is the cell surface coat which labels rapidly (within 1 min) and is then spontaneously released into the medium. A second source is derived from H2DIDS that slowly entered the cells. Consequently, at least four modes of interaction exist between H2DIDS and ascites tumor cells. These include both reversible and irreversible binding to membrane components which regulate anion permeability, irreversible binding to cell surface proteins or glycocalyx, and finally incorporation of H2DIDS into the intracellular phase.


Inhibitory and stimulatory effects of amiloride analogues on sodium transport in frog skin.

Effects of amiloride analogues on Na transport were studied in isolated skins of the frog Rana ridibunda. The pattern of structure-activity relationship of these compounds showed that both the -NH2 group at position 5 and Cl at position 6 of the pyrazine ring of the amiloride molecule were important for their biological activity. The paramount role of the groups at position 5 was further demonstrated by the striking properties of an analogue resulting from dimethylation of that -NH2 group.  A stimulation of Na transport, opposite to the effect of amiloride itself, was observed in this instance. The increase in Na transport could already be seen at 10(-6) M and was equivalent to the measured increase in Na influx, reversible, dose-dependent, and additive to the natriferic action of oxytocin. Such characteristics resemble those reported with "external" agents like propranolol and La3+. Furthermore, mutual inhibition was observed between the stimulatory effects of this analogue and those of propranolol or La3+. These results suggest that the analogue may be considered as another "external" agent acting at sites of the external membrane distinct from those activated by cAMP but similar to the Ca sites described by Herrera and Curran (Herrera, F.C., Curran, P.F. 1963. J. Gen. Physiol. 46:999).


Capacitance and conductance as tools for the measurement of asymmetric surface potentials and energy barriers of lipid bilayer membranes.

A simple method for determination of asymmetric surface potentials in lipid bilayers is described. The method is based on the dependence of bilayer capacitance on transmembrane voltage. The capacitance is measured by rectifying in 90 degrees component of an applied alternating current signal. A superimposed slow triangular wave results in a hysteresis-like time course of capacitance. The center of the hysteresis figure is shifted along the voltage axis by an amount equal to the difference of the dipole plus surface-charge potentials on the two sides of the bilayer (capacitance minimization potential). Alternatively, such bilayer asymmetry was studied by using the current-voltage characteristics in the presence of nonactin as a carrier. This analysis was based on the integrated Nernst-Planck equation, assuming a trapezoidal energy barrier and equilibrium of the surface reactions. The two methods gave consistent results for the surface potentials of phosphatidyl serine membranes asymmetrically shielded with calcium. In addition, the current analysis yields the positions of the corners of the barrier, found to be set in 13% for this lipid.


Evolution of the differential regulation of duplicate genes after polyploidization.

In the 50 million years since the polyploidization event that gave rise to the catostomid family of fishes the duplicate genes encoding isozymes have undergone different fates. Ample opportunity has been available for regulatory evolution of these duplicate genes. Approximately half the duplicate genes have lost their expressions during this time. Of the duplicate genes remaining, the majority have diverged to different extents in their expression within and among adult tissues. The pattern of divergence of duplicate gene expression is consistent with the accumulation of mutations at regulatory genes. The absence of a correlation of extent of divergence of gene expression with the level of genetic variability for isozymes at these loci is consistent with the view that the rates of regulatory gene and structural gene evolution are uncoupled. The magnitude of divergence of duplicate gene expressions varies among tissues, enzymes, and species. Little correlation was found with the extent of divergence of duplicate gene expression within a species and its degree of morphological "conservatism", although species pairs which are increasingly taxonomically distant are less likely to share specific patterns of differential gene expression. Probable phylogenetic times of origin of several patterns of differential gene expression have been proposed. Some patterns of differential gene expression have evolved in recent evolutionary times and are specific to one or a few species, whereas at least one pattern of differential gene expression is present in nearly all species and probably arose soon after the polyploidization event. Multilocus isozymes, formed by polyploidization, provide a useful model system for studying the forces responsible for the maintenance of duplicate genes and the evolution of these once identical genes to new spatially and temporally specific patterns of regulation.


Effect of changes in population size on the correlation between mutation rate and heterozygosity.

The effect of changes in population size on the correlation between mutation rate and heterozygosity was studied by using two models: sudden change in population size and gradual change. It was shown that the results for the two models are close to each other, unless the rate of change for the latter is exceedingly slow. Thus, in many cases, the former model, which is much simpler than the latter, can be used to treat the present problem. Numerical computations showed that the correlation in a population that is expanding or has expanded in the recent past is stronger while the correlation in a population that is decreasing or has experienced a population reduction or bottleneck in the recent past is weaker than that for an equilibrium population with the same mean heterozygosity. However, regardless of whether the population is at equilibrium or not, the proportion of variation in heterozygosity that is attributable to variation in molecular weight over loci is rather small if the mean heterozygosity of the population is low, say of the order 0.05 or smaller.


Energetics of peptide bond formation at elevated temperatures.

The free energies of formation of the peptide bond between carbobenzoxy-glycine and L-phenylalanine amide in aqueous solution at temperatures up to 60 degree C were calculated from experimentally determined equilibrium constants. The reaction was catalyzed by a thermophylic enzyme. The thermodynamic energy barrier to peptide bond formation was found to decrease with increasing temperature: the standard free energy of peptide bond formation did appear to become negative in the region of 60 degrees C. The possible significance of these results for peptide bond formation under prebiotic conditions is discussed.


The molecular heterogeneity and diversity of reptilian keratins.

Reptile keratins produce complex electrophoretic patterns, contain a number of size classes, and contain protein fractions analogous to the fractions found in other keratins. Thus, reptile keratins are similar to the heterogenous keratins of birds and mammals, and quite different from amphibian epidermal keratins. This heterogeneity may be related to the multiple functions performed by the epidermis of these organisms. The chemical diversity of reptile keratins seems to depend on the morphological differences between the tissues in which they occur. This situation is also found among these proteins in mammals and birds suggesting that keratin diversity is related to the morphological and presumably functional differentiation of epidermal tissues. The distribution of the keratin fractions in each tissue contributes to this diversity but the significance of these fractional differences is uncertain. A comparison of the half-cystine and glycine content of vertebrate alpha and ø keratins suggests that the alpha and ø proteins of reptiles may be related to the soft alpha keratins of mammals and amphibians. Mammalian hard keratins probably represent a uniquely derived group of proteins which are unlike the other vertebrate keratins. The presence of a "high sulphur" matrix component in both hard mammalian alpha and reptilian ø keratins may represent some form of molecular convergence which provides these distantly related proteins with similar physical or organizational properties.


The catalysis of nucleotide polymerization by compounds of divalent lead.

Soluble lead salts and a number of lead-containing minerals catalyze the formation of oligonucleotides from nucleoside 5'-phosphorimidazolides. The effectiveness of lead compounds correlates strongly with their solubility. Under optimal conditions we were able to obtain 18% of pentamer and higher oligomers from ImpA. Reactions involving ImpU gave smaller yields.


Surgical immunology: a historical review of its role in the armamentarium of the surgical oncologist.

Immunology is taking its place in multimodality therapy of malignant diseases-currently an adjuvant role. Historical development of this role and definition of terms and principles are herein presented in brief fashion.


Surgical management of radiation enteritis.

In the great majority of patients treated with radiation, only transitory injury to the bowel occurs, but in five percent of patients, permanent damage to the small bowel or rectum is seen. Symptoms of radiation enteropathy may begin four to six months after the treatment is completed or may not present until several years later. Most often, the patient presents with abdominal pain, diarrhea, hematochezia, and signs of malnutrition. Others may present, initially, with intestinal obstruction, perforation, or fistulization. It is important to differentiate this clinical syndrome from recurrent cancer by appropriate radiological studies and biopsies.This paper presents four patients who were treated with radiation for invasive carcinoma of the cervix and subsequently developed radiation enteritis. All were treated surgically and are surviving.


Surgical management in sicklemia.

A review of the history and pathophysiology of sickle cell disease is given. The clinical types (crises) are discussed along with their relationship to surgical occurrences, both elective and emergency. Specifics of perioperative management are discussed and the cardinal features of importance are enumerated. A retrospective study of sickle cell disease in a community hospital is presented, outlining the surgical experience over a ten-year period.


Traumatic diaphragmatic hernias: analysis of six cases.

During three years, from January 1975 through December 1977, the authors saw six cases of traumatic left diaphragmatic hernias, all of whom survived. All were males aged 17 to 56 years, with an average age of 30 years. Four (67 percent) of the cases resulted from blunt abdominal trauma while two (33 percent) were due to stab wounds of the left lower chest. Admitting chest x-ray findings were diagnostic for all acute hernias due to blunt trauma and for all hernias presenting with a delayed interval. Digital exploration of all penetrating lower chest wounds is recommended by some authors if exploratory laparotomy is not contemplated. Our preferred approach for the repair of the hernias includes (1) laparotomy for all acute cases, (2) thoracotomy for delayed cases, and (3) separate abdominal thoracic incisions whenever a combined approach is considered necessary. The repair should be carried out in two layers with nonabsorbable sutures.


Rupture of cervical esophagus from blunt trauma with concomitant fracture dislocation of C4-C5 vertebrae.

A patient is presented who had sustained a high posterior cervical esophageal laceration (secondary to an automobile accident) with concomitant fracture of the C(4) - C(5) spine. It was treated by Gulbrandson conversional method. To the author's knowledge, this represents the first recorded rupture of the cervical esophagus associated with high cord lesions as a result of blunt trauma to the neck.


Moyamoya disease in black adults.

A 40-year-old hypertensive black female, who suddenly developed aphasia, lethargy, and a right hemiparesis, and a 42-year-old non-hypertensive black male, who suddenly developed intractable headache, drowsiness, and vomiting, were found by angiography to have moyamoya disease. This condition is characterized by a decreased caliber of the internal carotid arteries and bilateral occlusion of the anterior and middle cerebral arteries with visualization of an extensive collateral network of tortuous blood vessels of the rete mirabile type at the base of the brain.


Colorectal carcinoma: a review of the experiences at Hubbard Hospital.

The records of 112 patients treated for carcinoma of the colon at Hubbard Hospital between 1956 and 1971 were reviewed. The mean age was 64.4 years and 64.9 percent were females. Only 27 percent presented with Duke's A lesions. The delay in seeking medical therapy averaged 4.48 months from onset of symptoms. Most patients presented with complications of their disease and the majority had other concurrent diseases which contributed significantly to the poor overall five-year survival figures.


Management of tuberculous pneumothorax in Nigeria.

Forty-eight patients with tuberculous pneumothorax treated at the University College Hospital in Ibadan, Nigeria, over a 40-month period were reviewed. This represents 90 percent of all patients admitted with nontraumatic "spontaneous" pneumothorax during the period of survey. This finding shows that pulmonary tuberculosis (still endemic in Nigeria) is the most common cause of spontaneous pneumothorax in Ibadan.Because of delay in presentation, over 70 percent of the patients presented with hydropneumothorax or pyopneumothorax, which tend to prolong the length of intubation days and the period of hospitalization. The most significant factors affecting prognosis are nutritional status of the patient, extent of parenchymal damage, severity of the bronchopleural fistula, and presence of empyema.The goal of therapy had been directed toward prompt intercostal tube drainage, complete evacuation of fluid and pus, improvement in the nutritional status of the patient, and effective chemotherapy. With this approach, open thoracotomy was rarely indicated and decortication was only necessary in five patients. Our results with intercostal tube drainage and chemotherapy alone have been very encouraging.


Transitional cloacogenic carcinoma of the anus and rectum: report of three cases.

Transitional cloacogenic carcinoma of the anus is one of the rarest tumors of the alimentary tract. It represents less than two percent of all anorectal cancers. Three cases are presented from the surgical files of George W. Hubbard Hospital, Meharry Medical College, which were collected during a period of 15 years.


Cystadenoma and cystadenocarcinoma of the pancreas.

Cystadenomas and cystadenocarcinomas of the pancreas are rare, with few cases encountered by any one surgeon or institution. Cystadenomas account for less than ten percent of all cystic lesions of the pancreas with less than 300 examples reported in the literature. Cystadenocarcinomas represent one percent of all pancreatic cancers with very few cases reported.This report is a presentation of a 48-year-old black female who was treated at Meharry Medical College for cystadenocarcinoma of the pancreas, and is followed by a review of the world literature.


Retained surgical sponge simulating a pancreatic mass.

An abdominal mass evaluated angiographically suggested either a carcinoma or a pseudocyst of the pancreas. Exploratory laparotomy revealed a cystic mass containing a surgical sponge left in the patient's abdomen during a surgical procedure 12 years previously. A review of the literature is included and complications caused by surgical foreign bodies and means of avoiding such complications are discussed.


Duodenum inversum.

Duodenum inversum is usually associated with chronic abdominal pain which is of unknown etiology. Incomplete rotation of the bowel may be associated with this anomaly. An unusually high incidence of pancreatitis, elevated bilirubin, and hypoalbuminemia was noted in this series of nine patients.


Cardiopulmonary parameters and prognosis after severe multiple trauma.

Comprehensive cardiopulmonary and metabolic monitoring of severely traumatized patients for 7 days from the time of injury has allowed us to determine parematers which correlate with survival and nonsurvival. The earliest and most persistent change is an increased pulmonary vascular resistance which results in right heart overload and failure. Left heart "failure" which has been previously described with acute respiratory failure and shock is shown to be a mathematical artifact caused by dilatation of the right heart and encroachment on left ventricular filling volume. Causes of death in most patients were not directly referable to right heart dysfunction but we postulate that hypercoagulability and microembolism could independently produce the observed pulmonary vascular changes as well as the multiple organ failure which usually was responsible for death. Resolution of this question will require more sophisticated hematologic evaluation.


Selective hepatic artery ligation: limitations and failures.

The hospital records of 540 consecutive patients with hepatic trauma were reviewed. Persistent arterial bleeding from hepatic wounds was encountered in approximately 10% of severe liver injuries. Compression of the porta hepatis will result in cessation of bleeding in such patients and subsequent ligature of the appropriate lobar artery will provide permanent, safe control of bleeding. Failures of selective hepatic artery ligation commonly result from incomplete diagnosis of the extent of injury to portal veins and hepatic veins.