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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 667 records · Page 37Linked to original sources

The pregnant guinea-pig as a model for studying influenza virus infection in utero: infection of foetal tissues in organ culture and in vivo.

Organ cultures of guinea-pig foetal tissues showed a similar pattern of susceptibility to influenza virus to that already observed for human (Rosztoczy et al., 1975) and ferret (Sweet, Toms and Smith, 1977) foetal tissues. Respiratory, alimentary and urogenital tract tissues were susceptible whereas neural and lymphopoietic tissues were insusceptible. However, of the foetal membranes (amnion, chorion, umbilical cord and placenta) only the chorion was susceptible, in contrast to the corresponding ferret tissues, all of which were susceptible. The insusceptibility of the placenta paralleled that of human placenta which is similarly haemomonochorial in structure. Following intracardial inoculation of high titre virus (ca 10(9-4) EBID50) into pregnant guinea-pigs virus was isolated from all foetal membranes (amnion, chorion, umbilical cord and placenta), but in low titre. Although sporadic isolations were made from foetal tissues (intestine, kidney, heart, liver and spleen) there was no evidence for viral replication in these tissues. These results are discussed in relation to possible infection of the human foetus in utero with influenza virus.

Animals↗

Investigations of reasons for the avirulence of the A7 strain of Semliki Forest virus in adult mice.

A strain of Semliki Forest virus (A7) which is avirulent in adult mice killed baby mice in a similar manner to strain V13 which was also virulent for adult mice. In the muscle and brains of baby mice A7 and V13 replicated and produced haemagglutinating activity similarly. Our previous suggestion that defective interfering particles were present in the brains of A7-infected adult mice appears not to be so. The interference formerly detected was due to an inhibitor present in brain tissue of adult and baby mice both normal and infected. Homogenates of A7-infected adult brain produced normal RNA species in BHK cells and not those characteristic of defective interfering particles. Organ culture experiments indicated that avirulence of A7 was not due to lack of release of virus from infected adult brain cells. Also, A7 as well as V13 was detected and was probably replicating in all parts of the brain and spinal cord that were sectioned and examined. Evidence is presented that suggests that the reason for the avirulence of A7 for adult mice compared with its virulence for baby mice may relate to a lower ability to replicate in brain tissue per se rather than to interaction with host defence mechanisms.

Age Factors↗

The pregnant ferret as a model for studying the congenital effects of influenza virus infection in utero: infection of foetal tissues in organ culture and in vivo.

Organ cultures of ferret foetal tissues showed a similar pattern of susceptibility to influenza virus to that already observed for human foetal tissues (Rosztoczy et al., 1975); respiratory, alimentary and urogenital tissues supported the replication of influenza virus but nervous and lymphopoietic tissues (those which, in man, are associated with foetal or postnatal abnormalities) were insusceptible. In contrast to corresponding human tissues, ferret foetal placenta and amnion readily supported viral replication although both human and ferret umbilical cord were susceptible. In limited experiments, neither the membranes nor the susceptible foetal tissues became infected after intranasal inoculation of pregnant ferrets of various gestational ages. However, after intracardial inoculation of pregnant ferrets with high titre virus (ca 10(9) EBID50) virus was isolated from both foetal membranes and foetuses. The membranes became infected at early, middle and late gestation, but virus appeared to cross the placental barrier to infect foetal tissues only in late gestation. At this stage virus could be isolated not only from those foetal tissues (respiratory, alimentary and urogenital) susceptible in organ culture, but also in small amounts from tissues which were insusceptible in organ culture (heart, lymphopoietic and nervous tissue). Virus was also isolated from foetal membranes and foetuses of late gestation ferrets following intracardial inoculation with a one hundred-fold lower dose of virus which, unlike the higher dose, did not induce a maternal febrile response. The pregnant ferret appears to be a suitable model for investigating the effects on development of foetal infection with influenza virus but it may have disadvantages with regard to the nature and strength of the placental barrier.

Animals↗

'Fifth pathway' in New York state medical schools.

During the academic year 1975-76, 259 students were enrolled in "fifth pathway" programs in New York and New Jersey. An analysis of students participating in programs in New York state schools revealed that a majority (87 percent) had received their undergraduate training at the Autonomous University of Guadalajara. The choice of graduate training of these students was similar to that of American graduates; however, the proportion of fifth pathway students selecting primary care specialties was significantly smaller than that of their American trained counterparts. Although the desirability of the fifth pathway has been a topic of frequent discussion, it is anticipated that for the next several years increasing numbers of students will be participants. It is, therefore, important to develop, at least on a regional level, uniform standards for admission and performance to assure the quality of this educational experience.

Career Choice↗

The formation of 2-hydroxymethylquinoline and quinaldine in greyhound urine.

2-Hydroxymethylquinoline and quinaldine are found in nonfresh greyhound urine as putrefactive bases. Their production as a function of time was investigated. This is affected by preservatives or refrigeration. 2-Hydroxymethylquinoline forms in greyhound urine, if non-preserved, in three or four days at room temperature while quinaldine takes as much as 10 days longer to form. Production of 2-hydroxymethylquinoline or quinaldine is not arrested but merely retarded by preservation or refrigeration. Sodium fluoride is one of the more effective preservatives. A method for the measurement of quinaldine and 2-hydroxymethylquinoline using gas chromatography is described. The columns used are Carbowax 6000 + potassium hydroxide on Chromosorb G and SE-30 on Chromosorb W.

Animals↗

Phytochrome-mediated assembly of polyribosomes in etiolated bean leaves. Evidence for post-transciptional regulation of development.

Light operating through phytochrome controls the proportion of total ribosomes present as polyribosomes in etiolated leaves of Phaseolus vulgaris. Similar responses but with slightly different time courses are elicited by brief red light treatment and by continuous far-red or white light. The increase in polyribosome proportions after red light treatment reaches a maximum within 2 h, after which the proportion steadily declines. Light treatment appears to lead to increased proportions of polyribosomes in higher size classes. This is most evident with continuous white light, but probably also occurs with red and far-red light. The increase in polyribosomes is due principally to cytoplasmic ribosomes although proportionately greater effects are observed in chloroplast ribosomes. Although cordycepin inhibits RNA synthesis by 85-90% within 3 h there is no depression of the light-mediated increase in polyribosome proportions when leaves are preincubated in the inhibitor for 3 h. The data therefore indicate that phytochrome is capable of controlling protein synthesis, and thus development, at a post-transciptional level.

Darkness↗

Chromophobe adenoma manifesting as a nasopharyngeal mass.

A 64-year-old woman had a sphenoid sinus tumor and nasopharyngeal mass verified to be a nasopharyngeal chromophobe adenoma with no evidence of sellar enlargement or involvement. The possibility that this mass arose from ectopic hypophyseal tissue located in the pharynx is proposed.

Adenoma, Chromophobe↗

Diabetic treatment and primary ventricular fibrillation in acute myocardial infarction.

The relation between mode of therapy and mortality rate and incidence of primary ventricular fibrillation was studied in 265 patients with diabetes mellitus and acute myocardial infarction. Sixty patients were being treated with diet only, 54 were receiving insulin and 151 were taking oral hypoglycemic agents. Fourteen patients (5.3 percent) had primary ventricular fibrillation, and all but one died. No statistically significant association was found between the incidence of primary ventricular fibrillation and the type of treatment for diabetes mellitus. Sixty-four (24.2 percent) of the 265 patients died during hospitalization. Mortality was greater among diabetic patients receiving oral therapy. However, after adjusting for age and sex, the difference among these three treatment regimens did not reach the P less than 0.05 level of significance.

Age Factors↗

Localization of phytochrome in etioplasts and its regulation in vitro of gibberellin levels.

Etioplasts isolated from barley leaves and purified on a Sephadex G-50 (coarse) column were characterized by electron microscopy and nucleic acid analysis. The majority of etioplasts retained an intact outer envelope, and contamination by other fragments was extremely low. The level of gibberellin-like substances extractable from intact etioplast suspensions was enhanced within 5 min of the termination of a saturating red irradiation, and the response was far-red reversible. Ultra-sonication caused a 3-fold increase in extractable activity both in dark control suspension and suspensions treated with red light. It is concluded that phytochrome, as a function of its interconversions, probably causes the transport of gibberellin from inside the etioplast into the surrounding medium. This leads to increased production of active gibberellins, possibly by release of feedback control of late steps of the biosynthetic pathway. Dual wavelength difference spectrophotometry has demonstrated the presence of a proportion of total cellular phytochrome within the etioplast.

Journal Article↗

Penetration of penicillin into human phagocytes containing Neisseria gonorrhoeae: intracellular survival and growth at optimum concentrations of antibiotic.

Phagocytes obtained from fresh human buffy coat (predominantly polymorphonuclear phagocytes) or from human buffy coat which had been incubated on a glass surface for 1 to 3 days (predominantly mononuclear phagocytes) were allowed to ingest gonococci, and then incubated with penicillin. More intracellular gonococci were killed at high than at low penicillin concentrations, indicating that penicillin penetrated the phagocytes. This was supported by autoradiography experiments with radiolabelled penicillin. A pilated, small-colony-forming gonococcal strain survived and multiplied for at least 15 h in polymorphonuclear phagocytes which were incubated with penicillin at the optimum concentration for killing the extracellular bacteria but not the intracellular ones; whereas a non-pilated, large-colony-forming strain survived for only 10 h. The former strain survived for at least 6 h in similar experiments with mononuclear phagocytes. Intracellular survival and in growth may be an important facet of the pathogenicity of gonococci.

Cell Membrane Permeability↗

Resistance of Neisseria gonorrhoeae grown in vivo to ingestion and digestion by phagocytes of human blood.

Attempts to study quantitatively the phagocytosis of gonococci from urethral pus failed because of the small numbers of organisms and technical difficulties. However, gonococci from chambers implanted subcutaneously in guinea pigs, which were similar to gonococci from urethral pus in their resistance to killing by human serum, were obtained in sufficient quantities for comparison in phagocytosis tests with the in vitro grown strains from which they were derived. Microscopic and viable counts of gonococci in phagocytes showed that in vivo grown organisms (strain BSV) were readily phagocytosed by human polymorphonuclear phagocytes. There was little difference betweee to ingestion. There was, however, a marked difference in the intracellular survival of strains BSV and BS during the first hour of phagocytosis. Whereas BSV organisms survived well, many BS organisms were killed. Subsequently, strain BSV and the survivors of the strain BS inoculum responded similarly to the intracellular bactericidins. These results were supported by electron microscopy of infected phagocytes. Resistance of gonococci in vivo to ingestion and digestion by human phagocytes seem to be important facets of the pathogenesis of gonorrhoea.

Humans↗

Morphological, biological and antigenic properties of Neisseria gonorrhoeae adapted to growth in guinea-pig subcutaneous chambers.

Gonococci (strain BS3) passaged three times and harvested directly from plastic chambers implanted subcutaneously in guinea pigs were compared with the parent strain (BS) grown in vitro. The strain grown in vivo produced smaller colonies than that grown in vitro and when examined directly in chamber fluid was sometimes not pilated. It was more resistant to the bactericidal action of human serum and more infective for guinea-pig chambers. In gel diffusion, extracts of the organisms adapted in vivo and cultured once on agar appeared to contain one or two antigens that were different from those in extracts of the in vitro grown organisms; and on polyacrylamide gels, electrophoresis of similar extracts showed one or more protein components for strain BS3 which were not seen for strain BS. Gonococci grown in guinea-pig subcutaneous chambers appear to be suitable for studies on the determinants of gonoccal pathogenicity.

Animals↗

Resistance of Neisseria gonorrhoeae to ingestion and digestion by phagocytes of human buffy coat.

In tests in vitro with the phagocytes of human buffy coat, a recent isolate of Neisseria gonorrhoeae, which was pilated, formed small colonies and resembled the virulent Kellogg type 2 (strain BS), resisted ingestion more than did another isolate (strain AL), which was non-pilated, formed large colonies and resembled the avirulent Kellogg type 4. Some members of both strains survived for significant periods within the phagocytes in test conditions that tended to minimise rather than maximise such survival; and strain BS had a greater capacity for intracellular survival than strain AL, with some of its members surviving for at least 8 h. Resistance to phagocytic ingestion is one important invasive mechanism of gonococci, and resistance to phagocytic digestion may also play a role in pathogenicity.

Cell Count↗