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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 415 records · Page 23Linked to original sources

Transformation in Bacillus subtilis: further characterization of a 75,000-dalton protein complex involved in binding and entry of donor DNA.

A 75,000-dalton protein complex purified from membranes of competent Bacillus subtilis cells was previously shown to be involved in both binding and entry of donor DNA during transformation. The complex, consisting of two polypeptides, a and b, in approximately equal amounts, showed strong DNA binding as well as nuclease activity (H. Smith, K. Wiersma, S. Bron, and G. Venema, J. Bacteriol. 156:101-108, 1983). In the present experiments, peptide mapping indicated that the two polypeptides are not related. Chromatography on benzoylated, naphthoylated DEAE-cellulose showed that polypeptide b generated single-stranded regions in double-stranded DNA. A considerable amount of the DNA was rendered acid soluble by polypeptide b. The nuclease activity of polypeptide b was reduced in the presence of polypeptide a. This resulted in an increased fraction of high-molecular-weight double-stranded DNA containing single-stranded regions. The acid-soluble DNA degradation products formed by polypeptide b consisted exclusively of oligonucleotides. In contrast to its nuclease activity, which was specifically directed toward double-stranded DNA, the DNA binding of the native 75,000-dalton complex to single-stranded DNA was at least as efficient as to double-stranded DNA.

Bacillus subtilis↗

Neonatal systemic candidiasis.

Ten babies who required neonatal intensive care developed systemic candidiasis. Eight were extremely preterm (28 weeks' gestation or less) and all received prolonged ventilation, multiple courses of broad spectrum antibiotics, and intravenous hyperalimentation. Diagnosis was established by culture of yeasts from suprapubic urine specimens; venous blood cultures proved unreliable. Initial treatment with 5-flucytosine alone in eight babies and combined with amphotericin B in two, eradicated the infection in nine babies, the treatment failure arising through diagnostic delay and development of resistance to 5-flucytosine. Prophylactic topical antifungal drugs, regular screening of suprapubic urine specimens, and prompt use of systemic antifungal agents before multifocal infection becomes established may reduce the incidence and improve outcome.

Amphotericin B↗

Medical care for the poor: finite resources, infinite need.

Health care in this nation is becoming multitiered--with the poor in jeopardy of being excluded from even minimal care--because of the mistaken belief that money can buy unlimited health care for everyone. But our medical resources are finite, and choices must be made on how to distribute those resources. These choices should be based on a carefully reasoned concept of distributive justice; but even more important, they should be rooted in a Christian sense of community and in the conviction that service to others is more important than life itself. At least three basic models of justice can be identified. Market justice follows the general rule, To each according to his or her ability to pay. Merit justice holds that medical care should be apportioned relative to patients' efforts to stay healthy. Needs-based justice maintains that individuals' needs should be the sole criterion for allocating health care. Developing and testing such concepts of justice is necessary, but it is not enough. As those with economic and social power increasingly capture society's medical resources to keep their own deaths at bay through costly and extraordinary forms of treatment, Christians may well be impelled to take a stand in behalf of those who are being deprived of basic care. This stand may even include forgoing extraordinary treatment for themselves and accepting the appropriateness of their own deaths. Such a witness to the world, however, must be founded in faith and in Christian belief regarding the meaning of death.

Christianity↗

Adsorption of Trypanosoma cruzi proteins to mammalian cells in vitro.

It has previously been shown using immunological techniques that antigens from Trypanosoma cruzi adsorb to mammalian cells. Here we have used radioactively-labelled T. cruzi antigens to investigate the nature of the antigens bound. We have demonstrated that numerous T. cruzi polypeptides rapidly become adsorbed to mammalian cells in tissue culture. These polypeptides dissociate from the mammalian cells only at a slow rate. We found no indication that the binding of the polypeptides was mediated by the specific binding of any one protein.

Adsorption↗

Further studies of the reasons for the lack of alveolar infection during influenza in ferrets.

Intratracheal inoculation of influenza virus in the ferret was followed by a more severe airway infection than that produced by nasal infection and was mainly bronchiolar rather than bronchial. Also, virus isolation from the alveolar zone of the lung together with immunofluorescence and immunoperoxidase techniques showed that some virus reached the alveoli. Nevertheless, there was no subsequent alveolitis suggesting the existence of a clearance phenomenon. Alveolar macrophages were shown to have phagocytosed virus in vivo and phagocytosis studies in vitro showed that two mechanisms could operate to eradicate the virus. First, a rapid destruction of virus and second an abortive cycle of replication which produced virus antigen but not infectious virus. Experiments with large doses of virus indicated that after intranasal inoculation little virus reached the alveoli so it would probably be quickly cleared by the macrophages.

Animals↗

Paradoxical expansion of intracranial tuberculomas during chemotherapy.

4 patients with tuberculosis, 3 of whom had tuberculous meningitis, were noted to have tuberculomas on computed tomographic scanning. During antituberculous chemotherapy the intracranial lesions increased in size in all 4 patients at a time when the clinical state and cerebrospinal-fluid abnormalities were improving; in 2 of the patients the regional lymph nodes also enlarged greatly. Though the expansion of the cerebral lesions caused anxiety and led to some changes in chemotherapy, the lesions eventually diminished in size.

Adult↗

Proteolytic capacities of cystic fibrosis and control fibroblasts towards Tamm-Horsfall glycoprotein.

125I-labelled Tamm-Horsfall glycoprotein was incubated at pH 5.0 and pH 7.4 with homogenates of cultured fibroblasts from cystic fibrosis patients and controls in order to compare the total proteolytic capacities of these cells. No significant breakdown could be observed at pH 7.4. Protein degradation at pH 5.0 occurred at comparable rates in cells from patients and controls, with the possible exception of one cystic fibrosis line. Therefore, a decreased proteolytic capacity cannot be a general cellular characteristic of cystic fibrosis. Though occurrence of heterogeneity cannot be excluded, the exception probably represents just random variation.

Cells, Cultured↗

Differential replication of attenuated and virulent influenza viruses in organ cultures of ferret bronchial epithelium. Brief report.

In contrast to its abundant replication in ferret nasal epithelium in vivo and in vitro, comparable to that of the virulent strains, the attenuated influenza virus A/PR/8/34 produced much lower yields than the virulent strains in organ cultures of bronchial epithelium agreeing with its relative inability to infect the lower respiratory tract of ferrets. The replication of another attenuated strain showed different temperature characteristics in bronchial epithelium to that in nasal turbinate epithelium.

Animals↗

Testicular steroidogenic response to human chorionic gonadotropin of fifteen male transsexuals on chronic estrogen treatment.

Fifteen transsexuals were prepared for surgery with estrogen treatment. The response to human chorionic gonadotropin (hCG) in the untreated state was similar to that of normal subjects when testosterone (T), estradiol-17 beta (E2), 17 alpha-hydroxyprogesterone (17 alpha-OHP), progesterone (P), 4-androstenedione (delta 4A), and dehydroepiandrosterone (DHA) were used as indices. Following estrogen therapy, plasma T, 17 alpha-OHP, and DHA levels were markedly reduced whereas delta 4A and P were not. In spite of the suppressive effects of estrogen, a good response to hCG was noted in such subjects in plasma levels of T, 17 alpha-OHP, and, to a lesser extent, delta 4A even after estrogen administration for 24 months. The high rates of 17 alpha-OHP to T induced by estrogen treatment is restored to normal by the administration of hCG.

17-alpha-Hydroxyprogesterone↗

Prostaglandin formation in the isolated human ductus arteriosus, aorta, pulmonary and umbilical arteries.

The prostaglandins comprise a large family of substances that includes primary prostaglandins, prostacyclin and thromboxane, all of which exhibit some vascular activity. The activity of each prostaglandin may be species - and organ - dependent, and the type of prostaglandin produced in a tissue is often dependent on the presence of terminal enzyme systems in that tissue. The prostaglandin endoperoxide PGH2 serves as a common intermediate for the enzymatic production of prostaglandins, thromboxanes and prostacyclin. We have obtained information on the biosynthesis of these compounds by the human ductus arteriosus, aorta, pulmonary and umbilical arteries in vitro. Vascular tissue samples were obtained from two fetuses of 16 to 18 weeks of gestation, two newborns of 26 and 35 weeks of gestation and in nine term infants. The vascular tissue samples were incubated with [1-14C]-arachidonic acid and/or [1-14C]-prostaglandin endoperoxide (PGH2). The study demonstrates the formation of prostaglandins and prostacyclins from all the vascular tissues and the formation of thromboxanes from the umbilical artery. The study implies that the above vessels contain "prostaglandin synthetase" enzymes as early as 16 weeks of gestation.

6-Ketoprostaglandin F1 alpha↗

Dissociation of serum prolactin response to sequential thyrotropin-releasing hormone and chlorpromazine stimulation in patients with primary empty sella syndrome.

The presence of galactorrhea and/or hyperprolactinemia in patients with the primary empty sella syndrome (PESS) has been proposed to be of hypothalamic etiology. To further elucidate this possible mechanism, sequential testing of 19 subjects with PESS with 500 micrograms thyrotropin-releasing hormone (TRH), followed by the injection of 0.7 mg/kg chlorpromazine (CPZ) 150 minutes later, was compared with results obtained in 6 patients with idiopathic galactorrhea (IG) and 3 normal adult women in the early follicular phase of the menstrual cycle. The thyroid-stimulating hormone and prolactin (PRL) response to TRH was similar in all three groups. The mean maximal increase of serum PRL following CPZ, however, was 16.1 +/- 18.5 ng/ml (standard deviation) in the PESS group, whereas the mean maximal PRL response was 68.6 +/- 40.9 ng/ml in subjects with IG and 67.7 +/- 48.1 ng/ml in the seven normal women. The impaired responsiveness of CPZ in the PESS group was significant (P less than 0.05) when compared with the normal CPZ response in the other two groups. The results of this study suggest that patients with PESS may have hypothalamic dysfunction, and that sequential testing of subjects with TRH and CPZ may be of value in differentiating patients with PESS from those with IG.

Adult↗

Patterns of creatine kinase release during acute myocardial infarction after nonsurgical reperfusion: comparison with conventional treatment and correlation with infarct size.

Coronary arteriography and biplane ventriculography were performed in 51 patients during the acute (mean of 6.6 hours after onset of symptoms) and chronic (1 to 3 months after admission) phase of myocardial infarction. Twenty-four patients were treated in a conventional manner. In 27 patients, reperfusion was achieved with intracoronary streptokinase after 24 +/- 20 minutes of infusion. Peak creatine kinase and cumulative creatine kinase release were derived from serial creatine kinase measurements. Ejection fraction and the length of the akinetic or dyskinetic segments were calculated in the chronic phase. The time interval between onset of symptoms and peak creatine kinase was significantly shorter for the streptokinase-treated patients as compared with the conventionally treated patients (13.5 +/- 5.3 versus 22.9 +/- 7.4 hours, p = 0.0001). Significant linear correlations were obtained for both streptokinase-treated and control patients, relating: 1) peak creatine kinase value to both length of the noncontracting segment and ejection fraction in the chronic phase, and 2) cumulative creatine kinase release to both length of the noncontracting segment and ejection fraction in the chronic phase. Patients treated with streptokinase experienced a relatively greater release of enzyme for a given infarct size as compared with those treated in a conventional manner. The difference in enzyme release between the two groups increased as infarct size increased. These observations may be explained by enhanced washout of enzyme from the infarct zone, secondary to reperfusion after intracoronary streptokinase therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

Studies on 1,2,3-triazoles. 10. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their S-oxides.

Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that of disodium cromoglycate, the most potent being 6,7-dimethyl-9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole and its 4,4-dioxide.

Animals↗

N-benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties.

In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.

4-Hydroxycoumarins↗

Peer review using a paired-comparison technique.

A paired-comparison technique is used to enable surgical residents and attending surgeons to make peer judgments of each other. Comparative peer judgments were made in three areas: the ability of the surgeon to make a diagnosis and to decide on a plan of active medical care, the operating ability of the surgeon, and the postoperative care of the patient. This method of peer judgment ensures the confidentiality of those making the judgments, and the analysis results in a final ranking of the surgeons and surgical residents with indicated significant differences (P less than 0.05) among them. The technique also includes an assessment of how consistent each judge is in making comparisons of fellow surgeons.

Clinical Competence↗

Fractionation of guinea pig serum for an inducer of gonococcal resistance to killing by human serum: active fractions containing glucopeptides similar to those from human red blood cells.

The resistance of gonococci to complement-mediated killing by serum is important in the pathogenesis of gonorrhoea. Most urethal strains lose this resistance on subculture. The host product(s) which induces the resistance in vivo is therefore fundamental to pathogenesis. Human genital secretions and some sera induced gonococci to serum resistance in vitro. Guinea pig serum was more active than human serum and low molecular weight fractions from it conferred resistance to gonococci in 3 h at 37 degrees C. Similar active fractions were obtained from human sera. Now guinea pig serum has been further fractionated for the low molecular weight inducer by membrane filtration, gel filtration on Sephadex G25, high performance liquid chromatography (HPLC) with a Spherisorb ODS reverse phase column, chromatography on Sephadex LH20 and HPLC with a Partisil SCX cation exchange column. The small yield (less than 1 mg from 400 ml serum) of highly active material was contaminated with breakdown products from the Partisil SCX column and a mixture of compounds. However, analysis indicated the presence of one or more small glucopeptides containing cysteine, glutamic acid, aspartic acid, threonine, serine, glycine, alanine, valine and lysine. Similar glucopeptides are liberated from fresh human red blood cells in slightly hypertonic saline and samples of them induced gonococci to serum resistance.

Animals↗