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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 433 records · Page 24Linked to original sources

Red blood cells, a source of factors which induce Neisseria gonorrhoeae to resistance to complement-mediated killing by human serum.

Lysates of guinea pig or human red blood cells (RBC) contain far more of the factors that induce resistance in gonococci to complement-mediated killing by fresh human serum that do plasma or serum. As was previously found with serum, most of the resistance-inducing activity of guinea pig RBC lysates was found in ultrafiltrates with molecular weights of less than 5000. In contrast, and as with human serum, most of the resistance-inducing activity of human RBC lysates did not pass ultrafilters which removed molecules of less than 5000 daltons, although some active material of low molecular weight was present.

Animals↗

Alteration of pyocin-sensitivity pattern of Neisseria gonorrhoeae is associated with induced resistance to killing by human serum.

A laboratory-grown strain of Neisseria gonorrhoeae, selected in vivo, BS4 (agar), is susceptible to complement-mediated killing by fresh human serum but is relatively resistant to killing by human phagocytes. It can be induced to serum resistance by incubation with a small molecular weight fraction of guinea pig serum. The serum-susceptible and induced-resistant forms show differences in pyocin sensitivity tests. This indicates either differences in the structure of their lipopolysaccharides or masking of some determinant(s). The pyocin sensitivity pattern of BS4 (agar) is only slightly different from that of a closely related strain, BSSH, which is more susceptible to killing by human phagocytes.

Bacteriocins↗

The biochemical challenge of microbial pathogenicity.

In the past decade there has been a revival of interest in microbial pathogenicity. The reasons for this revival are two-fold. First, infectious disease is still with us despite the impact of the antibiotic era; for example, the rise of bacterial and fungal infections in compromised patients and the lack of a good general antiviral drug. Second, the subject of microbial pathogenicity is ripe for application in techniques of biochemistry, molecular biology and genetics that have developed in other areas of biology over the past twenty years; and the potential of these techniques is particularly attractive to young people, who are entering the field in increasing numbers. In this lecture I shall survey the methods and difficulties of investigating microbial pathogenicity and what we know of the main aspects of the subject at the molecular level. I shall use bacteria as examples because more is known about them than other types of microbes. Lack of space prevents quoting original papers in such a wide-ranging task; in most cases reference is made to authoritative reviews.

Adhesiveness↗

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

A 75,000-dalton protein complex involved in DNA binding during transformation was purified from membranes of competent Bacillus subtilis cells. Previous results (Smith et al., J. Bacteriol. 156:101-108, 1983) showed that the complex contained two polypeptides, polypeptide a (molecular weight, 18,000; isoelectric point, 5.0) and polypeptide b (molecular weight, 17,000; isoelectric point, 4.7) in approximately equal amounts. In the present experiments the two polypeptides were extracted from two-dimensional gels and studied separately and in combination with respect to DNA binding and nuclease activities. For DNA binding the interaction of both polypeptides was required. DNA binding occurred efficiently in the presence of EDTA. Nuclease activity was restricted to polypeptide b. The nucleolytic properties of b were identical to those of the native 75,000-dalton complex. Polypeptide a affected b by reducing its nuclease activity. Analysis of the nuclease subunit b on DNA-containing polyacrylamide gels revealed nuclease activities at four different molecular weight positions. These activities were identical to the major competence-specific nuclease activities which were previously implicated in the entry of donor DNA during transformation (Mulder and Venema, J. Bacteriol. 152:166-174, 1982). These results indicate that the 75,000-dalton protein complex is composed of two different competence-specific polypeptides involved in both binding and entry of donor DNA. The possible roles of the two polypeptides in the transformation of B. subtilis are discussed.

Bacillus subtilis↗

Induction by human serum of resistance to serum in Neisseria gonorrhoeae: A clinical survey of patients with gonorrhoea.

Serum from 74 female and 170 male patients with gonorrhoea and from 72 male and 123 female controls was tested for its ability to induce in gonococci resistance to complement mediated killing by human serum. We confirmed two findings of a previous survey: firstly, a higher percentage of serum samples from women suffering their first infection than from female controls induced high resistance; secondly, no serum sample taken from infected women with complications (mainly salpingitis) induced high resistance. The number of serum samples from female patients with repeat infection was too small for conclusions to be drawn. In men, however, there were no significant differences between patients and controls, or between patients with first or repeat infection, in the percentage whose serum induced high resistance. The pattern of these results on the induction of resistance to serum correlates with the general clinical aspects of gonococcal infections; namely, wide clinical differences in symptoms in women contrasting with a more uniform pattern in men.

Blood Bactericidal Activity↗

Intracranial meningioma unmasked by elective general anesthesia: report of three cases.

Three cases of intracranial meningioma unmasked by elective general anesthesia are reported. In each case, the meningioma was either asymptomatic or so subtly symptomatic that no suspicion of intracranial tumor had been entertained preoperatively. Each patient presented with failure to wake up after routine general anesthesia for a nonneurosurgical procedure. The management of unexplained failure to wake up after uncomplicated general anesthesia is discussed. Early computed tomographic scanning and neurosurgical consultation are suggested in such situations.

Aged↗

The role of cellular susceptibility in the declining severity of respiratory influenza of ferrets with age.

A comparison was made, both in vivo and in organ culture, between newborn (1-day-old) and suckling (15-day-old) ferrets of lower respiratory tract tissue infected with a virulent strain (clone 7a) of influenza virus. Newborn ferrets were killed by influenza virus following intranasal inoculation but suckling ferrets were almost as resistant as adult ferrets. In newborn ferrets there was a rapid, severe and progressive infection of lung tissue with infection of alveolar cells as well as those of bronchial and bronchiolar epithelium (assessed by monitoring virus infectivity and by fluorescent antibody staining). In suckling ferrets, as previously shown for adult animals, the lung infection was less severe, less persistent and confined to the epithelium of bronchi with only a small bronchiolar involvement and even less alveolar cell infection. These differences observed in vivo were repeated in organ cultures obtained from various areas of the lung. i.e. alveolar and airway epithelial cells of newborn ferrets exhibited a greater susceptibility than those of older ferrets. Thus, it appears that one factor determining the greater susceptibility of the lower respiratory tract of newborn ferrets is a greater inherent susceptibility of alveolar and airway epithelial cells to infection with influenza virus. Other factors may also be involved and have yet to be investigated.

Aging↗

The role of lung development in the age-related susceptibility of ferrets to influenza virus.

Newborn (I-day-old) ferrets died following intranasal inoculation of influenza virus (clone 7a) but suckling (15-day-old) ferrets were almost as resistant as adult ferrets. Many of the deaths in newborn ferrets were consequent upon an increased lower respiratory tract infection. One reason for the latter was an increase in susceptibility of both ciliated epithelium and alveolar cells in newborn ferret lungs when compared with the corresponding cells in adult and suckling ferrets (Coates et al. 1984). Work reported here shows that the lungs of newborn ferrets possess a greater proportion of ciliated epithelium-lined airway in comparison with the lungs of suckling and adult ferrets. This situation might also contribute to the increased susceptibility of the lower respiratory tract although the difficulties of assessing this influence precisely are discussed. In addition, the occlusion of the narrower airways of the immature lung in the infected newborn ferret contributes to the increased respiratory complications.

Age Factors↗

Rocket-ship psychophysics. Assessing visual functioning in young children.

A set of psychophysical procedures is described for rapidly measuring visual functions such as spatial contrast sensitivity, flicker fusion, and rod and cone two-color increment thresholds in young children. The psychophysical procedures, disguised as electronic space games, use a forced-choice paradigm combined with the method of descending limits. Because children enjoy the tasks and are highly motivated, the tests yield good sensory thresholds in a short period of time. However, when thresholds from 6-8-year-old children are compared with those of adults, the children have slightly higher thresholds for all of the functions tested. The differences are ascribed to the tendency of children to adopt a guessing strategy when stimuli are close to threshold.

Adolescent↗

Drug reservoirs in topical therapy.

The nictitating membrane, corneal epithelium, and corneal stroma were investigated as drug reservoirs. A hydrophilic drug, D,L-epinephrine HCl, or a lipophilic drug, chloramphenicol, was applied topically to rabbit eyes. Tissue levels of radioactive drug-plus-metabolites and unmetabolized epinephrine were assayed up to 24 hrs later. On a per-mg-tissue basis, concentrations of epinephrine-plus-metabolites in the stroma-endothelium were similar to or higher than those in the epithelium. The percentages of radioactivity representing unmetabolized epinephrine in the stroma-endothelium were found to be similar to or higher than those in the epithelium. On a per-mg-tissue basis, concentrations of chloramphenicol-plus-metabolites were significantly higher in the epithelium than in the stroma-endothelium during the first 130 min after drug application. While the physical properties of these drugs determined whether a higher concentration was found in the epithelium or stroma-endothelium, the ninefold greater mass of the stroma-endothelium made it the major drug reservoir on a per-whole-tissue basis. The presence or absence of a nictitating membrane had little effect on the level of either drug in the epithelium, stromal-endothelium, or aqueous humor.

Animals↗

Role of maternal immunity in the protection of newborn ferrets against infection with a virulent influenza virus.

Intranasal infection of newborn ferrets with a virulent strain of influenza virus invariably resulted in their deaths following virus replication to high titre in both lung and nasal turbinates (Collie et al., 1980). However, a similar challenge of newborn ferrets born to mothers immunized by infection with virulent or attenuated viruses resulted in complete protection; no virus replicated in their lungs and little or no virus was isolated from their nasal turbinates. Protection appeared to be antibody-mediated since it was sub-type-specific and milk-derived since newborn ferrets born to non-immune mothers but fostered onto immune mothers exhibited a similar level of protection to neonates born to and suckled by immune mothers.

Animals↗

Bias in treatment assignment in controlled clinical trials.

Controlled clinical trials of the treatment of acute myocardial infarction offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment. A group of 145 papers was divided into those in which the randomization process was blinded (57 papers), those in which it may have been unblinded (45 papers), and those in which the controls were selected by a nonrandom process (43 papers). At least one prognostic variable was maldistributed (P less than 0.05) in 14.0 per cent of the blinded-randomization studies, in 26.7 per cent of the unblinded-randomization studies, and in 58.1 per cent of the nonrandomized studies. Differences in case-fatality rates between treatment and control groups (P less than 0.05) were found in 8.8 per cent of the blinded-randomization studies, 24.4 per cent of the unblinded-randomization studies, and 58.1 per cent of the nonrandomized studies. These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration.

Clinical Trials as Topic↗

Ultrastructural features of phagocytosis and intracellular killing of Candida albicans by mouse polymorphonuclear phagocyte monolayers.

Phagocyte monolayers provided a simple method of following ultrastructural events associated with phagocytosis and intracellular killing of Candida albicans. Preformed monolayers of mouse polymorphonuclear (PMN) phagocytes attached to glass coverslips were incubated with blastospore phase C. albicans and then examined by scanning and transmission electron microscopy. Scanning electron microscopy revealed phagocytosis of C. albicans by mouse phagocytes. Ingestion of the organism was facilitated by the production of lamellipodia by the phagocytes. Transmission electron microscopy revealed complete phagocytosis of C. albicans and the fusion of lysosomal granules with loose and tight phagosomes. Ingested C. albicans remained structurally intact after 2 hr incubation in blastospore-free medium. However, cytoplasmic alterations were clearly evident, with a patchy loss of electron density. Alterations of the blastospore cell wall were also observed, with complete disruption of the plasma membrane but the wall remaining morphologically intact.

Animals↗

Social class as a prognostic variable in acute lymphoblastic leukaemia.

We studied the relationship between social class and prognosis in children with acute lymphoblastic leukaemia. Seventy children who were commencing on curative therapy, and who received central nervous system prophylaxis, were included in the study. Children from social classes 1 to 5 had a significantly better five-year survival rate and duration of first remission than children from social classes 6 and 7. There was no apparent difference either in the treatment given to the two groups or in the clinical and haematological parameters studied. A study of the causes of this difference in survival could lead to better over-all results in the treatment of childhood leukaemia.

Black or African American↗

Association of adrenocorticosteroid therapy and peptic-ulcer disease.

We reexamined the association between corticosteroid therapy and subsequent peptic ulceration or gastrointestinal hemorrhage by pooling data from 71 controlled clinical trials in which patients were randomized to systemic corticosteroids (or ACTH) or to nonsteroid therapy. Of 3064 steroid-treated patients evaluated for peptic ulcer, 55 (1.8 per cent) had ulcers, as compared with 23 of 2897 controls (0.8 per cent) (relative risk, 2.3; 95 per cent confidence interval, 1.4 to 3.7). Of 3135 steroid-treated patients evaluated for gastrointestinal hemorrhage, 78 (2.5 per cent) had bleeding, as compared with 48 of 2976 controls (1.6 per cent) (relative risk, 1.5; 95 per cent confidence interval, 1.1 to 2.2). The incidence of ulcers varied directly with the dosage of steroids. When separate analyses were performed for studies that were double-blind, used only oral steroids, used only parenteral steroids, or excluded patients with a history of ulcer, the trend remained consistent but did not always reach statistical significance. This study strongly suggests that corticosteroids do increase the risk of peptic ulcers and gastrointestinal hemorrhage.

Adrenal Cortex Hormones↗