Biomedical subjects
Publications and source records attributed to C Walker.
There is no evidence to support the suggestion that a widespread programme of vision screening at age 3 1/2 should be instituted. Some of the practical problems and defects of such a programme are outlined. If the issues raised are to be resolved by further research, identification of preschoolchildren who have visual problems will be facilitated by a screening procedure involving refraction and possibly a cover test.
The effects of prostaglandin E1 (PGE1) on the adult respiratory distress syndrome were studied in the septic primate (Macaca fascicularis). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe septic shock and adult respiratory distress syndrome. Primates, if living, were killed 4 h after completion of the E. coli infusion. Three groups of primates were studied (n = 4 in each group). The control group (Group 1) received PGE1 at 100 ng/kg/min throughout the experiment. The septic group (Group 2) received a 30-min infusion of E. coli. The treatment group (Group 3) received a continuous PGE1 infusion (100 ng/kg/min) along with the E. coli infusion which was begun 30 min after the PGE1 infusion was started. Control primates had hemodynamic changes consistent with the vasodilatory effect of PGE1 (heart rate and cardiac output increased; blood pressure and systemic vascular resistance (SVR) decreased). All control animals survived the experiment and had no evidence of pulmonary damage. Primates given E. coli developed severe hypotension, decreased SVR, and lung injury evidenced by pulmonary edema, decreased oxygenation, and increased extravascular lung water. Primates treated with both PGE1 and E. coli developed similar cardiovascular and pulmonary changes as the septic group. There was no statistically significant difference between Group 2 and Group 3 animals with regard to mean arterial blood pressure, SVR, extravascular lung water, alveolar-arterial oxygen difference, or survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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The ability of the hypomethylating agent 5-azacytidine to transform normal primary rat tracheal epithelial cells was determined. A single 24-h exposure to 5-azacytidine resulted in the transformation of rat tracheal epithelial cells at concentrations of the cytosine analogue ranging from 1 to 4 microM. Doses of 5-azacytidine that produced these enhanced growth transformants were nonmutagenic as measured by the induction of 6-thioguanine or ouabain resistance. In addition, the hypomethylating agent 5-azadeoxycytidine also transformed primary rat tracheal epithelial cells, whereas 6-azacytidine, a cytosine analogue which does not induce DNA hypomethylation, did not. Enhanced growth transformants resulting from 5-azacytidine exposure continued to progress in the absence of further treatment to give rise to variants with indefinite growth capacity which ultimately became neoplastic. These results indicate that hypomethylating agents can transform normal cells and suggest that changes in DNA methylation may occur during the initial stages of neoplastic transformation.
The mammalian fetus expresses a variety of paternal histocompatible, oncofetal, and trophoblast antigens against which the mother can mount an immune response. Survival of the "fetal graft" appears to depend upon local immunosuppressive mechanisms in lymph nodes draining the uterus and at the intrauterine implanation site itself. Nonspecific not-T-Fc-receptor-bearing small lymphocytes containing cytoplasmic granules present in successfully allopregnant mice can suppress both the generation of maternal-antipaternal killer T cells and the infiltration of cytotoxic T lymphocytes into sponge-matrix allografts during the effector phase of the immune response. These suppressor cells are deficient at the implantation sites of xenogeneic and allogeneic mouse embryos that are susceptible to maternal immunity and are destined to resorb. A soluble suppressor factor of approximately 100,000 daltons in size can be obtained from the suppressor cells and acts to block the response of T cells to interleukin-2 by interfering with IL-2 receptors. The development of the suppressor cells in the decidua requires certain hormonal signals as well as signals provided by trophoblast cells. Freshly explanted or cultured murine trophoblast cell lines elaborate soluble factor(s) that are active in recruitment or activation of suppressor cells. Since suppressor cells may be isolated from decidua of successfully allopregnant humans, the suppressor cell mechanism and its regulation may represent a key factor in the protection of the "fetal allograft" from rejection by maternal immunity.
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Neutrophil granulocytes are most active producers of potentially toxic free oxygen radicals. Since other functions of granulocytes can be affected by lymphokines or monokines, we investigated whether granulocyte oxygenation activity can also be influenced by such cellular mediators. Human granulocytes emitted strong chemiluminescence after addition of culture supernatants from human mononuclear cells stimulated with bacterial lipopolysaccharide (LPS). Response of the granulocytes was dose-dependent and was inhibited up to 90% or more by superoxide dismutase. This granulocyte chemiluminescence inducer-activity (GCI-activity) in the LPS-induced supernatants was heat-labile and sensitive to trypsin treatment. Addition of cycloheximide to the cultures inhibited the generation of GCI-activity by 80%. On HPLC gel filtration GCI-activity eluted with two distinct peaks corresponding to molecular weights of 60 +/- 10 KDa and between 1 and 5 KDa. Murine interleukin 1, human recombinant interferon-alpha and -gamma were devoid of GCI-activity. When mononuclear cells were fractionated by plastic adherence or counterflow elutriation, monocytes appeared to be the source of GCI-activity. Therefore, it appears that granulocyte oxygenation activity can be enhanced strongly by a cellular mediator derived from monocytes. This interaction of monocytes and granulocytes may constitute a new and potent pathway of phagocyte-dependent production of highly reactive and potentially toxic oxygen radicals.
To analyze whether atherosclerotic risk factors, including systemic hypertension, an elevated serum cholesterol level, smoking and diabetes, were associated with the presence of aortic stenosis (AS) in adults, 105 adults who had AS without coronary artery disease (CAD) were compared with 110 control subjects who had other types of valvular disease, 170 control subjects who underwent catheterization and had neither valvular disease nor CAD, and 269 matched control subjects who underwent general surgery. When using each control group separately or in combination, no risk factor showed consistent evidence of a significant association with the development of AS. If the true magnitudes of these associations are of the order previously reported for the development of CAD, the power of our study for detecting statistical significance ranges from 56 to 99%. In a supplemental analysis, 45 cases with both AS and CAD did not have a higher prevalence of risk factors than cases without CAD. Although a weak association between atherosclerotic risk factors and AS cannot be excluded, any such association is unlikely to be as strong as for predicting CAD.
Skeletal muscle fibers developing in vitro synthesize predominantly fast-myosin light chains, with a small contribution (less than 10%) from slow-myosin light chain 2. Muscle fibers can be cocultured with a rat adrenal pheochromocytoma-derived nerve cell line (PC12) known to display properties similar to sympathetic neurons. PC12 cells cultured alone synthesize catecholamines and respond to nerve growth factor by synthesizing acetylcholine and extending neurite structures. They also synthesize significant amounts of acetylcholine in the presence of nonneuronal cell types, including muscle. When cocultures of skeletal muscle fibers and PC12 cells are established, the muscle cells respond with an increased level of slow light chain 2 synthesis. Myosin light chains were identified by two-dimensional gel electrophoresis and immunoblotting with an antiserum specific to slow light chain 2.
Eleven monoclonal antibodies, directed versus the T8 glycoprotein, were compared using enzyme digestion, phylogenetic comparisons, cross-blocking of antibody binding, and blocking of specific cell-mediated lympholysis (CML). It was found that none of the 11 anti-T8 antibodies tested define the same epitope on the T8 glycoprotein. Some of these antibodies react, however, with closely related structures, as shown by cross-blocking of antibody binding and similar enzyme sensitivity of the epitopes. Moreover, these structural related epitopes show a similar involvement in the effector phase of CML reactions, since the antibodies to these neighboring epitopes inhibit the same CML reactions. Thus, it is possible to apply structural and functional criteria to define "regions" on the T8 glycoprotein, some of which are consistently involved in CML reactions, some never, and some of these regions appear to be involved in specific effector-target cell combinations only.
The ability of cyclosporin A (CS-A) to inhibit induced lymphocyte activation and to modify expression of membrane receptors was assessed on human T helper cells. Flow cytometric cell cycle analyses of acridine orange-stained cells showed that CS-A (0.5 micrograms/ml) inhibits the G0-G1 activation process of a substantial proportion of PHA- and Con A-stimulated lymphocytes. The expression of Tac, OKT9 and 4F2 antigens (previously shown to be expressed or increased on activated cells) was investigated by immunofluorescence. Fewer cells expressed the Tac and OKT9 antigens after activation in presence of CS-A, but the percentage of 4F2-positive cells remained unchanged. Analyses of receptor densities measured by fluorescence intensity revealed for all three investigated antigens a decreased receptor density on positive cells in presence of CS-A. Thus, CS-A not only inhibited cell activation (G0-G1 transition) and the expression of Tac, OKT9 and 4F2 antigens, but it also diminished the number of Tac, OKT9 and 4F2 antigens per cell. Assessing specifically the activation of OKT4 (helper) and OKT8 (cytotoxic) cells after 24 h, either by double-fluorescence or by cell fractionation with anti-OKT4 or anti-OKT8 antibodies plus complement, showed that preferentially OKT4 cell activation as well as expression of Tac and OKT9 antigens on those cells was inhibited in the presence of CS-A.
Frequency and severity of nausea and of vomiting during pregnancy, and of pronounced dietary cravings and aversions, were determined in a series of South African rural and urban black, Indian, coloured (European-African-Malay) and white women. Frequency of severe nausea ranged from 3.8% in rural blacks to 19.8% in white women, and of severe vomiting from 3.1% in rural blacks to 17.8% in white and Indian women. Proportions in the other groups were intermediate. Pronounced cravings, claimed by 67-84% in the various groups, included sour, savoury and sweet foods, also fruit and milk. Aversions were claimed by 45-81% of the women in the different groups with meat, fish, coffee and fatty foods, the foods most often avoided. Pica, the consumption of such substances as earth, clay, varied ethnically and regionally; frequency was high in rural and urban black women (44.0% and 38.3%), but much lower (5%) in Indian, coloured and white women.
Mutants of Escherichia coli K-12 deficient in L-serine deaminase (L-SD) activity have been isolated. These strains required thiamine and grew normally when it was provided. The decrease in L-SD activity caused no obvious metabolic deficiency. A study of revertants and transductants showed that a single mutation was responsible for the thiamine requirement and for the decrease in L-SD activity.
Escherichia coli L-serine deaminase (L-SD) in crude extracts made in glycylglycine could be activated by incubation with iron sulfate and dithiothreitol. This activation could also be demonstrated in vitro in two mutants which were physiologically deficient in L-SD activity in vivo. This suggests that these mutants were deficient not in L-SD but in an enzyme(s) activating L-SD. The suggestion is made that production of a functional L-SD in vivo requires activation of the structural gene product by an enzyme or enzymes that reduce the protein to an active form.
Spectacle correction of unusually hypermetropic refractions from age 1 year did not reduce the incidence of squint or amblyopia, nor did it lead to a reduction in the severity of residual amblyopia after subsequent occlusion.
The purpose of this study was to evaluate the use of clindamycin hydrochloride as an adjunct to conventional periodontal therapy in the treatment of patients who had previously been unsuccessfully treated with scaling, periodontal surgery and the use of tetracycline. Thirteen patients with a history of "refractory" periodontitis were thoroughly scaled and monitored by repeated attachment level measurements for the presence of active destructive periodontitis. Disease activity was defined as a 3-mm loss in attachment from baseline measurements or the occurrence of a periodontal abscess. When active disease was detected, each patient was scaled again and placed on clindamycin hydrochloride 150 mg qid for 7 days. Following the adjunctive use of clindamycin in combination with scaling, the incidence of gingival sites demonstrating active disease in the group of 13 patients decreased from an annual rate of 10.7 to 0.5%. Each patient demonstrated a decreased incidence of active sites per unit of time. Clinical parameters such as probing depth, gingival redness, bleeding on probing and suppuration showed dramatic improvement at 12 months after clindamycin therapy. The percentage of pockets with probing depths greater than 6 mm, 4 to 6 mm and 1 to 3 mm changed from 11 to 2%, 38 to 24% and 51 to 74% respectively, following clindamycin therapy as compared to scaling alone. The percentage of sites bleeding on probing decreased from 33% after scaling alone to 8% following clindamycin and scaling. Gingival redness decreased from 36 to 1% of sites. Suppuration also decreased from 8% of buccal or lingual surfaces after scaling alone to 1% of surfaces following scaling and clindamycin.(ABSTRACT TRUNCATED AT 250 WORDS)