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Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 919 records · Page 51Linked to original sources

Factors affecting complement activation by Staphylococcus aureus cell walls, their components, and mutants altered in teichoic acid.

In a previous study, Staphylococcus aureus purified cell walls (PCW), consisting of peptidoglycan (PG) plus covalently linked teichoic acid (TA), were found to be more active in complement consumption than isolated PG. Isolated TA has now been shown to be capable of activating complement. Mild sonication markedly increased the ability of PG to activate complement but had essentially no effect on the activities of PCW and TA. Optimal sonication of PG did not yield activities equal to those of PCW in dose-response and kinetic studies, which may imply that TA plays some role in complement consumption. Sonication did not lead to solubilization of PCW or PG but may have enhanced the activity of PG in complement consumption by better dispersing PG particles, thereby exposing more surface area. Lysostaphin solubilization of PCW and PG markedly decreased their activities in complement consumption. The PCW of an S. aureus TA-deficient mutant, which were mostly PG, caused similar amounts of complement consumption as the parent strain PCW. Of the treatments of PCW commonly used to isolate PG, formamide and periodate extractions in particular led to PG preparations with lower activities in complement consumption than the PCW from which they were prepared, although these activities were stimulated by sonication. When whole organisms were studied by using a TA-deficient mutant, a mutant with an additional cell surface polymer, and the TA-containing parent strains and complement consumption by these strains was compared, no difference was found in either the rate or the degree of complement activation. This led to experiments demonstrating that both material released extracellularly from staphylococci and the cytoplasmic fraction of S. aureus were active in complement consumption. The results of these experiments indicate that both physical and chemical factors must be considered in studies of complement activation by isolated bacterial cell wall components. Under certain conditions, staphylococcal TA may enhance complement activation, but studies with whole organisms clearly show that this cell wall constituent does not play an essential role in this process. In addition, studies of complement consumption with intact organisms have demonstrated that there may be contributions both from cell surface components and from material released by the cells.

Cell Wall↗

Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin.

Streptococcus pyogenes, bearing M-protein on its surface, resists opsonization by normal human serum and subsequent phagocytosis by human polymorphonuclear leukocytes. Previous studies have shown that M-protein positive organisms are poorly opsonized by the alternate pathway of complement. In an attempt to define further the role of the surface components of S. pyogenes in this process, we examined the ability of clindamycin, an antibiotic that inhibits protein biosynthesis, to alter bacterial opsonization. An M-protein positive strain of S. pyogenes was grown in varying concentrations of clindamycin at levels lower than those which inhibited growth, i.e., at levels less than the minimal inhibitory concentration. These bacteria were incubated with purified human polymorphonuclear leukocytes and peripheral blood monocytes. Significant enhancement of bacterial opsonization, phagocytosis, and killing resulted. Measurement of complement consumption and binding of the third component of complement (C3) onto the bacterial surface demonstrated that organisms grown in the presence of clindamycin activated complement more readily and fixed more C3 on their surface. Electron microscopy revealed the probable basis for these findings. Streptococci exposed to clindamycin during growth were largely denuded of surface "fuzz," the hairlike structures bearing M-protein. We conclude that the incorporation of clindamycin at concentrations that fail to inhibit growth of S. pyogenes nevertheless causes significant changes in the capacity of these bacteria to resist opsonization by serum complement. These findings support the hypothesis that M-protein inhibits bacterial opsonization by interfering with effective complement activation on the bacterial surface.

Antigens, Bacterial↗

Immune complexes facilitate uptake of antigen from the gut.

Radiolabeled DNP-ovalbumin was injected with and without DNP-specific antibody into ligated gut segments of neonatal rats. The transfer of this labeled protein to mesenteric lymph nodes and binding to gut tissue was examined. When the antigen, DNP-ovalbumin, was present in the gut in an immune complex from a selective localization of antigen in the mesenteric lymph node was observed. These data suggest that immune complexes in milk could potentially modulate neonatal immunological development.

Animals↗

Distribution of glomerular basement membrane antigens in diseased human kidneys.

We have previously shown, using high resolution epifluorescence microscopy, that heterologous rabbit antihuman glomerular basement membrane (GBM) antibody (RAHGBM) stains the GBM of normal human kidney in a bilaminar distribution along the endothelial and epithelial aspects of the GBM. In contrast, Goodpasture (GP) antibody stains a single linear component along the inner aspect of the GBM. In the present study, alterations in the staining reactivity of these components appear consistently to correlate with the known morphologic changes in various glomerulopathies. In idiopathic nephrotic syndrome, no changes from normal were observed. In membranous glomerulopathy, the inner RAHGBM antigen was preserved, but the outer antigen showed an irregular beaded alteration adjacent to membranous GBM immune deposits. In diabetic glomerulopathy, striking increase in the inner RAHGBM component was evident with markedly increased separation from the outer RAHGBM line. In membranoproliferative glomerulonephritis (MPGN), loss of the inner component but preservation of the outer RAHGBM line was evident; however, in type I MPGN, GP antigen was preserved as a single linear component, but in type II MPGN, there was splitting of GP antigen by GBM-dense deposit material into a double linear array along the endothelial and epithelial aspects of the GBM. These observations serve to substantiate our earlier findings that antigenic and nonantigenic components of the GBM are partitioned in the glomerular capillary wall; their selective characteristic alteration in various glomerulopathies additionally supports this view.

Antigens↗

Squamous cell carcinoma of the pancreas.

Epidermoid cancer of the pancreas is a rare variety of this malignancy. A case is presented. It has a characteristic angiographic appearance. Though in the past it has had a prognosis similar to the more common adenocarcinoma of the pancreas, a chemotherapeutic agent effective against epidermoid tumors at other sites has been effective in a case reported in the recent cancer treatment literature.

Aged↗

Neonatal macrosomia in maternal diabetes.

In order to determine the effect of maternal diabetes on the somatic growth of the rat fetus and to elucidate mechanisms underlying the control of fetal growth, concentrations of DNA and proteins and DNA polymerase-alpha activities in neonates were examined. The maternal status was classified as normal (no urinary glucose excretion), mildly diabetic (0.01-0.99 g/day urinary glucose), and severely diabetic (1.00 g/day or more urinary glucose). The total DNA contents in mg/neonate were 26.8 +/- 2.2 (mean +/- SEM), 31.3 +/- 2.5, and 29.4 +/- 2.7 for neonates from normal, mildly diabetic and severely diabetic mothers, respectively. The DNA polymerase activities in (cpm/g neonate) X 10(-3) for the same groups of neonates were 432 +/- 58, 1,008 +/- 74, and 888 +/- 118, respectively. These results indicate that the neonatal macrosomia disappears as the severity of maternal diabetes increases. Furthermore, DNA polymerase is one of possible biochemical sites through which macrosomia is manifested in diabetic pregnancies.

Animals↗

Temporal sequencing of verbal and nonverbal materials: the effect of laterality of lesion.

The effect of laterality of cerebral lesion on sequencing ability, which is an ability to process two or more stimulus events with respect to the order in which they occur, was examined. Patients with either left or right hemisphere lesions performed on verbal and nonverbal sequencing tasks. Left hemisphere lesioned patients were inferior to the right hemisphere lesioned patients on verbal sequencing tasks, while the right hemisphere lesioned patients were inferior to the left hemisphere lesioned patients on nonverbal sequencing tasks. Impaired performance of the right hemisphere lesioned patients on sequencing tasks raises questions with respect to the notion that sequencing per se is processed in the left hemisphere. Our results demonstrate that sequencing ability, as many other abilities, follows the rule of material-specific laterality of hemispheric asymmetry: the left hemisphere associated with verbal sequencing ability and the right hemisphere associated with nonverbal sequencing ability.

Aphasia↗

Chemotaxigenesis by encapsulated Staphylococcus aureus M.

Although encapsulated Staphylococcus aureus M is not opsonized by normal human serum, as a chemotaxigen this organism behaved similarly to an unencapsulated variant strain. For optimal chemotaxigenesis, an intact classical complement pathway was required, and C5a appeared to be the major chemotaxin.

Chemotactic Factors↗

Opsonization of four Bacteroides species: role of the classical complement pathway and immunoglobulin.

Previous investigators have suggested that opsonization of two Bacteroides species is mediated exclusively by the alternative complement pathway and requires immunoglobulins. In this study, the nature of the opsonic factors in nonimmune human serum for four species of Bacteroides was investigated by measuring uptake of [(3)H]thymidine-labeled bacteria by human polymorphonuclear leukocytes. Normal human serum, C2-deficient serum, immunoglobulin-deficient serum, and serum chelated with ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid (EGTA), MgEGTA, and ethylenediaminetetraacetic acid (EDTA) were used as opsonic sources. Heat inactivation of each of these sera significantly reduced its opsonic activity for all four Bacteroides species, suggesting that serum complement was essential for effective opsonization. All strains were opsonized in the absence of the classical complement pathway; however, kinetics studies revealed that opsonization proceeded at a significantly faster rate when the classical complement pathway was intact. Although two strains were opsonized in immunoglobulin-deficient sera, opsonization was less efficient and appeared to occur via the alternative complement pathway. Unexpectedly, all strains were well opsonized by the classical complement pathway in 10% serum which had been effectively chelated with EGTA or EDTA. The explanation for this finding is unknown; however, it is possible that cell wall cations of Bacteroides species may participate in the activation of complement in chelated serum, resulting in effective opsonization. It was also found that Bacteroides, when incubated with an Escherichia coli strain in normal serum, could compete for opsonins and thereby reduce phagocytosis of E. coli. It is possible that competition for opsonins among bacterial species contributes to the synergistic role these organisms share in mixed floral infections.

Bacteroides↗

Alterations in serum opsonic activity and complement levels in pneumococcal disease.

Pneumococcal opsonic activity and concentrations of pneumococcal capsular polysaccharide antigen, C3, C4 factor B, C3 and factor B breakdown products were measured in the serum obtained acutely from 12 patients with serious pneumococcal disease. One patient showed markedly reduced pneumococcal opsonic activity, borderline-low C3, and the presence of C3 and factor B breakdown products and died. Although eight additional patients showed depressed levels of C3 or C4 or the presence of C3 or factor B breakdown products, none had reduced pneumococcal opsonic activity. All of the three remaining patients had normal opsonic activity and C3 and C4 levels. Covalescent serum was obtained from eight patients; six had normal C3 and C4 levels, and two had persistent C4 depression. These data show that complement is activated during pneumococcal disease and suggest that extensive complement activation may impair pneumococcal opsonic activity in certain patients and thereby compromise an important host defense mechanism.

Antigens, Bacterial↗

Evaluation of irradiated mandibles using emission tomography, bone scans, and radiography.

This study compared radiographs, bone scans, and computed emission tomograms with histologic findings in irradiated mandibles of adult Rhesus monkeys. Although osteocytes were lost in the path of the beam, many vessels were partially or totally occluded, the periosteum degenerated, the marrow became fibrotic, and cancellous bone proliferated abundantly, no changes were noted with radiography, conventional bone scanning, or computed emission tomograms. These clinical methods of examination may misrepresent the true condition of irradiated bone because of inadequate sensitivity or balance among factors that control radioactive tracer uptake in bone.

Animals↗