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Biomedical subjects

J L Stewart

Publications and source records attributed to J L Stewart.

At least 37 records · Page 2Linked to original sources

Hearing loss and otitis media on Guam: impact of professional services.

In less than two decades, there has been a dramatic reduction in the prevalence of otitis media and perforations among Guam's school-aged children. In addition, hearing loss due to chronic middle ear disease as a cause of disqualification from military service has dropped from a first rank order cause to next-to-last. However, there has been no reduction in the prevalence of otitis media in the preschool population. The reduction in chronic ear disease is the result of improved access to primary care, intensive hearing screening, wide availability of audiologic diagnostic and follow-up services, and comprehensive otologic care. It is essential that these services continue to be available to Guam's children to avoid a reversal of these dramatic gains. Attention must now focus on how to achieve similar gains for Micronesian children who remain restricted in their access to these resources.

Adolescent↗

The medical home and PL 99-457 in Hawaii.

The concept of the "medical home" was adopted by the Hawaii Medical Association and the Hawaii Chapter of the American Academy of Pediatrics in the Child Health Plan over 10 years ago. The medical home is an integrated system of services that focuses on the well-being of the child, within the context of the family. Primary health care under the medical home would be continuous and comprehensive, addressing the needs of the whole child. It would provide coordinated care that is family-centered, community-based. Several recent publications have emphasized the importance of the medical home in providing access to a continuum of medical and health services to enable young children to develop and maintain a state of optimal health.

Child↗

Evidence that C5b recognizes and mediates C8 incorporation into the cytolytic complex of complement.

The aim of this study was to identify constituents of the intermediate C5b-7 complex of human complement that mediate binding of C8 and formation of C5b-8. Analysis of interactions between purified C8 and C5, C6, or C7 indicate that C5 and C8 associate to form a dimer in solution. This interaction is specific and involves a single C5 binding site located on the beta-subunit of C8. Simultaneous interaction of C8 with C5 and C9 in solution suggests that during assembly of the cytolytic C5b-9 complex on membranes, C8 binds to C5b-7 through association of beta with C5b, after which C9 associates through interaction with the previously identified C9-specific site on the alpha-subunit. Other evidence of interaction with C5b was provided by the fact that C8 can bind purified C5b6. Also, in situ cross-linking experiments showed that within C5b-8, the beta-subunit is in close proximity to C5b. These results indicate that C8 binding to C5b-7 is mediated by a specific C5b recognition site on beta, thus explaining the requirement for this subunit in C5b-8 formation. They also reveal that C5b contains a specific site for interaction with beta.

Binding Sites↗

Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8.

The basis for the physical association between C8 and C9 in solution was examined by isolating the noncovalently associated alpha-gamma and beta subunits of C8 and determining their respective affinities for C9. Results indicate that only alpha-gamma associates with C9 and this association, though reversible, is complete at near equimolar ratios of each component. Further experiments using purified alpha or gamma revealed that only alpha was capable of forming a stable complex with C9. Although the strength of this interaction was dependent on salt concentration, association was observed in buffer of physiological ionic strength and in human serum. These results establish that the domain on C8 responsible for interaction with C9 is located entirely within alpha. In related experiments, addition of beta to performed dimers of either (alpha-gamma + C9) or (alpha + C9) resulted in complete association of this subunit. These particular results indicate that there are two physically distinct sites on alpha that separately mediate association of alpha with beta and with C9. Furthermore, occupation of one site does not impair interaction at the other.

Complement C8↗

Prevalence of otitis media in selected populations on Pohnpei: a preliminary study.

There are no previously published studies on the prevalence of otitis media in Micronesia. As part of an Otitis Media Workshop to train health care workers from the Federated States of Micronesia in the identification and treatment of otitis media, 5-point prevalence studies were conducted to explore the prevalence of otitis media in infants, Head Start, elementary and secondary age students. The results showed an especially high prevalence among the visualized tympanic membranes of the well infants, with 46-47% of the infants showing evidence of otitis media. Of the 1338 ears visualized, 985 or 74% were within the range of normal. Two-hundred and sixteen, or 16% showed evidence of extensive past or mild present disease, with the remaining 10% showing active disease. There were a total of 31 perforations among the 779 persons examined between the ages of two months and twenty-five years, representing 4% of the ears examined. The perforation rate for this population was 39.79 per 1000. The results are discussed as well as their implications for developing areas with limited resources for primary, secondary and tertiary health care.

Adolescent↗

Measurement of the ratio of the eighth and ninth components of human complement on complement-lysed membranes.

The mole ratio of the eighth (C8) and ninth (C9) components of human complement on membranes carrying the cytolytic C5b-9 complex was measured by direct binding assays. Erythrocytes from two different species were used as the membrane system. Antibody-treated sheep erythrocytes carrying a relatively small number of precursive membrane-bound C5b-7 complexes were prepared by exposure to human C8-depleted serum. These complexes were subsequently converted to C5b-8 by addition of saturating amounts of C8. Parallel binding assays using 125I-C8 were used to determine the exact amount bound and thus the number of C5b-8 complexes per cell. These cells were subsequently incubated with excess 125I-C9 and the amount bound relative to C8 on the membrane was measured. Results indicated the C8:C9 ratio remained constant at approximately 1:4 as the number of complexes varied from 40 to 310 per cell. Similar results were obtained regardless of whether C8 and C9 were added sequentially or simultaneously to cells bearing C5b-7. For comparison, experiments were also performed using membranes that contained a high number of complexes. Here, rabbit erythrocytes which carried approximately 25 000 C5b-7 per cell were incubated with limited amounts of C8 to form C5b-8 complexes on the membrane surface, the exact number of which was measured by 125I-C8 binding assays. When erythrocytes prepared in this manner were incubated with excess 125I-C9, the ratio of C8:C9 on the membrane was found to be essentially constant at approximately 1:3 as the number of these complexes varied from 50 to 4000 per cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of prenatal exposure to structurally diverse chemicals on the ontogeny of rat dehydrogenases.

Activity levels of sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in the livers and brains of rats treated prenatally with 3,4,3',4'-tetrachlorobiphenyl (4CB, 3 mg/kg/day), diethylstilbestrol (DES, 10 micrograms/kg/day), zeranol (ZN, 4mg/kg/day), and cadmium (Cd, 25 mg/kg/day) and compared with enzyme levels for control groups. Enzyme activities were measured at days 15, 17, 19, and 21 prenatally, and days 1, 5, 10, 21, 35, and 56 postnatally. SDH activity was not altered by treatment with 4CB, DES, or ZN, but Cd produced reduced levels in both liver and brain of sexually mature offspring. The patterns of LDH and G6PDH, including sexual differentiation of the latter in adult liver, were not affected by any of the treatments in either tissue. The developmental profiles of each of these enzymes in untreated animals is unique, suggesting that a similar catalytic mechanism is not a factor in determining the patterns of their developmental accumulation.

Animals↗

Studies of the association of the eighth and ninth components of human complement within the membrane-bound cytolytic complex.

The association of the eighth (C8) and ninth (C9) components of human complement within membrane-bound C5b-9 was investigated using the photosensitive cross-linking reagent N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate. Reaction of this reagent with either the purified alpha-gamma or beta subunit of C8 resulted in the introduction of 6-8 mol/mol of photosensitive 6-(4'-azido-2'-nitrophenylamino)hexanoate (ANH) as an intrinsic ligand on each protein. The resulting ANH-(alpha-gamma) or ANH-(beta) was capable of recombining with equimolar amounts of beta or alpha-gamma, respectively, to yield ANH-C8. Parallel modifications of purified C9 resulted in incorporation of 3-4 mol/mol of ANH-ligand. Both ANH-C8 and ANH-C9 retained their ability to incorporate into C5b-9. Two approaches were used to determine the proximity of C8 subunits to C9 within C5b-9. In one, the complex was assembled on erythrocytes by incubating EAC1-7 cells separately with each form of ANH-C8 and subsequently saturating with 125I-C9. After lysis, membranes were irradiated, solubilized, and analyzed by gel electrophoresis. Cross-linking was assessed by a shift in electrophoretic mobility of 125I-C9 to a higher molecular weight. Results using either form of ANH-C8 in C5b-9 showed that, although at least 30% was involved in cross-linking, none was cross-linked to C9. Similar results were obtained using a second approach in which cross-linker and radiolabel were transposed between C8 and C9. Here, EAC1-7 cells were incubated first with 125I-C8 containing either 125I-(alpha-gamma) or 125I-(beta) and subsequently with ANH-C9. Although at least 48% of ANH-C9 in C5b-9 was involved in cross-linking in these experiments, no cross-linking to either subunit of C8 was detected. These results suggest that C8 is not in close physical association with C9 within membrane-bound C5b-9.

Azides↗

Indicators of developmental toxicity following prenatal administration of hormonally active compounds in the rat. II. Pattern of maternal weight gain.

Chronic prenatal exposure of rats to diethylstilbestrol, zeranol, or 3,4,3',4'-tetrachlorobiphenyl produced quantitative and qualitative differences in the cumulative pattern of weight gain during pregnancy. Each of the three compounds, however, exhibited unique characteristics with respect to the effect of increased dose on this response, as well as in the relationship of reduced weight gain to perinatal mortality. The weight deficit after diethylstilbestrol treatment was found to reside in the dam herself, not in any compartment of the gravid uterus. The pattern of maternal weight gain is a useful indicator of developmental toxicity permitting discrimination among structurally diverse chemical agents.

Animals↗