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Biomedical subjects

J S Schultz

Publications and source records attributed to J S Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1986

Kinetic analysis in single, intact cells by microspectrophotometry: evidence for two populations of erythrocytes in an individual heterozygous for glucose-6-phosphate dehydrogenase deficiency.

A microspectrophotometric technique was used to measure the kinetics of methemoglobin reduction in intact, unaltered human erythrocytes. Reduction was catalyzed by endogenous NADPH-methemoglobin reductase in the presence of Nile Blue. The technique was applied to the study of erythrocytes from a female donor with decreased glucose-6-phosphate dehydrogenase (G-6-PD) activity. The individual was shown to be heterozygous for deficiency of G-6-PD. The kinetic study revealed two distinct populations of erythrocytes that were nearly equal in number. One cell population showed reduction rates between 0 and 25% of normal, whereas the second cell population displayed rates within the range seen for normal cells. Single-cell indices of cell size, cell hemoglobin content, and ratio of cell hemoglobin to cell size did not correlate with single-cell reduction rates and were not significantly different between the two populations. These results provide quantitative support for the X-inactivation hypothesis in G-6-PD deficiency.

Adult↗
PubMed1986

Accelerated autoimmune disease and lymphoreticular neoplasms in F1 hybrid PN/NZB and NZB/PN mice.

This report describes the first studies of inheritance of autoimmunity in inbred Palmerston North (PN) mice, a model of systemic lupus erythematosus (SLE). Mating of PN mice with the nonautoimmune DBA/2 strain produced evidence that PN disease had a recessive mode of inheritance. When PN mice were crossed with autoimmune NZB mice, female offspring from both crosses developed anti-DNA antibodies and died prematurely with vasculitis, renal disease, and lymphomas. In contrast, reciprocal hybrid males had different patterns of mortality; PN/NZB males from the PN female X NZB male mating had moderately prolonged life spans, whereas NZB/PN males from the opposite cross (NZB female X PN male) had prolonged survival to the mean age of 104 weeks. To determine if testicular hormones were solely responsible for increased longevity in hybrid males, PN/NZB and NZB/PN mice were castrated at 2 weeks of age and compared to sham-operated littermate controls. Prepubertal castration did not influence longevity in PN/NZB males, but loss of gonadal hormones significantly reduced life spans in reciprocal NZB/PN males. Female hybrids were not affected by oophorectomy. Because castration changed disease expression only in male hybrids from the NZB female X PN male cross, it was concluded that parentage influenced sensitivity to the protective effects of male hormones. Although surgical sterilization had disparate effects on males, castrated PN/NZB and NZB/PN males consistently outlived oophorectomized females. The lack of clear-cut reversal of disease in males subjected to early castration suggested that nonhormonal, possibly genetic, factors contributed to longevity in both groups of male hybrids.

Animals↗
PubMed1985

Exchange of macromolecules between peritoneal cavity and plasma.

The exchange of fluorescein isothiocyanate-labeled dextrans ranging in weight-averaged molecular weight from 19,400 to 160,000 and 125I-bovine serum albumin (BSA) between dialysis fluid (5% BSA in Krebs-Ringer solution) in the peritoneal cavity and the plasma was studied in anesthetized female Sprague-Dawley rats. Plasma and peritoneal samples were collected for 3-4 h after either 1) an intraperitoneal injection of dialysis fluid with tracer or 2) an intravenous injection of tracer material simultaneously with an intraperitoneal injection of dialysis solution without tracer. Analysis of the data by means of a mathematical model of the transport process suggests a functional asymmetry in transport of large molecules across the blood capillary wall. Substances injected intravenously have a net transport from the blood capillaries to the peritoneal cavity. Substances of molecular weight greater than or equal to 39,000 transport from the cavity to the plasma via peritoneal lymphatics; 19,400 molecular-weight dextran transports from the cavity to the plasma primarily via lymphatics with some blood capillary uptake. Tissue diffusivities and capillary mass transport coefficients are derived for the substances tested.

Animals↗
PubMed1985

A distributed model of peritoneal-plasma transport: analysis of experimental data in the rat.

Transport of uncharged, water-soluble substances (ranging in molecular weight from 180 to 5,000) between the fluid in the peritoneal cavity and plasma was studied in anesthetized female Sprague-Dawley rats. In certain experiments the effect of fluid shifts on the transport was observed by manipulating the effective osmotic pressure or the hydrostatic pressure of the dialysis fluid. Parameters for the distributed model outlined in previous work were obtained from the experimental data for the substances tested. Capillary membrane transport was modeled by pore theory. A single pore radius of 40 A and a pore density of 600 cm-2 were satisfactory. Tissue diffusivities for these substances were found to correspond closely to those in the literature. Additional simulations were performed with a three-compartment model and the results were compared with those of the distributed model.

Animals↗
PubMed1985

HLA-B18 is associated with decreased levels of isoproterenol-stimulated cAMP in lymphocytes.

One hundred fifty-nine individuals were typed for HLA-A and B antigens and levels of isoproterenol-stimulated, lymphocyte cAMP. No significant age, sex, or caffeine effects on the natural log of the lymphocyte cAMP variable (ln cAMP) were found. A comparison of mean ln cAMP levels between individuals who carried a particular antigen (homozygous or heterozygous) and individuals who did not carry the antigen identified a highly significant decrease in ln cAMP levels associated with the HLA-B18 antigen. We estimated that 18.9% of the variability in ln cAMP was attributable to the HLA-B18 antigen. In addition, 38% of the variability in ln cAMP was attributable to factors that aggregate in families that were independent of the HLA-B18 effect. A weaker association of A10 with lymphocyte cAMP might be due to linkage disequilibrium between A10 and B18.

Adolescent↗
PubMed1985

HLA-DR and MT associations with the clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis.

Significant HLA-DR and MT associations were observed with certain clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis (PO-JRA). An increase in the MTI frequency was found in 56 children with PO-JRA in comparison to 95 normal controls. This association was limited to children with a younger age of onset (less than 6 years) and a persistent pauciarticular course. An increase in HLA-DRW8 and a decrease in DR4 were associated with a younger age of onset and antinuclear antibody (ANA) seropositivity. In addition, an increased frequency of DR5 was seen in ANA positive children. All of these HLA-DR and MT associations were independent of coassociating Ia specificities.

Antibodies, Antinuclear↗
PubMed1985

HLA antigens, phytohemagglutinin stimulation, and corticosteroid response.

Although it is clear that the major histocompatibility complex is associated with lymphocyte glucocorticoid sensitivity in mice, there has been less evidence for a similar relationship in man. We have typed 158 individuals for: (1) 13 A locus and 16 B locus antigens, (2) degree of stimulation of their purified lymphocytes by phytohemagglutinin A (PHA), and (3) degree of inhibition of the PHA stimulation by prednisolone and prednisolone-21-hemisuccinate. In contrasts of individuals with a particular antigen (homozygous or heterozygous) with all remaining individuals, HLA-B7 was found to be associated with an enhancing effect on the log stimulation by PHA while other antigens of these series did not have significant associations. In similar contrasts, A10 was associated with a decrease in sensitivity to glucocorticoid inhibition of PHA stimulation as measured by the log I50 of the suppression of PHA stimulation. Other antigens of these series were not found to have significant associations with the glucocorticoid sensitivity of lymphocytes in this assay.

Adolescent↗
PubMed1984

A distributed model of peritoneal-plasma transport: theoretical considerations.

Transport of water-soluble substances between the peritoneal cavity and the plasma was modeled with a distributed approach. The model includes diffusion and convection through tissue as well as membrane transport across blood capillaries, which are assumed to be distributed uniformly in the tissue. Lymphatic uptake via the diaphragm is also included. Transport in the remainder of the body is modeled by a system of compartments. The resulting system of mass balances and rate equations is solved numerically to provide predictions of peritoneal volume and concentrations in plasma, peritoneal fluid, and tissue surrounding the cavity. The model sensitivity is explored by varying key parameters to determine whether the changes would have a significant effect on model output. Key parameters include peritoneal surface area, tissue diffusivity, capillary permeability, tissue void fraction, and hydrostatic and osmotic pressures in the capillaries and interstitium.

Absorption↗
PubMed1983

Hybrid immune response to parental liver tissue grafts.

Parental-to-F1-hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F1 recipients demonstrate an immunological response to the parental graft. Female F1 recipients, particularly those carrying the H-2b haplotype, respond vigorously to male parental liver grafts. However F1 female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F1 females as long as the F1 carries the H-2b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F1 and C3H.SW animals, a response which is absent in C3H females. Female F1 hybrids carrying the H-2b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F1 response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F1 hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (C3H X B6 or B10)F1 hybrids.

Animals↗
PubMed1982

Liver tissue graft rejection in murine major histocompatibility complex mutants.

Liver tissue grafts between seven H-2 mutants and their parental strains have been studied. Each of these mutants was originally identified by reciprocal mutant--parental strain skin graft rejection. However, liver grafts among mutants and parental standard strains are not uniformly rejected. Liver graft rejection also fails to correlate with mutant--parental stimulation on CML and MLC. In addition, the immune reaction pattern of female mutant animals against grafts of male liver differs from the reaction pattern found in parental standard strains. Several explanations for the differences between immune response to liver and skin grafts are proposed, including different T cell subsets involved in recognition, availability of antigenic sites to immunocompetent cells, and structural differences between mutant and parental H-2 antigens.

Animals↗
PubMed1981

HLA profile and Reiter's syndrome.

The analysis of the clinical and HLA profiles of 99 patients with Reiter's syndrome is reported. Antigen HLA-B27, which has previously been firmly associated with Reiter's syndrome, predisposes patients to develop disease features which reflect articular involvement. The HLA haplotype A2, B27 was found to be at an elevated frequency in our Reiter's syndrome sample, and the latter two antigens are also associated with a general increase in disease severity. Conversely, antigen BW35 appears to be protective against certain features of the syndrome. Patients with certain antigenic profiles (namely A2 and A3 together with B27) tend to develop certain syndrome manifestations earlier in the course of the disease than those with other antigens.

Arthritis, Reactive↗
PubMed1981

Antinuclear factors in murine alloantisera.

We have demonstrated that anti-Thy 1.1 and certain of H-2 alloantisera contain an antinuclear factor (ANF) detected by fluorescent antimouse IgG. The incidence of ANF positive antisera that we report may actually be an underestimate. ANF is present in sera not only from our laboratory but also from other sources; thus ANF is not an artifact of our laboratory. ANF is not identical to alloantibody, and the ANF appears to be of an autoimmune nature. A variety of environmental and genetic factors may influence the appearance of ANF in anti-H-2 sera, but we believe that the consistent detection of ANF in sera directed against H-2.31,34 or against H-2.4 suggest that some specific aspect of immune stimulation by these H-2 antigens, and likely by other H-2 antigenic specifications, induces the appearance of ANF. It is not known whether it is these K and D antigens or other determinants associated with the H-2 complex that may actually provide the immune stimulation for ANF induction. The particular mechanisms that may be operating to induce ANF cannot be determined at present. We are continuing with experiments to define what parameters influence the appearance of ANF in alloantisera.

Animals↗