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Biomedical subjects

R J Harbeck

Publications and source records attributed to R J Harbeck.

At least 55 records · Page 3Linked to original sources
PubMed1984

The in vivo and in vitro glomerular deposition of isolated anti-double-stranded-DNA antibodies in NZB/W mice.

Employing a hydroxyapatite double-stranded (ds) DNA column for affinity chromatography, anti-ds-DNA antibodies were isolated from the sera of aging NZB/W mice. These antibodies were radiolabeled and injected intravenously into NZB/W mice at various ages. Significant deposition of radiolabeled antibodies were shown to occur in NZB/W mice 4 months of age and older. While the injected antibodies displayed heterogeneity in their isoelectric points (pI's), those antibodies which bound to the kidney were restricted to a more alkaline pI range. Glomerular cultures were prepared from NZB/W mice at various ages and incubated with radiolabeled anti-ds-DNA antibodies with restricted pI's. Antibodies having pI's between 7 and 9 bound in vitro to glomeruli obtained from 9-month-old NZB/W mice but not to glomeruli obtained from 2-month-old mice. In contrast, antibodies with pI's between 5 and 7 were unable to bind to glomeruli obtained from either age group. An exchange between free antibodies and antibodies bound to glomeruli was also demonstrated to occur in vitro. These findings suggest the presence of subpopulations of anti-ds-DNA antibodies which preferentially bind to glomeruli containing immune complexes.

Aging↗
PubMed1983

Human tonsillar IgE biosynthesis in vitro. I. Enhancement of IgE and IgG synthesis in the presence of pokeweed mitogen by T-cell irradiation.

A study of the events regulating human IgE biosynthesis in vitro was undertaken with tonsillar lymphocytes. IgG synthesis was also studied to evaluate the specificity of our observations. T-cell irradiation significantly enhanced synthesis of IgE by pokeweed mitogen (PWM)-stimulated B cells from 12 of 18 donors and IgG in all 18 donors. This enhancement was the result of de novo immunoglobulin synthesis, since the amount of IgE and IgG spontaneously released from lysed and lysed-and-cultured mononuclear cells was significantly less than that detected in the cell cultures, and the augmentation was completely ablated by the treatment of the cells with cycloheximide or mitomycin C. Enhancement was also dependent on the presence of PWM; T-cell irradiation did not enhance IgE synthesis in unstimulated cultures. Moreover, this enhancement was also observed in the co-cultures of B cells and allogeneic irradiated T cells. These observations suggest that radiosensitive T cells exert a suppressive activity that contributes to regulation of human IgE and IgG synthesis and that the suppressor function as well as the helper function can overcome allogeneic disparities.

Adolescent↗
PubMed1983

Permeability of the blood cerebrospinal fluid barrier during acute immune complex disease.

Changes in the permeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (blood-CSF) barrier in rabbits were assessed by using a sensitive double isotope technique at different times after the induction of acute immune complex disease (AICD). Induction of AICD was done with a single large dose of bovine serum albumin, whereas controls received only saline. Animals were sacrificed 6, 9, 12, 15, and 18 days after induction. Extravasation of protein was measured by injecting rabbits i.v. with 131I-rabbit serum albumin (RSA) 24 hr before sacrifice. In order to correct for intravascular blood volume, 125I-RSA was injected 5 min before sacrifice. Extravascular blood equivalents (EVBE), a measure of barrier permeability, were elevated in the CSF of rabbits sacrificed on days 12 and 15. None of the brain regions from any of the animal groups showed any changes or significant differences from controls in EVBE values on these days. These results indicate that there was an increase in the permeability of the blood-CSF barrier to radiolabeled albumin but not in the BBB proper during the time that CSF IgG levels were elevated in AICD. The potential significance of these findings for the mechanisms mediating central nervous system involvement in systemic lupus erythematosus is discussed.

Acute Disease↗
PubMed1982

Suppression of water intake by immune complex formation in the hypothalamus. Implications for systemic lupus erythematosus.

Immune complex formation in the perifornical region of the hypothalamus resulted in depressed water consumption in rats, but did not consistently alter body temperature. The antibody with an unrelated antigen did not affect water consumption or body temperature. These results support the notion that immune complex reactions within the central nervous system can alter behavior.

Animals↗
PubMed1982

Suppressed immune response in infant monkeys associated with maternal separation.

The effect of maternal separation on an in vitro measure of the cellular immune response was studied in infant bonnet monkeys (Macaca radiata). Using a modified mixed-species separation paradigm, bonnet mother-infant pairs were each housed with a single adult female pigtailed monkey (Macaca nemestrina). Over a 14-day separation period, the infants showed a suppression of lymphocyte proliferation in response to mitogens relative to a 14-day baseline period which preceded separation. The lymphocyte response was restored following reunion. During separation, infants were initially agitated, and this was followed by observations of reduced activity and a slouched posture. Behaviors returned to baseline conditions following reunion. It was concluded that suppressed immunological functioning may be included among the pathophysiological consequences of maternal separation in infant monkeys.

Animals↗
PubMed1982

A comparison of anti-DNA antibodies from serum and kidney eluates of NZB x NZW F1 mice.

The qualitative aspects of anti-DNA antibodies from the serum and those eluted from the kidney of (NZB x NZW)F1 (B/W) mice were evaluated in terms of their class and subclass specificity, avidity and isoelectric profile. Serum anti-DNA binding was demonstrated in both the IgG and IgM classes. In addition, all subclasses of IgG studied (IgG1, IgG2a, and IgG2b) were shown to bind DNA. Avidity measurements indicate that the avidity of isolated serum IgG for 125I labeled DNA decreases with age in B/W mice, while the avidity of isolated serum IgM remains relatively unchanged. Anti-DNA antibodies eluted from kidneys were found to be predominantly of the IgG1 and IgG2a subclasses. Equal amounts of both high and low avidity antibodies to DNA were demonstrated in the kidney eluates at all ages studied. Furthermore, the dissociation curves of these antibodies remained relatively unchanged with age. The isoelectric spectrum of serum antibodies to DNA obtained from mice at 4 to 11 months of age demonstrated considerable heterogeneity covering the pH range of 6 to 8.5. In contrast, the anti-DNA antibodies eluted from the kidney are slightly more basic in nature having isoelectric points between 7.2 to 9.0. This study suggests that distinct subpopulations of anti-DNA antibodies exist and that these may play an important role in the development of murine lupus nephritis.

Animals↗
PubMed1979

Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice.

Young, syngeneic thymocytes and spleen cells were administered to F1 hybrids of New Zealand Black by New Zealand White (NZB/W) mice beginning at 3 weeks of age and were continuted at 2-week intervals for 8 to 9 months. The development of autoimmunity as assessed by measuring the incidence and level of anti-DNA antibody, the degree of renal involvement, and the survival of recipient mice was evaluated and compared to a control group of animals. No significant differences were noted in these parameters in mice receiving cell transfers as compared to the control group. Therefore, in contrast to other reports, these results suggest that the transfer of young thymus or spleen cells into aging NZB/W mice fails to influence immunoregulation and the subsequent development of autoimmunity.

Animals↗
PubMed1978

A naturally occurring antibody in New Zealand mice cytotoxic to dissociated cerebellar cells.

A spontaneously occurring antibody cytotoxic to dissociated cells of the neonate mouse cerebellum was found in the sera of some New Zealand (NZ) mice. No significant activity was found in the sera of six non-autoimmune mouse strains. The degree of cytotoxicity was similar towards both allogeneic and syngeneic cells. Absorption of the cytotoxic sera with brain and kidney homogenates removed the reactivity, while liver removed less reactivity. Absorptions with thymocytes and several other tissue homogenates and cells had no effect on the cytotoxicity levels, nor was there a correlation between the levels of thymocytotoxicity and cerebellar cell cytotoxicity. The antibody cytotoxic for cerebellar cells could not be demonstrated in the cerebrospinal fluid (CSF) of any mice examined, including a mouse with high serum cytotoxic levels. Gel filtration of reactive sera indicated that the antibody is of the IgM class.

Animals↗
PubMed1977

Central nervous system involvement in SLE. Diagnostic profile and clinical features.

The clinical course and diagnostic profile of 13 patients with central nervous system involvement and systemic lupus erythematosus (CNS-SLE) are presented. The diagnostic yield for each procedure was measured as the precent abnormal: CSF total protein was 38%; increased CSF IgG 69%; decreased CSF hemolytic C4 10%; increased CSF anti-DNA 64%; electroencephalogram 80%; flow brain scan 50%; and static brain scan 0%. No single procedure was consistently abnormal, but the battery of tests provided a useful and specific CNS-SLE diagnostic profile.

Adrenal Cortex Hormones↗
PubMed1975

The prognostic and therapeutic implications of DNA:anti-DNA immune complexes in systemic lupus erythematosus (SLE).

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.

Adolescent↗
PubMed1975

Comparison of DNA binding in normal population, general hospital laboratory personnel, and personnel from laboratories studying SLE.

Sera from 18 of 56 individuals working in SLE laboratories bound more than 30 per cent of 0.1 mug of 125-I denatured calf thymus DNA, in an ammonium sulfate precipitation assay. Only two of 58 normal non-laboratory personnel and four of 40 sera from routine hospital laboratory personnel bound more than 30 per cent. Statistical analysis of these results with the Kolmogorov-Smirnov nonparametric test indicated this was a very significant difference (p less than .001). Using native DNA as a test antigen a similar pattern was seen, but it was not as clear cut. Part of this increased reactivity is heat labile. Further studies must be carried out before an adequate interpretation of these findings is possible.

Animals↗
PubMed1975

Studies on the nature of circulating DNA in systemic lupus erythematosus (SLE).

The isolation and purification of DNA from the sera of patients with SLE is described. Buoyant density determinations of this DNA using CsCl gradients suggest in some cases that it may be of endogenous origin. DNA from the synovial fluid of an SLE patient with septic arthritis was also shown to have a buoyant density of human DNA as well as being of considerable size variation. In addition, this synovial fluid contained antibody to DNA and evidence of DNA:anti-DNA complexes, suggesting that immune complexes composed of human DNA and antibody may be involved in the pathogenesis of the arthritis. Also described are preliminary experiments characterizing the conformation of the DNA present in DNA:anti-DNA immune complexes.

Animals↗