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Biomedical subjects

J Goldman

Publications and source records attributed to J Goldman.

At least 163 records · Page 9Linked to original sources
PubMed1989

Changes in calcium homeostasis during aging and Alzheimer's disease.

Several observations indirectly suggest that intracellular calcium regulation may be altered by aging and Alzheimer's disease. Thus, calcium homeostasis was examined directly in skin fibroblasts from Alzheimer's patients and compared to cells from normal young and elderly controls. Alterations in both bound and free calcium were noted; cells from Alzheimer's donors have higher levels of bound calcium but lower concentrations of free intracellular calcium when compared to cells from young and normal aged donors. These changes in calcium homeostasis may be physiologically significant, since processes that require transient elevations of intracellular free calcium, such as cell spreading, decline in the Alzheimer's cells. In summary, cultured skin fibroblasts from normal aged and Alzheimer's patients demonstrate deficits in calcium homeostasis and other metabolic processes when compared to cells from young donors.

Aging↗
PubMed1989

Role of the newborn's sex in mixed maternal-newborn lymphocyte culture reactivity.

One-way-stimulated mixed mother-newborn lymphocyte cultures (MMNLC) from male and female newborns were evaluated and compared shortly after delivery. Newborn sex-correlated differences were observed in the strength of the MMNLC reactivity with responding maternal as well as newborn cells. The reactivity of MMNLC with responding maternal cells from male as compared to female newborns was significantly less inhibited in maternal and newborn serum. The inhibitory effect of maternal serum on maternal and male newborn lymphocytes in MMNLC seems to be correlated to the sex of the previous child delivered and was significantly lower when the present as well as the previous baby were of the same sex, e.g. 2 boys. The results suggest that fetal-male-specific Y-chromosome-correlated histocompatibility antigens may specifically influence the maternal immune response to her fetus.

Female↗
PubMed1989

Lymphocyte subpopulations in mother and newborn: correlation with sex of the newborn and number of pregnancies.

T cell subsets were defined with monoclonal antibodies of the OKT series, OKT3, OKT4 and OKT8, in 23 male and 22 female newborns and in their mothers 4-10 h after delivery. The data were compared and statistically evaluated between mother and newborn, between male and female newborns as well as between parity groups. The results indicate that the distribution of OKT4 and OKT8+ cells is different in mother and newborn and a significantly increased percentage of OKT4+ cells and a significantly decreased percentage of OKT3+ cells was observed in newborns as compared to their mothers after the first and second delivery. For maternal cells from male as compared to female newborns the percentage of OKT4+ was significantly decreased after the second delivery. OKT8+ cells in the mother were significantly decreased after the second as well as after three or more deliveries of male as compared to female newborns. With increasing parity the percentage of OKT3+, OKT4+ and OKT8+ cells decreased slowly for both sexes and the difference was significant between primi- and multiparae. The present findings suggest a possible role of the newborn sex and of parity in the distribution of specific T cell subsets in mother and newborn shortly after delivery.

Antibodies, Monoclonal↗
PubMed1989

Correlation of sperm and endocrine measures with reproductive success in rodents.

This paper compares the statistical precision and biological sensitivity of multiple indices of reproductive function to infertility in the male rodent. The studies discussed include those that examined reproductive function in the male following perinatal exposure to reproductive toxicants and others in which the compounds were administered to young-adult males, often with very diverse results. For example, some chemicals that alter sex differentiation reduce fertility by affecting breeding performance alone (polychlorinated biphenyls (PCBs), fenarimol, or losulazine), without altering sperm and testicular measures. Others also markedly alter sex differentiation of the genitalia, the accessory glands and the testis in addition to their effects on central nervous system (CNS) sex differentiation and mating behavior (testosterone, flutamide, cyproterone acetate, tamoxifen, estradiol and diethylstilbestrol (DES)). In contrast, prenatal exposure to compounds that alter primary germ cell survival (busulphan, congo red) induce partial gonadal/germ cell agenesis without altering sex differentiation. These chemicals dramatically reduce testicular sperm production in the male offspring, and the most severely affected males are infertile. In a series of studies conducted in our laboratory, young male rats were exposed to known reproductive toxicants in a dose related manner from puberty, through young adulthood and breeding. We have found that the profile of effects varies considerably depending upon the chemical's mechanism of toxicity. When a compound produced infertility through direct effects of testicular function (Carbendazim (MBC) and dibutyl phthalate (DBP)), then testis weight, testicular histology, and testicular sperm head counts provided sensitive indicators of toxicity. In general, dramatic reductions in sperm production are required to induce infertility and these changes were accompanied by elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and changes in human chorionic gonadotropin (hCG)-stimulated testosterone synthesis. Chemicals that have hormonal activity, alter the internal endocrine environment, or directly effect CNS function induce a completely different profile of effects. For example, estrogen administration alters the function of the seminal vesicle and the endocrine system, and reduces epididymal sperm reserves; while testicular measures are relatively unaffected. Since very different spectrums of effects are produced by different compounds, no single endpoint will consistently be the most sensitive indicator of reproductive toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Anomalous Raji cell activity related to DNA binding in some patients with autoimmune disease.

We examined sera from patients with autoimmune disease that showed a discrepancy between the Raji cell assay and other tests for circulating immune complexes where the Raji cell activity was highly elevated. Using gel filtration chromatography, we found that the Raji cell activity was associated with monomeric IgG and little evidence of aggregates in the samples. Samples elevated for circulating immune complexes by all tests showed aggregates with associated Raji cell activity. The activity in discrepant samples was decreased by up to 40% by absorption of the IgG fraction with DNA-cellulose prior to the Raji cell assay. It is suggested that binding by autoantibodies to the Raji cell membrane is due to a variety of mechanisms.

Adsorption↗
PubMed1988

Comparative biochemical and genetic characterization of clonally related human B-cell lines secreting pathogenic anti-Pr2 cold agglutinins.

To study the biology of cold autoimmune hemolytic anemia, Epstein-Barr virus (EBV)-transformed B-cell clones were established from a patient with splenic lymphoma associated with immune hemolysis due to an anti-Pr2 cold autoantibody. Studies were performed comparing the cold autoantibody present in culture supernatants of these cell lines to the pathogenic cold autoantibodies present in the patient's plasma. Cytogenetic studies of splenic lymphocytes demonstrated an abnormal karyotype (51XX, +3, +9, +12, +13, +18). After EBV transformation, eight clones secreting IgM, kappa anti-Pr were isolated; each clone had the same abnormal karyotype as above. DNA isolated from the clones and spleen was analyzed by Southern blot hybridization with JH, C mu, and C kappa probes; identical gene rearrangements were seen in each case. Anti-Pr antibodies, isolated from culture supernatant and serum were compared by isoelectric focusing (IEF) and demonstrated similar banding patterns. Distinctive binding patterns, however, were observed in 2/8 clones, suggesting structural differences. Adsorption studies with red blood cells further showed that the observed IEF banding patterns were solely due to anti-Pr cold autoantibody. With a thin-layer chromatography method, the biochemical determinants recognized by the cold autoantibodies were defined as glycolipids containing Neu Ac alpha 2-3Gal beta 1-4Glc sequences. The data demonstrate that the autoantibodies of the EBV-transformed B-cell lines were similar to the pathogenic monoclonal serum autoantibody in both structure and specificity. These clonal cell lines may thus serve to further study the biology of human B-cell lymphomas with defined autoantibody specificity.

Adult↗
PubMed1988

The genomic breakpoint in a patient with Philadelphia-positive acute leukemia is 5' of the breakpoint cluster region.

We report a case of acute leukemia in which studies at presentation showed both myeloid and lymphoid cell surface markers. At relapse membrane markers studies were consistent with a leukemia of B-lymphoid lineage. However, immunoglobulin (Ig) and T cell receptor (TCR) beta chain genes were both found in a rearranged configuration. The majority of metaphases from the leukemic cells at presentation showed the Philadelphia chromosome, t(9;22)(q34;q11), whereas a minority were normal. At relapse both Ph-positive and -negative metaphases were still present in the bone marrow but some of the Ph-negative metaphases had acquired an additional chromosome #19 [47,XY, + 19]. Southern analysis of DNA from leukemic bone marrow cells at diagnosis showed no rearrangement of breakpoint cluster region (bcr). There was no bcr-abl chimeric mRNA typical of Ph-positive chronic myeloid leukemia (CML). However, the cells expressed an abl-related protein of Mr 190 kd with enhanced tyrosine kinase activity. Leukemic cell metaphases were studied by the technique of in situ hybridization with probes for C-lambda, sis, abl, and 5' bcr. The c-abl probe mapped to chromosome 22q11 in Ph-positive metaphases. The 5' bcr probe mapped to 9q+ in the Ph-positive metaphases and the C-lambda gene mapped to the Ph chromosome. Thus, the genomic breakpoint in this patient must lie upstream of the BCR defined by study of Ph-positive CML and downstream of the C-lambda gene locus. We speculate that the Ph-negative cells in this patient may represent a leukemic proliferation susceptible to acquisition of specific chromosomal changes.

Adult↗
PubMed1988

The development of a protocol to assess reproductive effects of toxicants in the rat.

The determination that a chemical poses a reproductive risk to man typically relies upon fertility studies using rodents. However, fertility in rodents is often difficult to disrupt and more sensitive indicators of reproductive function should be included in the risk assessment process. The present discussion compares the sensitivity of fertility to other endpoints following exposure to known reproductive toxicants. In our studies rats were dosed from weaning through puberty , gestation, and lactation. The reproductive function of the male, the female, and the offspring was assessed. The effects of methoxychlor, carbendazim (MBC), dibutyl phthalate (DBP), and lindane are discussed and compared to fertility. For each compound a ratio (SR = sensitivity ratio) of the lowest effect level (LEL) for infertility or reduced fecundity to the LEL for the most sensitive physiologic endpoint was calculated. The SR should be large when a compound produces effects over a wide range of doses, but should equal unity when the dose-response curve is very steep. For methoxychlor, which blocked implantation, pubertal landmarks and estrous cyclicity provided rapid and sensitive indicators of the subsequent reproductive failure. The SR = 8 (100/12) for methoxychlor using data from females. In contrast, DBP and MBC directly altered testicular function, and for these compounds, sperm and testicular measures provided sensitive indicators of toxicity. The SR for MBC was 2 (100/50), while DBP had a SR of 1 (500/500). In the lindane study, fertility was not reduced but most of the pups (F1) died shortly after birth. The SR for lindane is equal to 0.5 (10/20). At 20 mg/kg the treated females were larger and their estrous cycles were erratic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Improved treatment for anovulation in polycystic ovarian disease utilizing the effect of progesterone on the inappropriate gonadotrophin release and clomiphene response.

The treatment of anovulatory, clomiphene-resistant patients with polycystic ovarian disease (PCOD) is difficult. Ten such women were given progesterone, 50 mg/day i.m. for 5 days to achieve luteal phase concentrations. Immediately following progesterone treatment, plasma concentrations of FSH were reduced in all patients (P = 0.001) and seven of the 10 had reduced plasma LH concentrations. Following the withdrawal bleeding these seven all became responsive to clomiphene as shown by ovulation, and three conceived after a single progesterone/clomiphene cycle. LH pulsatility, studied in five women over 4 h, before and immediately following progesterone treatment, showed a slowing of the pulse frequency (62 +/- 26 min to 105 +/- 51 min, P less than 0.05) and an increase in pulse amplitude (6 +/- 1.9 IU/l to 16.7 +/- 20 IU/l). The LH and FSH response to GnRH was blunted by progesterone. It would thus appear that progesterone modulates LH pulsatility and reduces pituitary sensitivity to GnRH, reducing LH levels and possibly inducing more FSH synthesis and storage, similar to its action in the normal ovulatory cycle. These changes provide a more favourable environment for ovulation induction by clomiphene and we suggest that short-term progesterone treatment may be utilized to improve the efficiency and results of clomiphene treatment in PCOD.

Anovulation↗
PubMed1988

Use of minisatellite DNA probes for recognition and characterization of relapse after allogeneic bone marrow transplantation.

Restriction fragment length polymorphisms can be used to distinguish blood and marrow cells from close relatives. We used two probes that recognize a series of dispersed and highly polymorphic tandem-repetitive minisatellite regions in the human genome that can be detected via a shared 10-15 base pair core sequence similar to the generalized recombination sequence (chi) of E. coli. We have studied the resulting individual-specific DNA fingerprints in 15 patients before and after allogeneic bone marrow transplantation performed for chronic myeloid leukaemia and in two patients transplanted for acute leukaemia. Early engraftment could be demonstrated at 3 weeks post-transplant based on the recognition of cells of donor origin. One patient who failed to engraft had only recipient type marrow cells 3 months post-transplant. Nine patients who relapsed after transplantation had only cells of recipient origin. In one patient who relapsed after transplantation with T-cell depleted donor marrow, fractionation studies showed that his T-cells at relapse were of recipient origin. We conclude that these minisatellite probes are valuable for characterizing the origin of different cell populations after marrow transplantation and could be useful for characterizing relapse when donor and recipient are of the same sex.

Acute Disease↗
PubMed1988

Sialic acid content and sialyltransferase activity in lymphocytes from neonates.

Venous blood from 24 healthy volunteers, 20-40 years old, and umbilical cord blood from 28 healthy full-term neonates, immediately after delivery, was used for the determination of lymphocyte sialic acid content and sialyltransferase activity. A significantly increased content of lymphocyte sialic acid and an increased sialyltransferase activity were observed in neonates as compared to adults. It is suggested that the increased sialic acid content of fetal lymphocytes may contribute to a possible masking effect of antigenic sites on fetal immunocompetent cells.

Adult↗
PubMed1988

Erroneous results with routine laboratory testing for immunoglobulins due to interference from circulating immune complexes in a case of hyperviscosity syndrome associated with autoimmune disease.

A patient with the hyperviscosity syndrome exhibited very high concentrations of intermediate to small circulating immune complexes (CIC), involving 40-50% of the IgG present, with IgG rheumatoid factor activity. We demonstrate that precipitation of CIC by polyethylene glycol in the reaction mixture caused interference with nephelometric methods for measuring IgM and IgA, and that failure of immunoglobulins to migrate, owing to molecular interactions, caused interference with radial immunodiffusion methods. Semiquantitative values for immunoglobulins were difficult to interpret on immunoelectrophoresis. As a result, IgM and IgA could only be quantitatively estimated by an end-point nephelometric approach that included a serum blank. Immunoelectrophoresis indicated that a large proportion of the immunoglobulins behaved as aggregates. Immunofixation electrophoresis did not reveal the presence of aggregates. The polyethylene glycol-IgG test provided an accurate assessment of the CIC concentration; the Raji cell and C1q-binding assays did not. Evidently, special techniques may be necessary for accurate determination of immunoglobulin concentrations when CIC concentrations are very high.

Aged↗
PubMed1987

Antibodies against the insulin receptor in paraneoplastic acanthosis nigricans.

Acanthosis nigricans is a skin disorder associated with endocrine abnormalities, autoimmune disease, and systemic malignancies. Insulin resistance is a common accompaniment of the nonmalignant varieties of acanthosis nigricans. A 44-year-old man is described with a functioning metastatic pheochromocytoma, acanthosis nigricans, and insulin-resistant diabetes mellitus. Studies of insulin action showed a low titer of anti-insulin antibodies and a very high titer of antibodies against the insulin receptor. This case documents for the first time insulin resistance due to anti-insulin receptor antibodies in a paraneoplastic variety of acanthosis nigricans.

Acanthosis Nigricans↗