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Biomedical subjects

M B Goldman

Publications and source records attributed to M B Goldman.

At least 73 records · Page 4Linked to original sources

Radioactive iodine therapy and breast cancer. A follow-up study of hyperthyroid women.

A follow-up study of 1,762 hyperthyroid women who were treated at the Massachusetts General Hospital Thyroid Unit between 1946 and 1964 was conducted. The average length of follow-up was 17.2 years. A 1978 mailing address or a death certificate was located for 92% of the women, and 88% of 1,058 living patients responded to a mail questionnaire. The standardized mortality ratio (SMR) for all causes of death was 1.3 (95% confidence interval (CI) 1.2-1.4). The standardized mortality ratios for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.7-1.1) and 1.3 (95% CI 0.8-1.9), respectively. More deaths than expected were observed from endocrine and metabolic diseases (SMR = 1.8, 95% CI 1.2-2.7), circulatory system diseases (SMR = 1.4, 95% CI 1.3-1.6), and respiratory system diseases (SMR = 1.9, 95% CI 1.3-2.6). The standardized incidence ratios (SIR) for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.8-1.1) and 1.2 (95% CI 0.9-1.5), respectively. A nonsignificant excess breast cancer risk was observed 10 years after the onset of thyroid symptoms and was present at the end of 30 years of observation. A statistically significant excess number of pancreatic cancer cases (SIR = 2.0, 95% CI 1.0-3.7) and a nonsignificant excess of brain cancer cases (SIR = 2.3, 95% CI 0.7-5.3) were observed. Eighty per cent of the women were treated with radioactive iodine. When age at treatment and year of treatment were controlled, women who were ever treated with radioactive iodine had a standardized rate ratio for breast cancer of 1.9 (95% CI 0.9-4.1), compared with those who were never treated with radioactive iodine. Women who developed hypothyroidism as a result of their treatment for hyperthyroidism did not have an increased risk of developing breast cancer (SIR = 1.1, 95% CI 0.8-1.6).

Adult↗

Effects of anti-C4 antibody on complement production by splenic and peritoneal macrophages.

We have previously shown that administration of anti-C4 antibody to cells in culture can suppress the synthesis and secretion of C4. Lymphoid cells must be present along with the C4 secreting macrophages to achieve suppression of full magnitude and long duration. In this publication we have demonstrated that treatment of peritoneal macrophages with intact anti-C4 antibody results in reduction of intracellular and secreted C4. Intracellular levels of pro-C4 rapidly returned to normal after removal of the suppressing antibody and extracellular levels of C4 secreted into the media returned to normal within 24-48 h. This is in marked contrast to our previously published results with splenic fragments where intracellular pro-C4 remained markedly reduced long after removal of anti-C4. Using pulse-chase experiments we now demonstrate that, after recovery from suppression, intracellular pro-C4 levels remain low in splenic macrophages because nascent C4 is processed through the cell more rapidly. This results in a smaller intracellular pool of C4, even in the face of normal or high levels of C4 synthesis in the postsuppression phase. Finally, we demonstrate that suppression of full magnitude and duration could only be achieved with intact anti-C4 antibody. F(ab')2 fragments were not capable of inducing complete suppression.

Animals↗

Differential memory function with dopaminergic versus anticholinergic treatment of drug-induced extrapyramidal symptoms.

Nine chronic schizophrenic patients being treated with high-potency antipsychotic medication and antiparkinsonian agents were enrolled in a double-blind, crossover trial comparing amantadine and trihexyphenidyl. Memory function was assessed with the Rey Auditory-Verbal Learning Test during each 6-week drug trial. The subjects performed significantly better while receiving amantadine. Examinations of computed tomographic studies of seven subjects revealed a significant inverse correlation between ventricle size and memory while they were taking trihexyphenidyl but not amantadine. This suggests that patients with underlying brain pathology may be particularly vulnerable to the memory-disrupting effects of anticholinergic agents.

Adult↗

The relationship of tubal infertility to barrier method and oral contraceptive use.

We studied past contraceptive use in 283 nulliparous infertile women who had a diagnosis of tubal adhesions or occlusion and in 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with barrier contraceptive use or oral contraceptive use was calculated using multivariate logistic regression to control for confounding by region, age, religion, education, smoking, number of sexual partners, time since menarche, and use of other contraceptive methods. Women who had ever used barrier methods of contraception were at a significantly decreased risk of tubal infertility (relative risk = 0.6; 95% confidence limits, 0.5 and 0.8). When type of barrier method used for the longest time was evaluated, those who used the diaphragm or condoms plus spermicides were at lower risk than those who used condoms or spermicides alone. Overall, past use of oral contraceptives neither increased nor decreased a woman's risk of tubal infertility, but there was evidence that the association between oral contraceptives and tubal infertility may vary by the amount of estrogen and type of progestogen in the oral contraceptive used. We conclude that contraceptive users who use barrier methods that combine both a mechanical and chemical barrier, such as diaphragms, cervical caps, and condoms plus spermicides, have the clearest protection against tubal damage.

Adult↗

The role of lymphoid cells in antibody-induced suppression of the fourth component of guinea pig complement.

Many laboratories have demonstrated that immunoglobulin production by B cells is controlled by networks of interacting lymphocytes and their products. Our laboratory has demonstrated that complement components produced by macrophages are also regulated by networks of interacting cells and humoral factors. Treatment of mice in vivo or guinea pig cells in vitro with anticomponent antibody specifically inhibits synthesis and secretion of the component by macrophages. We have further characterized the cellular basis for in vitro suppression of the fourth component of guinea pig complement. C4 suppression has been accomplished with dispersed spleen cells as well as intact splenic fragments. This facilitated examination of the cells responsible for long-term C4 suppression. The data suggested that C4 suppression required either cell contact or sufficient concentrations of soluble factors. Long-term suppression of C4 depends upon a lymphoid cell contained in the spleen and in lymph nodes but absent or in insufficient concentration in the peritoneum. The lymphocyte that actively maintains suppression was negative for the guinea pig T-cell marker detected by the monoclonal antibody mc8BE6. Therefore, the critical cell is either another T-cell subset or non-T lymphocyte. These data demonstrate that a network of interacting cells analogous to that proposed to regulate antibody synthesis is also involved in regulating some nonlymphoid cell products.

Animals↗

Murine sex-limited protein expression requires androgens and pituitary hormones.

Levels of the murine sex-limited protein (Slp) were measured by an enzyme-linked immunosorbent assay in normal and hypophysectomized female CDF1 (Slpa) mice before and after a 15-day treatment with testosterone proprionate. Both groups of mice initially had undetectable levels of circulating Slp. After treatment, Slp serum levels of the nonhypophysectomized group had risen significantly above the Slp serum levels of the hypophysectomized group and the pretreatment controls. This indicates that the pituitary gland is necessary for the androgen-induced expression of Slp.

Animals↗

Demeclocycline improves hyponatremia in chronic schizophrenics.

Serum sodium concentration increased significantly in eight hyponatremic schizophrenic subjects treated with demeclocycline. The incidence of severe hyponatremic episodes was significantly reduced. The authors argue that mild impairments in urinary dilution contribute to water intoxication in most chronic psychotics who develop this syndrome. Demeclocycline may help these patients.

Adult↗

Antibody-induced suppression and postsuppression stimulation of complement in vitro. III. Long-term C4 suppression is actively maintained by a soluble suppressor factor (FsC4).

Previous work in our laboratory established that individual complement components can be regulated in vivo by administration of specific antibody or immunocompetent cells to newborns and in vitro by administration of specific antibody to cultured peritoneal macrophages or splenic fragments. Antibody-induced suppression of C4 was much longer lasting in cultured guinea pig splenic fragments than in cultured guinea pig peritoneal macrophages, suggesting that splenic fragments contained elements necessary for long-term suppression that were not present in the macrophage monolayers. This publication presents data in support of this concept. Antibody-treated splenic fragments from normal guinea pigs--but not from C4-deficient guinea pigs--elaborated a soluble factor (FsC4) that suppressed C4 production in previously untreated splenic fragments. FsC4 activity was most potent in splenic fragment culture supernatants at those times when intracellular and secreted C4 hemolytic activity and C4 antigen were at their lowest. C4 itself or a fragment of C4 was therefore unlikely to mediate suppression in this system. Residual anti-C4 antibody was ruled out as a mediator of FsC4 activity since it was shown by two independent methods that the amount of anti-C4 antibody carried over with the supernatant was orders of magnitude less than the amount necessary to cause suppression or to neutralize fluid phase C4 in fresh splenic fragment cultures. Preliminary data revealed that FsC4 activity may be mediated by two or more distinct molecular species or may be mediated by a single molecule that exhibits secondary size and charge heterogeneity. The identification of factors that are capable of regulating C4 suggests that, as with immunoglobulins, complement components may be regulated by complex networks of immunocompetent cells and their soluble products.

Animals↗

Enhancement by cyclic AMP of antibody-induced suppression of the fourth component of complement.

Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.

1-Methyl-3-isobutylxanthine↗

Antibody-induced suppression and postsuppression stimulation of complement in vitro. II. Intracellular and extracellular changes in C4 during long-term C4 suppression in guinea pig splenic fragments.

Suppression of the synthesis of the fourth component of complement in vitro was originally accomplished by exposing cultured guinea pig peritoneal cells to anti-C4 alloantisera. When guinea pig splenic fragments were used instead of peritoneal cells, equivalent antibody treatment produced C4 suppression of significantly longer duration, lasting weeks instead of days after removal of antibody. As with peritoneal cell monolayers, antibody treatment induced specific suppression of C4 followed by nonspecific stimulation of C4 and other proteins such as C2. Although IgG2 is more readily sequestered by splenic tissue, both IgG1 and IgG2 antibodies were effective in inducing and maintaining suppression. Experiments with radiolabeled antibody demonstrated that a small amount (less than 5%) of the original dose of antibody was retained by the splenic fragments. Because there was no continuous slow release of that antibody, long-term suppression of C4 cannot be explained as a fluid-phase neutralization reaction. Because antibody treatment might induce production of aberrant C4 molecules with no functional activity, C4 antigens was also studied. Tissue culture supernatants were assayed by using an ELISA for C4. In none of these experiments was extracellular C4 antigen detectable immediately after antibody treatment. Extracellular and intracellular C4 were immunoprecipitated from biosynthetically labeled tissue cultures and analyzed by SDS-PAGE. Antibody treatment suppressed intracellular C4 as well as extracellular C4. Although extracellular C4 levels of antibody-treated cultures eventually returned to levels comparable to untreated cultures, intracellular C4 levels of treated fragments remained lower than controls for the full period of observation (22 days). Therefore, a short (4-day) exposure to anti-C4 antibody induced long-term effects that profoundly altered regulation of C4 synthesis and secretion by cultured splenic macrophages.

Animals↗

Enhancement of macrophage survival and complement production by factors from cloned T cells.

The addition of supernatants of some cloned mouse T cell lines to guinea pig peritoneal cells in tissue culture increased the production of the second (C2) and fourth (C4) components of complement as well as the enzyme beta-glucuronidase. Enumeration of cell populations demonstrated a simultaneous increase in cell survival. Supernatants that augmented functions of the cultured cells were obtained after alloantigen stimulation of a T cell line of C57BL/6 origin termed L2, but supernatants from a variant cell line derived from L2 and termed L2V had no effect. A delay of as little as 24 h in the addition of L2 T cell factors at the start of the cultures markedly diminished the effects on the cultured cells that were ordinarily observed 1-2 weeks later. These experiments suggest that, in this xenogenic system, complement-enhancing activity is part of a general stimulation of macrophages by cloned T cell factors.

Animals↗

Intermittent neuroleptic therapy and tardive dyskinesia: a literature review.

Many authorities advocate neuroleptic-free periods for patients on chronic neuroleptics as a means of reducing the incidence or severity of tardive dyskinesia. This practice continues, despite the absence of any controlled clinical studies showing that intermittent therapy reduces the incidence or progression of tardive dyskinesia. After reviewing the pertinent clinical and animal literature, the authors conclude that there are few data to support the use of intermittent therapy as a means of reducing tardive dyskinesia and, in fact, evidence suggests it may increase the risk of persistent tardive dyskinesia.

Animals↗

Genetic control of C6 polymorphism and C6 deficiency in rabbits.

The genetic control of the sixth component of complement (C6) in rabbits has been studied by quantitation of C6 functional and antigenic levels and identification of polymorphism by isoelectric focusing (IEF) in gels. Patterns of inheritance of C6 variants in families carrying a silent gene for C6 were examined, and it was found that 3 common plasma phenotypic variants, C6 A, C6 B, and C6 QO were under the genetic control of allelic genes, C6*A, C6*B, and C6*QO. In IEF patterns, C6 A could be identified by its isoelectric point that was slightly more acidic than that of C6 B. C6 QO was undetectable because it lacked functional and antigenic activity. The C6*A/C6*B genotype displayed a mixed IEF pattern with bands characteristic of both C6 A and C6 B. Functional and antigenic levels of C6 that were found in heterozygous C6*A/C6*QO and C6*B/C6*QO rabbits were approximately one-half of the C6 levels found in the corresponding homozygous animals. The phenotypic variation closely resembles that previously observed in humans and rhesus monkeys, as well as preliminary data in rabbits. The patterns of inheritance indicated that the two common C6 structural genes and the deficiency gene were allelic variants at the same genetic locus.

Animals↗