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Biomedical subjects

M B Goldman

Publications and source records attributed to M B Goldman.

At least 19 recordsLinked to original sources
PubMed1992

T lymphocytes mediate immunologic control of C3 gene expression.

Immunologic control of C3 gene expression by tissue macrophages can be accomplished by treatment of spleen fragments with anti-C3 antibody. We now demonstrate that suppression of C3 requires participation of T lymphocytes of both the CD4+ and CD8+ phenotypes. Pretreatment of splenic tissue with anti-Thy-1.2 monoclonal antibody blocks the ability of the anti-C3 antibody to induce C3 suppression. Reduction in either the CD4+ or CD8+ subpopulations of T lymphocytes also abrogates C3 suppression demonstrating that both T cell subsets are required in addition to the inducing antibody. Artificially elevating intracellular levels of cAMP with cholera toxin can partially substitute for the effects mediated by T cells in this reaction. Therefore, normal expression of the C3 gene can be suppressed by a regulatory network that requires the presence of a specific inducing antibody and T lymphocytes of both the CD4+ and CD8+ subsets. This regulatory network has many similarities to regulatory networks that have been well documented in suppression of specific murine immunoglobulin allotypes.

Animals↗
PubMed1992

Repetitive behaviors in chronically institutionalized schizophrenic patients.

Repetitive dysfunctional behaviors (e.g., polydipsia, bulimia, hoarding, mannerisms) are frequently observed in chronically institutionalized schizophrenics, cause significant morbidity and are readily reproduced in animal models. The goal of this study was to assess the frequency and severity of these behaviors. Thirty-two chronic schizophrenics on an extended treatment unit were rated on the Elgin Behavioral Rating Scale, which includes eight repetitive behaviors and eight positive and negative symptoms. Forty-seven percent of the patients exhibited at least one severe, or 2 moderate, repetitive behaviors, while 63% exhibited at least one severe or 2 moderate positive or negative symptoms. The mean total score (+/- SD) on the eight repetitive behaviors (10.3 +/- 6.1) was about 2/3 that for the eight positive and negative symptoms (15.3 +/- 8.9, t = 4.1, p = .0001). Interrater reliability for the repetitive behaviors was similar to that for the positive and negative symptoms. Repetitive behaviors were positively related to male gender, white race and total length of hospitalization. Repetitive dysfunctional behaviors are frequently observed and can be reliably rated in chronically institutionalized schizophrenics.

Adult↗
PubMed1992

Benign thyroid diseases and the risk of death from breast cancer.

A survey of the causes of death among women with benign thyroid disease was conducted to assess the risk of breast cancer mortality in thyroid patients. The study population was all women diagnosed with one of several types of thyroid disease at the Massachusetts General Hospital Thyroid Clinic from 1925 to 1974. A population-based comparison group was matched to the Clinic patients for age and socioeconomic status, resulting in a total of 9,520 matched pairs. A search of the Massachusetts mortality records located death certificates for 10.9% (1,039) of the Thyroid Clinic patients and 10.5% (995) of the comparison women. Cancer was the cause of death in 21% (218) of the Thyroid Clinic patients and 24% (239) of the comparison women. Fewer patients than comparison women died from cancers of the digestive organs (30.2 vs. 45.5%), but more patients died from thyroid cancer (3.7 vs. 0%), lymphatic and hematopoietic cancers (11.5 vs. 4.2%), and cancers of other sites (8.3 vs. 3.8%). Breast cancer deaths accounted for 21.6% of cancer deaths in the patients and 22.2% of cancer deaths in the comparison women. When specific thyroid diagnoses were considered, the percent of all deaths due to breast cancer ranged from 1.9 to 5.6%, compared to 5.3% in the comparison women. Of the diagnostic groups studied, patients with Hashimoto's thyroiditis had the lowest percent of deaths due to breast cancer, while those with nontoxic nodular goiter had the highest.

Adult↗
PubMed1991

Immunologic control of C3 gene expression in tissue macrophages.

Antigenic suppression of individual complement components can be induced when newborn animals or cells in tissue culture are treated for a period of time with antibody directed against that component. The initial exposure to antibody induces a network involving regulatory lymphocytes and soluble factors. Antigenic suppression has been accomplished either in vivo or in vitro with all three members of the evolutionarily related family C3, C4, and C5. In this report we have demonstrated that antigenic suppression is mainly the result of posttranscriptional regulation. After antibody treatment is terminated, during a period in which C3 protein is undetectable by sensitive assays, C3 mRNA is often briefly increased, after which it is modestly reduced. Therefore, the major mechanisms mediating immunologic control of C3 synthesis and secretion are not directly related to steady-state levels of C3 mRNA. The initially increased levels of C3 mRNA prove that there is no simple direct quantitative relationship between C3 mRNA and C3 synthesis and secretion. The later decreases in C3 mRNA levels are not sufficient to explain the quantitatively greater decreases in C3 synthesis. Therefore, the rate determining step in immune regulation of C3 production occurs after transcription. Regulation could be mediated by altered stability of C3 mRNA in the presence of antibody, formation of a defective primary transcript, defective processing of the transcript resulting in an abnormal mRNA, or a defective C3 translational apparatus. Although regulation is multifactorial, interference with translation is most likely to predominate.

Animals↗
PubMed1991

Subfertility and the risk of low birth weight.

OBJECTIVE: We evaluated the association between subfertility and low birth weight infants. DESIGN: Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes. SETTING: Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980. PATIENTS, PARTICIPANTS: Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year). MAIN OUTCOME MEASURE(S): The relative risk of low birth weight was estimated using the cumulative incidence risk ratio. RESULTS: After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4). CONCLUSIONS: In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth.

Coffee↗
PubMed1991

A rational approach to disorders of water balance in psychiatric patients.

Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-induced disorders of water balance, which include excessive water intake, excessive water excretion, and impaired water excretion. Patients with these disorders manifest polydipsia and polyuria with or without symptomatic hyponatremia (low serum sodium concentration). Other serious sequelae include life-threatening water intoxication. The author reviews the physiology of normal water balance and the mechanism, causes, clinical presentation, and diagnosis of disorders of water balance. Interventions must first focus on identifying reversible factors. Medication-induced water imbalance can usually be reversed without compromising treatment of the underlying psychiatric disorder. A fully effective treatment for idiopathic polydipsia has not been found, although providing optimal treatment for the underlying psychiatric disorder often helps. Monitoring changes in body weight, in conjunction with measures of serum sodium, prevents water intoxication.

Drinking↗
PubMed1990

Cancer mortality in women with thyroid disease.

A retrospective follow-up study of 7338 women with either nontoxic nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, or no thyroid disease was conducted. All women patients at the Massachusetts General Hospital Thyroid Clinic who were seen between 1925 and 1974 and who were treated for a minimum of 1 year were traced. A total of 2231 women (30.4%) were dead and 2012 women (27.4%) were alive as of December 31, 1978. Partial follow-up information was available for the remaining 3095 women (42.2%). The average length of follow-up was 15.2 years. When losses to follow-up were withdrawn at the time of their loss, the standardized mortality ratios (SMR) for all causes of death were 1.2 [95% confidence interval (CI), 1.1-1.3] for women with nontoxic nodular goiter, 1.2 (95% CI 1.0-1.3) for those with thyroid adenoma, 1.4 (95% CI 1.3-1.5) for women with hyperthyroidism, 1.5 (95% CI 1.3-1.7) for hypothyroid women, 1.2 (95% CI 0.9-1.5) for those with Hashimoto's thyroiditis, and 1.5 (95% CI 1.4-1.6) for those without thyroid disease. For deaths from all cancers, the standardized mortality ratios were 1.5 (95% CI 1.2-1.8) for women with nontoxic nodular goiter, 1.5 (95% CI 1.1-1.9) for those with thyroid adenoma, 1.2 (95% CI 1.0-1.4) for women with hyperthyroidism, 1.0 (95% CI 0.7-1.4) for the hypothyroid women, 1.2 (95% CI 0.7-2.1) for those with Hashimoto's thyroiditis, and 1.3 (95% CI 1.0-1.5) for those women without thyroid disease. When specific cancer sites were studied, excess numbers of deaths were observed from breast cancer in women with nontoxic nodular goiter (SMR = 1.6, 95% CI 1.0-2.6) and from lymphatic and hematopoietic cancer in women with nontoxic nodular goiter (SMR = 2.4, 95% CI 1.2-4.3) and thyroid adenoma (SMR = 2.7, 95% CI 1.1-5.2). An increase in thyroid cancer risk was observed in women with thyroid adenoma (SMR = 11.7, 95% CI 1.3-42.1) but was based on only two deaths. In hyperthyroid women, statistically significant increases in the number of deaths were observed from pancreatic cancer (SMR = 2.6, 95% CI 1.4-4.3) and respiratory cancer (SMR = 2.2, 95% CI 1.3-3.5), but not breast cancer (SMR = 1.3, 95% CI 0.8-1.8). When the data were stratified by the time between the onset of thyroid symptoms and death, a nonsignificant excess number of cancer deaths was observed in hyperthyroid women who died 20 or more years after their symptoms began.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1988

Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia.

Water intoxication is a serious problem in many patients with chronic psychiatric illness. In an effort to determine the mechanism of this disorder, we investigated the osmoregulation of water intake and antidiuretic function in psychiatric patients with polydipsia and hyponatremia and in matched controls with psychiatric illness but neither polydipsia nor hyponatremia. We found that a water load suppressed plasma osmolality and vasopressin and urine osmolality in both groups, but that urinary dilution and free water clearance were impaired in the patients with hyponatremia, even though plasma levels of vasopressin and solute clearance were similar in the two groups. Moreover, during water loading and infusion of hypertonic saline, the plasma level of vasopressin was higher at any given plasma osmolality in the test patients than in the controls, indicating a downward resetting of the osmostat. Patients' estimates of the amount of water they desired were shown to correlate significantly with the amount of water consumed and, at any given level of plasma osmolality, appeared to be higher in the test patients than in the controls. We conclude that psychiatric patients with polydipsia and hyponatremia have unexplained defects in urinary dilution, the osmoregulation of water intake, and the secretion of vasopressin.

Adult↗
PubMed1988

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↗
PubMed1988

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↗