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Biomedical subjects

M B Goldman

Publications and source records attributed to M B Goldman.

87 records · Page 5Linked to original sources

Estrogen profiles of primiparous and nulliparous women in Athens, Greece.

Urine estrogens of 144 primiparous women and 122 nulliparous women of similar age were measured. The primiparae were at least 6 months post pregnancy. The ratio of the estriol concentration to the sum of the concentrations of estrone and estradiol (the estriol ratio) was higher among primiparous women under 25 years of age than among nulliparous women of the same age. The difference was greater in specimens collected in the luteal phase of the menstrual cycle than in those collected in the follicular phase and was statistically significant (P less than 0.05, one-tailed t-test) only in the luteal phase. The high estriol ratios of the primiparous women did not decline with increasing interval after pregnancy, at least up to 24 months. Among the younger women, significantly lower levels of pregnanediol, suggestive of a higher frequency of anovular menstrual cycles, were also seen in the nulliparous women. The findings were consistent with the hypothesis that the protective effect against breast cancer of a full-term pregnancy at an early age operates either through a change in the pattern of estrogen metabolism induced by the pregnancy or through a change in the frequency of ovular cycles.

Adolescent↗

Cell-mediated suppression of the fifth component of complement in mice.

Suppression of levels of circulating C5 in (C5- C5+)F1 hybrids by administration of (C5- C5-) parental lymphoid cells in the neonatal period has been accomplished with the three strain combinations tested ((SWR X RIII)F1, (A/He x RIII)F1, and (SWR X DBA/1)F1). Suppression was shown to be specific for C5 and not accompanied by reductions of C1, C2, C6, or other major groups of blood proteins. This demonstrated that the C5 reduction was not due to activation of complement (C) with resultant hypercatabolism of C components. When there was a concurrent chronic GVH reaction induced by lymphoid cells administered to offspring of H-2 incompatible parents, there was usually a resultant hypergammaglobulinemia that was also unrelated to the presence or absence of C5 suppression. Effective suppression required preimmunization of either the cell donor, the mother of the F1 hybrids, or both. This suggests that either two cell types or a single cell plus a humoral factor are required for suppression in this system.

Animals↗

Use of protein A--containing Staphylococcus aureus as an immunoadsorbent in radioimmunoassays to separate antibody-bound from free antigen.

Heat killed, formalinized Cowan I strain Staphylococcus aureus (PASA) was examined for its utility as a solid-phase immunoadsorbent in various RIA procedures. Specific antibody could be adsorbed to PASA and then reacted with radiolabeled and unlabeled hormone, or alternatively, PASA could be added to antibody-hormone mixture in order to separate antibody-bound from free antigen. Both methods compared favorably with the more standard double-antibody method in each system tested. Antibodies produced by rabbits, guinea pigs, monkeys, and humans were precipitated equally by PASA and double antibody, whereas antibody raised in sheep was precipitated much less by PASA than by double antibody. Antibody bound to PASA was found to reach equilibrium of binding more slowly than unbound antibody for both rapid (TRH) and slow (rPRL) reactions. Binding of either free of complexed IgG by PASA, however, was extremely rapid, reaching equilibrium in less than 30 sec. This rapid binding was utilized in kinetic experiments which would not have been possible with slower-reacting precipitating agents. The versatility permitted by this propertly constitutes one of the most useful characteristics of PASA. Other important attributes of PASA include its convenience, economy, and wide applicability.

Antibodies↗

Antibody-induced suppression of the fifth component of complement in mice.

We have shown that administration of anti-C5 antibody to newborn mice heterozygous for C5 deficiency can suppress C5 levels for prolonged periods. This is analogous to antibody-induced immunoglobulin allotype and idiotype suppression. Only certain sources of anti-C5 are effective in suppression. Of the three antisera extensively tested in (SWR x RIII)F1 hybrids, A/He anti-RIII was the most effective, SWR anti-RIII was less effective, and SWR anti-DBA/1 was ineffective. Only certain strain combinations of F1 hybrids are susceptible to C5 suppression. C5 suppression was seen with (SWR x RIII)F1 hybrids but not (SWR x DBA/1)F1 hybrids. Kinetics of C5 suppression suggest a requirement for an active, ongoing process in the maintenance of low C5 levels.

Animals↗

Functional and biochemical properties of the early classical complement system of mice.

Mouse serum and EDTA plasma were subjected to low ionicity precipitation, gel filtration, and ion exchange chromatography in an attempt to purify C1, C4, and C2 to functional and chemical homogeneity. In marked contrast to human and guinea pig components, those of the mouse could not be separated by these techniques. Except for partial separation of C1 from C4 and C2 on DE-52 cellulose columuns with EDTA in the eluting buffers, there was no separation of those three components on ion exchange chromatographic columns. Sephadex G-200 gel filtration columns, or with precipitation of euglobulins from serum or plasma. Generation of EAC142 by incubation of EA in whole serum followed first order kinetics when mouse serum was used and second (or greater) order kinetics when human or guinea pig sera were used. Generation of EAC142 by incubation of EA in whole mouse serum followed by incubation in EDTA containing buffers resulted in rapid loss of all three activities from the cell. These experiments indicated that there were significant differences between the early classical C system of mice and those of human and guinea pig. In addition, they indicated that under a variety of in vitro conditions, murine C1, C4, and C2 behaved biochemically and functionally as a unit. The reasons for the major differences in behavior of the murine C components with not become clear until methods to stabilize their function are found so that they can survive multiple purification steps.

Animals↗

Relationship of functional levels of early components of complement to the H-2 complex of mice.

The relationship between the H-2 complex and the complement system was studied by performing functional assays for whole complement and individual complement components on sera from congenic mice of B10 and C3H backgrounds. Levels of whole complement activity were seen to be influenced by S region genes, confirming the work of others. Levels of C3 through C9, however, were independent of the H-I genotypes suggesting that the differences in whole complement activities were due to variation in levels of C1, C4 or C2. Titrations of these three earliest acting classical complement components were performed on sera from mice of nine strains of the B10 background and four strains of the C3H background. It was shown that functional levels of C1, C4, and C2 were all under control of genes within or very closely linked to the S region.

Animals↗

Membrane-associated immunoglobulin of rabbit peripheral blood lymphocytes: allelic exclusion at the b locus.

Light chain allotypic determinants were demonstrated on the surface of peripheral blood lymphocytes of rabbits. By means of a combined immunofluorescent and autoradiographic technique, a great majority of the individual lymphocytes of rabbits heteroxygous at the b locus were shown to have detectable quantities of only one allotype. A small proportion of lymphocytes appeared to possess both allelic forms of L chains.

Alleles↗

Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group.

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.

Adult↗