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Biomedical subjects

S A Feig

Publications and source records attributed to S A Feig.

At least 163 records · Page 9Linked to original sources

Influence of monovalent cation concentrations on monocyte-mediated ADCC.

Monocyte-mediated ADCC was inhibited by ouabain, which blocks active transport of Na+ and K+ by the membrane Na+K+-ATPase. Inhibition of ADCC was incomplete, however, even when monovalent cation transport was completely inhibited. On the other hand, increasing the duration of exposure to ouabain did result in complete inhibition of ADCC. ADCC was also depressed by incubation of monocytes in media with low (less than or equal to 1.5 mEq/l) or high (greater than or equal to mEq/l) K+ concentrations. The results suggest that monocyte ADCC is dependent upon monovalent cation concentrations (secondarily altered by ouabain exposure) but not upon active Na+K+ transport per se. Finally, since monovalent cation transport-related glycolysis accounted for essentially all of the previously observed increase in monocyte glycolysis associated with monocyte ADCC, we hypothesize that exposure of monocytes to sensitizing antiserum in the ADCC assay results in increased monocyte membrane permeability to monovalent cations.

Animals↗

Evaluation of the surgical aspects of staging laparotomy for Hodgkin's disease in children.

Experience with 72 children in which the type of staging laparotomy recommended by the Intergroup Hodgkin's Disease in Childhood Study (IHDCS) was employed (1967-1981) is reviewed. Laparotomy altered the stage in 35% of these patients including advance in stage (I-II to III-IV) in 24 patients, and reduction in stage (III to II) in one patient. In adults, Stage III disease is divided into III1 and III2 on the basis of the presence or absence of lower abdominal node involvement; and prognosis is significantly better in III1. Nine patients from two additional institutions were included in a special study of Stage III disease. This included 22 children in III1 and 11 children in III2. Although the children with Stage B (systemic symptoms) disease were concentrated in III2, none of the measured difference between these two groups were significant. No fatal postsplenectomy sepsis has been noted since the use of pneumococcal vaccine and prophylactic penicillin became standard.

Abdomen↗

Inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity by ouabain: relationship between cytotoxic function, glycolysis, and intracellular cation homeostasis.

Ouabain, a specific inhibitor of membrane Na+K+-ATPase, was used to study the relationship between monovalent cation, homeostasis and cytotoxic effector function. 5 X 10(-6) M ouabain completely inhibited monocyte monovalent cation active transport within 30 min but caused only 50% inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity (MMADCC) in a subsequent 20-hr assay. Longer (6-hr) preincubation of monocytes in ouabain was required for nearly complete inhibition of cytotoxic function. The previously reported augmentation of monocyte glycolysis caused by the sensitizing antiserum was decreased by 71% in 5 X 10(-6) M ouabain, identifying monovalent cation transport as the cellular function utilizing a major portion of the ATP generated by this augmentation of glycolysis. The lag in inhibition of MMADCC indicated, however, that a delayed effect of ouabain (e.g., changes in intracellular [K+] and [Na+]), and not the rapid ouabain inhibition of cation transport, caused inhibition of cytotoxic function. Four additional findings support this interpretation: i) a 30-min preincubation in ouabain caused little inhibition of MMADCC in a 4-hr assay; ii) monocytes lost cytotoxic activity when incubated in medium (0.2 mEq/cytotoxic activity when incubated in medium (0.2 mEq/liter) that reduces intracellular [K+]; iii) the rapid recovery of cytotoxic activity after readjustment of extracellular [K+] to 6 mEq/liter was blocked by ouabain; iv) increasing membrane K+ permeability by valinomycin while blocking active transport by ouabain caused 50% inhibition under conditions in which neither agent alone significantly affected MMADCC. Thus, it is suggested that homeostasis of monocyte intracellular [K+] and [Na+], but not monovalent cation active transport per se, is required for cytotoxic function.

Antibody-Dependent Cell Cytotoxicity↗

Immunologic classification of childhood acute lymphocytic leukemia.

Immunologic approaches to the classification of acute lymphocytic leukemia (ALL) have led to a new awareness of the heterogeneity of this disease. Surface membrane markers including surface membrane immunoglobulin, complement receptors, and sheep erythrocyte (E) receptors have demonstrated at least three subtypes of ALL, which include non-B, non-T, ALL, T-ALL, and B-ALL. In addition, hetero-antisera to Ia-like antigens and ALL-associated antigens have been used to positively identify non-B, non-T ALL, which was previously a diagnosis of exclusion. This paper reports 17 cases of childhood ALL whose lymphoblasts were studied for surface membrane immunoglobulin, sheep erythrocyte receptors, and the presence of four antigens detected by well-characterized heteroantisera. Every non-B, non-T lymphoblast was positively identified by the Ia-like antiserum and/or the ALL antiserum. One T lymphoblast was identified by E receptors and the T antiserum, whereas two did not have E receptors but did react to the T antiserum. None of these three T lymphoblasts reacted with the Ia-like antiserum.

Adolescent↗

Aplastic anemia: biology and treatment.

Aplastic anemia is characterized by decreased bone marrow function with inadequate production of erythrocytes, granulocytes, and platelets. Marrow failure may be caused by absence of or defects in hematopoietic stem cells, abnormalities of the bone marrow microenvironment, ineffective cell-to-cell interactions, or immune disorders. Although most patients with aplastic anemia have normal immunity, some have abnormalities of T- and B-lymphocytes. Rare patients have an immune cause of marrow failure. Treatment of aplastic anemia involves blood transfusions and withdrawal of potential causal factors. Efforts to stimulate hematopoiesis with androgens, corticosteroids, and other drugs have been largely unsuccessful. Some patients may recover after treatment with antithymocyte globulin or other immunosuppressive agents. Bone marrow transplantation is the preferred treatment for patients with severe aplastic anemia who have a human-leukocyte-antigen-identical related donor. Transplants of hematopoietic stem cells obtained from alternative sources, such as fetal liver cells or stem cells from long-term, in-vitro cultures, also may be useful.

Androgens↗

Advantages and limitations of physical examination and mammography in breast cancer screening.

Among 167 breast cancers detected on screening by xeromammography and physical examination, the accuracy of each modality was found to depend not only on the size and stage of the tumor itself but also on the structure and composition of the surrounding breast tissue. Overall, 53% (89/167) of cancers were found on physical examination and 78% (131/167) on xeromammography. Mammographic accuracy was greatest for large breasts and fatty breasts but was reduced for small breasts, dense breasts, and retroareolar lesions. The proportion of tumors with negative findings on physical examination was equal among women above and below 50 years of age.

Age Factors↗

Pathologic discriminants of breast cancers detected on screening by mammography and physical examination.

Pathologic discriminants such as lesion size, ratio of infiltrating to intraductal growth, histologic type, histologic grade, percentage tubule formation, lymph vessel invasion, and axillary lymph node metastases were used to analyze 183 breast cancers detected on screening by mammography and physical examination. In general, cancers detected only on mammography should be associated with favorable long-term survival because of their early stage. These lesions had histologic features indicating significant potential for subsequent metastatic spread, which would have occurred had screening been performed by physical examination alone.

Breast Neoplasms↗

Multicentricity of non-palpable breast cancer.

One hundred eighty-nine biopsies have been performed for clinically occult mammary lesions, detectable by mammography but not clinically apparent. Fifty-two cancers were demonstrated within this group, including 26 invasive ductal cancers, seven micro-invasive ductal cancers, 14 non-invasive ductal cancers, and five lobular carcinomas in situ. All mastectomy specimens were examined for multicentric foci of breast cancer in quadrants other than that in which the primary lesion was located. Of the invasive ductal cancers, 40% were multicentric. Of the micro-invasive ductal cancers, 57.1% were multicentric. Of the non-invasive ductal cancers, 45.5% were multicentric. The one mastectomy specimen from a patient with lobular carcinoma in situ did not have evidence of residual disease. The overall incidence of multicentricity in the 43 specimens examined was 44.2%. These findings suggested that any therapeutic procedure for either invasive or non-invasive ductal carcinoma that does not include total mastectomy may leave behind foci of cancer, which are a threat to the patient.

Breast Neoplasms↗

Clinically occult breast cancer. Multicentricity and implications for treatment.

Two hundred thirty-two biopsies have been performed for nonpalpable mammary lesions, detectable by mammography, but not clinically apparent. Sixty-two malignancies were demonstrated within this group, including thirty invasive ductal cancers, seven minimally invasive ductal cancers, 20 noninvasive ductal cancers, and five lobular carcinomas-in situ. When mastectomy specimens were examined for evidence of multifocal cancer in quadrants other than that in which the primary was located, 39.6% of the breasts examined demonstrated evidence of multifocal cancer ductal or lobular, invasive or non-invasive. These findings suggest that any therapeutic procedure for invasive or noninvasive ductal cancer which does not include total mastectomy may leave behind foci of cancer which may be a threat to the patient.

Adult↗

Glucose metabolism of human mononuclear cell subpopulations.

Previous studies have demonstrated metabolic dysfunction in the mononuclear cells of some children with abnormal cell-mediated immunity. Interpretation of these observations has been complicated by the extreme heterogeneity of cell types examined. The glycolytic metabolism of relatively enriched T-cells, non-T mononuclear cells (NTM), non-T lymphocytes (NTL), and monocytes was studied in an attempt to measure the metabolism of subpopulations of mononuclear cells. Lactate production by monocytes was 11 times greater than that of T-cells and 2 1/2 times greater than that of non-T lymphocytes. Exposure to phytohemagglutinin (PHA) stimulated glycolytic metabolism in T-cells but did not stimulate glucose utilization or lactate production in NTM. Even when T-cells were maximally stimulated by PHA, their observed metabolism was still lower than that of NTL. The ATP content of T lymphocytes and NTL was similar and was constant under the conditions of incubation. The initial ATP content of monocytes was higher than that of lymphocytes, and diminished during incubation. Tricarboxylic acid cycle activity did not contribute significantly to ATP synthesis in any of the mononuclear cell subpopulations, under the conditions of incubation used in this study. Significant hexose monophosphate shunt activity was observed in all mononuclear cell types. These studies demonstrate major metabolic differences between mononuclear cell subtypes. Any correlation of metabolic observation with clinical dysfunction of mononuclear cells requires the study of relatively pure cell populations.

Adult↗

Biological determinants of radiation-induced human breast cancer.

This is the second in a three part series on the hypothetical risk from X-ray mammography. It will review those aspects of breast anatomy, histology, physiology, and pathology which are pertinent to radiation carcinogenesis. Radiation-induced breast cancers are histologically identical to the naturally occurring type in that they arise from the ductal epithelium and consist of a similar proportion of infiltrating and intraductal lesions. As indicated from mortality/incidence ratios, their prognosis is no worse, and may even be better, than that of naturally occurring lesions. Their location within the breast may depend on the distribution of absorbed radiation. Possible explanations for the increased resistance to radiation effect in women over 30 years of age at time of exposure will be evaluated. these include regression of the glandular target tissue, hormonal changes, and parity. Examples of age-related sensitivity and hormonal dependence in other radiation-induced human and animal tumors will be discussed.

Age Factors↗

Traumatic arteriovenous fistulae of the scalp.

Two cases of traumatic arteriovenous fistula of the scalp are described. To our knowledge, only six such cases with angiographic correlation have been previously reported in the literature. While the clinical diagnosis of arteriovenous fistula of the scalp is often not difficult, angiography plays an important role in guiding the surgeon by demonstrating multiplicity of feeding vessels and their origin from various trunks. One of our cases showed feeding vessels from the occipital artery and cervical branches of the vertebral and subclavian arteries. Our second case revealed superficial temporal and occipital arteries to be the feeding vessels. Total excision of the arteriovenous fistula rather than simple ligation should be performed to prevent recurrence, which results because of extensive collateral supply.

Adolescent↗

Prognostic factors of breast neoplasms detected on screening by mammography and physical examination.

A total of 183 neoplasms detected on screening women between the ages of 45 and 64 by mammography and physical examination were analyzed according to multiple histologic parameters. In general, tumors apparent only on mammography should be associcated with favorable long-term survival because of their early stage. These lesions had histologic features indicating significant potential for subsequent metastatic spread. This analysis strongly suggests that mammographic screening of asymptomatic women both above and below 50 years of age can substantially reduce breast cancer mortality.

Breast Neoplasms↗

Neonatal mononuclear cell metabolism: further evidence for diminished monocyte function in the neonate.

The metabolic capacity of neonatal monocytes was compared to the metabolic capacity of adult monocytes by two entirely different methods: the selective diminution of monocyte contamination of whole mononuclear cells and the isolation of relatively purified populations of monocytes. Monocyte removal from whole mononuclear cells produced a diminution in the pyruvate kinase (PK) activity (from 28.6 +/- 1.1 to 15.6 +/- 1.2 nmoles/min/10(7) cells) and an increase in adenosine triphosphate (ATP) content (from 7.9 +/- 1.0 to 9.5 +/- 0.8 nmoles/10(7) cells) in adult cells. No change in PK activity (from 13.5 +/- 1.3 to 14.0 +/- 1.3) was observed in cord cells, but the ATP content of cord cells was higher after monocytes depletion (from 4.7 +/- 0.5 to 6.2 +- 0.7). The suggestion of metabolic vulnerability was confirmed by metabolic analysis of isolated adult and cord monocytes. The PK activity of adult monocytes was greater than that of cord monocytes (57 +/- 9 and 25 +/- 0.3, respectively) and the ATP content of adult monocytes (5.7 +/- 0.2) was greater than that of cord monocytes (2.3 +/- 0.1). The data confirm prior observations of diminished energy metabolism in neonatal mononucler cells and suggest that the metabolic perturbations may, in part, correlate with functional immaturity of the neonatal monocyte.

Adenosine Triphosphate↗