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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 523 records · Page 29Linked to original sources
PubMed1981

Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages.

Flaviviruses, when complexed with antibody at subneutralizing concentrations, show enhanced replication in human and simian peripheral blood leukocytes (ref. 1, and J.S.M.P. and J.S.P., unpublished observations) and in P388 D1 and other macrophage cell lines. A comparable phenomenon has been demonstrated with alphaviruses and Bunyaviruses in P388 D1 cells, (J.S.M.P. and J.S.P., unpublished observations) but cells lacking macrophage characteristics fail to show antibody-dependent enhancement (ADE) of viral replication. It has been suggested that the macrophage Fc receptor (FcR) provides an efficient route of entry of virus through the attachment of non-neutralized virus-antibody complexes and that for those viruses that escape destruction by the phagocyte, antibody results in a paradoxical increase in virus replication. West Nile virus (WNV) replication in the P388 D1 macrophage cell line provides a reproducible model system for studying ADE of viral replication. Mouse macrophages have two FcRs-FcRI, which is trypsin-sensitive and binds IgG2a, and FcRII, which is trypsin-resistant and binds IgG2b and IgG1 complexes. The FcR has been purified using rat anti-mouse FcR monoclonal antibody which blocks FcRII. We show here that anti-FcRIgG and its Fab fragment block ADE of virus replication by anti-WNV monoclonal antibodies.

Animals↗
PubMed1981

F4/80, a monoclonal antibody directed specifically against the mouse macrophage.

A hybridoma clone which secretes a macrophage (M phi)-specific monoclonal antibody, F4/80, was produced by fusing spleen cells from a rat hyperimmunized with cultured thioglycollate-induced mouse peritoneal M phi with a mouse myeloma, NS1. Binding of antibody to primary cells and cell lines was detected by radioimmune indirect binding assay, autoradiography or fluorescence-activated cell sorter analysis. F4/80 binds to mouse M phi from the peritoneal cavity or other sources, blood monocytes, M phi derived from bone marrow precursors in culture and M phi-like cell lines, but not to other cells, including polymorphonuclear leukocytes, lymphocytes or fibroblasts. F4/80 does not bind to M phi via Fc receptors, is not cytotoxic and is of the rat IgG2b subclass. Since F4/80 binds to all M phi defined by adherence, morphology and immune phagocytosis, it provides a new marker to define the M phi in the mouse. Large differences in expression of antigen F4/80 were found, depending on intraperitoneal stimulation, time in culture and stage of maturation. Immunoprecipitation experiments demonstrated that the antigen F4/80 is part of a component of Mr 160000 which is synthesized by the M phi and, at least in part, exposed on the cell surface.

Animals↗
PubMed1981

The pathogenesis of infantile malignant osteopetrosis: bone mineral metabolism and complications in five infants.

Bone mineral metabolism was studied in five infants aged 8 to 22 months with severe osteopetrosis. There were findings consistent with biochemical osteomalacia. These included hypocalcemia, hypophosphatemia, high serum acid phosphatase and alkaline phosphatase activity, high levels of serum parathyroid hormone, and high urinary cyclic AMP. Serum 1,25(OH)2 vitamin D3 level was high in the one patient tested. Radiographs in all infants revealed rachitic changes in the metaphyses. However, dense bones on radiographs, calcium balance studies, and radio-calcium absorption studies demonstrated markedly positive calcium balance. Iliac crest bone biopsies showed increased quantity of woven bone with abundant numbers of osteoclasts, excessive amounts of osteoid, myelofibrosis, and a decreased number of Howship's lacunae. The wide bands of unmineralized osteoid did not take up tetracycline. In vitro bone resorbing activity due to osteoclast activating factor from cultured stimulated leukocytes was normal. Bone turnover however, was now as evidenced by low urinary hydroxyproline levels. We interpret these findings as indicating there is decreased bone remodeling and resorption in spite of increased humoral stimuli and osteoclasts. Since calcitonin levels were normal for age, the most likely cause of the impaired bone remodeling sequence was defective osteoclast function. We postulate that there may be a common genetic defect in phagocyte cells, including monocytes, neutrophils and osteoclasts, which accounts for the abnormalities of mineral metabolism and previously reported hematologic, neurologic, and infectious complications.

Biopsy, Needle↗
PubMed1981

Urolithiasis in patients with spinal cord injury.

The composition of the stone was determined in 24 paraplegic patients from whom 26 stones were surgically removed. Twenty-five of the 26 stones consisted of 90 per cent magnesium ammonium phosphate and 10 per cent carbonate apatite. The remaining single stone was composed of 90 per cent calcium oxalate and 10 per cent magnesium ammonium phosphate. Renal function improved significantly with the removal of the stones.

Adult↗
PubMed1981

Alcohol and high-density lipoprotein cholesterol: causal inference from diverse study designs.

The association between reported alcohol intake and plasma high-density lipoprotein (HDL) cholesterol concentration is examined in an effort to establish whether it was a cause-and-effect basis. A cross-sectional descriptive study of several populations reveals a strong and consistent dose-response pattern: Social drinkers have mean HDL cholesterol levels that are higher than those of teetotalers by as much as 33%. Cross-sectional analyses in another epidemiological study reveal the association to be independent of potential confounding factors such as smoking and body weight, and longitudinal analyses suggest that it is also not a result of certain unmeasured sources of confounding. A small experiment reveals a 15% reduction in HDL cholesterol levels among social drinkers who abstain from alcohol from a 2-week period. The evidence supports the conclusion that alcohol habits are probably one of the determinants of plasma HDL cholesterol level. A clarification of the relevance of this phenomenon to clinical medicine awaits future clinical efforts.

Alcohol Drinking↗
PubMed1980

Cerebrospinal fluid involvement in patients with adult acute leukaemia and non-Hodgkin's lymphoma.

One hundred and thirty-four cases of adult acute leukaemia and 212 cases of non-Hodgkin's lymphoma treated by the Combined Haematology Division of Sydney Hospital over a four year period were reviewed to establish the incidence of central nervous system (CNS) involvement. The sole diagnostic criterion considered was positive cerebro-spinal fluid (CSF) cytology. The detected incidences of 21% and 5 . 2% respectively in long term surviving adults with leukaemia and those with non-Hodgkin's lymphoma are similar to other series. Unusual findings were the relatively low incidence of involvement in acute myelomonocytic leukaemia and unexpectedly high incidence in diffuse poorly differentiated lymphocytic lymphoma. Cytocentrifugation using the Cytospin has proved to be a useful technique in detecting small numbers of abnormal cells in the CSF.

Acute Disease↗
PubMed1980

Family life education for the handicapped.

Only a small percentage of America's handicapped population presently receives adequate instruction in family life education. The development of healthy attitudes and a positive self-concept are enhanced by education in sexuality with openness toward this sensitive area. Parents are the primary sex educators of their children, with schools, religious groups and various community agencies playing a supplementary role. In not educating handicapped individuals, society further burdens them with additional insecurities and feelings of inadequacy. People who are exposed to family life education programs tend to act more responsibly in their personal relationships and feel better about themselves.

Child↗
PubMed1979

Secretion of plasminogen activator by bone marrow-derived mononuclear phagocytes and its enhancement by colony-stimulating factor.

We have studied the production of plasminogen activator (PA) by mononuclear phagocytes derived from mouse bone marrow precursor cells (CFU-C) in culture. Bone marrow-derived macrophages (BMDM) obtained after 6-8-d cultivation in a liquid medium containing L-cell-conditioned medium (LCM), a source of colony stimulating factor (CSF), showed a high level of fibrinolytic activity comparable to that of thioglycollate medium-induced peritoneal macrophages (TPM) and at least 20-fold higher than that of resident peritoneal macrophages (RPM). Fibrinolysis was a result of active secretion of PA into the culture medium and plaques of caseinolysis could be detected by an overlay assay over all macrophage colonies formed after cloning of bone marrow cells in culture. When the fibrinolytic activity of BMDM harvested at different times was investigated, it was found that the level of PA activity of a given BMDM population correlated well with the incidence of cells (5-15 percent) able to proliferate and form colonies in agar after 7-14 d, somewhat more slowly than CFU-C. This correlation between the level of PA secretion and the incidence of agar colony-forming cells was also found with other mononuclear phagocyte populations. Active fibrinolysis and slow growing colony-forming cells were observed at the same time as adherent macrophages appeared, 2-3 d after the start of bone marrow culture, they persisted for 10 d before declining. Some of the factors which influenced PA production by BMDM were examined. Fibrinolysis could be enhanced two- to fourfold by exposing the cells for 4 h to concanavalin A (Con A), to medium conditioned by Con A-stimulated spleen cells and to LCM, but not by phagocytosis of latex particles. The substance in LCM that stimulated PA production appeared to be identical to CSF. Mononuclear phagocyte targets differed in their response to LCM, which stimulated fibrinolysis readily in BMDM, to a lesser extent in TPM and not at all in RPM. We conclude that CSF stimulates both proliferation and fibrinolytic activity in BMDM and that the level of macrophage activation, as defined by PA production, can be further enhanced by lymphokines. Induction of PA in BMDM provides a rapid and sensitive assay for measuring the activity of CSF and defining its role in macrophage activation.

Animals↗
PubMed1979

Limitations of exercise testing in critical left coronary artery disease.

Exercise testing was evaluated in 51 patients with critical left coronary artery disease (LCA) documented by coronary arteriography within two weeks of their bicycle ergometer (26 patients) or treadmill (25 patients) electrocardiographic study. Adequate tests, as defined by the patient having reached 85% of predicted maximum heart rate, were achieved in only 16 patients on the ergometer (62%) and in 21 (84%) on the treadmill. Nevertheless mean maximum double product (220 vs 232) and mean exercise time (4.6 min vs 5.0 min.) were similar (p:NS). The sensitivity for ergometry and treadmill testing was 75 and 62% respectively. If however we include those negative studies in which for various reasons patients were unable to achieve 85% of their predicted maximal heart rate (i.e., inadequate studies), sensitivity was only 46 and 52% respectively. Thus a sizable group of patients with critical LCA disease cannot adequately perform exercise tests especially on the ergometer; and over half of all such patients studied will be found for one reason or another to respond negatively, regardless of exercise protocol.

Blood Pressure↗
PubMed1979

Corrected transposition of great vessels and Ebstein's anomaly of tricuspid valve. Echocardiographic findings.

A case is reported concerning echocardiographic findings in a patient with congenital corrected transposition of the great vessels and Ebstein's anomaly of the tricuspid valve. This presented an unusual opportunity to study atrioventricular valve closure in a patient in whom the Ebstein's malformation involved the systemic atrioventricular valve. The mitral to tricuspid valve closure interval was 68 milliseconds and represented significant delay in tricuspid valve closure. This closure interval is similar to closure intervals previously reported for patients with Ebstein's anomaly without ventricular inversion.

Ebstein Anomaly↗