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Biomedical subjects

M Hoffman

Publications and source records attributed to M Hoffman.

At least 307 records · Page 17Linked to original sources

Clearance and distribution of recombinant murine gamma-interferon in mice.

Recombinant murine gamma-interferon (rIFN-gamma) was radiolabeled by a novel procedure which does not require the use of preiodinated Bolton-Hunter reagent (specific activities of 0.5-3.0 microCi/micrograms). Gel filtration chromatography of the radiolabeled preparation yielded two peaks. The early eluting peak contained disulfide stabilized aggregates with minimal interferon antiviral activity. The second peak contained activity that was consistently greater than or equal to that of the nonradiolabeled rIFN-gamma. Two bands with apparent molecular weights of 17,000 and 34,000 were observed when the second peak was analyzed by SDS gel electrophoresis. Fractions comprising each of the two chromatography peaks were pooled separately and subjected to gel filtration again on identical columns 24 h after completion of the first column run. The elution volumes of each peak remained unchanged suggesting that the two forms are not in rapid equilibrium. The plasma clearance rates of [125I]rIFN-gamma before and after purification by chromatography were initially rapid but multiphasic. The slower phases of clearance did not result from stable association of the rIFN-gamma with plasma proteins. In organ distribution studies, the liver and spleen sequestered significant amounts of [125I]rIFN-gamma; however, the highest concentration of rIFN-gamma was recovered in the kidneys. A functional nephrectomy procedure was used to further study the role of the kidneys in rIFN-gamma clearance. Eliminating the kidneys significantly increased the amount of rIFN-gamma retained in the circulation, particularly at later times when the vascular [125I]rIFN-gamma levels were approximately threefold higher than in nonnephrectomized mice.

Animals↗

Western Cape local authority compliance with tuberculosis policy, 1984.

Local authority compliance with the national tuberculosis regimen in 1984 was examined in 29 of the 32 largest local authorities in the western Cape. The variability in management practices was especially evident with respect to children. The effects of the relative lack of uniformity and deviations from recommended policy need to be determined.

Child↗

A family study of multiple mutations of alpha and delta glycophorins (glycophorins A and B).

Glycophorins alpha and delta are the carriers of the antigens of the MNSs blood system; this report documents the presence of three glycophorin mutations in two individuals of a 16 member family. Erythrocytes were examined by serology, sodium dodecyl sulfate electrophoresis, and immunoblotting. The inheritance pattern and immunoblot profile revealed: (1) A variant Dantu glycophorin showed properties consistent with a delta-alpha glycophorin hybrid structure, previously noted in other individuals. The gene responsible for the Dantu glycophorin in this family is linked to a gene coding for an M-specific alpha glycophorin. (2) Another variant glycophorin, Mi-III glycophorin, was first revealed by immunoblotting and subsequently confirmed by erythrocyte antigen typing. This autosomal dominant trait is associated with N blood group activity and the inheritance pattern indicates that it could be a variant of delta glycophorin. (3) In the individuals with both Dantu and Mi-III glycophorins a delta glycophorin deficiency was observed suggesting that a deletion or alteration of delta gene may exist cis to the Dantu gene. Our findings that document clustering of multiple mutations in MNSs gene loci in the propositus family are very unusual as such variants are relatively rare.

Female↗

Alpha 2 macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages.

alpha 2-Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically "fast" form by reaction with a proteinase or methylamine. All alpha 2M "fast" forms bind to a specific high-affinity receptor on macrophages. alpha 2M "fast" forms inhibit the interferon-gamma (IFN)-induced increase in macrophage Ia expression. This study examined whether alpha 2M-proteinase complexes alter prostaglandin (PG) E2 synthesis, and whether PGE2 mediates alpha 2M "fast" forms effects on macrophage Ia expression. Culture with alpha 2M "fast" forms increased PGE2 accumulation in the medium over control values in a dose-dependent manner. Culture with IFN alone did not increase PGE2 levels, but potentiated the effect of alpha 2M-proteinase complexes on PGE2 levels. Inhibition of PGE2 synthesis did not alter the inhibitory effect of alpha 2M-proteinase complexes on IFN-induced Ia expression. However, exogenous PGE2 did suppress IFN-induced Ia expression. Thus, alpha 2M-proteinase complexes increase macrophage PGE2 synthesis, but increased synthesis of PGE2 or other cyclooxygenase products is not the mediator of antagonism of IFN-induced Ia expression by alpha 2M-proteinase complexes.

Animals↗

Reduced trypsin-binding capacity of alpha 2-macroglobulin in the peritoneal fluid of women with endometriosis: possible relevance to alterations in macrophase function.

Alpha 2-macroglobulin (alpha 2M) is a plasma protein with proteinase inhibitor and immune modulatory capabilities. The amounts of alpha 2M in peritoneal fluid (PF) from women with endometriosis and women with noninflammatory gynecologic conditions were analyzed by functional (trypsin binding) and immunologic assays. The most important finding of this study was that a significant amount of the alpha 2M in the peritoneal fluid of patients with endometriosis had been inactivated by an as yet undetermined mechanism. The concentration and total amount of immunologically reactive alpha 2M in the samples varied widely and was not significantly different between the groups. However, women with endometriosis had significantly lower amounts of functional alpha 2M than did women without endometriosis. There was no significant difference between functional and immunologic measurements of alpha 2M in samples from women without endometriosis. Women with endometriosis, however, had less functional than immunologically reactive alpha 2M. This discrepancy was not due to inactivation of alpha 2M by having previously bound proteinase. Alpha 2M-proteinase complexes can down-regulate macrophase functions. It is possible that decreased proteinase-binding ability of alpha 2M may play a role in the pathogenesis of endometriosis and associated infertility by decreasing negative feedback control of macrophage activities.

Ascitic Fluid↗

Surgical management of heparin-associated thrombocytopenia. Strategies in the treatment of venous and arterial thromboembolism.

We report the vascular surgical strategies and results in 13 patients with heparin-associated thrombocytopenia and describe useful in vitro techniques for the evaluation of anticoagulant therapy. Thirteen of 40 patients with heparin-associated thrombocytopenia had 18 cardiovascular procedures done to save life or limb. Greenfield filters were placed in eight patients to prevent pulmonary embolism. Eight patients had 10 arterial procedures, with alternative anticoagulation that used dextran or warfarin in five cases. In three cases iloprost, a derivative of prostacyclin and a potent platelet inhibitor, was infused intraoperatively and heparin was given. Both the use of alternative anticoagulants and platelet suppression by iloprost were clinically effective strategies. The concurrent measurement of plasma levels of beta-thromboglobulin and fibrinopeptide A in two patients confirmed that both approaches can successfully prevent activation of platelets and plasma coagulation during arterial surgery. One operative death occurred; all vascular reconstructions remained patent at 3 to 6 months. In two patients who received heparin alone for arterial surgery, both procedures resulted in thrombosis and limb loss. When major venous thromboembolism is complicated by heparin-associated thrombocytopenia, insertion of a Greenfield vena cava filter should be considered if there is significant risk of pulmonary embolism. When necessary, arterial surgery is feasible in patients with heparin-associated thrombocytopenia if alternative anticoagulation or adequate suppression of platelet reactivity can be achieved.

Dextrans↗

Scientific prognosis of trends in the development of cardiovascular surgery in the socialist countries.

The growing incidence and importance of cardiovascular diseases in a number of countries calls for systematic quest for most efficient methods of treatment, which besides prevention and drug therapy include also surgical treatment. A group of experts from member countries of the Council for Mutual Economic Assistance (CMEA) has worked out a scientific prognosis of trends of the development of cardiovascular surgery, which include surgical treatment of ischaemic heart disease, congenital and acquired heart defects, renovascular hypertension and affection of the aortic arch. The prognosis includes also an estimate of the number of operations which will have to be performed in the mentioned diseases per 1 million inhabitants of the CMEA member countries.

Cardiac Surgical Procedures↗

Tumor necrosis factor-alpha induces increased hydrogen peroxide production and Fc receptor expression, but not increased Ia antigen expression by peritoneal macrophages.

It has recently been shown that tumor necrosis factor (TNF) induces increased Ia antigen expression on a malignant murine macrophage cell line, and that TNF is synergistic with gamma interferon (IFN) in inducing Ia expression. This finding raises the possibility that TNF serves as a non-interferon macrophage activating factor in vivo. Since it is known that TNF has different effects on malignant and benign cells, we chose to evaluate the effects of recombinant TNF on primary cultures of murine peritoneal macrophages (MP). Neither human nor murine TNF increased the proportion of MP which expressed Ia antigen, and TNF actually partially prevented the IFN-induced increase in Ia. However, culture with TNF activated MP for increased hydrogen peroxide production in response to phorbol myristate acetate (PMA) and antagonized the IFN-induced decrease in the proportion of the MP bearing receptors for the Fc region of IgG2b. TNF and IFN were additive in increasing peroxide production. Both human and murine TNF had the same effects on MP, and MP from C3H/HeN (endotoxin sensitive) and C3H/HeJ (endotoxin resistant) mice responded comparably to TNF and IFN. Our results support the hypothesis that TNF has some macrophage-activating activity, but its effects are selective and not identical with those of IFN.

Animals↗

Affiliation patterns among cancer patients.

Affiliation preferences of 150 cancer out-patients were assessed in the waiting-room and day-to-day life. Results indicated the vast majority avoided fellow patients, preferring to be alone or with healthy people. Similarly, patients tended to avoid the topic of illness in their social contacts. Moreover, those desiring to be with the healthy displayed the highest levels of negative emotion. Finally, avoidance of fellow patients was higher among males, the elderly, and the more highly educated. Overall, the findings were inconsistent with the thesis that those under stress seek out others in similar straits, as suggested by Schachter's emotional comparison theory or Will's downward comparison theory. Rather, they support Rofé's utility theory of stress and affiliation.

Adolescent↗

The effect of fibrin polymerization inhibitors on quantitative measurements of plasma fibrinogen.

A number of reports have highlighted discrepancies between the DuPont aca and fibrometer-based methods for quantitating plasma fibrinogen levels. Although many authors have suggested that the presence of fibrin(ogen) degradation products are in some way responsible for the discrepancies, no direct test of this hypothesis has been carried out. In this report, the authors demonstrate that inhibitors of fibrin monomer polymerization have different effects on the aca and fibrometer assays of fibrinogen. Fibrin polymerization inhibitors allow short soluble fibrin polymers to assemble that can scatter light and are therefore detected by the aca method. However, these short polymers do not gel and thus are not detected by the fibrometer. Therefore, the fibrometer method gives lower fibrinogen values than the aca in the presence of fibrin polymerization inhibitors. The authors also assayed plasma from a patient whose fibrinogen did not polymerize normally and therefore was not measurable by the fibrometer assay. The dysfibrinogenemic plasma assayed by the aca method recorded normal fibrinogen levels. In conclusion, the DuPont aca fibrinogen assay is insensitive to alterations of fibrin polymerization whether from inhibitors or a defective fibrinogen molecule.

Blood Coagulation Tests↗

Students' attitudes to small-group work in community health.

To encourage fourth-year medical students to review their ethnocentric attitudes to the politicized issues of population and undernutrition in South Africa, small-group work (SGW) was introduced during a month's teaching in community health at the University of Cape Town. We tested several formats for these sessions and chose one which seemed effective. This study examined the remaining students' attitudes to SGW as a means of briefly examining complex emotive topics. Sixty-nine students of a class of 168 were asked to complete a Likert questionnaire on their attitudes to SGW. Fifty-five students (79.7%) agreed that group work had allowed them to engage the topics briefly but usefully and 62 (90%) thought that the topics lent themselves to SGW. While 52 (75.3%) were not confused, 5 (7.2%) were confused by SGW. Thirty-nine students (56.5%) preferred lectures, tutorials or seminars to SGW. Thirty-seven students (53.6%) needed more fact to benefit fully from the SGW. Students found SGW appropriate for briefly examining these topics but wanted more fact to benefit fully from the sessions. The survey yielded valuable feedback from students on SGW as a means of addressing controversial and attitude-laden issues of central importance to the delivery of effective health care in Southern Africa.

Attitude of Health Personnel↗