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Biomedical subjects

S Pollack

Publications and source records attributed to S Pollack.

At least 199 records · Page 11Linked to original sources

A study of HLA antigen association in localized and generalized granuloma annulare.

HLA-A and -B antigen frequencies were studied in 78 patients, 35 with localized granuloma annulare and 43 with generalized granuloma annulare (GA). Twenty-eight patients in each group were also typed for HLA-DR antigens. A group of 200 healthy age-matched subjects served as controls. HLA-A31 and B35 were increased significantly in patients with generalized GA, but not in the localized form. HLA-DR antigen distribution showed no significant variation.

Female↗

C1 esterase inhibitor deficiency in X-linked hypogammaglobulinaemia: an anomaly fostering anaphylactoid reactions following intramuscular gammaglobulin administration.

A patient with apparent X-linked agammaglobulinaemia was found to be inordinately susceptible to anaphylactoid reactions to intramuscular injections of gammaglobulin. The patient was found also to have low levels of C1 esterase inhibitor (C1 INH). The possibility that the C1 INH deficiency and in this patient, whether genetic or acquired, fostered the susceptibility to the production of anaphylactoid reactions after gammaglobulin injections urges further studies of the association of C1 INH deficiency and anaphylactoid reactions to gammaglobulin injections. The possibility that C1 INH levels like C1q levels may be low in hypogammaglobulinaemic patients as a consequence of increased catabolism of this regulator of the complement system when IgG levels are low is considered.

Adult↗

Transient immunoregulatory perturbation during the acute phase of rheumatic fever.

An abnormal immune response directed at streptococcal antigen is currently thought to be involved in the development of autoimmune phenomena in rheumatic fever (RF). We studied T-cell subsets using the OKT monoclonal antibodies in 13 patients with newly-diagnosed RF. No difference was found in the total number of T cells or in the proportion of helper T cells (OKT4+) at the acute phase (56.6 +/- 6.9) as compared to the recovery phase (55.2 +/- 9.2). However, a significantly decreased proportion of suppressor T cells (OKT8+) was observed during the acute phase (17.2 +/- 6) as compared to the recovery phase (26.4 +/- 5.3) (p less than 0.001). The T4/T8 ratio was significantly higher during the initial phase (3.65 +/- 1.04) and returned to normal later (2.12 +/- 0.39) (p less than 0.002). The results of our study indicate that in the acute phase of RF many patients had low levels of suppressor T cells which return to normal after recovery. Thus, reduced proportion of suppressor T cells might be an indicator for the active phase of RF. Decreased suppressor cell activity may also be involved in the development of autoimmune phenomena in RF.

Acute Disease↗

Induction of tumor immunity and natural killer cell cytotoxicity in mice by 5-halo-6-phenyl pyrimidinone.

We have investigated the effect of pyrimidinone molecule 2-amino-5-iodo-6-phenyl-4 pyrimidinone (AIPP) on natural killer (NK) cell lytic potential and on the growth of ascitic mammary adenocarcinoma, ACA-755, in B6D2F1 mice. Our studies demonstrated that AIPP was effective in both the prophylaxis and the therapy of this tumor and that the antitumor effect was mediated via induction of NK cell lytic activity. In vitro characterization studies showed that the AIPP-induced cytotoxic cells were not macrophages and exhibited characteristics of NK cells such as morphology of the large granular lymphocytes and sensitivity to asialo GM-1 antibody. Analysis of the mechanism of potentiation of NK cell cytotoxic function by AIPP indicated that the enhancement of cytotoxicity was accomplished by recruitment of NK cell tumor-binding potential (primarily those with large granular lymphocytic morphology) as well as by increased frequency of lytic NK cells. These studies implicate NK cells in the defense against malignant tumors and suggest that regional therapy with AIPP may represent a new therapeutic modality for treatment of cancer.

Animals↗

Iron release from transferrin: synergistic interaction between adenosine triphosphate and an ammonium sulfate fraction of hemolysate.

In previous work we have shown that red cell hemolysates, at neutral pH, will release iron from transferrin; with molecular sieve chromatography, that activity separated into low molecular weight and high molecular weight components, both susceptible to destruction by phosphatases. Thus the possibility that nucleotides might be involved was suggested. We have studied the interaction of adenosine triphosphate (ATP) and an ammonium sulfate fraction of hemolysate with transferrin. ATP, as well as adenosine diphosphate and 2,3-diphosphoglyceric acid, interacts synergistically with the ammonium sulfate hemolysate fraction to promote iron release from transferrin. This activity is not limited to phosphorylated compounds, because citrate shows a similar effect. This activity is not a nonspecific chelating effect, because deferoxamine is without activity. All the synergistic anions labilize transferrin's HCO3. We therefore suggest that they form a non-HCO3 ternary complex with transferrin and iron, and that release of iron from this complex is promoted by a high molecular weight constituent of the hemolysate.

2,3-Diphosphoglycerate↗

Twice-daily administration of oral verapamil in the treatment of essential hypertension.

The antihypertensive effect of twice-daily administration of verapamil hydrochloride was evaluated in 21 adult patients with mild to moderate essential hypertension. Following four weeks of placebo therapy, verapamil was given for four weeks with a treatment goal of sitting diastolic blood pressure (BP) of less than 90 mm Hg, or to a maximum dose of 160 mg twice daily. Sitting and standing BPs, heart rate, and verapamil plasma levels were determined weekly, ten to 12 hours post dose. At the maximal dose (mean, 154 +/- 19.2 mg), heart rate was not affected, side effects were minimal, and sitting diastolic BP was significantly reduced from placebo baseline, with 12 of 21 patients having a fall in sitting diastolic BP of 10 mm Hg or more or less than 90 mm Hg. A trough verapamil plasma level of greater than 80 ng/mL was associated with a good hypotensive response. These data indicate the safety and utility of twice-daily verapamil administration for the treatment of essential hypertension and suggest the value of obtaining verapamil plasma levels as a guide to dosage determination.

Administration, Oral↗

Low molecular weight iron in guinea pig reticulocytes.

The low molecular weight iron found in the guinea pig reticulocyte has been partially characterized. On thin layer chromatography it is distinguishable from the iron complexes of a variety of nucleotides, sugars, and amino acids. On paper chromatography it comigrates with a 250-nm absorbing, orcinol-positive material. The eluted count peak contains phosphorus. Approximately 1 microgram of iron is recovered from 1 ml of hemolyzed red cells. Preparation under nitrogen improves recovery of low molecular weight iron, suggesting that the iron is in the ferrous oxidation state.

Animals↗

Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: relation to duration of treatment.

Recently, abnormalities of cell-mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia-A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T-helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T-suppressor cells, Con A-activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.

Acquired Immunodeficiency Syndrome↗

Monocyte suppressor function in burns: T cell-monocyte interaction in mediating suppression.

Reduced in vitro T cell mitogen-induced transformation, low proportion of T cells and increased proportion of non-T cells were found in blood mononuclear cells of patients with severe burns 3-12 days after the injury. High spontaneous proliferation of non-T cells was observed and could be related mainly to the B cell fraction. Monocytes mediated suppression of mitogen-stimulated T cell proliferation. We further studied the role of monocytes in the enhanced suppressor activity of Con A-activated T cells and found that in this assay system, the patient's T cells mediated suppression in collaboration with monocytes. In vitro, increased suppressor function was probably the result of in vivo stimulation of inhibitory activity ascribed to both monocytes and T cells of patients. Addition of indomethacin to cell cultures markedly reduced suppression of lymphocyte proliferation. Less significant reduction was noted when the patient's T cells were activated in vitro by Con A. Adjuvant treatment of burn patients with indomethacin may play a role in alleviating suppression of immune response in these patients.

Adolescent↗

A rationale for the treatment of difficult basal cell and squamous cell carcinomas of the skin.

During a 56-month period, 1,348 patients with either basal cell or squamous cell carcinoma of the skin underwent microscopically controlled excision (Mohs' fresh-tissue technique) by a dermatologic surgeon. Of these 1,348 patients, 394 required various types of wound reconstruction by a plastic surgeon. The average dimensions of these wounds were 5 X 3.5 cm, with a range of 1.5 to 20.0 cm in diameter. There were postoperative complications in 13.9% of the 394 patients. The recurrence rate in these 394 patients, to date, for basal cell carcinoma is 5.2% and for squamous cell carcinoma, 11.9%. The advantages of this treatment arrangement include maximum conservation of normal tissue with provision of more reliable complete tumor excision, optimum time utilization by both dermatologic and plastic surgeons, separation of the responsibility for tumor ablation from that for wound reconstruction, and, in many instances, economic savings. We recommend this method of management for difficult, high-risk basal cell or squamous cell carcinomas.

Adult↗

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol.

Adult↗

B-cell function in common variable immunodeficiency: suppression of in vitro anti-sheep erythrocytes antibody production by T cells and monocytes.

Peripheral blood mononuclear (PBM) cells from five of 21 patients with common variable immunodeficiency (CVI) stimulated in vitro by antigen produced antibodies normally. In 11 of the 16 non-responders, removal of adherent suppressor cells by Sephadex G-10 or removal of monocytes or OKT8 positive suppressor lymphocytes by other means of separation made antibody responses demonstrable. Cells adherent to the G-10 column had suppressor function in the autologous antigen driven system; the suppressor activity appeared to be due to adherent T cells in some patients and to adherent monocytes in others. The suppressor cell functions in these patients did not correlate significantly with the number of cells positive for monoclonal antibodies OKT8 or Leu-2. Factors suppressing antibody production in this system were found in normal serum but usually not in serum of the patients with CVI studied. Substances in normal serum which enhance antibody production in this system when added late in culture were present in serum of patients with CVI. Any abnormality of interleukin-1 production by monocytes of these patients did not seem relevant to the immunodeficiency.

Adolescent↗