Biomedical subjects
V Zakuth
Publications and source records attributed to V Zakuth.
Normal reduction of nitroblue tetrazolium by neutrophils of splenectomized individuals.
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The immune system in familial Mediterranean fever.
Familial Mediterranean fever (FMF) is a genetic disorder with an obscure aetiology. In attempts to investigate a possible immunoregulatory imbalance involved in this disease we tested 24 FMF patients for suppressor T cell activity and for chemotaxis of mononuclear cells. The suppressor T cell activity and chemotaxis were decreased in untreated FMF patients as compared to colchicine treated patients or normal controls. Amyloid FMF patients manifested significantly increased chemotactic activity, while the suppressor T cell activity was normal. This finding may extend our knowledge concerning the immune mechanism involved in FMF.
Lack of proliferation to alloantigen in a sibling of two infants with severe combined immunodeficiency (SCID).
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Dialysis-induced eosinophilia.
Blood eosinophils were counted by the counting-chamber method in 21 regular hemodialysis patients. Before dialysis, eosinophil counts were within the normal range in all patients (mean 98 cells/mm3, range 6-350). After the first 15 min of hemodialysis, with not reused coils or hollow-fiber dialysers, a significant drop in eosinophil counts was noted in all patients. The mean drop was 37.5% of the initial value (range 28-100%). At the end of the 5-hour dialysis, the eosinophil counts rose significantly in all patients but 1. The mean rise was 521% of the initial counts (range 22.3-1576%). Simultaneous neutrophil counts showed the already described drop at 15 min with a return to predialysis levels at 5 h. Predialysis IgE serum concentrations were lower than normal (mean 24.8, range 4.5-58 units/ml), and did not change at the end of the dialysis. It seems that pulmonary sequestration is responsible for both neutropenia and eosinopenia early in dialysis. The marked eosinophilia at 5 h may be the result of a release of eosinophilotactic substances induced by the dialysis procedure itself.
Suppressor T cell activity in splenectomized subjects.
The effect of splenectomy on the expression of suppressor activity of peripheral blood lymphocytes was examined in this study. 63 soldiers splenectomized for trauma or hematological diseases one to 24 years earlier, were studied by measuring the suppressor cell activity (using the Con A method), and lymphocyte blast transformation in response to lectines (PHA, Con A, PWM). There was a decrease in suppressor cell activity in 15 (23.8%) of the splenectomized patients. This decrease was greater in subjects splenectomized for trauma than in those splenectomized electively (24% and 22% respectively). The decrease was related to length to time from surgery being highest in the first 5 years after removal of the spleen and was more frequent in females (43%). The mean of the stimulation indices calculated from the mitogenic response to PHA, PWM and Con A was lower in the splenectomized patients with reduced suppressor activity than in those with normal suppressor activity. The findings of our present study supports the view that splenectomy interferes with normal immunoregulatory mechanisms and suggests that pyogenic infections are not the sole hazard of this procedure.
Suppression of lymphocyte reactivity in vitro by a soluble factor secreted by explants of human decidua.
The immunologic mechanisms that protect the fetus from rejection were the subject of numerous investigations. Reports showing the uterus as a favorable site of implantation focused our attention to the decidua which is the maternal tissue intimately attached to fetal structures. Explants of human decidua were cultured for periods of 24 h and incubation media tested for their immunosuppressive activity. The incubation medium of human decidua when added to cultures of human lymphocytes suppressed both their reactivity to lectins and their activity in the mixed lymphocyte reaction. The results of these experiments suggest that decidual tissue releases a soluble factor which is a potent inhibitor of cell-mediated immunity.
Immunological functions in children years after recovery from protein calorie malnutrition (PCM) in their early infancy.
The immune functions were evaluated in 30 children, aged one year to 9 8/12 years, who had suffered during their early infancy from protein-calorie malnutrition (PCM) as the result of intractable diarrhea. Twelve healthy children matched for age and sex served as controls. All 42 children responded normally to intradermal injections of tuberculin and candida antigens. The reduction of nitrous blue tetrazolium (NBT) by the polymorphonuclear leucocytes (PMN) was normal. Apart from the lower concentrations of IgM in the post-PCM group--145 +/- 67 mg % as compared to 212.8 +/- 46 mg % (p less than 0.005)--no differences were noted in the other serum immunoglobulin and complement levels. The response to phytohaemagglutinins (PHA) in two different concentrations was significantly enhanced in the post-PCM group (p less than 0.05). The per cent of T cells in both groups was normal. The results of this study indicate that most immunologic parameters return to normal after a healthy nutritional status has been achieved, with the exception of some abnormalities in IgM production and lymphocyte reactivity to PHA. These need further investigation.
Decreased serum tuftsin concentrations in sickle cell disease.
The serum concentrations of the phagocytosis-stimulating peptide, tuftsin, were determined by radioimmunoassay in 21 patients with sickle cell disease and in 12 healthy controls. The mean serum tuftsin concentration was significantly lower in patient with haemoglobin SS disease (154.3 +/- 35.1 ng/ml; 308.6 +/- 70.2 nmol/l, P < 0.01) and in patients with haemoglobin SC and CC disease (180.9 +/- 42.7 ng/ml; 361.8 +/- 85.4 nmol/l, P < 0.05) than in healthy controls (228.7 +/- 46.7 ng/ml; 457.4 +/- 93.4 nmol/1). Tuftsin deficiency is an indicator of splenic hypofunction and may contribute to the increased susceptibility of patients with sickle cell disease to severe infection.
Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes.
Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.
[Infective hazards of splenectomy--facts and theories].
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Specific binding sites for the phagocytosis stimulating peptide tuftsin on human polymorphonuclear leukocytes and monocytes.
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Synthesis and biological activity of tuftsin and of [O = C Thr1]-tuftsin. A novel synthetic route to peptides containing N-terminal L -O = C Thr and L - O = C Ser residues.
The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.
Decreased tuftsin concentrations in patients who have undergone splenectomy.
Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin's disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin's disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin's disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin's disease should perhaps be reconsidered.
Tuftsin and some analogs: synthesis and interaction with human polymorphonuclear leukocytes.
The phagocytosis-stimulating tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, was synthesized by both conventional and polymeric-reagent approaches. Using a combination of the two methods several analogs were prepared, including: [Ala1]tuftsin, [Lys1]tuftsin, [Ser1]tuftsin, [Val1]tuftsin, acetyl-tuftsin, p-aminophenylacetyl-tuftsin and tyrosyl-tuftsin. [Des-Thr1]tuftsin and [omega-NO2(4)]tuftsin were synthesized using a conventional procedure. The effects of synthetic peptides on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes were investigated. Tuftsin and to a lesser extent [Lys1]tuftsin and [Ser1]tuftsin were found to stimulate phagocytosis, whereas the other analogs synthesized as well as [Ser1]tuftsin exhibited inhibitory effects to tuftsin's action. Tuftsin alone has stimulated nitroblue tetrazolium reduction; [Des-Thr1]tuftsin and [Ala1]tuftsin repressed this stimulation, while the other peptides showed no effect.
Radioimmunoassay of the phagocytosis-stimulating peptide tuftsin in normal and splenectomized subjects.
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Persistence of in vitro lymphocyte response to tuberculin skin test negative children immunized with BCG in infancy.
PPD stimulated lymphocyte reactivity was tested in 119 children aged 11 to 12 years. The lymphocyte responses was evaluated by measuring the extent of tritiated thymidine incorporation by cultured cells. In a group of sixty-four tuberculin negative children who had been BCG vaccinated in the neonatal period, lymphocyte response was significantly greater than in a group of non-vaccinated tuberculin negative children matched for sex. The highest reactivity appeared in another group of children vaccinated in infancy and tuberculin positive. Lymphocytes from BCG vaccinated children retain some sensitivity to tuberculin even years after the BCG vaccination and even at the time when the skin reactivity disappeared.