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Biomedical subjects

Z T Handzel

Publications and source records attributed to Z T Handzel.

At least 55 records · Page 3Linked to original sources

A controlled trial of treatment of acquired immunodeficiency in severe measles with thymic humoral factor.

A randomized controlled trial of treatment with thymic humoral factor (THF) in 20 children with severe complicated acute measles infection, resulted in objective benefit as evidenced by improvement in the ESR and a fall in C-reactive protein, fewer complications and a reduced incidence of secondary herpes infection. An increased ratio of helper to suppressor T cells (OKT4/OKT8 ratio) and a greater lymphocyte transformation response to phytohaemagglutin was seen in those children receiving THF. We conclude that THF treatment helps to prevent the development of complications particularly secondary viral infections possibly by enhancing cell-mediated immune responses.

Child, Preschool↗

Cell-mediated immune suppression due to alfathesin in short-term anaesthesia.

The immunosuppressive effects on cell-mediated immunity of alfathesin, when used as the sole agent for short-term anaesthesia, were investigated in ten women undergoing pregnancy termination. Cell-mediated immunity was evaluated by E rosette formation in peripheral blood (reflecting the percentage of T lymphocytes) and by proliferative responses to the mitogens concanavalin A and phyto-haemagglutinin in various concentrations. Measurements were made before alfathesin was administered, and again after 60 minutes, two days and seven days. Significant reductions in the percentage of E rosettes in peripheral blood and in mitogenic responses to concanavalin A were observed 60 minutes after administration of alfathesin. A model is proposed in which alfathesin binds to lymphocytic membrane receptors, thus affecting in vitro cell-mediated immune reactions.

Abortion, Induced↗

Cell mediated immunity and effects of "thymic humoral factor" in 15 patients with SSPE.

Cell mediated immunity (CMI) in 15 patients with subacute sclerosing panencephalitis (SSPE) was assessed by E-rosette formation, leucocyte migration inhibition factor (LIF) production, and proliferative responses to mitogens. In eleven patients, one or more of these parameters were impaired. These defects varied among the different patients and no consistent or uniform pattern of immune deficiency could be demonstrated. Although no single patient had a generalized reduction of all the T-cell functions, a diminished percentage of E-rosetting cells was the most frequent abnormal parameter (7 out of 15 patients). There was no correlation between the clinical state of the patients and the immune defects. Thymic humoral factor (THF), a thymic hormone, reconstituted at least one CMI impaired function especially the reduced levels of E-rosette forming cells in 7 out of 9 patients. It seems unlikely that a generalized cell-mediated defect is the underlying cause of this disease, but immunomodulatory therapy should be considered in some selected cases.

Child↗

Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever.

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Adolescent↗

Cellular immunity in children with coeliac disease.

The experimental evidence implicating defective cell-mediated immunity in coeliac disease, a condition where symptomatology is believed to be due to immunological reaction to wheat gluten, is often inconsistent and sometimes controversial. Studies of certain parameters of cellular immunity in four groups of pediatric patients were performed: coeliac patients on normal diet; coeliac patients consuming gluten-free diet; children with cow's milk sensitivity. In all these assays no significant differences were found between treated or untreated coeliac children, infants with milk allergy or the gastro-intestinal control groups. On the basis of this study we could find no evidence of impairment of cell-mediated immunity in coeliac children. This conclusion is compatible with the hypothesis that intestinal damage may be due to a subpopulation of lymphocytes sensitive to gluten in persons with normal immune systems. In adults where abnormalities of cell-mediated immunity have sometimes been noted, the reason could be a loss of lymphocytes from the damaged mucosa of the gastrointestinal tract following prolonged antigenic stimulation. This indicated the need for strict adherence to a gluten-free-diet.

Adolescent↗

Effect of gluten-free diet on an immunological assay for coeliac disease.

The leucocyte migration inhibition factor (LIF) test for the presence of lymphocytes sensitised to gluten was evaluated over the past 4 years in patients with coeliac disease and correlated with the presence of gluten in the patients' diet. 149 LIF tests were done in 66 coeliac patients, 35 of whom were on a normal diet. However, 7 of 8 clinically and histologically diagnosed cases of coeliac disease who were LIF negative when first tested on a normal diet became LIF positive when placed on a gluten-free diet, so that 94% of patients with coeliac disease were LIF positive. On a prolonged gluten-free diet about 50% of LIF-positive cases became negative. The response to the LIF test seems to be related to gluten intake, with higher LIF values when the patient is taking gluten, and lower values when gluten is eliminated from the diet.

Celiac Disease↗

Immunological assay for the diagnosis of coeliac disease: interaction between purified gluten fractions.

Increased leukocyte migration inhibition factor (LIF) production by coeliac patients' lymphocytes is a reliable immunologic test for gluten-sensitive coeliac disease providing the small peptide subfractions of gluten are used as mitogens. To investigate discrepancies in results obtained in various published studies, subfractions (B2 and B3) of crude gluten peptic tryptic digest [Frazer's fraction III (F3)] were used singly and in combination as mitogens in coeliac patients and compared in various doses with F3. There was significant increased production of LIF with B2 or B3 when tested separately as compared to a mixture of B2 +/- B3 or to F3. LIF production with B2 or B3 was 23.7 +/- 6.9%; with B2 + B3, it was 10.65 +/- 14.7% (t = 4.05; P less than 0.0005); and with F3, it was 9.2 +/- 10.2% (t = 5.8; P less than 0.0005). There was no difference in the response between B2 + B3 and F3 (t = 0.4; P = 0.32). Studies of LIF production following stimulation by various doses and combinations of gluten mitogens in the same patient gave the best results with B2 or B3 in 10 microgram doses, with a tendency to less LIF production with higher dosages or combinations of B2 + B3 or F3, even to abolition of LIF production in some coeliac cases. The LIF assay is a reliable immunologic test for gluten sensitivity, providing the B2 or B3 subfractions are used as mitogens.

Adolescent↗

In vitro cell-mediated immunologic assay for cow's milk allergy.

The production of a lymphokine, the leukocyte-migration-inhibition factor (LIF), by peripheral blood lymphocytes in response to an in vitro challenge with bovine beta-lactoglobulin was assayed in infants and children suspected of having allergy to cow's milk protein. Of the patients studied, 24 had cow's milk allergy, 24 were normal control subjects, 18 had recovered from milk allergy, 10 were newborns, and 10 were babies suffering from acute gastroenteritis. All patients with milk allergy demonstrated significant LIF production in response to beta-lactoglobulin (23.5% +/- 6.4%). In the normal control subjects, LIF was 3.1% +/- 4.3% (P < .0005). Only two of the 24 control subjects and two of the ten newborns had high-normal values bordering on the positive. None of the ten babies with acute gastroenteritis gave a positive response. Most of the children who had recovered from milk allergy and were ingesting cow's milk had negative assays. This cell-mediated immune assay is shown to be a reliable test for the diagnosis of sensitivity to milk protein in infants and children, and for determining dietary treatment and when this treatment can be safely terminated. In most cases, its use should eliminate the need for the potentially dangerous and ethically questionable provocation test, as well as the need for repeated intestinal biopsies.

Animals↗

Production of immune and viral interferon by lymphocytes of newborn infants.

The ability of lymphocytes from newborn infants to produce two types of interferon was compared with that of lymphocytes from older children and adults. Cord blood lymphocytes were as capable of producing both viral interferon (stable at pH 2.0) following stimulation with polyriboinosinic acid-polyribocytidilic acid and immune interferon (unstable at pH 2.0) following stimulation with phytohemagglutinin as lymphocytes from older individuals. In a mixture of mononuclear and polymorphonuclear cells, it was the former that produced the interferon. Interferon may be important in the defense mechanism of the newborn infant against viruses and other microbial agents.

Adult↗

Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome.

Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia.

Ataxia Telangiectasia↗

Participation of a histamine-Sepharose-adherent subpopulation of human mononuclear cells in the production of leucocyte migration inhibition factor (LIF) in healthy children.

The separation of mouse splenic T lymphocytes into distinct subpopulations by fractionation on histamine-rabbit serum albumin Sepharose (H-RSAS) columns has been described. The H-RSAS-adherent T cells have been attributed regulatory functions associated with B cell activity, T cell-mediated cytotoxicity and the secretion of mediators such as immuno-interferon. The possibility that H-RSAS-adherent T cells exert a similar regulatory effect on an in vitro parameter of T cell-mediated immunity was investigated by assaying the production of leucocyte migration inhibition factor (LIF) in human blood samples, using the agarose droplet method. Phytohaemagglutinin (PHA) and BCG-purified protein derivative (PPD) were used as stimulants of LIF secretion which was measured as a percentage of inhibition of linear leucocytic migration. In normal individuals a highly significant (P less than 0.001) decrease was demonstrated in the production of LIF by peripheral blood leucocytes depleted of H-RSAS-adherent cells. Migration inhibition dropped from 36 +/- 11.7% to 21.2 +/- 12.9% in eighteen cases tested with PHA and from 29.3 +/- 11.7% to 17.2 +/- 9.8% in twelve cases tested with PPD. These results suggest the existence of a lymphocytic subpopulation involved in LIF production which expresses histamine receptors.

Cell Adhesion↗

An in-vitro immunological assay for diagnosis of coeliac disease.

Production of leucocyte-migration-inhibition factor (L.I.F.) by peripheral-blood lymphocytes in response to challenge with gluten fractions was studied in 55 patients with coeliac disease and in 32 controls. 96% of the patients with coeliac disease demonstrated significant L.I.F. reaction in response to gluten fractions irrespective of their dietary status. Only 2 out of 32 controls had a positive reaction. This was in response to the B2 or B3 fraction, but never to both. The agarose microdroplet method of L.I.F. assay is reliable and technically simple enough for use in most clinical laboratories. The assay of L.I.F. production by peripheral-blood lymphocytes in response to gluten fractions, would be a useful adjunct in the diagnosis of gluten-sensitive enteropathy.

Adolescent↗