[Transfusion therapy in patients with severe aplastic anemia after bone marrow transplantation].
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Biomedical subjects
Publications and source records attributed to A Kastelan.
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Nonclassical steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is defined by clinical and hormonal criteria that distinguishes it from the classical 21-hydroxylase deficiency. No estimates of the gene frequency of nonclassical 21-hydroxylase deficiency, also called attenuated, late-onset, acquired, and cryptic adrenal hyperplasia, have been published thus far. Here, we have used HLA-B genotype data in families containing multiple members affected with nonclassical 21-hydroxylase deficiency together with the results of quantitative hormonal tests to arrive at estimates of gene and disease frequencies for this disorder. We found nonclassical 21-hydroxylase deficiency to be a far more common disorder than classical 21-hydroxylase deficiency, which occurs in 1/8,000 births. The prevalence of the disease in Ashkenazi Jews was 3.7%; in Hispanics, 1.9%; in Yugoslavs, 1.6%; in Italians, 0.3%; and in the diverse Caucasian population, 0.1%. The gene for nonclassical 21-hydroxylase deficiency is in genetic linkage disequilibrium with HLA-B14 in Ashkenazi Jews, Hispanics, and Italians, but not in Yugoslavs or in a diverse, non-Jewish, Caucasian group. The penetrance of nonclassical 21-hydroxylase deficiency gene in the HLA-B14 containing haplotypes was incomplete. Thus, nonclassical 21-hydroxylase deficiency is probably the most frequent autosomal recessive genetic disorder in man and is especially frequent in Ashkenazi Jews, Hispanics, Italians, and Yugoslavs.
This is a 21-month-old boy with pseudohypoaldosteronism (PHA) in coincidence with celiac disease. The diagnosis of PHA was made on the basis of hyponatremia, hyperkalemia and large urinary salt losses, as well as high renin activity and aldosterone levels and increased urinary plasma aldosterone. Whereas mineralocorticoid therapy was ineffective, salt therapy has proven successful. The patient's HLA type was found to be characteristic of gluten-enteropathy (A1, B8, DR3). The combination of PHA and celiac disease has not yet been described and is probably a coincidence. However, it is suggested that other PHA patients be typed in order to investigate the segregation between HLA type, PHA and celiac disease.
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We wish to present in this paper the main clinical, roentgenological and immunogenetic characteristics of our patients with the ankylosing spondylitis syndrome, who do not possess the HLA-B27 antigen. Of 553 patients permanently treated in the Ward for Rheumatic Diseases of the Medical Faculty in Zagreb, 16 patients (7 women and 9 men) have been found who do not have the HLA-B27 antigen. Their average age was 39.6 (men: 46; women: 33; range: 25-66) years. The diagnosis of ankylosing spondylitis had been made on the basis of the Rome criteria (1) and that of sacroiliitis on the criteria of Hart and Robinson (2). HLA antigens were determined on the peripheral blood lymphocytes using the microcytotoxic test according to Terasaki and McClelland (3).
A murine allo-immune A.TH anti-A.TL (anti-Iak) serum pool and sera from individual immunized mice were tested on a large panel of human DR typed B cells, obtained from peripheral blood (PBL-B cells), and human lymphoid tumour cells. The anti-Iak serum pool appeared to be a useful reagent both in cytotoxicity and immunofluorescence for the examination of the presence of class-2 HLA molecules on tumour cells. Only one discrepancy was observed when the pool was tested in parallel with a xeno-anti-human B-cell serum on the cells of 56 lymphoid tumours. Nine sera from individual mice were tested on a panel of 93 PBL-B cells. Some of these sera reacted significantly more weakly with human B cells positive for the DR5 and/or DR7 antigens.
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The concentration of testosterone was determined in sera of 122 HLA-typed women. Subsequently the women were classified in the category below or above the mean serum testosterone concentration. When the frequencies of HLA antigens were compared in these two categories of women, it was found that HLA-B5 and HLA-B12 antigens were significantly increased in the category of women with serum testosterone level above the mean concentration (P less than 0.01 and P less than 0.05, respectively). The frequency of HLA-B8 antigen was significantly decreased in the same category of women (P less than 0.05). The comparisons of the mean testosterone values of each HLA antigen and the variance analysis have also shown significant differences between the mean of HLA-B8 antigen and the means of other HLA antigens--HLA-A2, A3, A9, B5, B12 and Bw35. These results gave further conclusive evidence that gene(s) inside HLA region influence either the androgen hormone metabolism itself or cellular sensitivity to hormonal action as it has been presented for congenital adrenal hyperplasia.
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Regional differences in serological features of chronic active hepatitis (CAH) were assessed from study of unselected patients with CAH, 53 from Zagreb, Yugoslavia and 53 from Melbourne, Australia. A group of 29 patients from Zagreb with chronic persistent hepatitis (CPH) was also included. The serological marker studied was immunofluorescence reactivity to cytoskeletal components, actin cables (AC) and intermediate filaments (IF), these being mostly responsible for the smooth muscle antibody reactivity which occurs in CAH. The Zagreb cases of CAH differed from the Melbourne cases by having a significantly lower frequency of anti-AC (8% vs 55%) and a significantly higher frequency of anti-IF (34% vs 15%), and correspondingly had a higher frequency of markers of hepatitis B virus (HBV) infection (HBsAg, 53% vs 8% and anti-HBc, 72% vs 34%), and a differing HLA profile, with HLA BW35 higher (38% vs 14%) and B8 lower (18% vs 56%). This study illustrates the differences among populations in expression of CAH, in that HBsAg is held to specify the HBV-associated type, and antibody to actin is held to specify the autoimmune type. These differences would be determined in part by environmental influences, notably HBV, and genetic influences, notably HLA, and are reflected by the differing patterns of immunofluorescence reactivity with the cellular cytoskeleton.
The concentration of plasma testosterone (T) and dihydrotestosterone (DHT) was determined in 2 groups of nonpregnant and pregnant women. The 1st group consisted of normal women and the 2nd of women with recurrent pregnancy disorders of unknown etiology. Significantly higher concentration of plasma DHT in nonpregnant women from the 2nd group was found (44.9 +/- 22 ng/100 ml) as compared to nonpregnant normals (24.2 +/- 5.2 ng/100 ml), p less than 0.01. There was no difference in the concentration of plasma T between the groups studied (p = 0.165).
Cadmium chloride (CdCl2) added to human lymphocyte culture inhibits the proliferative response induced by phytohaemagglutinin (PHA), pokeweed mitogen and allogenic lymphocytes in mixed lymphocyte reaction. Minimally effective concentrations of CdCl2 were 3.3, 1.6 and 1.6 microM, respectively. The inhibition was greatest when CdCl2 was added at initiation of cultures and declined if the addition of CdCl2 was postponed. The presence of CdCl2, regardless of the presence of PHA during the first 24 h of incubation suppressed the proliferative response to subsequent stimulation with PHA, indicating that cadmium affects an early step of blastogenic transformation.
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A single ipl injection of 0.25 mg CP into CBA mice led to accumulation of macrophages in the pleural cavity, but it did not influence RES as an injection given iv ipl CP caused a three-to-five-fold increase in the number of nucleated cells in the pleural cavity which persisted at least 14 days. Of these cells 86% were macrophages as shown by their esterase activity. Less than 30% of cells from the pleural cavity of normal mice were esterase positive. Macrophages from the pleural cavity of CP-treated mice were capable of destroying in vitro cultures of a syngeneic mammary carcinoma, while normal pleural macrophages exerted no effect; the former were not cytotoxic for either syngeneic or allogeneic embryo fibroblasts. Ipl CP protected mice against iv injected mammary carcinoma cells; given to mice 7 days after iv inoculation of tumor cells it significantly reduced the number of tumor nodules in their lungs.
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The frequencies of HLA antigens were determined in an experimental group of women with recurrent gestational disorders mainly expressed as spontaneous abortions of unknown etiology. The estimated antigen frequencies in this group were compared with the antigen frequencies in 158 unrelated persons (79 couples with no record of secondary infertility). A significantly higher frequency of antigen HLA-A9 was found in the experimental group as compared with the controls (corrected P = 0.0015). A greater degree of HLA compatibility was found between each woman from this group and her husband, considering 45 couples, as compared with 79 control couples. These results indicate that gene(s) close to the HLA region may have an influence on the reproductive performance in humans.
Balkan endemic nephropathy, a fatal family disease with unknown aetiology and pathogenesis is typical for three neighbouring regions in Bulgaria, Yugoslavia and Rumania. HLA typing of 180 patients from the endemic area in Bulgaria was done and the antigen frequencies were compared with 1264 healthy controls. An increased frequency (P less than 0.001) of the antigen HLA-B18 in the patients was demonstrated.