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E D Albert

Publications and source records attributed to E D Albert.

At least 109 records · Page 6Linked to original sources

Enhanced lymphocyte stimulation by bacterial lysates after treatment of probands.

The proliferative response of lymphocyte cultures upon the addition of a mixture of antigens from the lysates of different bacteria (Paspat) to the culture medium was investigated using lymphocytes of groups of probands that investigated using lymphocytes of groups of probands that had been treated with the i.c. test preparation (T.P.1, group I), the lyophilized test preparation given orally (T.P.2, group II), a commercially available lyophilized bacterial lysate of similar composition given orally (T.P.3, group III), or with placebo (group IV). Lymphocyte cultures were set up on day 0 (before treatment), day 40 and day 70 (after treatment). The results show, that T.P.1 and T.P.2 produce a dose dependent proliferative response in lymphocyte cultures with a peak reactivity between 70 and 210 micrograms/ml. The degree of stimulation obtained with the bacterial lysate in different concentrations is increased in groups I and II over the stimulation obtained before treatment. Groups I and II which were treated with T.P.1 (i.c.) and T.P.2 (orally) are significantly different in their response to the bacterial lysate from the groups treated with T.P.3 or placebo on days 40 and 70. Evidence is presented that the stimulation obtained is predominantly a proliferation of T-cells.

Antigens, Bacterial↗

A comprehensive search for segregation distortion in HLA.

Segregation distortion, the non-Mendelian segregation of gametes, has been well documented among diverse groups of organisms. These cases are characterized by extreme segregation ratios found only in males. Previous reports have suggested the existence of segregation distortion operating in the HLA system of humans, a tightly linked complex of genes which regulates the immune system. In mice, some alleles of the T/t complex, which is linked to H-2 (the HLA homologue of mice), cause extreme segregation distortion in wild mice populations. Here we report on the examination of a large body of pedigree data on non-diseased families, scored for the alleles of five HLA region loci. We searched for segregation distortion on the basis of five different models of inheritance: allelic, haplotypic, genotypic, diffuse occurrence in families, and autosomal effects on the sex ratio. There was no clear evidence for segregation distortion. In particular, the possibility of extreme levels of segregation distortion was firmly rejected in the populations examined, thus reducing the likelihood of common distortion-causing HLA associated haplotypes in our species.

Alleles↗

Characterization of DR blank alleles by restriction fragment length polymorphism (RFLP).

Using a combination of conventional DR serology and RFLP analysis of DR beta and DQ beta, we have been able to identify two different types of DR antigens which belong so far to the DR blank group. The antigen DR-LOT is found on a haplotype A29, Bw60, Cw3, DRblank, DRw52, DQw1. The DR beta-EcoRI RFLP pattern of this haplotype is different from the patterns observed for DR1, DR2, DR3, DR4, DR5, DRw6, DR7, DRw8, DRw9, DRw10, and appears to be composed of a combination of DR2 and DRw6. The DQ beta-EcoRI pattern shows that this haplotype carries the DQw1 split DQR2.6. The second DR blank antigen which we found in a total of five individuals (three unrelated persons and two parents) on B35 positive haplotypes is characterized by a DR beta-EcoRI RFLP pattern indistinguishable from DR1 and by negative reaction with anti-DR1 sera. This antigen appears to be identical to what has been described by Cambon-Thomsen et al. (1986) and Bidwell et al. (1985) as HLA-DR-BON and DR"BR" respectively. We have demonstrated that this antigen is in strong linkage disequilibrium with the DQw1 split DQR1.

Alleles↗

Immunogenetics of rheumatoid arthritis in Israel.

In an attempt to study the variation of associations between HLA and rheumatoid disease a population of 44 Ashkenazi and 29 non-Ashkenazi patients with Rheumatoid Arthritis were tested for HLA-A, B, C and DR antigens and compared with the relevant control groups. In contrast to the results obtained in Middle European or North American Caucasians, Rheumatoid Arthritis in Israel is not associated with B15 and Cw3, indicating that it is very unlikely that B- and C-locus antigens are involved in coding for disease susceptibility for RA. The allele DR4 which is found associated with RA in almost all populations tested so far was in the total patient group (47.9%) slightly but not significantly more frequent than in the control group (38.3%). This difference was entirely due to a nonsignificant increase in the frequency of DR4 in the Ashkenazi patients (54.5%) compared to controls (40%), while the frequency of DR4 in non-Ashkenazi patients and controls was virtually identical (38.0% vs 36.7%). Another surprising finding was that the frequency of HLA-DR1, which has been reported to be increased in different populations of patients with RA was found to be completely normal in the present study on Israeli patients. The alleles of the Bf and the GLO system did not show any significant difference between patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗

Different gene defects in the salt-wasting (SW), simple virilizing (SV), and nonclassical (NC) types of congenital adrenal hyperplasia (CAH).

HLA (human leucocyte antigens) alleles and plasma 17-hydroxyprogesterone levels after ACTH stimulation were studied in 134 German families of patients with salt-wasting (SW), simple virilizing (SV), and nonclassical (NC) late-onset forms of CAH. HLA typing revealed a genetic difference between the two classical disease forms. SW-CAH was strongly associated with Bw47 and SV-CAH was closely linked to B5. The nearly complete connection of NC-CAH with B14 was confirmed. Bw47 and B14 were mostly components of the normally rare haplotypes A3, Bw47, DR7 and Aw33, B14, DR1, respectively. They did not occur in the families' disease-unaffected haplotypes. The HLA linkage data were consistent with those obtained from the ACTH stimulation test which showed a higher 17-hydroxyprogesterone increase in the group of genetically defined heterozygous relatives of SW patients than in the groups of heterozygous members of SV and NC families.

17-alpha-Hydroxyprogesterone↗

Genetic differences between the salt-wasting, simple virilizing, and nonclassical types of congenital adrenal hyperplasia.

Human leukocyte antigen (HLA) alleles and plasma 17-hydroxyprogesterone levels after ACTH stimulation were studied in 134 German families of patients with the salt-wasting (SW), simple virilizing (SV), or nonclassical (NC) late-onset form of congenital adrenal hyperplasia (CAH). Unexpected hormonal evidence for CAH was found in 6 otherwise healthy members of the relatives' group, who, therefore, were considered to be NC cryptic cases. HLA typing revealed a genetic difference between the 2 classical disease forms; SW CAH was strongly associated with Bw47, whereas SV CAH was closely linked to B5(w51). It also confirmed the nearly complete connection of NC CAH with B14. These alleles, especially Bw47 and B14, are mostly components of normally rare haplotypes: A3,Bw47,DR7 and Aw33,B14,DR1, respectively. They do not occur in the families' disease-unaffected haplotypes. Thus, it may be that all or almost all individuals from the general population bearing 1 of them are in fact CAH heterozygotes. Moreover, it seems possible to predict the severity of an infant's disease from his genomic type. The HLA linkage data were consistent with those obtained from ACTH testing, which showed significantly higher 17-hydroxyprogesterone increases in the genetically defined heterozygous relatives of SW patients than in the respective members of SV families. Of the families, 2 were also informative for mapping of the CAH disease gene(s) within the HLA-B to Glo interval.

17-alpha-Hydroxyprogesterone↗

[Arthropathy in idiopathic hemochromatosis].

In 22 of 35 patients (63%) with idiopathic hemochromatosis arthropathy could be demonstrated. In 20 patients the metacarpophalangeal joints (mainly II and III) with preference of the right hand were affected. Chondrocalcinosis of the wrist and knee was found both in two patients with metacarpophalangeal joint disease and in two patients without metacarpophalangeal disease. Further joints affected were the wrists (14), the other finger joints (11), and the knees (6). The dominant clinical complaint was pain in motion. Swelling and redness were rare findings only in case of acute exacerbations. The radiologic changes in the metacarpophalangeal joints were narrowing of the joint spaces, subchondral cysts, sclerosis of subchondral bone of metacarpal heads, and marginal osteophytic appositions at the joints. In one third of the patients arthropathy was evident before the diagnosis of idiopathic hemochromatosis was made. Histocompatibility testing confirmed that HLA-A3 is significantly more frequent in patients with idiopathic hemochromatosis than in normal persons. A statistically significant difference concerning HLA-phenotypes between patients with arthropathy and patients without arthropathy could not be detected. There was no case of arthropathy when 98 relatives of the patients were examined. However, idiopathic hemochromatosis was first detected in ten persons of this group.

Chondrocalcinosis↗

Heterogeneity of HLA-D(DR)4 detected by primary and secondary mixed-lymphocyte-culture reactions and by individual HLA-DR4 antisera.

One of our panel families (Sb), in which the paternal haplotypes Dw4, DR4 (a) and Dwblank, DR4 (b) segregate, was tested in primary mixed lymphocyte culture (1.MLC) and in the primed lymphocyte test (PLT). In the 1.MLC, cells which carry the a haplotype strongly stimulate b-haplotype cells, and vice versa. For the PLT, lymphocytes of two family-members were primed against the a haplotype and two against the b haplotype. A strong positive restimulation (RR greater than or equal to 60%) occurred only with cells bearing the original stimulating haplotype. The PLs were tested later against families St and Sm, which possess DR4 haplotypes, and against a panel of 73 unrelated persons. The results show heterogeneity of D(DR)4, suggesting at least three different subgroups: D(DR)4a, present on DR4 cells which strongly restimulate the anti-a PLs; D(DR)4b, on DR4 cells which strongly restimulate the anti-b PLs, and D(DR)4c, on the DR4 cells, which do not restimulate any of the PLs tested here. It seems also possible to differentiate between these subgroups with conventional DR-serology, as the 8W sera 903 and 981 react only with a-haplotype cells of family Sb, and ths 8W sera 872 and 1045 react only with b-haplotype cells.

Antilymphocyte Serum↗

Soluble HLA antigens in normal human immunoglobulin preparations.

Nine lots of normal human immunoglobulin produced in Bulgaria and India, prepared from venous or placental blood, were assayed for the presence of HLA antigens by the inhibition of cytotoxicity of HLA alloantisera using two different absorption procedures. The results indicate that the normal human immunoglobulin preparations tested here contain soluble HLA antigens as demonstrated by the inhibition of HLA alloantisera. Most of the higher frequency antigens of the HLA-A, B, C and DR locus appear to be present in the Ig-preparations. In samples from India there appears to be a lack of HLA-A3 antigen, which corresponds to the low frequency of A3 in this population. Immunoglobulins produced from different raw materials contain different amounts of soluble HLA antigens.

Absorption↗

[Bone marrow transplantation for aplastic anaemia (author's transl)].

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

Adolescent↗

[Bone marrow transplantation for relapsed, acute leukaemia (author's transl)].

Seventeen patients with relapsed, acute leukemia were grafted with bone marrow from HLA-identical siblings by the 'Munich Cooperative Group for Bone Marrow Transplantation' during the period from August 1975 to June 1980. The antileukemic and immunosuppressive conditioning treatment consisted of high doses of bischlorethyl nitrosourea, Cytosine-Arabinoside and Cyclophosphamide, as well as, total body irradiation of about 9 Gy (midline body dose) from dual 60Cobalt sources. Methotrexate was given to all patients for prophylaxis of graft-versus-host disease (GvHD). Nine patients received marrow that was treated with anti-T-cell globulin (ATCG) "in vitro".--Crossreacting antibodies against hemopoietic stem cells were removed by absorption. Two of 5 evaluable patients given untreated marrow developed chronic GvHD, while patients given ATCG-treated marrow did not show unequivocal symptoms of GvHD. Six patients are in complete remission one to 33 months following bone marrow transplantation (b.m.t.) Five patients died with relapses of leukemia between 3 1/2 and 24 months following b.m.t., 3 patients died with interstitial pneumonia within 3 months of b.m.t. and 3 patients died with insufficient graft function within 4 weeks of b.m.t. Four of thirteen patients that were grafted more than 6 months ago are presently alive and in continuous complete remission at 11, 14, 29 and 33 months following b.m.t. Our results confirm that longterm remissions can be obtained with b.m.t. in patients with acute leukemia in advanced stage.

Acute Disease↗