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Biomedical subjects

E Sommer

Publications and source records attributed to E Sommer.

At least 19 recordsLinked to original sources

A subset of HLA-DR9 molecules is detected by a polymorphic monoclonal antibody on lymphoblastoid cell lines but not on peripheral blood lymphocytes.

Some mAbs recognizing polymorphic epitopes of HLA-DR molecules exhibit striking differences of reactivity with the same HLA-DR molecules expressed by different cell types. In this study, we investigated the basis for the differential reactivity of the polymorphic anti-DR mAb OHA TM901 with HLA-DR9 molecules expressed by human PBLs or LCLs. By immunoprecipitation experiments we showed that OHA TM901 recognizes a subset of HLA-DR9 molecules from LCLs. This subset corresponds to HLA-DR9 molecules containing immature-type oligosaccharides. The absence of OHA TM901 reactivity with HLA-DR9 PBLs, as revealed by cytofluorometry analysis, suggests that this subset is either not expressed or expressed at a very low level on PBLs. These results indicate that overexpression of HLA-DR molecules in immortalized LCLs could lead to cell-surface expression of underglycosylated forms which are generally not found on the cell surface of PBLs.

Antibodies, Monoclonal

[Contribution of the ophthalmologist to presymptomatic diagnosis of familial adenomatous polyposis (FAP)].

Familial adenomatous polyposis (FAP) represents a hereditary precancerous condition. Symptoms often appear malignant transformation only. For persons at risk early recognition of gene carriers is essential. Approximately 80% of the patients show congenital hypertrophy of the retinal pigment epithelium (CHRPE) that can be recognized before clinical manifestation of FAP. In order to predict FAP 9 patients and 10 persons at risk from 6 FAP families were examined by endoscopy, molecular genetical and ophthalmological methods. Four patients from two families each had bilaterally 4 CHRPE; four persons at risk did not have CHRPE. This is in accordance with endoscopic and molecular genetic results. The five patients and six persons at risk from the other four families did not have CHRPE, i.e., the percentage of CHRPE in the FAP patients examined was only 45%. Funduscopy permits early identification of gene carriers in families where the FAP patients have CHRPE. CHRPE is not present in persons at risk in these families, it is not necessary to conduct invasive diagnostic measures. Funduscopy should always be done in FAP patients and in persons at risk from CHRPE-positive families. An endoscopic examination should be recommended when CHRPE is observed incidentally in a person with a negative family history for FAP.

Adenomatous Polyposis Coli

Clinical implications from studies of HLA antigens in idiopathic nephrotic syndrome in children.

HLA class I and II antigen frequencies were determined in two large cohorts of children with idiopathic nephrotic syndrome (NS) from Southwest France (n = 199) and Southwest Germany (n = 152) and compared with unrelated healthy individuals from the same geographical areas. Strength of HLA association was expressed by the relative risk (RR) estimated by Odd's ratio. We examined 105 steroid-resistant and 242 steroid-sensitive NS patients who were subdivided in non-relapsers, infrequent relapsers and frequent relapsers or steroid-dependent patients. In steroid-sensitive patients significant associations were found with HLA-DR7 (RR 5.1 in French, 3.2 in Germans), -DQ2 (RR 4.7/2.3) and with the phenotypic combination HLA-DR3/DR7 (RR 5.6/7.7). Significant negative associations were encountered with HLA-DR2, -DR6 and -DQ1. The associations were stronger in frequent relapsers/steroid-dependent patients than in infrequent relapsers and were not significant in non-relapsers. In steroid-resistant patients the only significant association found was with the combined occurrence of HLA-DR3/DR7. We propose that in childhood NS tissue typing for selected HLA class II antigens is helpful in prediciting the clinical course.

Adolescent

Analysis of HLA-A/B recombinant families with new polymorphic markers.

The MHC in humans is a much studied region of the genome, the genes of which display a high rate of polymorphism and a high rate of linkage disequilibrium. Four families in which intra-class-I recombination has occurred have been analyzed with six polymorphic markers between HLA-A and -B in order to determine the full haplotypes of the whole families and to localize the points of crossover. The previously proposed order of the markers was confirmed by recombination mapping. In one family, the crossover was shown to have occurred in the 20-kb stretch of DNA bounded by the two markers (P3B and P5) between which no evidence of linkage disequilibrium was found, a region which constitutes of only about 1% of the distance between HLA-A and HLA-B. Although supportive of the suggestion of a hot spot of recombination in this region, based on the apparent lack of linkage disequilibrium between the markers P3B and P5, more such families need to be tested in order to confirm or refute this hypothesis.

Crossing Over, Genetic

New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells.

Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules.

Animals

[Measuring contrast sensitivity using visual acuity tests in retinal and optic nerve diseases].

The luminance contrast needed to discern various test types was measured with monochromatic and achromatic light to detect discrete functional deficiencies of the retina and optic nerve in cases of normal visual acuity. Landolt rings corresponding to visual acuity levels from 0.04 to 1.0 were used as test types. A significant increase in the necessary minimum contrast was detectable with blue test light on large Landolt rings in patients with diabetic retinopathy, ocular hypertension and glaucoma and with green or yellow test light on medium-sized and small Landolt rings in patients with central serous chorioidopathy and optic atrophy. The additional contrast needed to reach the maximum visual acuity amounts to 14-100% compared with normal visual acuity, depending on the color of the test light and the diagnosis. The amount of contrast needed is greatest in retinal diseases, and it is therefore possible to a certain extent to distinguish these from diseases of the optic nerve.

Humans

[Immunologic phenomena in patients with proliferative retinopathy in diabetes mellitus type 1].

As a rule, in long-lasting diabetes type 1 there appear vascular complications in a form of proliferative retinopathy. While looking for the causes of fast vascular changes, the authors considered the possibility of immunological disorders. They started prospective examinations of patients with diabetes type 1 and proliferative retinopathy changes in the fundus of the eye. The authors evaluated the activity of angiogenic factors released by mononuclear cells isolated from peripheral blood of the patients examined. The authors found a significantly higher activity of these factors in patients with proliferative retinopathy in comparison with a control group of healthy persons and a group of patients with diabetes type 1 and simple retinopathy. The results obtained may indicate to immunological changes in the pathogenesis of proliferative retinopathy.

Adult

[Nocardiosis of the lung].

A rare case of pulmonary nocardiosis is reported. The patient was a non-immunodeficient Vietnamese woman. The age of the patient was 31 years.

Adult

A new HLA-D specificity associated with DR blank: D-BON.

Since 1980, a DR blank specificity undefined by serology but known to segregate in families linked to DQw1 has been recognized. We describe a Caucasoid family, BON... where 4 among 8 children are homozygous for such a specificity; their cells can be used as homozygous typing cells and the specificity defined is provisionally called D-BON. There is no known consanguinity in this family. The homozygous D-BON cells carry DR molecules as shown by their reactivity with monomorphic anti-DR monoclonal antibodies. In a random family material consisting of 210 haplotypes, the gene frequency of D-BON is between 1 and 2%, which corresponds to about 40% of the DR blank frequency. The D-BON specificity seems associated with DQw1 and also with B35 and C4B2.

Adult

Platelet absorption on the test tray (PATT): a rapid method for the screening of HLA class II antibodies using the two-colour fluorescence method.

Several strategies have been proposed for the screening of alloantisera towards HLA class II antigens. Most often the absorption of the sera with platelets is required in order to remove their anti-HLA-A, B, C activity. We have developed a simple micromethod for platelet absorption of sera: platelet absorption on the test tray (PATT); 0.5 microliter of platelet suspension is incubated with 0.5 microliter of the serum to be absorbed in the same tray which is subsequently used for the microlymphocytotoxicity by the two-colour fluorescence method. This technique is proved to be almost as efficient as classical absorption procedures: out of 44 anti-HLA-A, B sera the T-cell activity is completely removed in 43 by a classical procedure as compared to 41 by PATT; only 8% discrepancies were found among 394 reactions. PATT was then used for anti-B lymphocyte screening in 419 anti-HLA-A, B sera; 4% of the sera remained cytotoxic towards T and B lymphocytes while 35% reacted only with B cells, several of them being DR specific. PATT can also be useful for T/B lymphocyte differential cross-matches before kidney transplantation. The method is now routinely used in our laboratory for anti-HLA class II antibody screening.

Absorption

[Effect of intestinal circulation on the osmotic balance between the intestinal lumen and blood in awake rats].

Total electrolyte concentrations in portal vein and aortic blood of unanesthetized rats were measured continuously by means of ultrafiltrate conductometry. Portal flow rate and mesenteric venous pressure (pmes) could also be measured. The last could be raised to any desired level by a specially developed portal vein clamp. Intraduodenal injections of water (0.5 or 1% BW) were given in a first series of experiments with and without sham-attacking (activating) the animal for 10 s and in a second series with and without raising pmes. Portal flow rate dropped in both cases. But whereas activation led to a decrease in the concentration changes in the v. portae and in arteriovenous differences, a rise in pmes had the opposite effect. Comparison of the total free water change in the v. portae (Mpo) with the quantity of water given (MH2O) revealed that Mpo/MH2O dropped in both series of experiments, provided that pmes was not increased by much more than 2 mm Hg (portal flow did not decrease much under normal). The differing results were explained by taking into account the specificities of blood circulation in the gut wall. The experiments have shown that even transient obstruction of gut tissue perfusion can delay dissipation of concentration imbalance between the gut and parenteral space, thus having adverse effects on the gut cells.

Animals

Studies on intestinal absorption by single-injection technique and continuous measurement of portal vein blood electrolyte concentration and hematocrit in the alert rat.

Whole blood and ultrafiltrate conductivity in the portal vein (as a measure of hematocrit and total electrolyte concentration, Cel, respectively) and arterial pressure of alert rats were measured continuously. Single intraduodenal injections of solutions iso- and hyperosmotic to blood (0.5 or 1 per cent of body weight) produced characteristic changes which were compared with those after the application of water. Whereas H2O and isosmotic passively absorbed substances (sorbose and urea) caused a very variable Cel drop, isosmotic actively absorbed nutrients elicited individually constant but interindividually different (glucose greater than alanine++ greater than arginine) changes due to solute coupled electrolyte free water transport. This was taken as evidence of variable paracellular shunt permeability playing a role in passive, but not in active absorption. The magnitude of Cel changes was related to absorption rate, which was confirmed by behaviour with hypertonic solutions, where osmotic activity in the gut was lost the sooner, the more rapid absorption rate was. Shunt permeability was temporarily blocked by arginine. Hct changes immediately after injections indicated fluid loss from portal vein blood, which could be evaluated in the case of mannitol. The thickness of the absorptive layer, obtained from latency of Cel change after urea, delivered values not exceeding 0,51 mm for the unstirred layer. The latencies after glucose and alanine were usually not much greater than after urea. Cel rise after hypertonic solutions had the same latency as Cel drop after water. Small arterial pressure changes after nutrient solutions, mostly absent after injections of water and NaCl, indicated circulatory effects originating in the gut in association with the former.

Alanine

HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM).

The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.

Adult