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M Brandt

Publications and source records attributed to M Brandt.

At least 91 records · Page 5Linked to original sources

Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies.

The first human monoclonal islet cell antibodies of the IgG class (MICA 1-6) obtained from an individual with Type 1 (insulin-dependent) diabetes mellitus were cytoplasmic islet cell antibodies selected by the indirect immunofluorescence test on pancreas sections. Surprisingly, they all recognized the 64 kDa autoantigen glutamate decarboxylase. In this study we investigated which typical features of cytoplasmic islet cell antibodies are represented by these monoclonals. We show by double immunofluorescence testing that MICA 1-6 stain pancreatic beta cells which is in agreement with the beta-cell specific expression of glutamate decarboxylase. In contrast an islet-reactive IgM monoclonal antibody obtained from a pre-diabetic individual stained all islet cells but lacked the tissue specificity of MICA 1-6 and must therefore be considered as a polyreactive IgM-antibody. We further demonstrate that MICA 1-6 revealed typical features of epitope sensitivity to biochemical treatment of the target tissue which has been demonstrated for islet cell antibodies, and which has been used to argue for a lipid rather than a protein nature of target antigens. Our results provide direct evidence that the epitopes recognized by the MICA are destroyed by methanol/chloroform treatment but reveal a high stability to Pronase digestion compared to proinsulin epitopes. Conformational protein epitopes in glutamate decarboxylase therefore show a sensitivity to biochemical treatment of sections such as ganglioside epitopes. MICA 1-6 share typical features of islet cell and 64 kDa antibodies and reveal that glutamate decarboxylase-reactive islet cell antibodies represent a subgroup of islet cell antibodies present in islet cell antibody-positive sera.

Animals↗

Feeding value of whole-crop wheat silage for ruminants related to stage of maturity and cutting height.

Wheat was harvested five times during maturation, ranging from the middle of the milk stage to the transition to yellow ripeness (YR, cutting height of 10 to 12 cm), and ensiled. At the last two stages of maturity, the plants also were cut at 34 to 36 cm. The effect of stage of maturity on digestibility of dietary OM by sheep fed at maintenance was modest, but significant (linear effect, P < 0.01, silage mean 69.4%). Voluntary intake of OM was affected differently by increasing stage of maturity: it first declined but then rose as wheat reached the YR stage (quadratic effect; P < 0.10, silage YR + 28 g/kg body weight). The energetic feeding potential, calculated as the voluntary intake of digestible OM, was not affected by stage of maturity or by cutting height (P > 0.1). When the proportion of stem decreased, OM digestibility increased by 2 to 3 percentage units, but voluntary intake was not changed (P > 0.1). Digestibility of crude fibre decreased, and digestibility of NDF and ADF tended to decrease with increasing stage of maturity (68 to 63%, 62 to 59% and 58 to 55% respectively), whereas the cell wall fractions analysed at the level of single sugars showed no distinct changes. In contrast, decreasing the proportion of stem increased the digestibility of all cell wall fractions except galactose and arabinose. Based on available information about the conservation problems associated with later stages of maturity, wheat should be harvested for whole-crop silage at the beginning of the dough stage with a normal, low cutting height.

Animals↗

Femoral remodeling after arthroplasty of the hip. Prospective randomized 5-year comparison of 120 cemented/uncemented cases of arthrosis.

We compared radiographically the femurs for 5 years after cemented (Landos Titane) and uncemented (Zweymüller/Endler) hip arthroplasty (THA) for coxarthrosis in 120 patients. The bone changes followed a characteristic time-course with rapid initial remodeling and almost no further changes after 3-4 years. No association between bone changes and clinical results was found. The groups did not differ in bone atrophy and ectopic bone formation, whereas the incidence of distal cortical hypertrophy and proximal radio-opaque double line was higher around uncemented stems. The age and body weight of the patients and the stem size did not affect the bone changes, but women with uncemented stems developed more bone atrophy than did men.

Aged↗

[Brain evolution of the human from the paleoneurologic viewpoint].

Paleoneurology interprets natural or artificial endocasts. It is, therefore, the only method which is able to provide direct information on the ancestry of the human brain. Australopithecus, Homo habilis and Homo erectus are of outstanding importance concerning human evolution. This short review deals with some well-preserved endocasts of these forms. Possibilities and limitations of paleoneurology are discussed with respect to the taxonomic attribution of fossil specimens. Functional aspects of the cortical sulcus pattern can be interpreted rather strictly and is, therefore, of considerably phylogenetic significance. It indicates that even some early hominids exhibit a human-like brain organization (e.g. KNM-ER 1470) while others (such a KNM-ER 1805) feature a rather pongid-like brain organization. However, controversy over the interpretation of endocasts from early hominids continues: It has not been possible to unequivocally demonstrate a human-like feature of the Australopithecus brain.

Animals↗

Human monoclonal islet cell antibodies from a patient with insulin-dependent diabetes mellitus reveal glutamate decarboxylase as the target antigen.

The autoimmune phenomena associated with destruction of the beta cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

Adolescent↗

In vitro prostaglandin release from and platelet-activating factor accumulation in isolated endometrial cells from pregnant and pseudopregnant rabbits.

Prostaglandin (PG) release from and platelet-activating factor (PAF) accumulation by enzymatically isolated endometrial epithelial and stromal cells from Day 6 pregnant and Day 6 pseudopregnant rabbits were studied in vitro, using RIA for PG measurement and a platelet aggregation assay for PAF measurement. On the first day of culture in serum-free media, PGF release into the medium was significantly higher from epithelial cells from Day 6 of pregnancy than from stromal cells from Day 6 of pregnancy or pseudopregnancy. PGE release did not differ significantly among these cell types. The addition of indomethacin (10(-5) M) to similar cultures inhibited release of both PGs from both cell types, but to a much greater extent from stromal than from epithelial cells. Significant stimulation of PG release by A23187 was achieved under all conditions on the fifth day of culture; PGE release was significantly greater than PGF release from stromal cells from Day 6 of pregnancy and pseudopregnancy, and release of both PGs from stromal cells was significantly greater from Day 6 of pregnancy than from Day 6 of pseudopregnancy. PG release from similar cells, cultured in medium containing 10% calf serum, was highest on the first or second day of culture and then, especially for PGF, declined with continued culture. PGE release was significantly higher than PGF release from stromal cells on the third and fourth days of culture. The ratios of PGF/PGE release from epithelial cells were significantly higher than those from stromal cells over the 5-day culture period for both reproductive stages. These ratios indicate the differential release of PGE and PGF from rabbit endometrial cell subpopulations and indicate a preferential release of PGE from stromal and of PGF from epithelial cells. Under basal conditions, PAF was not detected in epithelial or stromal cells cultured for 2 or 4 days, or in the associated culture media. If PAF had been released into the medium, it would have rapidly metabolized. Short exposure to calcium ionophore A23187 (10(-5) M) was able to stimulate PAF accumulation in epithelial and stroma cells in serum-free media, probably via the remodeling pathway. PAF was not detected in the medium. Intracellular PAF accumulation after exposure to A23187 (10(-5) M) for 5 min was significantly greater on the second day of culture than on the fourth day in epithelial and stromal cells from Day 6 of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The use of DiI-marked hepatocytes to demonstrate orthotopic, intrahepatic engraftment following hepatocellular transplantation.

A novel method is described for marking primary hepatocytes with the fluorescent dye DiI prior to hepatocellular transplantation and identifying these cells within the hepatic parenchyma of recipient animals by fluorescence microscopy and flow cytometry. Optimal conditions are described for marking cells with DiI in suspension or in monolayer cultures prior to transplantation. DiI is shown to be nontoxic to hepatocytes and not to be exchanged between adjacent cells in vitro. Histological analysis of transplanted tissues shows DiI staining of engrafted hepatocytes and phagocytotic cells (Kupffer cells). This analysis shows that hepatocytes engraft within the hepatic parenchyma and exhibit a histological appearance indistinguishable from normal by conventional hematoxylin and eosin staining. Many previous reports of hepatocellular transplantation have been limited by their inability to unequivocally identify transplanted cells within the liver. These data illustrate the importance of having specific markers for transplanted cells that engraft in an orthotopic location and assume a normal morphological appearance.

Animals↗

A single Trp121 to Ala121 mutation in human cyclophilin alters cyclosporin A affinity and peptidyl-prolyl isomerase activity.

Fluorescence and NMR spectral data have suggested an interaction between the single tryptophan in cyclophilin (CyP) and its high affinity ligand cyclosporin A (CsA). To study this interaction, a site mutation of Trp121 to Ala was introduced into human cyclophilin (CyP) and the encoded protein was expressed in E. coli. The Ala121 mutant was shown to catalyze the peptidyl-prolyl cis-trans isomerase (rotomase) reaction with several peptide substrates, albeit at less than ten percent the rate of the purified recombinant human CyP. Values for the apparent inhibition constant (Ki,app) of cyclosporin A with the human CyP and the Ala121 mutant were determined to be 1.6 +/- 0.4 nM and 640 +/- 90 nM, respectively by tight-binding inhibition analysis. The greater loss of affinity for CsA binding (400-fold) than for rotomase catalysis (20 fold) suggests that the catalytic and CsA binding properties associated with CyP can be decoupled as has been observed with an homologous protein found in E. coli (Liu, J. & Walsh, C.T. (1990) Proc. Natl. Acad. Sci. USA 87, 4028-4032).

Alanine↗

Antenatal diagnosis of ovarian cysts: natural history and therapeutic implications.

A retrospective study from 1980 to 1990 shows 29 ovarian cysts in 27 patients diagnosed by prenatal ultrasound performed between 28 and 38 weeks of gestation. Ten patients underwent surgery, 17 patients were observed with serial ultrasound. Delayed good quality sonograms after spontaneous resolution of the cyst in a selected group of 7 patients showed restoration of a normal ovarian anatomy. The size of the cyst and/or its sonographic characteristics are the 2 main factors for deciding a conservative or a surgical management.

Female↗