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Biomedical subjects

W Richter

Publications and source records attributed to W Richter.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

[Radioimmunoscintigraphy of colorectal tumors with 99m-Tc marked CEA antibodies. Indications and clinical value].

In Germany, radioimmunoscintigraphy (RIS) (scintigraphic, specific imaging of benign and malignant diseases by radioactively labelled monoclonal antibodies) has been employed since 1985 in clinical trials involving patients with colorectal cancer. After proving successful for identifying primary tumors, RIS is now increasingly being used for the early diagnosis of recurrent and metastatic lesions. In this prospective study involving 75 patients with colorectal tumors confirmed by endoscopy and biopsy, it was shown that RIS using the SPECT technique with 99m-Tc-labelled monoclonal CEA antibodies has a sensitivity of 78% in the detection of local recurrent disease in cases in which diagnostic work-up has been inconclusive.

Adult↗
PubMed1992

Ochratoxin A production in Bavarian cereal grains stored at 15 and 19% moisture content.

Wheat, barley, and maize, each in 15-kg parcels at 15 and 19% initial moisture content (IMC), were kept in a Bavarian farm granary from June through November 1990. During this period, the grain at each IMC was analyzed for mycotoxins and monitored for grain temperature, carbon dioxide, seed germination, and microfloral incidence and abundance. Barley and maize stored for 20 weeks at 19% IMC contained ochratoxin A in amounts of 70 and 90 microg/kg, respectively. This mycotoxin was not detected in wheat stored at 19% IMC, nor in the grains stored at 15% IMC. Aflatoxin B1, sterigmatocystin, citrinin, and zearalenone were also assayed but not detected in grains stored at either IMC. Principal component analysis of the data indicated that ochratoxin A was produced in a damp niche in maize, when abundant metabolic activity and CO2 production by Penicillium glandicola and Aspergillus spp. were common.

Edible Grain↗
PubMed1992

Antibodies to the M(r) 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired beta-cell function.

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the M(r) 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p less than 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ beta chain (p less than 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Dextran sulfate-dependent fusion of liposomes containing cationic stearylamine.

The incorporation of the positively charged stearylamine into phosphatidylcholine liposomes was studied by measuring electrophoretic mobilities. Up to a molar ratio SA/PC = 0.5 an increase of the positive zeta potential can be observed. Addition of the negatively charged macromolecule dextran sulfate leads to a change of the sign of the surface potential of the PC/SA liposomes indicating binding of the macromolecule to the surface. This process is accompanied by an increase in turbidity, which is dependent on the molecular weight of the dextran sulfate and the SA concentration (measured by turbidimetry). Using the NBD/Rh and Pyr-PC fluorescence assays the fusion of SA containing liposomes was investigated. A strong influence of the SA content and molecular weight of dextran sulfate on the fusion extent was observed. The fusion extent is proportional to the SA content in the PC membrane and the molecular weight of dextran sulfate. PC/SA/PE liposomes exhibit a higher fusion extent after addition of dextran sulfate compared to PC/SA liposomes indicating that PE additionally destabilizes the bilayer. Freeze-fracture electron microscopy reveals that the reaction products are large complexes composed of multilamellar stacks of tightly packed, straight membranes and aggregated vesicles. The tight packing of the membranes in the stacks (and the narrow contact of the aggregated vesicles) indicates a strong adherence of opposite membrane surfaces induced by dextran sulfate.

Amines↗
PubMed1992

Redox cycling of potential antitumor aziridinyl quinones.

The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthesized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase in the presence of BABQ derivatives. At low concentrations (< 10 microM) some BABQ derivatives turned out to inhibit the production of superoxide and hydroxyl radicals by xanthine oxidase, while the effect on the xanthine-oxidase-induced production of hydrogen peroxide was much less pronounced. Induction of DNA strand breaks by reactive oxygen species generated by xanthine oxidase was also inhibited by BABQ derivatives. The DNA damage was comparable to the amount of hydroxyl radicals produced. The inhibiting effect on hydroxyl radical production can be explained as a consequence of the lowered level of superoxide, which disrupts the Haber-Weiss reaction sequence. The inhibitory effect of BABQ derivatives on superoxide formation correlated with their one-electron reduction potentials: BABQ derivatives with a high reduction potential scavenge superoxide anion radicals produced by xanthine oxidase, leading to reduced BABQ species and production of hydrogen peroxide from reoxidation of reduced BABQ. This study, using a unique series of BABQ derivatives with an extended range of reduction potentials, demonstrates that the formation of superoxide and hydroxyl radicals by bioreductively activated antitumor quinones can in principle be uncoupled from alkylating activity.

Antineoplastic Agents↗
PubMed1992

[The value of radioimmunoscintigraphy compared to computed tomography in the diagnosis and relapse diagnosis of colorectal tumors].

Radioimmunoscintigraphy (= RIS, scintigraphic "specific" imaging of benign and malignant diseases by means of radioactively marked monoclonal antibodies) has been performed in Germany in clinical studies since 1985 in patients suffering from colorectal cancer. After having been successfully proven in primary studies, RIS is now being used in the early diagnosis of recurrences and metastases. In the prospective study presented here the clinical usefulness of RIS was assessed in comparison against well-tried diagnostic methods including computed tomography in patients suffering from colorectal cancer. It was shown that RIS in SPECT technique (= single photon emission computed tomography) with 99mTc-labelled monoclonal CEA antibodies can visualise local recurrences if diagnostic findings are doubtful, with a sensitivity of 78% versus 50% for CT findings.

Adult↗
PubMed1992

Regression of left ventricular hypertrophy.

Since our first studies on hypertrophy regression, this parameter has achieved an increasing interest in the treatment of hypertension. During the past 8 years we studied different groups of antihypertensive drugs with the use of magnetic resonance imaging (MRI). This article discusses the antihypertensive drug carvedilol. We examined 17 patients with diastolic blood pressure of at least 95 mm Hg and left ventricular wall thickness of at least 15 mm. Measurements were carried out before and after treatment with 25 mg/day carvedilol for 6 months. We demonstrated a significant regression of septal thickness from 17.7 to 16.3 mm. At each wall, three measurements at different points were performed by MRI and the means were calculated. Left ventricular ejection fraction and wall motion did not show any significant changes in radionuclide ventriculography after treatment. The diastolic blood pressure was reduced from 98.0 to 88.7 mm Hg. All differences are significant (p less than 0.05). There was no significant correlation between the extent of regression of septal hypertrophy and the degree of pretherapeutic hypertrophy, the age of patients, or the dimension of blood pressure reduction.

Animals↗
PubMed1992

Chemical and physiological properties of polysucrose, a new marker of intestinal permeability to macromolecules.

To measure intestinal absorption of macromolecules we have developed a new technique employing synthetic polysucrose polymers as probe molecules. Polysucrose (PS) is water-soluble, nontoxic, resistant to intestinal enzymes, spherical and can be produced with a molecular weight distribution that relates to the size of many normal food proteins. Normally, a very small fraction of large molecules passes the exclusion barrier of the healthy intestine. Thus, quantification of resorbed macromolecules requires assays of high sensitivity. For detection of PS in various biological fluids, micro-ELISAs have been established. PS with a mean molecular weight of 14,700 daltons (PS 15,000) is rapidly excreted into the urine. Twenty-one healthy volunteers who orally ingested 1 g of this preparation showed a 12-hour urine excretion of 0.018% (interquartile range 0.014-0.022).

Adult↗
PubMed1992

Is it still adequate to study the nervous system using methods of catalytic enzyme histochemistry?

The frequent use of methods different from enzyme histochemistry evokes the question, whether it is still useful to apply methods of catalytic enzyme histochemistry to study the nervous system. In this brief overview it is shown, that catalytic enzyme histochemistry can still contribute to a better understanding of nervous system function. This was enabled by methodological progress, i.e., the modification of already existing procedures or the development of new techniques for the visualization and measurement of enzymes in tissue sections using their catalytic properties. The methods for acetylcholinesterase, monoamine oxidase as well as certain exoglycosidases and phosphatases will be given as examples. The application of these procedures as well as of methods for proteases, oxyradical-generating oxidases and enzymes involved in the metabolism of amino acid and other transmitters will illustrate, that qualitative (localization) and quantitative (measurement) catalytic enzyme histochemistry can still contribute to a better understanding of nervous system function.

Animals↗
PubMed1992

[Brain scintigraphy (SPECT) with thallium-201 in primary brain tumors].

We evaluated the role of thallium-201 single-photon emission-computed tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201 SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningiomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changing proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up.

Adult↗
PubMed1992

[The place of radioimmunoscintigraphy in the diagnosis and follow-up of ovarian cancer in comparison with computed tomography and second-look surgery].

In this prospective study the diagnostic capability of radioimmunoscintigraphy (RIS) was compared with that of computed tomography (CT) and of "second look" surgery as primary diagnostic procedures in 27 patients and in the follow-up of 52 women suspected of suffering from ovarian cancer. The results were compared with immunohistochemical findings and CA125 serum levels. For primary diagnosis sensitivity, specificity and diagnostic accuracy of RIS was 100%, 60% and 90%, resp. In follow-up, sensitivity for local recurrencies was 75% and specificity 68%. Peritoneal carcinosis in the pelvis and lower abdominal region was better detectable by RIS, but for detection of liver metastases CT showed better results. CT and RIS could not replace "second look" surgery.

Adult↗
PubMed1991

On the interaction between chromaffin granule membranes and intragranular vesicles--theory and analysis of freeze-fracture micrographs.

We present a model for the calculation of intragranular vesicle adhesion energy in a two-vesicle system consisting of an external secretory vesicle (chromaffin granule) and an intragranular vesicle (IGV) that adheres from the inside to the granule membrane. The geometrical parameters characterizing the granule-IGV systems were derived from freeze-fracture electron micrographs. Adhesion is brought about by incubation of the granules in hyperosmolar sucrose solutions. It is accompanied by a deformation of the granule because the intragranular vesicle bulges it outwards, and by segregation of intramembraneous particles from the adherent part of the granule membrane. Adhesion prevents the deformed granules from osmotic reexpansion and, therefore, causes hyperosmotic relaxation lysis. We estimated specific adhesion energy at -3 erg/cm2, a value which is 10 - 1000 times larger than the energy of van der Waals interaction between membranes. This large interaction energy probably results from changes of the granule core induced by dehydration. A minimization of the interface between the granule core and adjacent membranes could exclude intragranular vesicles from the core and squeeze them towards the granule membrane. This might induce a new kind of interaction between both membranes, which is irreversible and causes lysis upon osmotic relaxation.

Adhesiveness↗
PubMed1991

Evidence that the osmotically fragile yeast S. cerevisiae VY1160 is an actin mutant.

The phenotype of the osmotically dependent S. cerevisiae mutant VY1160 is caused by a single chromosomal mutation, termed srb, with pleiotropic effect. Compared with cells of the parental strain S288C, it was shown that the size and surface structure of the mutant cells are changed. The latter are sensitive to elevated cultivation temperatures as well as to hypotonic pressure and mechanical stress. In these cases, specific plasma membrane alteration were revealed by freeze-fracture electron microscopy. The total actin content is only 88% (21.4 micrograms actin/mg protein) of that of S288C cells. Remarkably, the mutant cells contain only 2.2 micrograms F-actin/mg protein, whereas the S288C cells have 10.3 micrograms F-actin/mg protein. Moreover, the level of reduced glutathione is found to be higher in the mutant cells (23.4 nmole/10(10) cells) than in the parental cells (15.2 nmole/10(10) cells). These results implicate that the srb mutation is localized in the actin gene.

Actins↗
PubMed1991

[The treatment of insertion desmopathy in the metatarsus of horses].

Metacarpal or metatarsal exostoses were diagnosed in 112 horses used for sport purposes between January 1976 to December 1987. Fourteen of these patients were treated surgically by subperiosteal removal of the exostosis. All animals which could be followed up had returned to their original use. The average time of use after discharge from the clinic was 38.4 months. Surgery was successful in completely removing the exostoses in 58.3% of these horses. The indications for anaesthesia and resection of the ulnar nerve are discussed.

Animals↗
PubMed1990

Short- and long-term effects of LDL-apheresis on lipoprotein (a) serum levels.

The effect of two extracorporeal elimination procedures for LDL on lipoprotein (a) concentrations in serum was studied in patients with heterozygous familial hypercholesterolemia. During a single apheresis serum lipoprotein (a) levels fell by 45% and 58%. Over a long-term period with weekly elimination lipoprotein (a) concentrations were lowered significantly by 43% (after 10-50 treatments) and 30% (after 51-99 treatments) compared to pre-treatment values. The rise during the week following apheresis was comparable to the corresponding reincrease of LDL-cholesterol and apolipoprotein B. We conclude that both apheresis techniques are very effective in reducing lipoprotein (a) serum levels.

Adult↗
PubMed1990

Reductive activation of potential antitumor bis(aziridinyl)benzoquinones by xanthine oxidase: competition between oxygen reduction and quinone reduction.

The reduction of a series of 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives with various 3,6 substituents by the enzyme xanthine oxidase has been studied. The reduction rate has been assayed by measuring the rate of reduction of cytochrome c, which is very efficiently reduced by reduced BABQ species. Under nitrogen, the reduction rate correlated with the quinone reduction potential and steric parameters. Comparing reduction rates under nitrogen and air demonstrates that at BABQ concentrations greater than 25 microM the competition for electrons from xanthine oxidase between oxygen and the BABQ derivative is dominated by the latter. This is also confirmed by the effect of superoxide dismutase (SOD): in the presence of a BABQ derivative, cytochrome c reduction can be totally inhibited by SOD, although the required amount of SOD depends on the redox potential of the quinones. This indicates that SOD causes the equilibrium between semiquinone and superoxide to shift, resulting in a decrease of the semiquinone concentration. It is concluded that reduction by xanthine oxidase is a simple and effective method for reducing aziridinylbenzoquinones.

Antineoplastic Agents↗