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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 433 records · Page 24Linked to original sources
PubMed1991

Apparent absence of glycogen branching enzyme activity in phosphofructokinase deficiency.

A 30-year-old woman with clinical features and biochemical findings of muscle phosphofructokinase deficiency was found to have a very low level of alpha-1,4-glucan:alpha-1,4-glucan-6-transglucosylase (branching enzyme, EC 2.4.1.18) activity in muscle. In contrast, branching enzyme activity in the leukocytes was in the range of control values. After sedimentation of the glycogen from muscle homogenates by centrifugation at 105,000 g, branching enzyme activity in muscle of the patient was similar to that of control subjects. This patient illustrates the possibility of falsely diagnosing branching enzyme deficiency when muscle glycogen content is elevated. It is likely that such an artefact may also cause a false positive diagnosis of branching enzyme deficiency in other metabolic diseases associated with glycogen accumulation.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1991

Bioavailability of bismuth from 205Bi-labelled pharmaceutical oral Bi-preparations in rats.

The bioavailability of 205Bi from various 205Bi-labelled pharmaceutical oral bismuth preparations was studied in rats. The intestinal absorption, calculated from 205Bi whole body retention and accumulated 205Bi urinary excretion, was small in general, but significantly higher (0.26-0.33% of dose) from oral bismuth citrates (basic bismuth citrate, colloidal bismuth subcitrate) as compared to basic bismuth nitrate, salicylate, gallate, and bismuth aluminate (0.04-0.11% of dose). After oral administration, the retained bismuth was mainly accumulated in the kidney, followed by bone, red blood cells and the lung. The whole body retention, faecal and urinary excretions of 205Bi were described by a three-compartment model. Biological 205Bi half-lives of 10, 36 and 295 h were derived in rats.

Administration, Oral↗
PubMed1991

Sialylated glycoconjugates in chromophobe cell renal carcinoma compared with other renal cell tumors. Indication of its development from the collecting duct epithelium.

The present study was designed to shed light on the extraordinary histochemical properties of the chromophobe cell renal carcinoma detected by Hale's colloidal iron reaction. Special emphasis was laid on the lectin histochemical analysis of cytoplasmic glycoconjugates. Binding of peanut agglutinin (PNA) and Erythrina cristagalli agglutinin (ECA) after enzymatic release of sialic acid and direct binding of Dolichos biflorus agglutinin (DBA) correlates well with the expression of binding sites for Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA) revealing abundant sialylated carbohydrate moieties within the cytoplasm. This characteristic binding pattern differs considerably from the faint staining observed in the majority of other renal carcinomas, thus confirming that the chromophobe cell renal carcinoma is a distinct entity. However, the lectin binding pattern of renal oncocytoma obviously resembles that of chromophobe carcinoma indicating a close relationship between these renal tumors. Detailed analysis of adjacent renal parenchyma revealed a lectin binding pattern quite similar to that described in the chromophobe carcinomas exclusively in the intercalated cells lining the collecting duct. This finding suggests that the chromophobe cell renal carcinoma originates from the collecting duct epithelium. The detection of small complexes consisting of altered epithelia which display the morphological characteristics of chromophobe carcinoma and the histochemical properties of intercalated cells probably indicates the emergence of preneoplastic lesions preceding the development of chromophobe carcinoma. Even though further studies are clearly needed to elucidate the physiological role of the cellular glycoconjugates detected, the present results already provide valuable insight into the histogenesis and pathogenesis of the chromophobe cell renal carcinoma.

Adenoma↗
PubMed1991

Inhibition of intestinal absorption and decorporation of radiocaesium in humans by hexacyanoferrates(II).

The effect of hexacyanoferrate(II) preparations, KFe[Fe(CN)6], (KFeHCF) anol Fe4[Fe(CN)6]3, (FeHCF) on intestinal radiocaesium absorption was studied in two male volunteers. The 134Cs absorption was decreased from 100 to 3-10% when 500-1000 mg KFeHCF or FeHCF were administered 10 min before the 134Cs-labelled test meal. However, when HCF was administered simultaneously with the test meal, the 134Cs absorption was decreased to only 38-63%. The biological half-time of previously absorbed 134Cs was reduced from 106 (73) to 44 (46) days by daily administration of 3 times 0.5 g KFeHCF. The 134Cs dose conversion factors lie below the values recommended by IRCP 30, indicating that the IRCP model represents a cautious description of the Cs biokinetics in our study.

Adult↗
PubMed1991

[Results of treatment with surface cauterization of polycystic ovaries in sterility patients].

In 39 women with polycystic ovaries (PCO) and a history of sterility, laparoscopic electrocautery of the surface of the ovaries was performed by a technique adapted from Gjoennaess (1984). Previous hormonal treatment with clomiphene and/or human menopausal gonadotropins had been unsuccessful in these patients, whilst 23 of them (59%) conceived within one year after surgery. Electrocautery was followed by a decrease of mean testosterone levels from 0.95 +/- 0.064 ng/ml to 0.48 +/- 0.041 ng/ml and a similar decline of dehydroepiandrosterone sulfate from 2.9 +/- 0.136 g/ml to 1.6 +/- 0.165 g/ml respectively. Laparoscopic ovarian electrocautery is however associated with the risk of postoperative adhesion formation. Therefore we advise this form of surgery only, when hormonal therapy failed or if it presents an unacceptable high risk of hyperstimulation or a multiple pregnancy.

Adult↗
PubMed1991

Noncontiguous regions in the extracellular domain of EGF receptor define ligand-binding specificity.

Murine epidermal growth factor (EGF) binds with approximately 250-fold higher binding affinity to the human EGF receptor (EGFR) than to the chicken EGFR. This difference in binding affinity enabled the identification of a major ligand-binding domain for EGF by studying the binding properties of various chicken/human EGFR chimera expressed in transfected cells lacking endogenous EGFR. It was shown that domain III of EGFR is a major ligand-binding region. Here, we analyze the binding properties of novel chicken/human chimera to further delineate the contact sequences in domain III and to assess the role of other regions of EGFR for their contribution to the display of high-affinity EGF binding. The chimeric receptors include chicken EGFR containing domain I of the human EGFR, chicken receptor containing domain I and III of the human EGFR, and two chimeric chicken EGFR containing either the amino terminal or the carboxy terminal halves of domain III of human EGFR, respectively. In addition, the binding of various human-specific anti-EGFR monoclonal antibodies that interfere with EGF binding is also compared. It is concluded that noncontiguous regions of the EGFR contribute additively to the binding of EGF. Each of the two halves of domain III has a similar contribution to the binding energy, and the sum of both is close to that of the entire domain III. This suggests that the folding of domain III juxtaposes sequences that together constitute the ligand-binding site. Domain I also provides a contribution to the binding energy, and the added contributions of both domain I and III to the binding energy generate the high-affinity binding site typical of human EGFR.

Animals↗
PubMed1991

Mannitol-specific phosphoenolpyruvate-dependent phosphotransferase system of Enterococcus faecalis: molecular cloning and nucleotide sequences of the enzyme IIIMtl gene and the mannitol-1-phosphate dehydrogenase gene, expression in Escherichia coli, and comparison of the gene products with similar enzymes.

Enzyme IIIMtl is part of the mannitol phosphotransferase system of Enterococcus faecalis. It is phosphorylated in a reaction sequence requiring enzyme I and heat-stable phosphocarrier protein (HPr). The phospho group is transferred from enzyme IIIMtl to enzyme IIMtl, which then catalyzes the uptake and concomitant phosphorylation of mannitol. The internalized mannitol-1-phosphate is oxidized to fructose-6-phosphate by mannitol-1-phosphate dehydrogenase. In this report we describe the cloning of the mtlF and mtlD genes, encoding enzyme IIIMtl and mannitol-1-phosphate dehydrogenase of E. faecalis, by a complementation system designed for cloning of gram-positive phosphotransferase system genes. The complete nucleotide sequences of mtlF, mtlD, and flanking regions were determined. From the gene sequences, the primary translation products are deduced to consist of 145 amino acids (enzyme IIIMtl) and 374 amino acids (mannitol-1-phosphate dehydrogenase). Amino acid sequence comparison confirmed a 41% similarity of E. faecalis enzyme IIIMtl to the hydrophilic enzyme IIIMtl-like portion of enzyme IIMtl of Escherichia coli and 45% similarity to enzyme IIIMtl of Staphylococcus carnosus. The putative N-terminal NAD+ binding domain of mannitol-1-phosphate dehydrogenase of E. faecalis shows a high degree of similarity with the N terminus of E. coli mannitol-1-phosphate dehydrogenase (T. Davis, M. Yamada, M. Elgort, and M. H. Saier, Jr., Mol. Microbiol. 2:405-412, 1988) and the N-terminal part of the translation product of S. carnosus mtlD, which was also determined in this study. There is 40% similarity between the dehydrogenases of E. faecalis and E. coli over the whole length of the enzymes. The organization of mannitol-specific genes in E. faecalis seems to be similar to the organization in S. carnosus. The open reading frame for enzyme IIIMtl E. faecalis is followed by a stem-loop structure, analogous to a typical Rho-independent terminator. We conclude that the mannitol-specific genes are organized in an operon and that the gene order is mtlA orfX mtlF mtlD.

Amino Acid Sequence↗
PubMed1991

A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1.

Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR; encoded by the flg gene) and other receptors with tyrosine kinase activity. It has been demonstrated that the src homology region 2 (SH2 domain) of PLC-gamma and of other signalling molecules such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85 direct their binding toward tyrosine-autophosphorylated regions of the epidermal growth factor or platelet-derived growth factor receptor. In this report, we describe the identification of Tyr-766 as an autophosphorylation site of flg-encoded FGFR by direct sequencing of a tyrosine-phosphorylated tryptic peptide isolated from the cytoplasmic domain of FGFR expressed in Escherichia coli. The same phosphopeptide was found in wild-type FGFR phosphorylated either in vitro or in living cells. Like other growth factor receptors, tyrosine-phosphorylated wild-type FGFR or its cytoplasmic domain becomes associated with intact PLC-gamma or with a fusion protein containing the SH2 domain of PLC-gamma. To delineate the site of association, we have examined the capacity of a 28-amino-acid tryptic peptide containing phosphorylated Tyr-766 to bind to various constructs containing SH2 and other domains of PLC-gamma. It is demonstrated that the tyrosine-phosphorylated peptide binds specifically to the SH2 domain but not to the SH3 domain or other regions of PLC-gamma. Hence, Tyr-766 and its flanking sequences represent a major binding site in FGFR for PLC-gamma. Alignment of the amino acid sequences surrounding Tyr-766 with corresponding regions of other FGFRs revealed conserved tyrosine residues in all known members of the FGFR family. We propose that homologous tyrosine-phosphorylated regions in other FGFRs also function as binding sites for PLC-gamma and therefore are involved in coupling to phosphatidylinositol breakdown.

Amino Acid Sequence↗
PubMed1991

A dominant negative mutation suppresses the function of normal epidermal growth factor receptors by heterodimerization.

Recent studies provide evidence that defective receptors can function as a dominant negative mutation suppressing the action of wild-type receptors. This causes various diminished responses in cell culture and developmental disorders in murine embryogenesis. Here, we describe a model system and a potential mechanism underlying the dominant suppressing response caused by defective epidermal growth factor (EGF) receptors. We used cultured 3T3 cells coexpressing human wild-type receptors and an inactive deletion mutant lacking most of the cytoplasmic domain. When expressed alone, EGF was able to stimulate the dimerization of either wild-type or mutant receptors in living cells as revealed by chemical covalent cross-linking experiments. In response to EGF, heterodimers and homodimers of wild-type and mutant receptors were observed in cells coexpressing both receptor species. However, only homodimers of wild-type EGF receptors underwent EGF-induced tyrosine autophosphorylation in living cells. These results indicate that the integrity of both receptor moieties within receptor dimers is essential for kinase activation and autophosphorylation. Moreover, the presence of mutant receptors in cells expressing wild-type receptors diminished the number of high-affinity binding sites for EGF, reduced the rate of receptor endocytosis and degradation, and diminished biological signalling via EGF receptors. We propose that heterodimerization with defective EGF receptors functions as a dominant negative mutation suppressing the activation and response of normal receptors by formation of unproductive heterodimers.

Animals↗
PubMed1991

Dysmegakaryopoiesis in myelodysplastic syndromes (MDS): an immunomorphometric study of bone marrow trephine biopsy specimens.

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens of the bone marrow in 40 patients (23 men and 17 women, mean age 62 years) with different subtypes of myelodysplastic syndromes (MDS) to determine dysmegakaryopoiesis, but particularly precursor cells--that is, pro- and megakaryoblasts. In 31 of the 40 patients the numbers of megakaryocytes were increased which was associated with a predominance of smaller cell forms (micromegakaryocytes). Compared with periodic acid Schiff, immunostaining with a formalin resistant monoclonal antibody against glycoprotein IIIa (Y2/51(CD61) showed a clinically important proportion of immature elements. These could be designated pro- and megakaryoblasts by taking morphometric measurements on smears and bone marrow sections. There was a relevant increase in the number of promegakaryoblasts in 32 patients, consistent with uncontrolled expansion of the precursor pool. Seventeen repeated bone marrow biopsy specimens taken after chemotherapy largely showed a decrease in the numbers of megakaryocytes including the precursor cell population. Moreover, morphometric evaluation disclosed that micromegakaryocytes in MDS differ significantly from those in chronic myeloid leukaemia (CML) due to distinctive nuclear features and a disturbed nuclear:cytoplasmic ratio. These changes generate a more pleomorphic or atypical appearance of this cell population in MDS, compared with micromegakaryocytes in CML. It is concluded that the disproportionate increase in megakaryocyte precursors and the grossly abnormal aspects of micromegakaryocytes in MDS are characteristics of the severe defect involving haematopoiesis in this disorder.

Adult↗
PubMed1991

Histochemical reactivity of the Geodia cydonium agglutinin (GCA) in human tissues.

We applied a peroxidase-antiperoxidase technique to study the distribution pattern and binding characteristics of the lectin from the marine sponge Geodia cydonium (Geodia cydonium agglutinin; GCA) in various human tissues. This lectin has been shown to possess a broad reactivity, but there was a distinct distribution of binding sites within the different organs. In the histochemical system GCA displayed no blood group specificity and labeled red blood cells, the vascular endothelium, and epithelial cells showing blood group antigen expression independent of the ABH blood group status. However, inhibition of GCA reactivity by simple sugars and complex carbohydrates demonstrated tissue-specific differences of lectin binding related to the ABH blood group status of the tissue and revealed information on the structural requirements of the histological lectin binding site. Tissues that totally lacked blood group antigens or that expressed only the H-antigen disclosed a GCA reactivity which was completely inhibited by lactose. In contrast, tissues that expressed blood group A- or blood group B-antigen exhibited a lactose-resistant lectin binding which was inhibited only by water-soluble blood group substance A from peptone A and by bovine glycophorin but not by other complex carbohydrates, including human glycophorin and human asialoglycophorin. Competitive inhibition studies in situ revealed that GCA binding was not inhibited by blood group type I/II carbohydrate sequence-specific lectins or by lectins with other sugar specificities. Inhibition by lactose of GCA binding to some histological sites indicates that the binding site consists of a beta-linked galactose-containing disaccharide. However, periodate oxidation of tissue sections had no effect on lectin binding, pointing to a subterminal location of the relevant sequence. The results obtained from inhibition studies with simple saccharides and complex carbohydrates in relation to the expression of ABH blood group antigens suggest a complex lectin combining site(s) in histological specimens. The lectin may possess either one binding site with a range of affinities for different carbohydrates (besides beta-linked disaccharides the GCA binding site accommodates to carbohydrate determinants carrying the blood group A or blood group B determinant), or may possess two different binding sites. Besides an acceptor site for beta-linked disaccharides, an additional binding site may exist accommodating to extended carbohydrate sequences related to A or B blood group structures. In conclusion, GCA represents a blood group-nonspecific lectin whose binding affinities are determined by the ABH blood group status of the tissue.

ABO Blood-Group System↗
PubMed1991

[Immunohistochemistry and morphometry of bone marrow in acquired immunodeficiency syndrome with special emphasis on megakaryopoiesis and macrophages].

An immunomorphometric study was performed on formalin-fixed and paraffin-embedded bone marrow biopsies in 20 patients with AIDS (18 males, 2 females-stage IV A-D). In comparison with a control group megakaryocytes (CD61-Y2/51) revealed not only a significant hyperplasia, but remarkably irregular shapes of cells and nuclei, together with a disturbance of the nuclear-cytoplasmic ratio. No predominance of micromegakaryocytes as in myelodysplastic syndromes was observable. Contrasting idiopathic (immune)-thrombocytopenia, HIV-infected patients with a pronounced depression of the platelet count did not show a significant elevation of the number of promegakaryoblasts. This feature is in keeping with findings of a severe impairment of progenitor cell proliferation and differentiation in AIDS. There was a pronounced increase in the macrophage population (PG-M1). This alteration may be related to inflammatory lesions accompanying this disorder as well as to an enforced and premature destruction of hematopoietic cell elements in the myeloid stroma.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Familial hemophagocytic lymphohistiocytosis].

7 cases of familial hemophagocytic lymphohistiocytosis were investigated by morphology and immunohistochemistry. Typical infiltrates composed of macrophages and lymphoid cells were found in various locations such as lymph nodes, spleen, liver, brain, and skin. The macrophages were positive for typical macrophage antibodies (Ki-M1, Ki-M1P) and showed features of activation by displaying a strong reaction with antibodies against lysosomal antigens (Ki-M1P, Ki-M6, Ki-M7, Ki-M8). In addition, they showed antigenic similarity to antigen-presenting cells (Vit-6 pos., S 100 pos.) and no conclusive evidence of in situ proliferation (Ki-67 neg). The lymphoid cells were mainly composed of more or less proliferating T-cells and a few B-cells.

Antibodies, Monoclonal↗
PubMed1991

Interactions between megakaryocytes and sinus wall. An ultrastructural study on bone marrow tissue in primary (essential) thrombocythemia.

An ultrastructural study was performed on bone marrow tissue in primary (essential) thrombocythemia to evaluate possible interactions between megakaryocytes and sinusoids. In addition to a preferential localization of megakaryocytes in the subendothelial space, two different kinds of cytoplasmic processes could be discriminated penetrating the sinus wall. Serial sections disclosed that megakaryocytes developed multiple pseudopod-like plump projections derived from their peripheral zone and devoid of organelles. It is tempting to speculate that these ameboid features could serve as anchors to keep the cell in a subendothelial position and to monitor changes occurring in circulation. The second type of cytoplasmic processes reaching into the vascular lumen consisted of tentacle-like elongated protrusions rich in organelles, apparently originating from the intermediate zone. These projections were thought to present either the beginning of megakaryocytes egress into circulation or putative platelets. Frequently, there was an intrasinusoidal localization of megakaryocytes which revealed numerous so-called platelet territories and apparently an enforced platelet shedding. Generally, these features are comparable with aspects obtained from animal studies, following excessively stimulated megakaryo- and thrombocytopoiesis by application of anti-platelet serum.

Bone Marrow↗
PubMed1991

[A new generation in varicose vein surgery?].

A new generation of varicose vein surgery is arising. Its invasivity is about half of what it has been. Therefore patients spend less time in hospital, their incapacity of work is reduced, they have less complications and the cosmetic results are much better. This progress has been made possible by different means. First of all smaller incisions are used for every step of the stripping procedure. Varicose branches are removed with small hooks through incisions of only 1-5 mm in length. Other techniques also help to reduce invasivity and to improve the results, such as the endoscopic treatment of Cockett's perforators, the skin closure with isoelastic adhesive tape and the bloodless operation field by Löfqvist's new roll-on tourniquet. The new diagnostic techniques help in two ways. First, they let the surgeon further reduce invasivity and second they allow for more dependable results. These newer operative techniques call for additional education. It is provided by the specialties which are engaged in phlebologic surgery anyhow, i.e. angiology, vascular and general surgery, dermatology and general medicine.

Endoscopes↗
PubMed1991

[A whole-blood micromethod to determine lymphocyte subsets in capillary blood, comparison with other methods of indirect immunofluorescence].

Six lymphocyte antigens were detected with monoclonal antibodies in 0.2 ml capillary blood by a whole blood micromethod. After the lysis of erythrocytes of one drop of blood the remaining cells were layered on slides and were stained by indirect immunofluorescence. The relative and absolute counts of the lymphocyte subsets were of normal value and did not differ from the counts of flow cytometry and of slide and tube tests.

Antibodies, Monoclonal↗
PubMed1991

Cryptosporidium sp. in stool specimens from diarrhoeic and asymptomatic individuals in the Magdeburg area (East Germany).

Unselected stool specimens from a total of 2,944 individuals with diarrhoea including 1,172 children under 14 years of age were investigated for Cryptosporidium oocysts in the Magdeburg area from 1987 to 1988, 43 (1.46%) were found positive. Three of these were additionally infected with bacterial pathogens (Campylobacter species). In all cases the symptoms of diarrhoea ceased spontaneously after an average of 8 days. The incidence was highest among children and infants under 6 years of age (2.50%). No cryptosporidia were found in stool specimens of 570 healthy individuals of all age groups. Cysts of Giardia sp. were detected more frequently in healthy than in diarrhoeic individuals (3.3% and 2.0%, respectively). The postulation to search for cryptosporidia in all cases of diarrhoea lasting longer than two days is inferred from these results.

Adolescent↗