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Biomedical subjects

R Kaufmann

Publications and source records attributed to R Kaufmann.

At least 217 records · Page 12Linked to original sources
PubMed1993

Mass spectrometric sequencing of linear peptides by product-ion analysis in a reflectron time-of-flight mass spectrometer using matrix-assisted laser desorption ionization.

In matrix-assisted laser desorption ionization (MALDI) a large fraction of analyte ions undergo post-source decay (PSD) during flight in the field-free drift path. By means of a modified two-stage reflectron, product ion time-of-flight spectra of medium-sized linear peptides (up to 2800 u) were recorded, containing full sequence information. Precision, accuracy and mass resolution of fragment ions were almost as good as obtained in high-energy collisionally activated dissociation (CAD) studies performed in four-sector instruments. Instrumental sensitivity was better by at least one order of magnitude. In reflectron time-of-flight mass spectrometry (RETOFMS) the cleavage pattern of PSD products is different from that obtained by high-energy and low-energy CAD. Activation mechanisms of PSD were found to be largely determined by collisional events (ion/neutral) occurring in the acceleration field during early plume expansion. Future potentials of PSD analysis after MALDI are discussed.

Mass Spectrometry↗
PubMed1993

Guillain-Barré syndrome following streptokinase therapy.

Clinical and laboratory data from a patient with Guillain-Barré syndrome indicated a probable etiological correlation of polyradiculitis to the intravenous administration of streptokinase. Oligoclonal IgG bands in the cerebrospinal fluid and serum were shown to be specific for streptokinase. Serum titers of streptokinase were elevated 64-fold for IgG, 16-fold for IgM, and 4-fold for IgA compared to controls. Clinical symptoms of Guillain-Barré syndrome are thought to result from streptokinase antibody complex mediated damage to the local blood-nerve barrier. The pathogenic relevance of autoantibodies to albumin and proteins of the central and peripheral nervous systems, occurring early after onset of symptoms, remains to be determined.

Autoantibodies↗
PubMed1993

Henoch-Schönlein purpura with ileitis terminalis.

Gastrointestinal manifestations of Henoch-Schönlein purpura commonly include abdominal pain and gastrointestinal bleeding as well as extraintestinal signs and symptoms. We report here on a 24-year-old man with gastrointestinal pain in whom the classical features of Henoch-Schönlein purpura appeared only 6 days after acute abdominal symptoms. At endoscopic investigation inflammation with aphthous lesions was detected at the terminal ileum, which is a common feature of Crohn's disease. The observation that vasculitic disorders such as Henoch-Schönlein purpura can present with inflammatory lesions at the terminal ileum which are indistinguishable from those of Crohn's disease underlines the potential vasculitic basis of the latter condition.

Adult↗
PubMed1993

Cellular and molecular composition of human skin in long-term xenografts on SCID mice.

We report on the immunophenotypical characterization of adult human skin transplanted onto severe combined immunodeficient (SCID) mice. Thirty animals were followed for up to 12 months after receiving split-thickness xenografts, of which 28 were tolerated for the whole test period. Antigen mapping revealed an almost complete preservation of human cellular and extracellular tissue components in long-term transplants including skin immune cells (Langerhans-cells, macrophages, lymphocytes) and also parts of the engrafted endothelium. Hence, xenografts on SCID mice offer a versatile experimental tool for the in vivo study of both human skin immune cell function and endothelial cell-mediated interactions in an environment completely devoid of interferences by adoptive host immune response.

Animals↗
PubMed1993

[Persistent pruritus after hydroxyethyl starch infusions. Retrospective long-term study of 266 cases].

In 266 patients receiving hydroxyethyl starch (HES) for otological indications, we retrospectively analysed the incidence of pruritus and its relationship to clinical and therapeutic parameters. We found that 32% of the patients developed pruritus, which characteristically appeared as pruritic crises. In 55% of pruritic patients onset after the HES medication had already been discontinued was reported. The symptoms persisted on average for 8.8 weeks. Pruritus was generalized, but with a predilection for the trunk and genitalia. Coincidental atopic disease or higher age did not promote pruritus. However, the incidence of pruritus correlated well with the cumulative dosage and also depended on the type and molecular weight of HES given (6% or 10%, mol.wt. 40 or 200 kDa). Light and electron microscopic assessment showed deposits of HES, especially within dermal macrophages and endothelial cells and adjacent to nerve fibres. Pathogenetically a histamine-independent pathway is probably responsible for the induction of pruritus. Hence, classic antihistaminic drugs had no therapeutic effect in our patients.

Adolescent↗
PubMed1993

[Osteoma cutis. Multiple miliary osteoma of the face].

Primary and secondary forms of ossification can be distinguished on the basis of the skin, with osteoma cutis occurring in primary forms. Three entities can be differentiated: solitary and generalized osteoma cutis and multiple miliary osteoma of the face. Clinically, multiple papules 2-3 mm in diameter are present, which histologically consist of bony trabeculae enclosing mature fat cells and, occasionally, marrow cells. We describe the clinical, radiological and histological features of a case of multiple miliary osteoma of the face in an otherwise healthy 55-year-old woman.

Biopsy↗
PubMed1992

Introduction of intersubunit disulfide bonds in the membrane-distal region of the influenza hemagglutinin abolishes membrane fusion activity.

Influenza virus hemagglutinin (HA) mediates viral entry into cells by a low pH-induced membrane fusion event in endosomes. A number of structural changes occur throughout the length of HA at the pH of fusion. To probe their significance and their necessity for fusion activity, we have prepared a site-directed mutant HA containing novel intersubunit disulfide bonds designed to cross-link covalently the membrane-distal domains of the trimer. These mutations inhibited the low pH-induced conformational changes and prevented HA-mediated membrane fusion; conditions that reduced the novel disulfide bonds restored membrane fusion activity. We conclude that structural rearrangements in the membrane distal region of the HA are required for membrane fusion activity.

Animals↗
PubMed1992

Peptide sequencing by matrix-assisted laser-desorption mass spectrometry.

A novel method of peptide sequencing by mass spectrometry is described. Metastable decay of laser-desorbed ions, taking place in the first field-free drift region of a reflection time-of-flight mass spectrometer, has been monitored to get structural information from larger peptides. Fragment ions from metastable decay are mass analysed by adjusting the potentials of the ion reflectron according to the kinetic energies of the ions. The features of the technique and its significance for future applications are outlined.

Amino Acid Sequence↗
PubMed1992

Hybridization relatedness of Israeli and U.S. bluetongue (BLU) serotypes using cDNA probes from BLU virus strain 11-UC8.

Partial cDNA clones representing 47%, 96%, and 98% of genome segments 7, 9, and 10, respectively, of a US bluetongue virus (BLU) 11 virulent strain were used to study, for the first time, the genetic relationships between Israeli BLU proto-serotypes and field isolates, and US BLU proto-serotypes. Their usefulness as group-specific identification probes was also determined. The viral nucleic acid was extracted from the infected cells and the purified dsRNA genome segments were fractionated by polyacrylamide gel electrophoresis, transferred to a nylon membrane and hybridized to the 32P labeled DNA probes. The three probes recognized all the samples tested. Genome segment 7, that code for the mayor inner capsid protein VP7, showed the most variation in the hybridization signal with the US proto-serotypes and all the Israeli samples studied. The genome segments 9 and 10 that code for the minor inner capsid protein VP6 and the nonstructural protein NS3, respectively, were highly conserved in all the samples tested despite their distant geographical regions of origin. The last two mentioned clones showed to be good group-specific probes for the identification of BLU samples from Israel and United States. The obtained cloned genetic probes were also tested against US epizootic haemorrhagic disease virus (EHDV) serotype 1 and 2 viral dsRNA, a distantly related orbivirus. None of them hybridized with the viral dsRNA of these two viruses.

Animals↗
PubMed1992

Preclinical models for human pre-embryo biopsy and genetic diagnosis. II. Polymerase chain reaction amplification of deoxyribonucleic acid from single lymphoblasts and blastomeres with mutation detection.

OBJECTIVE: To demonstrate the use of the polymerase chain reaction in the amplification of deoxyribonucleic acid (DNA) from single human lymphoblasts and mouse blastomeres. Amplified target genes for diagnosis of sickle cell anemia and Tay-Sachs are shown. Similarly, the sparce fur mouse model for ornithine transcarbamylase deficiency was used as an X-linked system for demonstration of mutation detection after biopsy of a single blastomere. A new diagnostic method for the detection of the ornithine transcarbamylase mutation using the restriction enzyme Mse I is presented. Accuracy and reproducibility were assured. DESIGN: Polymerase chain reaction proficiency test for amplification from single cells was studied. Also, accuracy of mutation detection systems was demonstrated. SETTING: Laboratories of The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. PATIENTS, PARTICIPANTS: We used the sparse fur mouse model and human blood cells. INTERVENTIONS: Pre-embryo biopsy, polymerase chain reaction amplification, and mutation detection were performed. MAIN OUTCOME MEASURES: Accuracy and reproducibility of DNA amplification without contamination, as well as efficient diagnostic analysis, from both single somatic and embryonic cells were shown. RESULTS: DNA amplification from single cells was uniformly rapid (6 to 10 hours) reproducible (n = 220) and accurate (n = 52). CONCLUSIONS: Our findings support the feasibility of clinical application for pre-embryo biopsy and genetic diagnosis of specific heritable diseases.

Amino Acid Sequence↗
PubMed1992

In vitro and in vivo evaluation of a hydrophilized silicone intraocular lens.

The surface of a silicone-disc intraocular lens (IOL) was hydrophilized by plasma etching (oxygen plasma) and compared to an untreated but otherwise identical IOL. Various methods of surface analysis were used to characterize the modification (e.g., X-ray photoelectron spectroscopy, contact angle estimation). A cytotoxic effect of the modified surface was excluded by cell culture experiments evaluating cell spreading, cell morphology, DNA and protein synthesis. In vivo experiments on rabbits indicated that the postoperative foreign-body reaction was not significantly affected by the hydrophilization of the IOL surface. Throughout the entire follow-up (12 weeks) we found less induced posterior synechias in the eyes with hydrophilized lenses than in those with untreated lenses (P = .009). While the IOL dislocations out of the capsular bag and the posterior capsular opacification rate did not differ significantly between the two groups of eyes, we did see special patterns of posterior capsular opacification on the posterior capsules of eyes with the hydrophilized IOL.

Animals↗
PubMed1992

CCKB receptor stimulation mediates [Ca2+]i increase but no PKC activation in Jurkat T-cells.

We have investigated the effect of cholecystokinin-octapeptide (CCK-8) on [Ca2+]i and protein kinase C (PKC) activity in Jurkat T-cells. CCK-8 produced a transient [Ca2+]i increase in the presence of extracellular Ca2+. While CCKB receptor antagonist L-365,260 abolished the elevation of [Ca2+]i, CCKA receptor antagonist L-364,718 was without effect. Moreover, the dihydropyridine calcium channel blocker nitrendipine was shown to block the observed calcium response. Results suggest that the calcium effect is caused by an interaction of CCK-8 with CCKB binding sites and an influx of external Ca2+ via dihydropyridine sensitive calcium channels might serve as a source for the increased [Ca2+]i. Because CCK-8 induced no PKC activation CCKB receptor mediated rise of intracellular calcium seems not to include activation of phospholipase C.

Benzodiazepinones↗
PubMed1992

Cytogenetic studies of skin fibroblast cultures from a karyotypically normal female with dyskeratosis congenita.

Skin fibroblast cultures from a female patient with dyskeratosis congenita revealed markedly increased frequencies of chromosomal breaks, hypodiploidy, and premature centromere disjunction. The frequencies of mitotic disturbances, like ana- and telophase bridges, lagging chromosomes, and micronuclei were almost as dramatically elevated as in cultures from two severely affected patients with Fanconi anemia. Provided that our patient is representative for an autosomal form of dyskeratosis congenita, this type of the disease seems to be characterized by chromosomal instability with a characteristic pattern of cytogenetic abnormalities.

Adult↗
PubMed1992

The HIV-1 surface protein gp120 has no effect on transmembrane signal transduction in T cells.

The ability of HIV-1 envelope glycoprotein gp120 to induce transmembrane signaling processes in human T cells and tumor T-cell lines was investigated. Differently glycosylated gp120 preparations were characterized with respect to their purity, the fraction of native gp120, and the affinity of the gp120-CD4 interaction. These data were used to establish experimental conditions that allow a substantial fraction of the CD4 receptor to be complexed with gp120 in the course of the experiments. The results are in contrast to several previous studies since no effect of gp120 on the intracellular Ca2+ concentration, the metabolism of inositol phosphates and arachidonic acid, protein kinase C translocation, and tyrosine phosphorylation was found. Cross-linking of the gp120:CD4 complex by anti-gp120 antibodies did not elicit additional effects.

Arachidonic Acids↗
PubMed1992

Electromechanical artificial heart with a new gear type and angled pump chambers.

The intrathoracic anatomical situation after explantation of the natural heart defines the maximum available space for the design of the housing as well as of the inlet- and outlet connectors of a fully implantable electromechanical artificial heart. Based on computer-assisted anatomical studies, a total artificial heart housing is designed which facilitates an oblique orientation of the pumping chambers for a better fluidmechanical and anatomical arrangement of the in- and outlet connectors. The pumping chamber geometry is based on modifications of an existing cardiac assist-system. Subsequently a mechanical gear which conforms to this anatomically adapted housing is developed.

Heart, Artificial↗
PubMed1992

Compact mock loops of the systemic and pulmonary circulation for blood pump testing.

Mock loops are an important tool for in vitro investigations of artificial blood pumps. The simple windkessel, throttle, and atrium principle was used for the mock loop design presented. The components of the systemic and the pulmonary mock loop were designed according to calculated numerical simulation parameters. The loops offer a compact design and simple handling. For simulating biventricular assist or total artificial heart (TAH), both loops can be coupled correspondingly. The numerical simulation and the first results with the loops show very good similarity to physiological data of systemic and pulmonary circulation. The measurements of pump characteristics are significant for quantitative comparison of different pump sizes and types, or driving systems.

Blood Circulation↗
PubMed1991

Heterogeneity of breast cancer risk in families of young breast cancer patients and controls.

Familial heterogeneity of breast cancer risk was assessed among 4,159 first-degree female relatives of 1,074 population-based, young breast cancer cases (aged 20-54 years) diagnosed from December 1, 1980 to December 31, 1982 and 4,120 first-degree female relatives of 998 age- and race-matched, population-based controls from the metropolitan Detroit, Michigan, area. The family risk index method used for analysis considers family size, age, and race differences among families in the assessment of family risk. Families of cases showed a higher risk of breast cancer than did families of controls, with case families 1.80 to 4.24 times more likely to be defined as high risk than control families; the magnitude of the risk differential was dependent on the definition of high risk. Within the case families only, familial heterogeneity of risk was suggested, with a small proportion of families (less than 5%) at lower risk of breast cancer than most case families. A number of reproductive risk factors, age, race, and histologic type of cancer for the proband, and several family characteristics were investigated to help characterize the case families at higher and lower risk.

Adult↗