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Biomedical subjects

H Fuchs

Publications and source records attributed to H Fuchs.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Elevated plasma prekallikrein level in patients with diabetes].

The contact activation of intrinsic pathway in the coagulation system accompanied by plasma kallikrein-induced kinin generation is thought to be involved in the pathogenesis of diabetic retinopathy. Plasma prekallikrein (PPK), a proenzyme of plasma kallikrein, is a single-chain glycoprotein synthesized mainly in the liver. The aim of our study was to evaluate plasma prekallikrein level in diabetic patients and to examine the relationship between PPK and the metabolic control of diabetes and development of retinopathy. In 53 diabetic patients and 33 healthy subjects as controls the following parameters have been assessed: plasma prekallikrein, serum fructosamine, glycated haemoglobin HbA1c, prothrombin time, partial thromboplastin time and antithrombin III (AT III). Compared to the control group, PPK level was significantly higher in diabetics, especially in patients with proliferative retinopathy. The significant positive correlations have been found between PPK and HbA1c in diabetic patients and between PPK and serum fructosamine concentration but only in diabetics without retinopathy. No differences in prothrombin time and AT III have been observed between diabetics and healthy subjects. A suggestion is presented on increase of plasma prekallikrein level in diabetics due to hyperglycaemia-stimulated glycoprotein over-synthesis in the liver, what would confirm the role of kallikrein-kinin system in the pathogenesis of microangiopathy.

Adult↗
PubMed1994

The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor.

The spirochete Borrelia burgdorferi is the causative agent of Lyme borreliosis (Lyme disease) and is transmitted to mammalian hosts by tick vectors. In humans, the bacteria induce a complex disease, which involves the skin, joints, heart, and nervous system. However, the pathogenic principles of this multisystem illness are far from being understood. To disseminate from the site of the tick bite and invade multiple organ sites, spirochetes have to penetrate normal tissue barriers, such as vascular basement membranes and other organized extracellular matrices. Substantial evidence from other invasive bacterial infections suggest that spirochetes may use endogenous or host-derived enzymes--in particular, proteinases--for this purpose. Here we show that B. burgdorferi binds human plasmin(ogen)--mainly via its outer cell surface lipoprotein A. Binding of plasminogen to spirochetal receptor leads to an accelerated formation of active plasmin in the presence of host-derived plasminogen activator. The cell-surface-associated plasmin cannot be regulated by the serum inhibitor alpha 2-antiplasmin and degrades high-molecular-weight glycoproteins, such as fibronectin. It is suggested that the acquisition of host-derived proteinase plasmin(ogen) contributes to the pathogenicity of B. burgdorferi.

Antigens, Surface↗
PubMed1994

[Selected parameters of blood coagulation and fibrinolysis and their relationship to the level of diabetes control in patients with insulin-dependent diabetes mellitus].

The aim of the study was to evaluate plasma concentration of fibrinogen, plasma activity of antithrombin III (AT-III) and plasma activity of plasminogen activator inhibitor (PAI-I) in insulin-dependent diabetic (IDDM) patients and the assessment of correlation between them and the parameters of glyco-metabolic control comprising glycemia and concentrations of fructosamine and glycated hemoglobin HbA1c. Eighteen IDDM patients (mean age 28.3 +/- 11.3 ys, mean duration of disease 12.2 +/- 5.3 ys) without over nephropathy and without macroangiopathy were investigated. Control group consisted of 8 healthy subjects. Plasma fibrinogen concentrations were similar in IDDM patients and in controls (3.54 +/- 0.45 g/l and 3.31 +/- 0.54 g/l respectively). Plasma activity of AT-III in diabetic patients (90.6 +/- 22.4%) was similar to that in healthy subjects (94.6 +/- 25.0%). Fibrinogen concentrations and AT-III activities showed no correlation with glycemia and concentrations of fructosamine and HbA1c. Plasma activity of PAI-I was significantly lower in diabetics than in controls (respectively 1.56 +/- 0.72 U/ml and 2.75 +/- 1.25 U/ml, p < 0.005). PAI-I activity correlated negatively with fasting blood glucose (p < 0.05) but did not correlate with concentrations of fructosamine or HbA1c. The results suggest that glycemic control in diabetic patients do not influence on concentrations of fibrinogen and activity of AT-III but diminished activity of PAI-I is related to hyperglycemia.

Adolescent↗
PubMed1993

Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis.

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis. High levels of DNA in the sputum make the sputum viscous and difficult to expectorate. Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to reduce the viscoelasticity of the sputum from CF patients. We have done a phase II double-blind randomised placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for 10 days. All patients had forced vital capacity (FVC) above 40% predicted and were clinically stable. Patients were followed up for 42 days from the start of drug/placebo administration. All 71 randomised patients, aged 16-55, completed every aspect of the study and baseline characteristics were similar in the two groups. Baseline forced expiratory volume in one second (FEV1) was 46% of predicted for patients randomised to rhDNase, and 48% for those randomised to placebo; and baseline FVC was 76% of predicted for both groups. The mean percentage change in FEV1 from baseline was a 13.3% rise on rhDNase and a 0.2% fall on placebo (p < 0.001). FVC rose 7.2% in the rhDNase group and 2.3% in the placebo group (not significant). There were no life-threatening adverse events and no anaphylactic reactions. There was no significant difference in side-effects between the groups. This study confirms that short-term administration of rhDNase in stable patients with cystic fibrosis is safe and improves lung function.

Adolescent↗
PubMed1993

Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells.

Murine epidermal Langerhans cells (LC) have been shown to internalize Leishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite-specific T cell response. The present study emphasizes the critical role of LC in leishmaniasis by documenting directly that LC have the ability to transport L. major from the skin to the draining lymph node (LN). This was revealed by irreversible labeling of LC with a fluorescent cell linker and in vivo tracking. In contrast, no migration to the LN was seen with L. major-infected macrophages. These findings were consistent with the results of mixed labeling immunohistology showing that early in infection the expression of parasite antigen in the LN draining the lesion was confined to dendritic cells and could not be detected in macrophages. Furthermore, dendritic cells in LN draining the site of cutaneous infection stimulated L. major-primed T cells in vitro and, most notably, were able to activate unprimed T cells capable of mediating parasite-specific delayed-type hypersensitivity reactivity in vivo. Taken together, the results indicate that LC capture L. major in the skin and transport it to the regional LN for initiation of the specific T cell immune response.

Animals↗
PubMed1993

Enzymatic modeling of the oligosaccharide chains of glycoproteins immobilized onto polystyrene surfaces.

A method for the modification of the oligosaccharide moiety of even small amounts of purified glycoproteins by enzymatic glycosylation and deglycosylation is described. The method includes noncovalent immobilization of the glycoproteins onto the polystyrene surface of the wells of microtiter plates used as reaction tubes, deglycosylation or glycosylation by incubation either with exoglycosidases or endoglycosidases or with glycosyltransferases, and the characterization of the modified glycan structures by probing them with lectins. Placental transferrin receptor employed as a model glycoprotein was modified in amounts of as little as 100 ng removing sialic acid residues, hybrid-type glycans or all types of N-glycans with neuraminidase, endo-beta-N-acetylglucosaminidase H or peptide-N4-(acetyl-beta-glucosaminyl) asparagine amidase. Asialotransferrin receptor was alpha-2,6-sialylated with alpha-2,6-sialyltransferase from rat liver, but could not be alpha-2,3-sialylated with alpha-2,3-sialyltransferase from porcine liver. Changes in the structure and in the relative amount of the oligosaccharides could be monitored semiquantitatively with high sensitivity by the binding of digoxigenin-labeled lectins and anti-digoxigenin Fab fragments. The method is easy to use, does not require immobilization of the enzymes employed, offers simple separation of the enzymes and the product, and leaves the protein intact for further studies.

Animals↗
PubMed1993

VISTAnet: interactive real-time calculation and display of 3-dimensional radiation dose: an application of gigabit networking.

Three-dimensional treatment planning can allow the clinician to create plans that are highly individualized for each patient. However, in lifting the constraints traditionally imposed by 2-dimensional planning, the clinician is faced with the need to compare a much larger number of plans. Although methods to automate that process are being developed, it is not yet clear how well they will perform. VISTAnet is a 3 year collaborative effort between the Departments of Radiation Oncology and Computer Science at the University of North Carolina, the North Carolina Supercomputing Center, BellSouth, and GTE with the medical goal of providing real-time 3-dimensional radiation dose calculation and display. With VISTAnet technology and resources, the user can inspect 3-dimensional treatment plans in real-time along with the associated dose volume histograms and can fine tune these plans in real-time with regard to beam position, weighting, wedging, and shape. Thus VISTAnet provides an alternate and, possibly, complementary approach to computerized searches for optimal radiation treatment plans. Building this system has required the development of very fast radiation dose code, methods for simultaneously manipulating and modifying multiple radiation beams, and new visualizations of 3-dimensional dose distributions.

Computer Communication Networks↗
PubMed1993

Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major.

Murine epidermal Langerhans cells (LC) have been demonstrated to stimulate a vigorous T cell response to Leishmania major, a cause of human cutaneous leishmaniasis. It was therefore of interest to analyze whether LC can take up viable parasites. Epidermal cells were obtained from mouse ear skin for incubation with L. major and subsequent detection of intracellular parasites by cytochemistry. Freshly isolated LC, but not cultured LC, phagocytosed L. major and the uptake was inhibited by antibodies to the complement receptor type 3. Electron microscopic studies revealed the presence of viable amastigotes within LC. Moreover, with double-labeling techniques, L. major-containing LC could also be detected in infected skin. The results demonstrate that LC can internalize L. major. Since the number of organisms per infected LC remained consistently low, the prime task of LC may not be the promotion of parasite spreading but the presentation of L. major antigen to T cells and, thus, the regulation of the cellular immunity during cutaneous leishmaniasis.

Acridine Orange↗
PubMed1993

Tumorectomy plus tamoxifen for the treatment of breast cancer in the elderly.

Between 1987 and 1991 a total of 37 breast cancer patients with a mean age of 78.8 (68-89) years underwent local tumor excision and were continuously given 20-30 mg tamoxifen. Thirteen patients presented with clinical stage I, 21 with stage II, two patients with stage III and one woman with stage IV. Surgical complications were minimal and hospital stay 3.5 days. Four patients were lost to follow-up. After a mean observation time of 44.5 months, three of the remaining patients developed local recurrence, which was excised, and 12 patients (32.4%) died. Death, however, was never related to breast cancer. One further patient developed visceral metastases after 46 months of treatment, which responded well to an increase in tamoxifen. The patient with osseous metastases at the time of diagnosis is still alive with stable disease after 75 months. Growing axillary lymph nodes were dissected 16 and 22 months after primary surgery in two patients. It is concluded from this series that limited surgery with hormonal therapy is an effective treatment of breast cancer in elderly patients.

Aged↗
PubMed1992

Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo.

Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.

Animals↗
PubMed1991

Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease.

The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.

Animals↗
PubMed1991

Dose-related effects of epinephrine on glucose production in conscious dogs.

The effects of increases in plasma epinephrine from 78 +/- 32 to 447 +/- 75, 1,812 +/- 97, or 2,495 +/- 427 pg/ml on glucose production, including gluconeogenesis, were determined in the conscious, overnight-fasted dog, using a combination of tracer [( 3-3H]glucose and [U-14C]alanine) and arteriovenous difference techniques. Insulin and glucagon were fixed at basal levels using a pancreatic clamp. Plasma glucose levels rose during the 180-min epinephrine infusion by 47 +/- 7, 42 +/- 22, and 74 +/- 25 mg/dl, respectively, in association with increases in hepatic glucose output of 1.04 +/- 0.22, 1.87 +/- 0.23, and 3.70 +/- 0.83 mg.kg-1.min-1 (at 15 min). Blood lactate levels rose by 1.52 +/- 0.24, 4.29 +/- 0.49, and 4.60 +/- 0.45 mmol/l, respectively, by 180 min, despite increases in hepatic uptake of lactate of 3.47 +/- 5.73, 12.83 +/- 3.46, and 37.00 +/- 4.20 mumol.kg-1.min-1. The intrahepatic gluconeogenic efficiency with which the liver converted the incoming alanine to glucose had risen by 84 +/- 40, 77 +/- 24, and 136 +/- 34% at 180 min, respectively. The latter effect plus the effect on net hepatic lactate uptake point to an intrahepatic action of high levels of the hormone in vivo. In conclusion, epinephrine produces dose-dependent increments in overall glucose production, which involve a progressive stimulation of both glycogenolysis (as assessed by glucose production at 15 min) and gluconeogenesis (assessed in the last 30 min of the study). The latter involves a peripheral action of the catecholamine to increase gluconeogenic substrate supply to the liver and may also involve a hepatic effect when high epinephrine levels are present.

Alanine↗
PubMed1991

Three-dimensional high-resolution volume rendering (HRVR) of computed tomography data: applications to otolaryngology-head and neck surgery.

Conventional computed tomographic display formats are not optimal for demonstrating three-dimensional anatomic relationships. In otolaryngology--head and neck surgery these critical relationships are often highly complex, and their complete understanding is essential to a successful surgical outcome. A new computer-generated image display format, high-resolution volume rendering (HRVR), facilities the understanding of these critical anatomic relationships by transforming conventional imaging data into clinically relevant 3-D images. Unlike many other 3-D reconstruction algorithms, HRVR suffers minimal data loss in the conversion process, which in turn provides for superior image resolution. This better allows the application of 3-D technology to small or complicated anatomic structures such as those frequently encountered in otolaryngology--head and neck surgery. Advances in computer-controlled manipulations that further enhance the evaluation of desired pathologic features have been achieved. This pilot study contains representative clinical cases chosen to illustrate the potential utility of HRVR in otolaryngology--head and neck surgery. The authors believe HRVR images will enhance the surgeon's understanding of the 3-D anatomic relationships that exist between critical pathologic features and surrounding vital structures.

Aged↗
PubMed1990

Percutaneous transhepatic gallstone dissolution with methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies.

In a total of 117 successfully punctured patients with gallbladder stones that were to be treated with methyl tert-butyl ether, 11 showed shell-like structured concrements on the CT scan. In 2 patients, pigment stones and very old concrements were suspected. In these 13 patients solitary stones dissolved in 2.9 hours, multiple stones in 10.8 hours, which corresponds to the treatment time of the total group. In 4 patients we diagnosed cholesterol stones, but dissolution was very slow, suggesting that the stones were covered with pigment. In 21 patients we found marked gallbladder anomalies, such as extreme septation, two-chamber gallbladders, gallbladder diverticula with a wedged stone, or gallbladders in which the fundus was positioned cranially. In these patients puncture time was prolonged by 25%. However, since in all patients the stones dissolved in the same time as in the total group (solitary stones; 3.1 hours: multiple stones: 10.4 hours) and since in 33% there was also sludge in the gallbladder, shape variants of the gallbladder obviously have no influence on the stone type. Whether they induce recurrent stones more often than normal gallbladders cannot be assessed at present. Shape variants of the gallbladder and layered stones on CT scan, however, do not represent a contraindication to MTBE therapy.

Cholecystography↗