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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 253 records · Page 14Linked to original sources

Intravenous immunoglobulin in HIV-I infected haemophilic patients.

In order to evaluate the efficacy of intravenous immunoglobulin (IVIG) in the early stages of HIV infection (patients without AIDS or AIDS related complex) a prospective controlled open trial was conducted in 36 patients (age 6-19 years) with haemophilia. Eighteen patients received 0.3 g/kg IVIG at two week intervals; 18 patients served as controls. Major criteria for the evaluation were progression of HIV disease assessed by the modified Brodt/Helm classification, number of infectious events and HIV associated thrombocytopenia, and the CD4+ T cell count. After 24 months of evaluation seven patients in the IVIG group and five patients in the control group deteriorated according to their staging, with one patient in each group developing AIDS. Thrombocytopenia and infectious events, but no severe bacterial infections, occurred in both groups in similar numbers. The absolute CD4+ T cell count decreased by 284/microliters in the IVIG group and by 143/microliters in the control group respectively (mean values). The statistical analysis of these criteria did not reveal any significant difference. In conclusion, IVIG was not effective in the early stages of HIV infection in patients with haemophilia. IVIG did not slow down the progression of HIV disease and did not prevent the development of an immunodeficiency as assessed by the CD4+ T cell count.

Adolescent↗

Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.

The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling.

Animals↗

Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo.

Low density lipoprotein modified by oxidation (Ox-LDL) causes adhesion of leukocytes to the endothelium, a feature common in early atherogenesis. Because leukocyte adhesion under various pathophysiological conditions involves superoxide generation, we explored the possibility that superoxide is likewise involved in leukocyte adhesion in response to Ox-LDL. For our studies, we used the dorsal skin fold chamber model for intravital microscopic observation of leukocyte-endothelium interactions in hamsters. We show here that injection of human LDL (4 mg/kg LDL cholesterol oxidatively modified by incubation in 7.5 microM Cu2+ for 18 hours at 37 degrees C) elicited in control hamsters (n = 7) the rolling and adhesion of circulating leukocytes along the endothelium of arterioles and postcapillary venules. This adhesion was significantly attenuated when hamsters were pretreated with bovine copper-zinc-superoxide dismutase (CuZn-SOD, 0.25 mg/kg, n = 7) or heparin (2,000 IU/kg, n = 7). The CuZn-SOD infusion and the heparin-induced release of extracellular SOD from endothelial cell surfaces to plasma resulted in nearly equal plasma SOD activities. Further inhibition of Ox-LDL-induced leukocyte adhesion could not be achieved by increasing the dose of CuZn-SOD to 5 mg/kg (n = 6). Pretreatment of the hamsters with inactivated CuZn-SOD showed no effect. These results indicate that Ox-LDL stimulates leukocyte adhesion through a superoxide-dependent step, and they indicate a possible mechanism by which antioxidants might inhibit the onset of experimental and clinical atherosclerosis.

Animals↗

Endothelin-like immunoreactivity in the aqueous humour and in conditioned medium from cultured ciliary epithelial cells.

Endothelin-like immunoreactivity was detected in human (15.6 +/- 2.7 pg/ml) and bovine (11.1 +/- 0.98 pg/ml) aqueous humour of the eye. These concentrations are 2-3 times higher than the corresponding plasma levels. Cultured human nonpigmented ciliary epithelial cells released endothelin-like immunoreactivity with a maximum of 2.1 +/- 0.32 pg/(cm2* 48 h). The release was stimulated by fetal calf serum, thrombin, carbachol and phorbol ester and blocked by cycloheximide. Immunocytochemistry showed cytoplasmic staining of cultured human nonpigmented ciliary epithelial cells for endothelin-1. Endothelin-1 was shown to induce contractions in isolated human ciliary muscle by isometric force measurements. Endothelin in the aqueous humour may play a role in the regulation of intraocular pressure.

Animals↗

The downregulation of growth-associated proteins in motoneurons at the onset of synapse elimination is controlled by muscle activity and IGF1.

Axonal growth during development and regeneration coincides with the expression of growth-associated proteins (GAPs), including GAP-43 and tubulin-alpha 1. Following contact with the target region and synaptogenesis, GAPs are downregulated. However, high levels of GAP-43 are expressed in some neurons in the adult CNS, indicating that its function may not be restricted to axonal growth. To define the type of signals that regulate GAP levels during development, we have determined whether GAP downregulation coincides with a defined phase of synapse development and whether it is controlled by the postsynaptic target. Levels of GAP-43 mRNA in spinal motoneurons and protein at the neuromuscular junction were analyzed in the developing neuromuscular system of chick and rat. In both species, GAP-43 mRNA declined rapidly at a time corresponding to the onset of synapse elimination, and nerve terminal GAP-43 immunoreactivity became undetectable with a delay of 2-3 d. In rat motoneurons, GAP-43 and tubulin-alpha 1 mRNA levels declined with a similar time course, indicating that at least two GAPs are downregulated at the same time. Blockade of neuromuscular transmission with either a pre- or a postsynaptically acting toxin prevented GAP downregulation, indicating that target activity affects GAP mRNA levels in motoneurons. Finally, counteracting the activity-dependent decline of muscle insulin-like growth factors during synapse elimination by local subcutaneous injections prevented motoneuron GAP downregulation, suggesting that these growth factors may be involved in the regulation of motoneuron GAPs by the muscle. These results demonstrate that motoneurons undergo target-sensitive changes in GAPs at the onset of synapse elimination. In addition, these results raise the possibility that termination of a presynaptic growth mode may be a prerequisite for synapse elimination.

Animals↗

[Riding arenas and different riding track surfaces in relation to the airway contamination in horses. Laboratory studies on riding surfaces].

29 samples of commonly used surfaces were tested for their water characteristics (litre weight, water capacity, water binding, water evaporation) and their contribution to airborne fungal spores (dust formation, dust setting). The results are discussed in comparison to the literature with regard to the environment. The results are: 1. Any surface--no matter of what material--eventually causes air pollution with fungal spores and dust. 2. Correct watering prevents air pollution by any surface. 3. Artificial products have no advantage over natural materials in the parameters tested. 4. The question of proper disposal of old surface material has to be clarified before purchase. The results show that a mixture of sand and wood shavings should be recommended as a surface for indoor arenas, especially in regard to environmental protection and proper disposal.

Air Pollution, Indoor↗

[Management of acute tendinitis].

Ultrasonography must be used in combination with physical examination for the appropriate diagnosis of acute tendon injuries. Therapy should be designed to return the tendon to its normal function and appearance. Local and systemic anti-inflammatory agents, cold hydrotherapy and massage minimize excessive scar formation and progressively increasing tensile forces directs scar tissue to replace the tendon function.

Acute Disease↗

Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate.

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.

Apolipoprotein A-I↗

Purification and spectral characterization of a b-type cytochrome from the plasma membrane of the archaebacterium Sulfolobus acidocaldarius.

For the first time the purification of a heme-b containing cytochrome from the plasma membrane of an extremely thermoacidophilic archaebacterium is described. The detergent solubilized 30 kDa polypeptide contains two heme-b centers and one copper ion. According to its low temperature spectra and CO-binding properties, it is likely to function as a cytochrome-o like terminal oxidase in the membrane. The purified cytochrome does not retain catalytic activity, however.

Cell Membrane↗

Bead cellulose derivatives as supports for immobilization and chromatographic purification of proteins.

Characteristic data are presented for Divicell, a macroporous bead cellulose with excellent flow parameters. The preparation of Divicell derivatives and their properties are described with respect to their application as chromatographic supports. The ion exchangers Divicell DEAE and Divicell CM were manufactured in two types with different exclusion limits and an available capacity for proteins of up to 100 mg/ml gel. Divicell Blue is a bead cellulose with covalently bound Cibacron Blue F3G-A and was found to be a very suitable adsorbent for the selective separation and purification of human serum albumin. Activation of Divicell with sodium periodate, epichlorohydrin and 5-norbornene-2,3-dicarboximido carbonochloridate provided activated supports used for immobilization of ligands in organic solvents and in aqueous solutions. Coupling of amines, diamines, amino acids, carbohydrates and proteins is described. The immobilized ligands retained their biological activity as determined by their specific adsorption of proteins. Divicell alkyl derivatives were tested in hydrophobic interaction chromatography with bovine serum albumin as a model. Examples are presented of the application of Divicell derivatives to the purification of biomacromolecules such as immunoglobulins and lectins by affinity chromatography. The results were comparable to those obtained using the corresponding Sepharose-derived absorbents.

Animals↗

Influence of type and extent of surgery on early results and survival time in glioblastoma multiforme.

We studied the influence of the type of surgery (microsurgery or macrosurgery) and extent (complete resection with lobectomy, complete resection alone, partial resection with lobectomy or partial resection alone) on early postoperative results and survival time in 118 consecutive patients who underwent surgery for glioblastoma multiforme. Early results were assessed by the Karnofsky score at 4 weeks postoperatively. Survival was compared using Kaplan-Meier curves and Mantel statistics. The median survival time (MST) after microsurgery (12.1 months) was significantly longer than that after macrosurgery (7.3 months). The longer survival after microsurgery was, however, largely attributable to better early results and a consequently higher proportion of patients who could undergo radiotherapy. Complete resection was superior to partial resection. Additional lobectomy did not appreciably influence the early results and the MST in completely resected tumours. So the MST after complete resection in the microsurgical group without lobectomy was 12.6 months, with lobectomy 12.9 months. In the macrosurgical group the respective values were 7.4 months without and 8.2 months with lobectomy. In incompletely resected tumours lobectomy worsened the early results compared to incomplete resection alone and led to a shorter MST.

Brain Neoplasms↗

Are there antiendometrial antibodies in sera of women with endometriosis?

STUDY OBJECTIVE: To identify and characterize the antiendometrial tissue specific antibody response in endometriosis patients. DESIGN: Retrospective. SETTING: Industrial research laboratory. PATIENTS: Twenty untreated women with laparoscopically diagnosed endometriosis, 10 healthy women without symptoms of endometriosis, 12 women in whom laparoscopy failed to yield evidence of endometriosis, 10 healthy men, and 4 individuals with elevated titers of serum antinuclear antibodies. RESULTS: Several immunological methods have been employed including immunofluorescence, hemagglutination, enzyme-linked immunoabsorbent assays, and protein blotting. Contrary to reports in the literature, results of these analyses have failed to demonstrate the presence of detectable levels of antiendometrial immunoreactivity in sera from patients with endometriosis. CONCLUSION: The association of endometrial autoimmunity with endometriosis remains to be established.

Autoantibodies↗

Regeneration of autologous and allogenic nerve grafts in a rat genetic model: preliminary report.

The authors report observations concerning rejection and regeneration processes of allogenic peripheral neural tissue, depending on different genetic mismatches in a rat model. Five groups representing different rat strains (n = 100) were subjected to orthotopic grafting of 2.5-cm segments of sciatic nerve. Combinations represented different genetic barriers, including the Major Histocompatibility Complex (MHC), a non-MHC, a subgroup (A) of the MHC, a group representing MHC plus non-MHC, and an autologous control group. Animals were examined after one, two, and 12 weeks; additional evaluations in some of the experimental groups were done at six and eight weeks. Regeneration in varying degrees was evident in all groups at 12 weeks.

Animals↗