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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 55 records · Page 3Linked to original sources

Biospecific adsorbents on the basis of chloroformate-activated bead cellulose.

Carbohydrate-derived polymers are activated by the chloroformate N-chlorocarbonyloxy-5-norbornene-2.3-dicarboximide (ClCOONB). The advantages of this activation method are presented. The application of bead cellulose as adsorbent for biomedical and biotechnological purposes is demonstrated. Examples for immunoglobulin purification, streptavidin isolation, and biotransformation of porcine insulin are given.

Bacterial Proteins

Evaluation of the white blood cell differential given by the new analyser Coulter STKS in both hematological and non-hematological patient groups.

The White Blood Cell differential given by the new analyser Coulter STKS was studied in a group of hospitalized patients originating from non-hematological departments (group 1; n = 290) and a group of patients suffering from an hematological disease (group 2; n = 106) with blood smear abnormalities. A good relationship between the reference method and the STKS results was shown in 200 patients without hematological abnormalities. Both sensitivity and reliability of alarms were evaluated in both groups. In group 1, we noticed respectively: 208 true negative, 40 true positive, 7 false negative, 35 false positive. Six of the seven false negative results were related to the presence of a slight myelemia without hematological significance, one to the presence of small quantity of circulating blasts with a leuconeutropenia. In group 2, all abnormalities seen on the blood smear were detected by the Coulter STKS either by an alarm message (93 cases) or by an increase of the lymphocyte population (9 cases) in some chronic lymphocyte leukemias, or by an important leuconeutropenia (4 cases) in acute treated leukemias. The results of the White Blood Cell differential performed with the Coulter STKS exhibited a good relationship with the reference method for normal bloods and a good reliability for detection of abnormal cells.

Erythrocyte Count

Determination of antineoplastic activity and toxicity of tumor necrosis factor (TNF) in animal experiments. Correlation to clinical findings.

Because of the deep evolutionary roots which macrophages and their products have, it should be possible to relate effects of the biological response modifier TNF observed in cancer patients with those determined in animal species. We have tested this hypothesis both with regard to antitumor efficacy and unwanted side-effects in murine tumor models. In the intramuscularly (i.m.) transplanted B16 melanoma, TNF had both after intratumoral (i.t.) and intravenous (i.v.) administration (qd 7-11, 14-17) a significant and dose-dependent effect on tumor growth. This effect was transitory and led only to a moderate increase in survival time of the animals. This correlates well with the also unsatisfactory clinical antineoplastic activity of TNF. From the measurement of body weight reduction, WBC counts, platelets, recalcification time, transaminases and body temperature in tumor bearing mice it can be concluded that there are close similarities to the side-effects observed in patients, although the level and/or time course of the noticed changes were differently expressed. In principle, it seems possible to predict clinical effects of biological response modifiers in animal experiments even if not all mechanisms are clearly understood.

Animals

Rapid, simple, and reliable doctor's office test for antibodies to human immunodeficiency virus 1 in serum.

This "Unit Test Method" assay for detecting anti-human immunodeficiency virus 1 antibody is suitable for nonlaboratory testing and has a sensitivity comparable with that of present enzyme immunoassay methods. The method does not require instrumentation, gives a result in less than 15 min, and incorporates a procedural control. Little technical expertise and hands-on time are required of the user.

Colorimetry

[Adverse effects of cyclosporin A with special reference to the peripheral nervous system].

Since the introduction of Cyclosporine A (CsA) in 1972, several studies have focused on its effects on experimental autologous peripheral nerve transplants. Although several studies have reported neurotoxicity of CsA in the central nervous system, no such data exist regarding the peripheral nervous system. The present study focuses on the effects of CsA in the therapeutic and toxic doses on axon regeneration, particularly the rate and quality of axon regeneration. Autologous nerve transplantation was performed in Lewis rats and axon regeneration evaluated clinically (motor function, body weight), electroneurographically and histologically. In transplanted nerves, even high doses of CsA (30 mg/kg bodyweight) did not lead to delayed or impaired axon regeneration. Long-term application in normal peripheral nerves did however cause axon degeneration with edema and vacuolisation of myelin sheaths, retraction of myelin sheaths from the node of Ranvier, and marked enhancement of the Schmidt-Lantermann incisures. As neurological side effects such as tremor and paresthesia have been reported under application of CsA in man, the above data might be of clinical relevance.

Animals

Combined segregation and linkage analysis for IDDM and HLA-DR under several ascertainment assumptions.

Combined segregation and linkage analysis of the Genetic Analysis Workshop 5 (GAW5) data suggests a complex basis for susceptibility to insulin-dependent diabetes mellitus (IDDM). One susceptibility gene, linked to the HLA-DR region, is additive on the liability scale (d = .49 +/- .15, t = 2.9 +/- .6) with a gene frequency q = .30 +/- .03. A second locus, with a gene frequency of q = .07 +/- .02, which is recessive and unlinked to HLA, is also suggested by the analysis. The ascertainment correction used has little effect on the results, presumably because most of the information comes from the cosegregation of HLA alleles and disease status. The results are consistent with a direct involvement of the HLA-DR region in susceptibility, but are not a proof of it.

Computer Simulation

Immunoelectrophoretic analyses of antigens shared by the vesicular fluid and cyst wall of Taenia crassiceps and Taenia saginata metacestodes.

In this study, the antigenic mosaic of the vesicular fluid (VF) and hydrosoluble cyst-wall extract (CWE) of T. crassiceps (Tc; harvested from mice) and T. saginata (Ts) metacestodes was analyzed by combined precipitation maps developed in single and bidimensional immunoelectrophoresis against the respective rabbit antiserum. Host-serum proteins demonstrated by immunodiffusion within TcVF (albumin, transferrin, IgG, and another five noncharacterized proteins), TcCWE (albumin, IgG, and six additional unknown proteins), TsVF (albumin) and TsCWE (albumin and IgG) were removed by immunoaffinity chromatography prior to immunoelectrophoretic analysis. Neither TcVF nor TcCWE contained demonstrable amounts of mouse IgM and IgA. In TcVF a total of 18 and in TcCWE a total of 36 parasitic antigens were recognized by the corresponding antiserum. In the case of TsVF and TsCWE, antiserum to the crude extract of T. saginata larvae developed a total of 26 and 30 precipitates, respectively. Examination of the precipitation maps developed by the respective heterologous antiserum (vice-versa testing) showed that both TcVF and TsVF contained ten antigens sharing identity. For TcCWE and TsCWE, nearly the same number of shared antigens (20 and 18, respectively) could be demonstrated. For screening of IgG antibodies against T. saginata metacestodes from heavily and moderately infected calves (n = 6) by ELISA, VF and CWE antigens of both Taenia species were found to be potent reagents; TsVF was the most sensitive antigen.

Animals

Molecular epidemiology and restriction site mapping of adenovirus 7 genome types.

From the United States, the Federal Republic of Germany, and other regions, 168 strains of AV7, isolated between 1961 and 1985, were analyzed by six restriction endonucleases and nine genome types were identified. The enzymes BamHI and HindIII were most discriminative. The genome type D5 (or 7b) predominated with 120 isolates since 1970 in both countries. Strains of D2 (7a) and D4 (7c) were isolated for a limited time, D3 for an extended time period. Several clusters of infections with the same genome type were found. Differences in pathogenicity could not be derived from our data. On the basis of restriction site mapping, most other genome types were similar to D5, one to D2 and one to the prototype (D1). The genomic relation between AV7 and AV3 is discussed and shown by a dendrogram.

Adenoviridae

Biliary lipid composition in patients with cystic fibrosis.

Lipid composition of gallbladder bile was determined in 20 patients with cystic fibrosis (CF) (9 females and 11 males, ranging in age from 3 to 18 years). The results were compared with 47 normal subjects matched for age, sex, and pubertal stage. In patients with CF, bile was undersaturated with cholesterol before puberty in both sexes and no differences with normal controls could be observed. After puberty, a similar increase in cholesterol saturation was noted in females with CF (85 +/- 15% vs. 130 +/- 38%, p less than 0.01) and normal controls (82 +/- 11% vs. 138 +/- 31%, p less than 0.01). No change in cholesterol saturation could be observed in male patients and controls after puberty. Molar percentage of chenodeoxycholic acid (CDCA) was lower (p less than 0.05) in postpubertal females (31 +/- 9%) and males (36 +/- 7%) with CF compared to controls (42 +/- 8% and 40 +/- 5%, respectively), while cholic acid (CA) was higher in all patients with CF. In females with CF, lithocholic acid (LCA) increased after puberty (2.2 +/- 0.8% vs. 5.3 +/- 2.6%, p less than 0.05) and was higher compared to controls (2.2 +/- 0.8%, p less than 0.001). An increase was also noted for deoxycholic acid (DCA) in postpubertal females with CF (1.7 +/- 2.6% vs. 10.8 +/- 7%, p less than 0.05), but it was lower in both sexes after puberty than in respective controls. The present results suggest that cholesterol saturation of bile in patients with CF is not different from respective controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease.

In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.

Adult

[Substitution therapy with alpha-1-Pi in patients with alpha-1-Pi deficiency and progressive pulmonary edema].

In a multi-centre study 20 patients with severe congenital alpha-1-Pi deficiency and progressive pulmonary emphysema received infusions of alpha-1-Pi concentrate from human plasma once weekly for six months, at an initial dosage of 60 mg/kg body-weight, in some instances slightly increased to achieve a minimum serum level above 70 mg/100 ml. The immunologically measured serum level of alpha-1-Pi rose 30 min after start of the infusion by a mean of 130% of normal, at an initial level of 13%. An exponential fall followed this rise. The lowest level occurred at the end of the first week, immediately before the next infusion, to 35% of normal, a serum level which is assumed still to provide an effective protection against elastases in the lung. There was also a definite increase of free inhibitors against both trypsin and leucocyte-elastase in serum of all patients, with a minimal level which for both was many times that of the initial value. There were no side-effects in more than 500 infusions and no dose reduction was necessary. During the entire course there were no significant changes in haematological, coagulation and biochemical test results, and lung function means remained constant. No antibodies against alpha-1-Pi were demonstrated, nor transmission of hepatitis B.

Clinical Trials as Topic

Structural analysis of polymers of sickle cell hemoglobin. III. Fibers within fascicles.

We have examined the structure of hemoglobin S fibers, which are associated into large bundles, or fascicles. Electron micrographs of embedded and cross-sectioned fascicles provide an end-on view of the component fibers. The cross-sectional images are rotationally blurred as a result of the twist of the fiber within the finite thickness of the section. We have applied restoration techniques to recover a deblurred image of the fiber. The first step in this procedure involved correlation averaging images of cross-sections of individual fibers in order to improve the signal-to-noise ratio. The rotationally blurred image was then geometrically transformed to polar co-ordinates. In this space, the rotational blur is transformed into a linear blur. The linearly blurred image is the convolution of the unblurred image and a point spread function that can be closely approximated by a square pulse. Deconvolution in Fourier space, followed by remapping to Cartesian co-ordinates, produced a deblurred image of the original micrograph. The deblurred images indicate that the fiber is comprised of 14 strands of hemoglobin S. This result provides confirmation of the fiber structure determined using helical reconstruction techniques and indicates that the association of fibers into ordered arrays does not alter their molecular structure.

Hemoglobin, Sickle