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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 289 records · Page 16Linked to original sources

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↗

[Nerve regeneration in autologous and allogeneic transplant of the sciatic nerve of the rat with and without immunosuppression by cyclosporin A].

The following experimental studies show different stages of regeneration and rejection in autologous and allogenic nerve grafts in 162 rats with and without immunosuppression with Cyclosporin A. Allografts were used in congenic rats differing only in major histocompatibility complex (MHC). Nerve regeneration was studied in autologous grafts with and without treatment with Cy A and with toxic doses of Cy A. No difference in nerve regeneration was seen in these groups. Allografts were transplanted between congenic rats type LEW 1 A and 1 U and vice versa with and without treatment with Cy A. Various degrees of rejection from slight to moderate were seen. Without Cy A-treatment, nerve grafts were totally destroyed after four weeks. With Cy A, nerve grafting resulted in complete regeneration.

Animals↗

Improved high-performance liquid chromatographic procedure for the determination of chlormethiazole levels following solid-phase extraction from plasma.

An improved high-performance liquid chromatographic method for the determination of chlormethiazole levels in plasma is described. The drug is extracted from plasma using commercially available reversed-phase extraction columns; recovery values obtained using Sep-Pak C18 and Bond Elut C1, C2, C4, C6, C8, C18 columns are compared. Separation was achieved by reversed-phase chromatography, using a mobile phase consisting of 0.025 M sodium acetate buffer, pH 4.5-acetonitrile (67:33) at a flow-rate of 1.6 ml/min in conjunction with a 15-cm Jones Chromatography Apex ODS column. The analytical column was protected by a Waters Assoc. Guard-Pak module containing a Guard-Pak CN insert. Using ultraviolet detection at 254 nm chlormethiazole levels in the region of 50 ng/ml can be measured with only 500 microliter of plasma.

Chlormethiazole↗

A phase II trial of diaziquone in patients with head and neck cancer.

Diaziquone (AZQ) is a lipophilic alkylating agent which crosses the blood-brain barrier and has marked antitumor activity in a broad spectrum of murine tumor systems. Myelosuppression has been the dose-limiting toxicity in phase I trials. In this study 36 patients with head and neck cancer received diaziquone. Thirty-one of these patients (28 male, 3 female) were evaluable for efficacy. The initial starting dose was 7 mg/m2/day X 5 days i.v. repeated every 28 days. Because of the severe myelosuppression encountered in the first four patients, the starting dose was decreased by 20% to 5.5 mg/m2/day X 5 days repeated every 28 days. The majority of patients were considered to be good-risk patients as evidenced by performance status (80% 0-1 Zubrod) and prior therapy. Even with this dosage reduction, myelosuppression (especially thrombocytopenia) was again the dose-limiting toxicity with 25% of patients experiencing granulocyte and platelet nadirs below 1000/mm3 and 50,000/mm3 respectively. Thirty-five percent of patients required a subsequent dosage reduction of 20% prior to receiving a second course of therapy. There was one complete (CR), four partial (PR) and three minor (MR) responses. All but the CR were of relatively short duration (mean of 30 days). The patient with a CR has remained disease-free for nearly 3 years. In this group of patients the activity of diaziquone as a single agent at this dose and schedule (CR + PR + MR = 26%; CR + PR = 16%) is less than that of methotrexate, bleomycin, and cis-platinum but is encouraging. Further trials utilizing combinations are warranted.

Adult↗

Circulating somatomedin-C levels and the effect of growth hormone-releasing factor on plasma levels of growth hormone and somatostatin-like immunoreactivity in obese children.

The effect of growth hormone-releasing factor (GRF) 1-44 on growth hormone and somatostatin release in plasma has been studied in 20 obese children. Twenty age and sex-matched children with normal weight served as controls. Mean peak growth hormone response in obese children after 1 microgram/kg body wt. GRF 1-44 was significantly lower than in controls (23.7 +/- 3.6 ng/ml vs. 41.1 +/- 3.0 ng/ml; P less than 0.01), as were mean integrated growth hormone response areas (1544 +/- 272 ng X ml-1 X 2 h vs. 2476 +/- 283 ng X ml-1 X 2 h; P less than 0.01). Mean plasma levels of somatostatin-like immunoreactivity did not change after GRF in both groups. Mean somatomedin-C levels in obese children were significantly higher compared to controls (1.6 +/- 0.4 U/ml vs. 0.86 +/- 0.4 U/ml; P less than 0.01). Somatomedin-C levels were not related to the integrated growth hormone responses. In conclusion there is no relation between somatomedin-C levels and the reduced growth hormone-releasing effect of GRF in obese children. GRF does not alter peripheral somatostatin-like immunoreactivity levels either in normal or obese children.

Adolescent↗

Effect of insulin-induced hypoglycemia on circulating levels of plasma growth hormone-releasing hormone and somatostatin in children.

In response to insulin-induced hypoglycemia (0.1 U insulin/kg body weight, i.v.) plasma levels of growth hormone-releasing hormone (GHRH), somatostatin (SLI), and growth hormone (GH) were measured by radioimmunoassay in 10 children with short stature. Insulin injection resulted in a significant increase in plasma GHRH values at 15 min (10.0 +/- 0.5 vs. 17.1 +/- 3.1 pg/ml; p less than 0.05) preceding the increase in plasma GH levels (1.5 +/- 0.4 vs. 13.6 +/- 1.2 ng/ml; p less than 0.001). SLI concentrations peaked between 15 and 60 min after insulin injection (20.9 +/- 1.2 vs. 47.1 +/- 6.2 pg/ml; p less than 0.01). No correlation was present between plasma GHRH or SLI levels and plasma GH concentrations. A significant negative correlation could be established between maximum increments of plasma GHRH and SLI levels (r = -0.843; p less than 0.01) in response to insulin injection. This finding suggests a possible relationship between these two hormones at peripheral level.

Adolescent↗

Plasma levels of growth hormone-releasing hormone and somatostatin in response to a mixed meal and during sleep in children.

Following a mixed meal, plasma levels of GHRH, GH, SRIH and insulin were measured in 7 prepubertal children with constitutional delay of growth and adolescence (CDGA) and in 3 children with proven GH-deficiency which responded to GHRH-injection. In children with CDGA, plasma levels of GHRH increased between 60 and 120 min (10.1 +/- 1.2 ng/l vs 25.5 +/- 4.4 ng/l; P less than 0.01). Although no GH increase occurred in patients with GH-deficiency, their plasma GHRH increases were comparable to those in CDGA children. No time relationship was present between circulating GHRH and GH, SRIH, or insulin, nor was there any correlation between their integrated hormone response areas. Sleep-induced plasma GHRH, GH and SRIH values were determined in 10 prepubertal children with CDGA. Spontaneous variations of plasma GHRH and GH values occurred with no temporal or quantitative relationship. SRIH values did not change during nocturnal sleep. In one child with GH-deficiency, comparable GHRH plasma fluctuations occurred, although GH values were all below 1 microgram/l. Our results support the concept that circulating GHRH does not only represent hypothalamic GHRH, but derives mainly from extrahypothalamic sources, possibly from the gastrointestinal tract.

Adolescent↗