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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 289 records · Page 16Linked to original sources
PubMed1995

Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat.

In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.

Animals↗
PubMed1995

The development of sexually dimorphic sensitivity to growth hormone (GH) feedback of the clonidine-induced GH surge in the rat.

This study investigates the development of sexually dimorphic sensitivity of the GH system to alpha 2-adrenergic stimulation and GH feedback in the rat. Sensitivity to alpha 2-adrenergic stimulation was tested with clonidine (CLN, an alpha 2-adrenergic agonist) which stimulates GH release in the adult male rat. Feedback was examined by testing whether human (h)GH suppressed the CLN-induced GH surge as previously demonstrated in adult male rats. The integrity of the pituitary and its capacity to respond to stimulation was tested at the end of the experiment by perifusing with GRF. Studies were conducted using a hypothalamic-pituitary coperifusion system which allows incubation of these tissues without the confounding influences of peripheral hormonal and extrahypothalamic neural factors. Tissue from prepubertal rats of 10, 20, 25 and 30 days of age, 50-day-old and adult rats (90-100 days) were evaluated. Results indicate that tissue from both male and female rats is sensitive to alpha 2-adrenergic stimulation at 10 days of age. In male tissue, there is an increase in GH release in response to CLN until 30 days of age, after which a slight decline in sensitivity occurs by 50 days of age and is maintained in adulthood. In regard to GH release from female tissue, a GH surge occurs in response to CLN until 30 days of age. At 50 days and in adulthood, this response is substantially diminished. Additionally, there is a profound sexual dimorphism in the capacity of hGH to suppress the CLN induced GH surge. In tissue from male rats, by 20 days of age there is an apparent GH-associated inhibition of the CLN-induced GH surge which is significant by 25 days, is more pronounced by 30 days of age, and is maintained after puberty at 50 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Two in-vivo protocols for testing virucidal efficacy of handwashing and hand disinfection.

Whole-hands and fingerpads of seven volunteers were contaminated with poliovirus type 1 Sabin strain in order to evaluate virucidal efficacy of different forms of handwashing and handrub with alcohols and alcohol-based disinfectants. In the whole-hand protocol, handwashing with unmedicated soap for 5 min and handrubbing with 80% ethanol yielded a log reduction factor (RF) of > 2, whereas the log RF by 96.8% ethanol exceeded 3.2. With the fingerpad model ethanol produced a greater log RF than iso- or n-propanol. Comparing five commercial hand disinfectants and a chlorine solution (1.0% chloramine T-solution) for handrub, Desderman and Promanum, both composed of ethanol, yielded log RFs of 2.47 and 2.26 respectively after an application time of 60 s, similar to 1.0% chloramine T-solution (log RF of 2.28). Autosept, Mucasept, and Sterillium, based on n-propanol and/or isopropanol, were found to be significantly less effective (log RFs of 1.16, 1.06 and 1.52 respectively). A comparison of a modified whole-hand and the fingerpad protocol with Promanum showed similar results with the two systems suggesting both models are suitable for testing the in-vivo efficacy of handwashing agents and hand disinfectants which are used without any water.

Adult↗
PubMed1995

[61-year-old patient with rapidly progressive cerebellar symptoms].

The rare case of a paraneoplastic, cerebellar degeneration is reported. In addition to the valuable early diagnosis of tumor disease, this paraneoplastic occurrence can also lead to false diagnoses in regard to both the underlying disease and the staging of the tumor. In the cases of known tumor disease, the assumption of cerebral metastasis is also possible.

Autoantibodies↗
PubMed1994

Proteoglycan synthesis by cultured human chondrocytes.

Iliac crest biopsies are important in the detection of human skeletal dysplasias. Therefore, culture of these cells may serve as a valuable method for studying proteoglycan metabolism in chondrocytes of individuals with skeletal abnormalities. Morphological and biochemical studies were performed on human iliac crest chondrocytes grown in monolayer and in agarose gels. Two proteoglycan populations of different hydrodynamic size and glycosaminoglycan composition were synthesized by cells grown in monolayer. Chondrocytes cultured in an agarose gel for 2 weeks synthesized proteoglycans identical to those of the native tissue with respect to hydrodynamic size and glycosaminoglycan chain length. However, the ratio of chondroitin-6-sulfate to chondroitin-4-sulfate was higher than in the native tissue. This ratio was not influenced by different sulfate concentrations in the medium. Moreover, treatment with ascorbic acid did not influence proteoglycan synthesis; however, there was a pericellular accumulation of proteoglycans.

Ascorbic Acid↗
PubMed1994

Preproteins of chloroplast envelope inner membrane contain targeting information for receptor-dependent import into fungal mitochondria.

The amino-terminal transit sequences of two preproteins destined for the chloroplast inner envelope membrane show similarities to mitochondrial presequences in the prevalence of positive charges and the potential formation of an amphipathic alpha-helix. We studied if these preproteins could be imported into mitochondria and found a low, yet significant import into isolated plant mitochondria. The plant mitochondria were previously shown not to import precursors of chloroplast stromal or thylakoidal proteins. To analyze the specificity of import into mitochondria we used the established import systems of fungal mitochondria. The envelope preproteins were efficiently imported into Saccharomyces cerevisiae or Neurospora crassa mitochondria. Their import showed the characteristics of specific mitochondrial protein uptake, including a requirement for the main receptor MOM19 (mitochondrial outer membrane protein of 19 kDa) and a membrane potential across the inner membrane, and depended on the presence of the chloroplast transit sequence. We conclude that some chloroplast transit sequences contain sufficient information for specific interaction with mitochondrial import receptors (at least from fungal sources).

Ascomycota↗
PubMed1994

Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer.

The prognostic impact of the proteolytic factors urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) was evaluated in 76 completely resected gastric cancer patients enrolled in a prospective study. All patients underwent macroscopically and microscopically residual tumor-free resection (category R0, Union International Contre Cancer, 1987). uPA and PAI-1 levels were quantified in detergent-extracted (Triton X-100) specimens of primary gastric tumors by enzyme-linked immunosorbent assays. Median values of 1.57 ng uPA/mg protein were determined in tumor tissue extracts compared to 0.14 ng uPA/mg protein in normal mucosa. For PAI-1, 0.93 ng PAI-1/mg protein versus 0.09 ng PAI-1/mg protein was calculated. uPA levels in tumor tissue extracts were significantly correlated with vascular invasion, Laurén classification, and WHO classification, whereas PAI-1 levels showed a significant correlation with advanced lymph node involvement, depth of invasion, tumor stage, site of tumor, and the Laurén, Borrmann, and WHO classifications. Elevated uPA and PAI-1 levels were found to be associated with poor prognosis. The optimal cutoff values indicating a group of patients with shorter survival were 1.5 ng uPA/mg protein and 1.25 ng PAI-1/mg protein, respectively (Classification and Regression Tree analysis). Patients with either high uPA or PAI-1 values were significantly associated with decreased survival (median time of survival was 23 months (high) versus 44 months (low). By univariate Cox regression analysis, it was shown that TNM categories, WHO classification, size of tumor, uPA and PAI-1 levels were all significantly associated with survival. However, in multivariate Cox regression analysis of these grouped variables, nodal status, PAI-1 levels, and WHO classification were the only independent prognostic factors. The relative risks of failure were 5-, 2.9-, and 2.4-fold, respectively. We conclude that PAI-1 and uPA positivity may serve as new prognostic factors in gastric cancer, predicting shorter survival even in clinically important subgroups of patients.

Adult↗
PubMed1994

No evidence for inhibition of human glutathione reductase by valproic acid.

The human red blood cell enzyme glutathione reductase (GR) was reported to be inhibited by the anticonvulsant drug valproic acid (VPA) [Cotariu et al., Biochem Pharmacol 43: 425-429, 1992]. When attempting to reproduce and extend these experiments, we could not detect any significant effect of VPA on glutathione reductase in haemolysates from 20 healthy children and 10 children under VPA therapy, no matter which concentration of the drug (0.9 or 1.8 mM in a haemolysate diluted by a factor of 50 or 1.8 mM directly in the assay), which incubation time (0-60 min) and which assay system were chosen. An influence of VPA on FAD-free apoglutathione reductase was also excluded. GR-activities of 10 children under VPA therapy (1.08 +/- 0.14 U/mL blood or 7.57 +/- 0.94 U/g Hb) were almost identical with the activities of age- and sex-matched controls (1.04 +/- 0.17 U/mL or 7.79 +/- 1.32 U/g Hb). No correlation between erythrocyte GR activity and serum levels of VPA was observed. Finally, incubation of crystalline human GR with VPA did not lead to enzyme inhibition; rather, in most experiments the enzyme was stabilized by incubation with VPA. Possible explanations for the discrepancies between the results of Cotariu et al. and our data are discussed.

Adolescent↗
PubMed1994

Prognostic value of DNA ploidy and c-erbB-2 oncoprotein overexpression in adenocarcinoma of Barrett's esophagus.

BACKGROUND: During the last two decades, a rising incidence of adenocarcinoma of the esophagus has been observed in the Western world. The prognostic relevance of tumor-biological factors, such as DNA ploidy or c-erbB-2 overexpression, for overall survival following complete resection is still unknown. METHODS: In a retrospective study of 80 patients with adenocarcinoma of Barrett's esophagus, the prognostic significance of flow cytometric DNA ploidy determination was investigated. Overexpression of c-erbB-2 oncoprotein was studied by immunohistochemical alkaline phosphatase-antialkaline phosphatase staining of formalin fixed, paraffin embedded tissue sections of the primary tumor. RESULTS: The rate of aneuploidy was 86%. Aneuploidy was significantly correlated with lymph node metastases only. c-erbB-2 oncoprotein overexpression of the primary tumor was detected in 15 patients (19%). A significant correlation was seen between c-erbB-2 overexpression and depth of tumor invasion, lymph node involvement, distant metastases, and status of residual tumor after resection (R category, International Union Against Cancer [UICC], 1987). All primary tumors with c-erbB-2 oncoprotein overexpression were aneuploid. In a multivariate Cox regression analysis for overall survival of those 62 patients (78%) whose tumor resection was macroscopically and microscopically complete (R0-UICC), depth of invasion, distant metastases, and c-erbB-2 overexpression were independent prognostic factors. The relative risk of death due to recurrence was nearly identical for patients with either c-erbB-2 oncoprotein overexpression or distant metastases: 4.06 (1.4-11.8) and 3.94 (1.6-9.5). In a multivariate Cox regression analysis of the subgroup of lymph node-negative patients (n = 26), the ploidy status of the primary tumor (defined as near-diploid plus tetraploid versus aneuploid plus multiploid) was the only independent prognostic factor for overall survival. CONCLUSIONS: These findings demonstrate that DNA ploidy as well as c-erbB-2 oncoprotein overexpression are valuable prognostic factors in patients with adenocarcinoma of Barrett's esophagus after complete tumor resection.

Adenocarcinoma↗
PubMed1994

Redox processes in malaria and other parasitic diseases. Determination of intracellular glutathione.

The role of oxidative stress resulting from production of reactive oxygen species and/or from suppression of the cellular antioxidant capacity in parasitic infections is shortly reviewed. The experimental part of the paper deals with the glutathione (GSH)--glutathione reductase (GR) system, a cornerstone of intracellular antioxidant defence mechanisms. For studying this system in parasitic diseases such as malaria new or modified methods are required. Total glutathione comprising GSH and glutathione disulphide (GSSG) in blood samples was assayed as follows. One volume of blood (> or = 10 microliters) is mixed with two volumes of 5% sulphosalicylic acid; after centrifugation (5 min, 10000 g), 10 microliters of supernatant is taken for spectrophotometric analysis using the 5,5'-dithiobis(2-nitrobenzoate) (DTNB)-glutathione recycling assay. When compared with the original method, the procedure reported here is more sensitive, less time-consuming, avoids unfavourable pH-values and leads to a sample which when frozen is stable for months. In a pilot study, the method was applied to 14 patients suffering from malaria caused by Plasmodium falciparum. The concentrations of erythrocyte glutathione were significantly decreased in the patients (1.42 +/- 0.47 mM, mean +/- SD) when compared to age- and sex-matched controls (2.11 +/- 0.45 mM, P < 0.01). The findings are contrasted with P. falciparum cultures in vitro where glutathione levels are known to be elevated. Based on the characteristics of GR a concept of determining the redox state of single cells is introduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Chronic esophagitis and subsequent morphological changes of the esophageal mucosa in Barrett's esophagus: a histological study of esophagectomy specimens.

Chronic esophagitis and the subsequent morphological changes of the esophageal mucosa were histologically studied in esophagectomy specimens from 15 patients with Barrett's esophagus. Basal layer hyperplasia with papillary elongation, intraepithelial eosinophils, and intraepithelial neutrophils were found in the squamous epithelium of all (100%), 7 (46.7%), and 14 (93.3%) of the 15 specimens, respectively. Moreover, a specialized type of Barrett's mucosa was found in the metaplastic columnar lining of all the specimens. The muscularis mucosae appeared intact beneath the squamous epithelium lining the proximal esophagus in 13 specimens (86.7%), while it became thick and "dual" beneath the metaplastic columnar epithelium lining the distal esophagus in 14 specimens (93.3%). This dual muscularis mucosae, as well as the metaplastic columnar epithelium, particularly the specialized type, may be part of the specific histological changes characteristic of Barrett's esophagus.

Aged↗
PubMed1994

Absorption of ipsapirone along the human gastrointestinal tract.

Isapirone-HCl (5 mg) was administered orally, rectally and locally, by a remote control drug delivery device (HF-capsule) into different segments of the gastrointestinal tract, to four young healthy male adults. The relative systemic bioavailability of the drug from the colon and rectum was 2-3-fold greater than that from the upper gastrointestinal tract. This supports a rationale for a prolonged-release formulation.

Administration, Oral↗
PubMed1994

Impaired synthesis of lipoxygenase products in glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism leading to a generalized intracellular GSH deficiency. Because GSH is required for leukotriene C4 (LTC4) synthesis, we studied synthesis and metabolism of several lipoxygenase products in two patients with GSD by radio-HPLC, UV spectrophotometry, and enzyme immunoassays. In both patients, LTC4 synthesis was significantly decreased in calcium ionophore-stimulated neutrophils (up to 0.4 ng/10(6) cells; controls, 5.0 +/- 0.9) and monocytes (up to 3.6 ng/10(6) cells; controls, 30.2 +/- 3.3). LTB4 synthesis was about seven times higher in GSD cells compared with controls, whereas synthesis of other 5-, 12-, and 15-lipoxygenase products and prostaglandin E2 was not affected. Neutrophils and monocytes from both patients showed a marked reduction in capacity to form [3H]LTC4 from [3H]LTA4 (9-14% of control values). Urinary LTE4 was finally found to be 50-fold lower in GSD, reflecting a decreased synthesis of cysteinyl LT in vivo. GSD may serve as a unique model for the linkage between LT synthesis and GSH metabolism in vivo.

Calcimycin↗