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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 325 records · Page 18Linked to original sources

Enteroadherent Escherichia coli and diarrhea in children: a prospective case-control study.

The relative contribution of diarrheagenic Escherichia coli was examined during a 1-year prospective study of hospitalized children in Clermont-Ferrand, France, including 220 case patients (with diarrhea) and 211 matched controls. Fecal isolates were characterized by means of their pattern of adherence to HEp-2 cells and by colony hybridization with DNA probes specific for the six categories of diarrheagenic E. coli. No enteroinvasive or enterotoxigenic E. coli isolates were isolated. Twenty-eight (6.5%) eae-positive isolates and 39 (9%) enteroaggregative E. coli isolates characterized with the aggregative adherence probe and/or by their adherence pattern were detected; they were equally distributed among the patients and the controls. Diffusely adhering E. coli was the predominant pathotype: 30.7% were detected by their adherence pattern and 13.7% were detected with the daaC probe. They were isolated with similar frequencies from the patients and the controls, thereby showing no association with diarrhea. However, daaC-positive strains were significantly associated with a past record of urinary tract infections. These results suggest that the diffusely adhering E. coli organisms isolated in the present study are not true intestinal pathogens but may be regarded as resident colonic strains.

Adolescent↗

Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity.

Male Sprague-Dawley rats fed a condensed milk diet were classified as either "obesity susceptible" (OS) or "obesity resistant" (OR) based on body weight increases attained after 12 wk. Overall caloric intake in OS rats was higher than in chow-fed controls, and OS rats were heavier than chow-fed controls or OR rats. There were no significant differences in blood glucose, serum insulin, ventricular weight, basal blood pressure, or heart rate. Pressor responses recorded after combined blockade with atropine and propranolol to eliminate reflex effects were identical for vasopressin, but those to norepinephrine were larger in OS than in OR rats, whereas those to angiotensin were larger in OS than in control rats. When baroreflex sensitivity was assessed using intravenously infused sodium nitroprusside or phenylephrine to alter systemic arterial pressure, differences in reflex tachycardia were equivocal, but reflex bradycardia was clearly inhibited in OS rats. These results show that, although basal blood pressure was unaffected in OS rats, their impaired reflex bradycardia along with enhanced pressor responsiveness to norepinephrine could predispose them to subsequent development of hypertension.

Adipose Tissue↗

Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects.

Urodilatin is involved in sodium homeostasis exerts sodium-state-dependent natriuretic and diuretic cts. Eight male volunteers participated in a study consisting of three consecutive phases of 7 days each. The volunteers a sodium diet with 52, 172.6, and 347.8 mmol um/day. Sodium excretion increased from 57.4 +/- 3.7 via .8 +/- 4.6 (P < 0.001) to 322.5 +/- 10.2 mmol/24 h (P < 0.001) at the end of each sodium diet. Urinary urodilatin excretion increased from 24.8 +/- 3.0 via 35.5 +/- 9.0 (P = 0.07) to 49.0 = mol/min (P < 0.01). At the end of each diet, urodilatin was infused for 2 h at 20 ng.kg body wt-1.min-1. Natriuresis increased after low- (4.1 to 52.9 mmol/h, P < 0.001), normal (6.9 to 44.9 mmol/h, P < 0.05), and high-sodium diet (20.1 to 102.9 mmol/h, P < 0.001). Diuresis increased from 174 to 709 (P < 0.001), 395 to 1,026 (P < 0.05), and 266 to 1,339 ml/h < 0.001). The present results indicate that endogenous urodilatin plays an important role in sodium homeostasis and that renal response to exogenous urodilatin is modulated by sodium balance.

Adaptation, Physiological↗

[Hormonally inactive hypophyseal adenomas: the results and late sequelae after surgery and radiotherapy].

PURPOSE: External radiation therapy for non functioning pituitary adenomas is clearly indicated in inoperable patients, after incomplete transsphenoidal microsurgery and in case of tumor progression. This retrospective analysis gives results and toxicity following surgery and postoperative radiotherapy of non-functioning pituitary adenomas. PATIENTS AND METHODS: Between 1983 and 1990, 50 patients with non-functioning pituitary adenomas received combined treatment at our institutions. Surgical approaches were transsphenoidal (61%), transcranial (24%) or a combination of both (15%) in short intervals. All 50 patients received a full-dose radiotherapy with single fractions between 1.9 and 2.1 Gy (median 1.9 Gy) and total doses between 46 and 63 Gy (median 48 Gy). Field sizes ranged between 20 and 72 cm2 (median 30 cm2). Endpoints of this study were: progression-free survival, late effects of brain, optic nerve and intracranial vessels, visual impairment and hypothalamic-pituitary dysfunction. Median follow-up was 54 months. RESULTS: Forty-seven of the 50 patients remained progression-free. Patients over age 60 years progressed more frequently (3/17) as compared to younger patients (0/33, p = 0.034). Following radiotherapy vision improved in 8 patients (16%), 14 patients (28%) experienced a visual impairment between 10% and 60% (according to the grading system of the German Ophthalmologic Society). In multivariate analysis no influence of age (p = 0.097) or biologically effective dose (BED) (p = 0.11) was seen on visual impairment. Three patients (6%) experienced late effects with optic neuropathy in 2 cases and temporal lobe necrosis in 1 case. Only the BED had a significant impact on late effects (p = 0.0094). Adrenal, thyroid and gonadal function abnormalities were present in 58%, 66% and 96% of the patients at last follow-up, respectively. CONCLUSIONS: Radiotherapy after incomplete transsphenoidal or transcranial surgery of non-functioning pituitary adenoma is an effective treatment. Future perspectives must include the better defining of high-risk patients and the reduction of late morbidity.

Adenoma↗

Evaluation of CI-973, a platinum analogue, in refractory or relapsed acute leukemia.

The purpose of the study was to define the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of CI-973 a new platinum analogue, in patients with refractory or relapsed acute leukemia. CI-973 was given as a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 150 mg/m2 to 1350 mg/m2 per course. Thirty-six patients were treated including 18 patients with acute myelogenous leukemia (AML), four with acute lymphocytic leukemia (ALL) and 14 with chronic myelogenous leukemia in blastic phase (CML-BP). Severe gastrointestinal and renal side-effects were the dose-limiting toxicities occurring in four of five patients treated with CI-973 1200 to 1350 mg/m2 per course. At the MTD of 1000 mg/m2 per course, three of 13 patients treated (23%) had moderate to severe nausea and vomiting, three (23%) had moderate diarrhea and one had moderate mucositis. Among 21 patients treated at > or = 1000 mg/m2 (15 AML, 6 CML-BP) no objective complete or partial responses were observed. Twelve of 18 patients (66%) with evaluable marrows on day 14 showed significant suppression of marrow blasts percentage and marrow leukemic infiltrate percentage. Tests for measurement of DNA adduct formation in leukemic cells in vivo after CI-973 therapy, and in vitro following exposure of leukemic cells to CI-973 were developed. This study defined the MTD of CI-973 to be 1000 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Gastrointestinal and renal side-effects were dose-limiting. No objective responses were noted in this heavily resistant population. Correlations between CI-973-induced DNA adduct formation and individual patient response to CI-973 will help to define its role in leukemia subsets.

Acute Disease↗

Expression of type VI collagen in uveal melanoma: its role in pattern formation and tumor progression.

Choroidal and ciliary body melanomas disseminate exclusively by a hematogenous route because there are no lymphatics inside the eye. Although angiogenesis is an absolute precondition for metastasis in this tumor system, not all morphologic expressions of tumor angiogenesis are associated with metastasis from choroidal and ciliary body melanomas. Specifically, the remodeling of the microcirculation to form vascular networks is very strongly associated with metastasis. Type VI collagen is upregulated in tissue remodeling and the generation of tissue patterns and is either not present in the normal choroid or present at very low levels. This study was designed to investigate the possible expression of type VI collagen in the stroma of choroidal and ciliary body melanomas. Type VI collagen was detected in tissue sections from five primary choroidal melanomas and three melanomas involving the choroid and ciliary body in the subendothelial compartment of the microcirculation and in avascular areas by immunohistochemistry. Melanoma cell lines were established from each of these tumors. Cultured melanoma cells invaded into type I collagen gels and expressed type VI collagen by immunohistochemistry. Using specific primers for human type VI collagen, the expected band size (413 base pairs) was isolated from one of the cell lines by reverse transcriptase PCR. The presence of type VI collagen in the melanoma tumor stroma reflects active remodeling of the uveal extracellular matrix microenvironment by the melanoma cells themselves. Before the formation of the microvasculature, the expression of type VI collagen and of the other matrix components, such as hyaluronan, to which it binds, may erect a scaffold permitting the formation of higher order stromal patterns such as vascular networks. These stromal patterns, which are markers of tumor progression, may be detectable clinically by a specialized form of ultrasonography that detects backscatterers of the same dimension as tissue compartments encircled by vascular loops in networks.

Base Sequence↗

[Hypoxyradiotherapy: changes in the oxygen partial pressure distribution in the tumor and in the healthy tissue under acute respiratory hypoxia].

PURPOSE: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation. MATERIAL AND METHODS: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system. RESULTS: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation. CONCLUSIONS: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Acute Disease↗

Retinoid-dependent transcription: the RAR/RXR-TBP-EIA/EIA-LA connection.

Retinoids play a fundamental role in regulating normal cell proliferation and differentiation. The most spectacular effects of retinoids in vitro can be observed with embryonal carcinoma (EC) cells that can be induced to differentiate into endodermal, mesodermal and neuroectodermal lineages. An early and essential step in the differentiation process is the activation of the retinoic acid receptor-beta 2 (RAR beta 2) promoter that requires a co-operation between RAR, the EC-cell specific adenovirus early gene product 1A (E1A)-like activity and the TATA-binding protein (TBP). In differentiated cells, this signalling pathway can be mimicked by ectopic expression of the adenoviral E1A protein. Here we show that E1A13S but not E1A12S augments the level of transcription. Analysis of the binding kinetics of E1A13S to TBP by the surface plasmon resonance (SPR) technique reveals that the affinity of TBP for a consensus TATA-box sequence is significantly and specifically increased by E1A13S only. Intriguingly, a specific interaction can only be obtained with crude TBP overexpressed in HeLa cells via vaccinia virus as opposed to bacterially expressed TBP, suggesting a cofactor requirement for the interaction. Co-immunoprecipitation experiments show that E1A13S is an integral component of the RNA polymerase II-specific TBP-containing complex in adenovirus transformed embryonal kidney 293 cells. Taken together the results suggest that E1A13S mediates transcriptional activation by providing a physical bridge between TBP/transcription factor IID (TFIID) and retinoic acid receptor.

Adenovirus E1A Proteins↗

[Reoxygenation in Yoshida sarcoma during different fractionated radiotherapy].

PURPOSE: Tumor reoxygenation is one of the most important factors determining the tumor control probability after radiotherapy. In experimental studies reoxygenation has been measured preferably after single dose irradiation. Only few data exist about changes in the hypoxic tumor fraction during fractionated radiotherapy. MATERIAL AND METHODS: The changes in the pO2 during fractionated radiotherapy were studied in Yoshida sarcoma transplanted to Wistar rats. Tissue oxygenation was assessed using a polarographic electrode system at the beginning, in the middle and at the end of radiation therapy. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. RESULTS: In the statistical analysis significant changes emerged in the mean, median, 10%-percentile and 0 to 2.5 mm Hg and 0 to 5.0 mm Hg values dependent on time. The tumors were significantly more hypoxic at the end of therapy. This trend became more pronounced with decreasing dose per fraction. CONCLUSIONS: The Yoshida sarcoma has no effective reoxygenation during fractionated radiotherapy.

Animals↗

Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation.

Acute renal failure is a serious problem following heart transplantation. In first uncontrolled clinical trials, Urodilatin revealed beneficial effects in the prophylaxis and therapy of acute renal failure following heart and liver transplantation. Here, we present the first randomized, placebo-controlled, double-blind study on 24 patients following heart transplantation to investigate whether prophylactic i.v. Urodilatin infusion can prevent acute renal failure requiring renal replacement therapy. Postoperative drug management was characterized by intravenous application of high furosemide, cyclosporine, and vancomycin doses. Urodilatin infusion was started postoperatively with a dose of 40 ng / kg bw / min for 6 days. 6 of the 12 patients in the Urodilatin group and 6 of the 12 patients in the placebo group had a stable diuresis (3 - 4 l / day) during the study period of 6 days. In contrast, the remaining 6 patients of each group developed oliguria / anuria and required subsequent hemofiltration / hemodialysis. Cumulative duration of hemofiltration (88 +/- 7.39 hours in the placebo treated patients versus 44 +/- 5.35 hours in the Urodilatin treated patients, p < 0. 05) as well as frequency of hemodialysis (3.0 +/- 0.49 times in the placebo group vs 1.2 +/- 0.29 times in the Urodilatin group, p < 0. 05) were significantly reduced using Urodilatin. Mean arterial blood pressure was stable during the Urodilatin infusion period and was not different to that observed in placebo patients. We conclude that Urodilatin does not reduce the incidence of acute renal failure and the subsequent requirement for hemofiltration / hemodialysis in our patient population, but seems to reduce the duration of hemofiltration and frequency of hemodialysis compared to the placebo group.

Acute Kidney Injury↗

Purification and characterization of protein PB of betaine reductase and its relationship to the corresponding proteins glycine reductase and sarcosine reductase from Eubacterium acidaminophilum.

Simple complementation assay systems were developed for the substrate-specific proteins PB of glycine reductase, sarcosine reductase, and betaine reductase, in which acetyl phosphate was detected as the product in all three cases. The betaine-specific subunits of protein B (PB betaine) responsible for betaine reductase activity were purified to homogeneity from cells of Eubacterium acidaminophilum. The molecular masses of the two different subunits were 45 kDa and 48 kDa according to SDS/PAGE. The molecular mass of the native protein was about 200 kDa, indicating and alpha 2 beta 2 structure. The glycine-specific protein B (PB glycine) was partially purified and subunits of 47 kDa and 27 kDa were N-terminally sequenced. The latter subunits cross-reacted with antibodies raised against PB betaine and showed high sequence similarity to the 45-kDa and 48-kDa subunits of PB betaine, respectively. [2-14C]Glycine could be covalently coupled to the 47-kDa subunit by treatment with borohydride. By the same procedure, [2-14C]sarcosine labeled a protein of the same size. Like the sarcosine reductase activity, this protein was not present in glycine-grown cells, indicating its specific involvement in sarcosine metabolism. The labile viologen-dependent formate dehydrogenase purified with the respective PB proteins and could be tentatively assigned to a 95-kDa protein.

Amino Acid Oxidoreductases↗

Computer networked scanning electron microscope for teaching, research, and industry applications.

A laboratory designed for teaching the operation of a scanning electron microscope (SEM) has been developed. The laboratory makes use of a computer network to allow remote operation of the SEM. Movable teaching stations, consisting of a computer, TV monitor, and joystick control, enable students to view the image on the SEM screen, move the sample, control the basic operating parameters of the microscope, and acquire X-ray spectra. Images can also be stored on the computers for image analysis or incorporation into reports. The great advantage of the system is that it has been designed to be flexible enough to allow operation from any location that has access to the Internet. The system is relatively inexpensive and uses nonproprietary computer technology available at any computer store. While the laboratory has been designed for teaching, the concept of a multiuser SEM facility that is inexpensive and easy to install should have applications in both industrial and research settings.

Computer Communication Networks↗

Characterization of fungally and mechanically transmitted isolates of barley mild mosaic virus: two strains in competition.

The virus populations of two French barley mild mosaic virus isolates have been characterized using Western blot, sequence, PCR, and RFLP analyses. One of the isolates (M) was obtained by mechanical transmission of the other, fungally transmitted isolate (P). The results obtained show that the two isolates contain distinct RNA1 and RNA2 molecules with respect to their nucleotide sequences, and hence contain distinct barley mild mosaic virus strains. One strain is present mainly in isolate P and closely resembles a Japanese and two German isolates. It contains an RNA2 of approximately 3.5 kb. The other strain is present mainly in isolate M and closely resembles a UK isolate. This strain contains a smaller RNA2 of approximately 2.4 kb. The results show that mechanical transmission causes a shift in the virus populations in favor of the mutant strain.

Amino Acid Sequence↗

Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy.

BACKGROUND: The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. METHODS AND RESULTS: The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37 degrees C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min-1 and was increased to 212 +/- 34% (P < .05) of the value at 15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally increased at 180 min-1 to 218 +/- 39% (P < .01). In the failing myocardium, average isometric tension was maximum at 60 min-1 (106 +/- 7% of the basal value at 15 min-1, P = NS) and then decreased continuously to 62 +/- 9% of the basal value at 180 min-1 (P < .002). In the failing myocardium, aequorin light emission was highest at 15 min-1. At 180 min-1, it was decreased to 71 +/- 7% of the basal value (P < .01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum (r = .92; n = 19; P < .001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60 +/- 0.51 versus 1.94 +/- 0.18 (nmol/L).min-1.mg protein-1, P < .005). CONCLUSIONS: These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.

Action Potentials↗

Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy.

BACKGROUND: Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins. METHODS AND RESULTS: Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n = 7) and in end-stage failing myocardium due to dilated cardiomyopathy (n = 14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium (P < .05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% (P < .001) or 33% (P < .05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% (P < .05) and relative to phospholamban by 28% (P < .05). CONCLUSIONS: Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗