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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 289 records · Page 16Linked to original sources
PubMed1992

Protein kinase C phosphorylates a 15 kDa protein but not phospholamban in intact rat cardiac myocytes.

In the present study the effects of the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) as well as the alpha- and beta-adrenoceptor agonists methoxamine and isoproterenol on protein phosphorylation of intact rat cardiac myocytes were investigated. TPA, isoproterenol and methoxamine were shown to stimulate phosphorylation of a 15 kDa protein. EC50 for TPA and isoproterenol were 4 x 10(-8) M and 5 x 10(-9) M respectively. The time course of phosphorylation by TPA and isoproterenol greatly differed, revealing a maximal phosphorylation (2.9-fold) after 10 min and 1 min respectively. Cell fractionation showed a significant enrichment of the 15 kDa protein in a crude membrane preparation. While the 15 kDa protein was the only phosphoprotein stimulated by TPA and methoxamine, isoproterenol additionally enhanced the 32Pi incorporation into four proteins corresponding to 6 kDa (phospholamban), 28 kDa, 97 kDa and 140 kDa. Furthermore, dephosphorylation of a 21 kDa substrate upon beta-adrenoceptor stimulation was observed. Phospholamban phosphorylation was effectively (max. 9.1-fold) stimulated by isoproterenol (EC50 of 5 x 10(-9) M), reaching a maximal phosphorylation state within 1 min. The present study clearly demonstrates: (1) TPA stimulates the phosphorylation of a membrane-localized 15 kDa protein and this effect can be mimicked by both isoproterenol and methoxamine; (2) TPA, in contrast to isoproterenol, does not change the phosphorylation state of phospholamban. Whilst phospholamban under in vitro conditions is known to be a substrate for protein kinase C, it does not appear to be accessible for the enzyme in intact cardiac myocytes.

Adrenergic alpha-Agonists↗
PubMed1992

Use of sialic acid analogues to define functional groups involved in binding to the influenza virus hemagglutinin.

The initial step of influenza infection is binding of the virus particles via their hemagglutinin to cell-surface sialic acids. This study was initiated to elucidate the functional groups of the nine-carbon sialic acid molecule which interact with the hemagglutinin and contribute to the affinity of this sugar to the protein. In order to address this question, synthetic sialic acid analogues were tested in a virus adsorption inhibition assay for their inhibitory potency. Modifications in three regions of the sialic acid molecule were evaluated: the glycerol side chain (C7-C9), the N-acetyl group at C5, and the carboxy group (C1). In the glycerol side chain, the hydroxy groups at C7 and C8 appear to be important for binding through hydrogen bonds, whereas the hydroxyl at C9 does not appear to be involved. The N-acetyl group is critical for the interaction of sialic acid with the hemagglutinin. The results suggest that its contribution is mediated through hydrophobic interactions of the methyl group. Finally, the orientation of the carboxy group is essential for the binding of sialic acid to the hemagglutinin. The information gained in this study will be useful in developing novel compounds which bind more avidly to the influenza virus hemagglutinin. Such a strategy may contribute to the design of new anti-influenza drugs.

Binding Sites↗
PubMed1992

Elucidation of the topological parameters of N-acetylneuraminic acid and some analogues involved in their interaction with the N-acetylneuraminate lyase from Clostridium perfringens.

A series of neuraminic acid derivatives modified in the side chain or at C-3, C-4 or C-5 were tested as substrates of inhibitors of N-acetylneuraminate lyase (EC 4.1.3.3) from Clostridium perfringens. The results, together with Km and Ki values reported previously, indicate that the region most important for the binding of sialic acids is an equatorial zone reaching from C-8 via the ring oxygen atom to C-4 of the sugar molecule, whereas the substituents at C-9 and C-5 may be varied to a higher extent without significantly disturbing enzyme action. It is shown that stereo-electronic factors are responsible for the immediate heterolytic fragmentation of the cyclic sialic acid into pyruvic acid and 2-acetamidomannose or a related C-6 sugar.

Clostridium perfringens↗
PubMed1992

Improvement of recombinant gene expression in Escherichia coli for glucose-controlled continuous and fed-batch cultures.

Escherichia coli TG1 (pHRW500) permanently expressed the human interferon alpha 1 gene (ifn alpha 1) directed by the tryptophan promoter (trpP.O) during continuous and fed-batch cultivation with a limited supply of glucose. The expression of ifn alpha 1 could be improved after insertion of the catabolite activator region (cap) upstream to trpP.O during cultivation of the modified E. coli TG1(pHRW500cap) in glucose-controlled continuous and fed-batch cultures. The cap-mediated stimulatory effect on the expression of cap-trpP.O-ifn alpha 1 increased with decreasing dilution rate. These results are in line with the increase in the level of cAMP with declining dilution rate and the well-known positive effects of cAMP-catabolite gene activator protein (CAP) at the transcriptional level. In addition, expression of the galactokinase gene (trpP.O-galK) in E. coli TG1(pDR720) could be improved in the same way with cap-trpP.O-galK in E. coli TG1(pDR720cap). Determinations of plasmid copy numbers, cellular amounts of galactokinase-mRNA, activity of galactokinase (AGalK) and the concentration of galactokinase at various dilution rates (D) strengthen the conclusion that the increase in AGalK with decreasing D was indeed due to the cap-mediated enhancement of transcription of the galK gene. We suggest that expression of other recombinant genes directed by various promoters that allow permanent transcription during growth with limited glucose supply in chemostat and fed-batch fermentors can be improved by appropriate insertion of the cap region.

Base Sequence↗
PubMed1992

The influence of different levels of PEEP on peripheral tissue perfusion measured by subcutaneous and transcutaneous oxygen tension.

OBJECTIVE: To compare subcutaneous (PscO2) and transcutaneous (PtcO2) oxygen tension measurements in relation to hemodynamic variables at different levels of PEEP, and to evaluate the usefulness of these measurements as monitors of peripheral tissue perfusion. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital. PATIENTS: Seven patients with gastric cancer who where undergoing total gastrectomy. INTERVENTIONS: Silicone catheter was placed in the upper arm and transcutaneous oxygen monitor was placed on the upper part of the chest. A pulmonary artery catheter was placed in the right pulmonary artery. MEASUREMENTS AND RESULTS: PscO2 and PtcO2 together with hemodynamic variables were measured at different levels of PEEP. Progressive increase of PEEP reduced cardiac index (CI) (p < 0.05) with a concomitant decrease of PscO2 (p < 0.05) and oxygen delivery (DO2) (p < 0.05). Changes in PtcO2 paralleled changes in arterial oxygen tension (PaO2), but no correlation was found between PtcO2, CI and DO2. CONCLUSION: PscO2 is a sensitive indicator of subcutaneous tissue perfusion, which can be used to identify the PEEP level, with optimum peripheral perfusion. PscO2 seems to be a more reliable indicator of tissue perfusion than PtcO2.

Aged↗
PubMed1992

Role of phospholamban in NO/EDRF-induced relaxation in rat aorta.

The role of endothelium-derived nitric oxide (NO) to cause smooth muscle phospholamban (PLB) phosphorylation was studied in the isolated perfused rat aorta precontracted with norepinephrine using a back-phosphorylation technique. NO-induced relaxation was associated with increased PLB-phosphorylation while norepinephrine as such was ineffective. Removal of endothelium significantly reduced PLB-phosphorylation in indomethacin treated vessels. Stimulation of NO-formation by ATP augmented PLB-phosphorylation in intact vessels but was ineffective in denuded aortas. The results indicate that PLB-phosphorylation of vascular smooth muscle plays an important role in mediating NO-dependent relaxation by enhancing Ca(++)-uptake into sarcoplasmic reticulum.

Adenosine Triphosphate↗
PubMed1992

Spermatic cord beta-human chorionic gonadotropin levels in seminoma and their clinical implications.

Current opinions differ as to the biological significance and treatment of pure seminoma associated with the serological establishment of beta-human chorionic gonadotropin. Between December 1987 and April 1990, 147 patients with malignant testicular tumors were treated. Of these patients 47 (32%) had a pure seminoma. In 35 of the 47 patients we measured the tumor markers beta-human chorionic gonadotropins and alpha-fetoprotein in the cubital vein blood and testicular vein blood. There were elevated beta-human chorionic gonadotropin levels in the cubital veins of 26% of the patients, in agreement with the literature. However, elevated levels were found in the testicular veins of 80% of the patients, which reflects the high sensitivity of marker identification in testicular vein blood. Apparently, most seminomas produce beta-human chorionic gonadotropin even if it is not detectable in the cubital vein. We believe that the presence of this marker in patients with pure seminoma is not an indication of greater tumor aggressiveness but of tumor mass.

Adult↗
PubMed1992

Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.

Glutathione Transferase↗
PubMed1992

Further practical experiences in the recognition and management of carcinoma in situ of the testis.

99 biopsies from the contralateral testis in patients with unilateral germ cell tumor were investigated using the semithin section technique. Four cases (4%) revealed a carcinoma in situ (CIS) pattern. Two patients underwent a local radiation (20 Gy), 2 patients received combination chemotherapy (cisplatin, etoposide and bleomycin; PEB). No tumor cells were found in control biopsies 4-8 months after therapy. Both biopsy specimens taken from radiated patients lacked also germ cells. In contrast, 1 patient who was treated with PEB and also another 1 presenting with a teratocarcinoma of apparently retroperitoneal origin and unilateral CIS revealed germ cells after chemotherapy. The present data suggest radiation therapy to be the first line treatment for CIS-bearing testes. In order to get informations about the distribution of CIS cells in the affected testes, one or two biopsies were additionally taken from macroscopically unsuspicious tissue surrounding various solid germ cell tumors (74 patients). 56 cases (76%) revealed CIS. Even considering the possibility of missing CIS, a screening biopsy is actually the only method for detecting early manifestations of germ cell tumors and should be performed routinely in contralateral testes of patients with germ cell tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Surgical treatment of acute epididymitis and its underlying diseases.

Two hundred and seventy of 1,031 patients (26%) treated for acute epididymitis between 1979 and 1989 underwent surgery for their disease. Eighty percent of these interventions were therapeutic, 20% diagnostic to exclude testicular torsion or tumor. Diagnostic procedures detected underlying diseases that required surgery in 278/1,031 patients (27%). Two hundred and sixteen of these diseases caused lower urinary tract obstruction and were potentially responsible for the acute epididymitis. There were striking differences in type and frequency of the surgery performed depending on the patients' age. Surgery of epididymitis was almost exclusively diagnostic in patients of a young age (exclusion of testicular torsion) and almost always therapeutic in patients of an old age (abscess, prolonged disease). The rate of surgery for underlying diseases was the same for the young (55%) and old (62%) age groups. Obstruction of the lower urinary tract was the predominant cause for surgical treatment of underlying diseases, being mainly due to malformation in the young age group and due to acquired obstructive diseases in the old.

Acute Disease↗
PubMed1992

Contrast sensitivity in clinical practice.

We collected and evaluated the results of contrast sensitivity (CS) examination by means of Vistech chart with an arranged testing distance 208 and 420 cm covering spatial frequencies 1.15-27.25 cycles/degree (c/deg). Our test was comprised of normal population and patients with chronic renal insufficiency including the group of waiting patients, dialysed patients and dialysed patients after neuroretinopathy and also patients after kidney transplantation and those with Alport's syndrome. We gave our attention to the results of visual acuity (VA) and contrast sensitivity (CS) examination in patients after surgery for detached retina, aphakic patients and patients with artephakia. We examined and evaluated CS in patients with intraocular hypertension. All patients reached the VA values 6/9-6/6. 1. The results of examination of 100 healthy persons of different age displayed significant differences in age groups covering all spatial frequencies between the groups 21-50, 51-60 and 61-80 years whereas in sets of higher age we registered differences in the region of medial spatial frequencies only. These data served us to create control groups in the individual partial groups. 2. Patients with chronic renal insufficiency have CS significantly lowered. These examinations suggest that there is a certain relation between renal and retinal functions and that the dialyzation treatment is not able as yet to compensate fully all changes evoked by renal insufficiency. A clear tendency to normalize CS after renal transplantation is suggestive of a certain reversibility of these changes. This is valid for transplant patients with a clear lens. If opacity of the posterior cortex of the lens occurs after a long-time cortisone treatment, a substantial fall in the CS curve is registered in all spatial frequencies in spite of the VA being 6/9-6/6. Patients with neuroretinopathy have CS always significantly disturbed. These changes are reversible although this reversibility is not complete. The new way of dialyzation treatment secures a relatively rapid normalisation of pathological changes in the fundus and repair of subjective functions. At the same time we came to the conclusion that the prognostic outlooks of these patients have become distinctly better as far as their subjective visual functions are concerned. 3. Patients after surgery for detached retina displayed in all cases in the operated eye highly reduced CS in median and low spatial frequencies simultaneously with a statistically significantly lower threshold visual acuity and reduced slope of the acuity function in the diseased eye.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

[Hodgkin's disease in HIV infection--detection of Epstein-Barr virus DNA in tongue epithelium and lymphoma].

We present an HIV-infected patient with lymphadenopathy syndrome in whom an unusually aggressive case of Hodgkin's disease developed. Examination of tissue excised from the lymphoma and of epithelial cells scraped from the tongue of the patient revealed Epstein-Barr virus (EBV). The relationship between an enhanced replication of EBV in the epithelium of the tongue and the elevated frequency of Hodgkin's lymphomas containing EBV-DNA among HIV-infected patients is discussed.

Adult↗
PubMed1992

Importance of dehydration in anastomotic and subcutaneous wound healing: an experimental study in rats.

OBJECTIVE: To find out if preoperative and postoperative dehydration adversely affect anastomotic and subcutaneous healing. DESIGN: Randomized study. MATERIAL: 18 Wistar rats. INTERVENTIONS: Dehydration established in nine rats by withdrawal of food and water for 24 hours before operation, and by injections of frusemide twice daily. Laparotomy and division of intestine 5-8 cm from the ileocaecal valve. Implantation of expanded polytetrafluoroethylene (ePTFE) tubes in the backs of the necks. All rats killed after five days. MAIN OUTCOME MEASURES: Measurements of weight loss and of hydroxyproline per centimetre in the ePTFE tubes and standardized biopsy specimens of the intestine. Presence of anastomotic dehiscence at necropsy. RESULTS: Preoperative and postoperative dehydration caused a 24% weight loss in the experimental group on day 5 compared with 8% in the control group. Dehydrated animals accumulated less collagen in the ePTFE tubes than control animals (p less than 0.05). There were three anastomotic breakdowns in the dehydrated group compared with one in the control group. There was a loose but significant correlation between collagen accumulation in the anastomoses and the weight of the animal (r = 0.5, p less than 0.05). CONCLUSION: Preoperative and postoperative dehydration has a deleterious effect on subcutaneous, and to a lesser extent on anastomotic healing in rats.

Anastomosis, Surgical↗
PubMed1992

Effect of tissue perfusion and oxygenation on accumulation of collagen in healing wounds. Randomized study in patients after major abdominal operations.

OBJECTIVE: To compare the accumulation of collagen in standardised wounds in patients who had abdominal operations and whose postoperative fluid replacement was decided either clinically or by measurements of subcutaneous oxygen tension (PscO2). DESIGN: Prospective randomised trial. SETTING: University Hospital. SUBJECTS: Twenty-nine patients with cancer or inflammatory bowel disease who were undergoing abdominal operations. INTERVENTIONS: Silicone rubber catheter placed in the upper arm to measure PscO2. Two tubes of expanded polytetrafluoroethylene (ePTFE) implanted subcutaneously parallel to the silicone rubber catheter to measure the amount of collagen accumulated. MAIN OUTCOME MEASURES: Amount of postoperative fluid replacement required in each group, and measurements of hydroxyproline/cm of the ePTFE tubes. RESULTS: The group treated according to PscO2 measurements received more fluid on the day of operation than the group treated according to clinical criteria (p < 0.05). They had accumulated more collagen in their ePTFE tubes by day 7 (p < 0.05). CONCLUSION: Replacement of fluid according to measurements of PscO2 rather than by clinical criteria results in improved accumulation of collagen in healing wounds.

Adult↗
PubMed1992

[Determination of correction based on natural visual acuity in myopes].

The authors demonstrate the possibility to assess the correction in ametropes according to the value of their natural vision. To this end they use normalized optotype tables with Landolt rings which have a constant diminution coefficient between individual consecutive lines. By means of this elaborated method the authors were able to assess in twenty myopic subjects that a correction of -1.0 corresponds to an improvement by four lines, one line thus corresponds to a correction of -0.25 dioptres.

Adult↗
PubMed1992

Lack of pharmacokinetic interaction as an equivalence problem.

The demonstration that concomitant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for the comparison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes.

Drug Interactions↗