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Biomedical subjects

K Kramer

Publications and source records attributed to K Kramer.

At least 91 records · Page 5Linked to original sources
PubMed1995

Monohydroxyethylrutoside as protector against chronic doxorubicin-induced cardiotoxicity.

1. The clinical use of the antitumour agent, doxorubicin, is largely limited by the development of a cumulative dose-related cardiotoxicity. This toxicity is generally believed to be caused by the formation of oxygen free radicals. In earlier studies it was established that flavonoids, naturally occurring antioxidants, can provide some degree of protection. In this study we investigated whether 7-monohydroxyethylrutoside (monoHER), a powerful antioxidative flavonoid with extremely low toxicity, can provide protection to an extent comparable to the clinically successful Cardioxane (ICRF-187). 2. Balb/c mice of 20-25 g were equipped i.p. with a telemeter to measure ECG. They were given 6 i.v. doses of doxorubicin (4 mg kg-1) at weekly intervals. ICRF-187 (50 mg kg-1) or monoHER (500 mg kg-1) were administered i.p. 1 h before doxorubicin administration. In the 2 monoHER groups the treatment continued with either 1 or 4 additional injections per week. A saline and monoHER treated group served as controls. After these 6 weeks, they were observed for another 2 weeks. 3. At the end of this study (week 8) the ST interval had increased by 16.7 +/- 2.7 ms (mean +/- s.e. mean) in doxorubicin-treated mice. At that time, the ST interval had increased by only 1.8 +/- 0.9 ms in ICRF-187 co-mediated mice and in monoHER co-medicated mice by only 1.7 +/- 0.8 and 5.1 +/- 1.7 ms (5- and 2-day schedule, respectively, all P < 0.001 relative to doxorubicin and not significantly different from control). The ECG of the control animals did not change during the entire study. The QRS complex did not change in either group.4. It can be concluded that monoHER protects against doxorubicin-induced cardiotoxicity and merits further evaluation in this respect.

Animals↗
PubMed1995

The use of telemetry to record electrocardiogram and heart rate in freely swimming rats.

Measurement of parameters from the circulatory system of laboratory animals can play an important role in pharmacological or toxicological research. To study the mutual interaction between physical exercise and antioxidant systems in rats, we selected swimming as a model for exercise performance. Swimming belongs to the natural behavior of the rat, and under proper experimental conditions, it primarily involves physical exercise with little emotional arousal. Therefore, we developed a swimming basin in which the intensity of exercise could be manipulated through speed and duration of swimming. A laser beam interruption system enables the rat to be followed during each swimming session. A motor-controlled following device, consisting of a rail and sledge connected to a position sensor, contains an antenna mounted in a receiver board. In this way, we can record the electrocardiogram (ECG) and heart rate (HR) with a commercially available telemetry transmitter implanted in the peritoneal cavity of freely swimming rats and evaluate the physical fitness (condition) of the swim-trained rats.

Animals↗
PubMed1994

In vitro release of [3H]5-hydroxytryptamine from fetal and maternal brain by drugs of abuse.

Cortical synaptosomes were prepared from pregnant dams (GD-17) and rat fetuses (ED-17), loaded with [3H]5-HT and assayed to evaluate release mediated by cocaine (COC), fenfluramine (FEN) and 3,4-methylenedioxymethamphetamine (MDMA). COC and FEN elicited a high-affinity (10(-9) M) release response in fetal tissue which was not apparent in the dam. MDMA-induced release was similar in magnitude in both tissue types. Consequently, the release of 5-HT from developing neurons may be one mechanism by which COC and FEN elicit their teratogenetic effects in utero.

3,4-Methylenedioxyamphetamine↗
PubMed1994

The involvement of nitric oxide synthase in the effect of histamine on guinea-pig airway smooth muscle in vitro.

The influence of histamine on nitric oxide synthase (NOS) in the development of airway smooth muscle hyperresponsiveness to histamine was investigated in vitro. In the absence of histamine, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) had no significant effect on the basal tone. However, precontraction of the tissues with histamine (0.3 microM) resulted in a significant contractile response to L-NAME in the preparations with intact epithelium. Removal of the epithelial layer decreased the responses to L-NAME. L-arginine could partially reverse the contraction produced by L-NAME. L-NAME enhanced the maximal response to histamine, but the sensitivity of the tracheal smooth muscle to histamine was not affected. These results suggest that, in the airway, histamine can activate NOS, resulting in the release of nitric oxide. The latter may be regarded as a local negative modulator to maintain the tissue in a physiological homeostasis.

Amino Acid Oxidoreductases↗
PubMed1994

Community nursing in Belgium, Germany and The Netherlands.

This paper contains a comparative study on community nursing in the Netherlands, Belgium and Germany, carried out in the region around Maastricht, where the borders of the three countries meet. The well-known problem of comparative studies (the incomparability of concepts and data) has been solved by using the same measuring instruments in the three countries. The comparison between the countries was on three aspects: the level of care dependency of the patients, the type and number of services provided and the nurses' job interpretation and job satisfaction. During 1 week in June or September 1991, 89 community nurses made records of all their home visits and nursing activities. In total the community nurses paid 5165 home visits to provide care to 1796 patients. The results indicate that both the level of care dependency of the patients as well as the type of care provided differs between the three countries. Belgian community nurses have the highest number of patients with a high level of care dependency. Curative services like technical nursing care and domestic care are most frequently provided by the German and Belgian community nurses. Informing, educating and supporting care is most frequently provided by the Dutch community nurses. The German community nurses spend less time on administration activities. With respect to job interpretation and job satisfaction the following results were found. The Dutch community nurses mentioned in their job interpretation many more preventive tasks, whereas the German community nurses more often mentioned domestic tasks. Concerning the hygienic and technical tasks, no significant differences were found between the three countries. Finally, job satisfaction is lowest in the Netherlands. Dutch community nurses are less satisfied with the work organization and the possibilities of autonomy and professionalization than the German and Belgian community nurses.

Belgium↗
PubMed1994

Naturally acquired antibodies against the major merozoite surface coat protein (MSP-1) of Plasmodium falciparum acquired by residents in an endemic area of Colombia.

A preliminary baseline epidemiological malaria survey was conducted in the village of Punta Soldado, Colombia. Parasite prevalence and density as well as serological data were obtained from 151 asymptomatic children and adults. Fifty individuals were infected with Plasmodium falciparum. The mean parasite density was 184 parasites/mm3. Greater than 90% of the sample population were P. falciparum antibody positive as detected by the indirect immunofluorescent antibody test (IFAT). The enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against the major merozoite surface protein (MSP-1) of P. falciparum. In this population, anti-MSP-1 antibody concentration is acquired in an age dependent manner with equal immunogenicity to both the N- and C-terminal regions of the molecule. Infection at the time of sampling was associated with a higher anti-MSP-1 antibody concentration than that found in non-infected individuals. Further studies are planned to assess the role of immune and non-immune factors in limiting the number of cases of severe malaria seen in this population.

Adolescent↗
PubMed1993

Epithelioid osteosarcoma of bone. Immunocytochemical evidence suggesting divergent epithelial and mesenchymal differentiation in a primary osseous neoplasm.

BACKGROUND: The combination of a primary osteosarcoma of bone with a second carcinomatous cell type has been recognized, although immunohistochemical studies currently have not been performed in an attempt to understand the histogenesis of such a tumor. METHODS: In this report, the authors performed immunohistochemical studies on a primary osseous carcinosarcoma. Using a biotin-streptavidin peroxidase conjugate technique, the expression of keratin, epithelial membrane antigen, and vimentin was analyzed. RESULTS: The epithelial cells expressed cytokeratin and epithelial membrane antigen but did not express vimentin. The mesenchymal cells strongly expressed vimentin, and only rare cells expressed cytokeratin. CONCLUSIONS: The clinical, morphologic, and immunophenotypic data in this instance strongly suggest divergent differentiation of a primitive multipotential uncommitted stem cell in a primary osseous tumor.

Adolescent↗
PubMed1993

Optimization of a monoclonal antibody-based enzyme immunoassay for the detection of terbuthylazine.

The application of immunoassays in pesticide residue analysis is of increasing interest due to the sensitivity, simple handling and fast throughput of samples. For a wide application of these assays, a sufficient supply of standardized antibodies over a long period of time is necessary. The monoclonal antibody technology is solving this problem with an increasing number of cell lines which produce antibodies against different pesticides. Hybridomas were produced by cell fusion of spleen cells from mice immunized with dichloroatrazine conjugated to bovine serum albumin and mouse myeloma cells (PAI-B3 Ag8I). After screening with a competitive enzyme immunoassay, a monoclonal antibody that was specific for terbuthylazine and was produced by a permanent hybridoma cell line was selected for immunoassay development and optimization. For this purpose, an antigen- and antibody-immobilized ELISA technique was improved by varying the test parameters. Comparing both methods, the latter turned out to be superior (50% binding = 0.8 microgram/l, detection limit = 0.14 microgram/l).

Antibodies, Monoclonal↗
PubMed1993

Control of physical exercise of rats in a swimming basin.

To study the mutual interaction between physical exercise and antioxidant systems in rats, we selected swimming as a model for exercise performance. Swimming belongs to the natural behavior of a rat, which under proper experimental conditions, primarily involves physical exercise with little emotional arousal. Therefore, we developed a swimming basin in which the intensity of exercise was manipulated by swimming speed and swimming duration. A laser beam interruption system enables recording of swimming patterns. For comparison we also used the basin to induce emotional arousal. Hereto the basin was transformed into a maze, in which unexpected blockade of a learned swimming route induced a panic-like emotional reaction. The antioxidant enzyme superoxide dismutase decreased in rat plasma after emotional arousal, not after physical exercise. Depletion of the antioxidant glutathione in the liver by diethyl maleate led to decrease of swimming performance. Noradrenaline but not adrenaline plasma levels increased in response to physical exercise. After emotional arousal the ratio noradrenaline/adrenaline did not change. In contrast, lactate only increased in response to emotional arousal. Plasma levels of glucose increased after both stress situations. Beta-adrenoceptor function, determined in the heart and in erythrocytes, only changed after physical exercise. The sensitivity to the beta-agonist (-)isoprenaline in the right atrium decreased and a downregulation of the beta-adrenoceptor density was observed in the erythrocyte.

Animals↗
PubMed1993

Use of telemetry to record electrocardiogram and heart rate in freely moving mice.

This paper describes for the first time the possibility to record the electrocardiogram (ECG) and heart rate (HR) with a commercially available telemetry and data acquisition system in freely moving mice. The system comprises a telemetry transmitter implanted in the peritoneal cavity and a receiver, placed underneath the home cage, an A/D converter (MacLab) and a Macintosh LC II 4/80 computer with software (MacLab, Chart/Scope). The raw analog ECG data are digitized within the MacLab and can be converted to HR data additionally. The effects of surgery for implanting the transmitter, handling and anesthesia by either Nembutal or a mixture of Hypnorm, Dormicum, and water, on the changes in ECG and HR were examined. The telemetry system for recording the ECG and HR provides an accurate and reliable method for monitoring the direct effects of handling on HR. By using this telemetry system, we maintain that measurements in freely moving animals are more efficient, reliable, and less labor-intensive than the measurement techniques described in the literature thus far.

Animals↗
PubMed1993

Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease.

The gag-homologous region of the human endogenous retrovirus K10 (HERV-K10) was amplified by PCR from human genomic DNA and was analyzed by DNA cloning, sequencing, and expression of open reading frames in the prokaryotic pATH expression system. The analysis of genomic DNA of three donors provided evidence that HERV-K10 genes contain an open reading frame of 1966 bp spanning the entire gag-homologous region. In the prokaryotic system the entire reading frame of the HERV-K10 gag gene could be expressed as a fusion protein exhibiting a molecular weight of about 110,000. In addition, when the gag-homologous region and the adjacent HERV-K10 protease gene were prokaryotically expressed, we observed a Gag-protease fusion protein that exhibited specific autoproteolytic activities and processing of HERV-K10 Gag protein. By introducing deletions on the right end of the putative protease gene an autocatalytic site could be localized within 300 bp of the putative HERV-K10 protease gene. For the first time, these results provide evidence that the HERV-K10 encodes a full-length Gag protein and a functional protease.

Base Sequence↗
PubMed1992

Small cell carcinoma of the lung. Treatment in the community.

The results of nonprotocol treatment of 232 patients with small cell lung cancer seen by a group of community-based medical oncologists over a 13-year period were evaluated. Factors associated with improved survival also were assessed. The following patient characteristics significantly improved survival: limited stage of disease at diagnosis, treatment of extensive (but not limited) disease with regimens including etoposide and cisplatin, tumor resection, age younger than 70 years, radiation therapy to the chest, and female sex (extensive disease only). Comparison of the data from this study with published results of protocol studies showed similar outcomes.

Aged↗
PubMed1992

Glutathione mobilization during cerebral ischemia and reperfusion in the rat.

1. Cerebral ischemia applied for 15 min and followed by a 30 min reperfusion did not change the glutathione (GSH) levels and beta-adrenoceptor density (Bmax) in brain cortex. 2. A significant increase in erythrocyte-lysate GSH concentration (vs control) and a significant decrease of Bmax values in erythrocyte membranes (vs control) was found at the same time. 3. Pretreatment with the alpha-adrenoceptor antagonist phentolamine (5 mg/kg i.p.) prevented the erythrocyte GSH increase but not the decrease of Bmax value. Pretreatment with the beta-antagonist propranolol (2 mg/kg i.p.) did not influence the increase in erythrocyte GSH but circumvented the decrease of Bmax.

Animals↗
PubMed1991

Do microscopic abnormalities at resection margins correlate with increased anastomotic recurrence in Crohn's disease? Retrospective analysis of 100 cases.

The relationship between histologic changes at resection margins and anastomotic recurrence was evaluated in patients with Crohn's disease. Pathology and medical records from 1960 to 1977 identified 100 patients who met the following criteria: 1) no prior surgery for Crohn's disease, 2) small bowel or small bowel and colonic resection with anastomosis done for Crohn's disease at the Cleveland Clinic, and 3) resection margins available for microscopic analysis. The following histologic features of the margins were evaluated: edema, inflammation, lymphoid aggregates, pyloric metaplasia, fibrosis, cryptitis and crypt abscesses, ulcers, granulomas, villous shortening, mucin depletion, neuronal hyperplasia, and transmural inflammation. Additionally, margins were categorized as histologically normal, showing nonspecific changes, showing changes suggestive of Crohn's disease, and showing changes diagnostic for Crohn's disease. Anastomotic recurrence occurred in 50 patients after an average follow-up period of 11.5 years. Cumulative recurrence-free rates for the four margin categories were not significantly different. Anastomotic recurrence was not associated with any clinical or histologic feature or combination of features.

Adolescent↗
PubMed1991

Substituent effect on the stereochemistry of H2-receptor antagonists of the phenylformamidine series. A conformation-dependent mode of interaction with the H2 receptor.

The influence of alkyl substitution on the stereoisomerism of the formamidine cation (E,E vs E,Z) of several N-substituted (imidazolylphenyl)formamidines (1-10) was investigated. As (imidazolylphenyl)formamidines having alkyl substituents of more than three carbon atoms bind to H2-receptor preparations in a pseudoirreversible mode causing unsurmountable antagonism, the four isomeric butylformamidines (5-7 and 9) having comparable lipophilic character but different E,E/E,Z composition were investigated in H2-receptor assays to determine quantitatively any difference in their pseudoirreversible inhibitory pattern. It was found that the geometry of the formamidine cation is affected by the steric bulk of the substituent on the formamidine nitrogen. A relationship between the percentage of the E,E conformation of the formamidine cation and degree of pseudoirreversible antagonism was also found. The present studies support the hypothesis that bidentate hydrogen bonding plays an important role in the interaction of (imidazolylphenyl)formamidines with the H2 receptor.

Amidines↗
PubMed1990

Irreversible H2-antagonism of the four isomeric butyl analogues of mifentidine.

It has been hypothesized that bidentate hydrogen bonding plays an important role in the interaction of imidazolylphenylformamidines with the H2-receptor. The present study, in which the degree of pseudo-irreversible H2-antagonism of the four isomeric butyl substituted mifentidine analogues was determined on the spontaneously beating right atrium of the male guinea-pig, lends further support to this hypothesis. In solution the EE/EZ ratio is different for the four isomeric butylated mifentidine analogues. The rank order of the percentage of E,E conformation, which favors a bidentate interaction, of the formamidine moiety parallels the rank order of pseudo-irreversible H2-antagonism.

Animals↗
PubMed1990

Evidence for cell type dependent mechanisms in agonist-induced down-regulation of beta-adrenoceptors.

Processing of the beta-adrenoceptors by mammalian tumor cells, Chang liver cells and HeLa cells both containing beta-2-adrenoceptors, was studied using 125I-labeled iodocyanopindolol and 3H-labeled CGP12177. No difference could be detected between the results obtained with these two ligands. During desensitization of these cells by the beta-adrenergic agonist isoproterenol a time dependent decrease of intracellular cyclic-AMP was accompanied by loss of beta-adrenoceptors. The loss of receptors could not be prevented by the cytoskeleton disrupting agents colchicine and cytochalasin B. The effect of the lysosomotropic agent chloroquine is dependent upon the cell type. It showed no effect on the agonist-induced down-regulation of beta-adrenoceptors on Chang liver cells in contrast to a prominent inhibiting effect on HeLa cells. These results highly suggest that lysosomal enzymes are involved in the process of down-regulation of beta-adrenoceptors on certain cell types only. Colchicine and cytochalasin B, as well as Gpp(NH)p were able to uncouple the guanine nucleotide binding protein and the beta-adrenoceptor. This uncoupling however, did not inhibit the loss of receptors measured by radioligand binding techniques during challenge with agonists. From experiments performed to separate membrane fractions on non-linear sucrose gradients it cannot be concluded that receptors are redistributed intracellular or in the plane of the membrane. Withdrawal of the agonist during receptor down-regulation resulted in the reappearance of measurable receptors within 20 hr for receptors on HeLa cells and within 60 hr for Chang liver cells. The reappearance of receptors could be totally blocked by cycloheximide, indicating that these receptors were newly synthesized and not internalized receptors. From the results of our experiments it is concluded that beta-adrenoceptors, present on Chang liver cells and HeLa cells are down-regulated during desensitization by isoproterenol without uptake in intracellular structures of the cells. The fate of these down-regulated receptors remains unclear. It is also concluded that no universal mechanism can be proposed for beta-adrenoceptor down-regulation on mammalian cells.

Adrenergic beta-Agonists↗