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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

771 records · Page 43Linked to original sources
PubMedDate not supplied

Alteration of aminoglycoside antibiotic ototoxicity: effect of semistarvation.

The effect of semistarvation on the toxicity and ototoxicity of tobramycin sulfate (TO) and gentamicin sulfate (GE) was investigated in guinea pigs by electrophysiological and histopathological methods. The presented data has shown that the toxicity and ototoxicity of aminoglycoside antibiotics is substantially increased when guinea pigs were semistarved. Our results should also warn researchers using semistarvation in their conditioning experiments which investigate the toxicity of different chemicals. Toxicity was greater in GE- than TO-treated animals, which caused the GE-treated animals to die during treatment or shortly after treatment. Thus, TO should be preferentially used because it has been shown to be less toxic and ototoxic in normal and altered nutritional conditions.

Animals↗
PubMedDate not supplied

[Breeding biology of the whiskered auklet (Aethia pygmaea): incubation, chick growth, and feather ontogenesis].

This is the second publication on the results of studies of the whiskered auklet breeding biology on Buldir Island. In 1993, according to the time of chick hatching the egg-laying period began in late April-early May. The single egg was incubated by both parents, which relieved each other once a day, usually at early night. Among the chicks under observation, the first hatched on June 11; the median of hatching was on June 17. After hatching, the egg shell usually remained in the nest. The chick was continuously brooded by one of parents for the first several days but since the age of 7-9 days, it stayed in the nest by itself during the daytime. Each parent fed the chick once a day, at early night, although occasional feedings were recorded also during daytime and at dawn. A newly hatched chick was covered by typical embryonal (natal) down. The remiges, rectrices, their coverts, and large feathers on pteryla humeralis had a mesoptile stage during their growth (the second down generation). The juvenile plumage consisted of semiplumes of types I and II and contour feathers of type I and, possibly, type II. In fledglings, the ornamental feathers were underdeveloped: the crest was absent and facial plumes only began growing. By reaching 100 g, the chicks left their nests at the age of about 37 days. A longer nesting period than in other Aethia auklets appears to be related to a low feeding rate due to the nocturnal activity in the colony.

Animals↗
PubMedDate not supplied

Relationship between 43 kDa epidermal growth factor-related clonogenic activity and clinical parameters for breast cancer.

The clonogenic activity of a previously purified 43 kDa EGF-related protein (16) was estimated in the urine of breast cancer patients. Increase of activity was statistically significant in lymph node-positive patients, in a group of patients with larger carcinomas, with accelerated tumor growth, in premenopausal patients and younger age and in estrogen receptor negative patients. In 31 patients the activity was estimated during polychemotherapy before surgery. Differences between the values at the begin and the end of treatment were compared between all groups by the Kruskal-Wallis test (p = 0.02). Patients with progressive disease showed increasing activities (mean values from 315 to 811) while in those with complete remission activity decreased (from 449 to 213). Partial- and non responders showed no change. In a long-term follow-up study with 25 patients the pre- and postoperative activities were estimated. In 17 of 18 patients who had no local recurrence or metastasis the activity declined after surgery, whereas in 6 of 7 patients who died, activity increased 2-5 fold prior to death. A life table analysis with a total of 101 patients revealed a trend to shorter survival in the group with higher activity (p = 0.042). These observations suggest a role for the EGF-like growth factor activity in the expression of the malignant phenotype and may have significance for breast cancer diagnosis and prognosis.

Aged↗
PubMedDate not supplied

In vitro and in vivo evaluation of a new Opaque system for metal ceramic restorations.

This study made an in vitro comparison of the shear strength in a corrosive solution, the scanning electron microscopy of the processing steps, and the x-ray powder diffraction analyses of a newly developed opaque system (Biopaque) with a traditional opaque-system (Opaque P). Clinically, two traditional opaque systems (Opaque P and Vita-VMK-Paint-On 88 opaque) were compared to Biopaque over a 4-year period. A total of 218 metal ceramic units were placed for 29 patients. One hundred ten were veneered with Biopaque, 50 with Opaque P, and 58 with Vita-VMK-Paint-On 88. The technical failure rate of the metal ceramic restorations was 9.6%, and the biological failure rate 5.5%. There was no significant difference of the shear strength in a corrosive solution between Biopaque and the traditional opaque system (Opaque). The x-ray powder diffraction analyses revealed that only the base paste of Biopaque was a newly developed material. In this study, the new opaque system (Biopaque) showed the same in vitro and in vivo results as the other conventional opaque systems. However, at least 5 years of clinical evaluation are necessary before this new opaque system can be completely recommended.

Adult↗
PubMedDate not supplied

[Victims of homicide crimes--social conditions and circumstances of the crime].

152 autopsies were performed in cases of homicide at the Institute for Legal Medicine of the Hannover Medical School and the documents concerning the social situation of the victims, the relationship between offenders and victims and the circumstances involved in the crime were analyzed. Among the victims who were employed, workers and craftsmen followed by the group working in the service industry and trade were most commonly involved. Foreigners were victimized in 8% of the cases. In 129 cases (88.4%) there was a single and in 11.6% multiple offenders. 78.3% of the victims were murdered by a person they knew. Among relatives (38.7%), parents were most frequently implicated (56.5%). Arguments were the most common reason followed by quarrels within relationships, robbery and sexual offences. In most cases, the location of the crime was the home of the victim or of the victim and offender. In 92.8% of the cases, the corpse was found at the location of the crime.

Adolescent↗
PubMedDate not supplied

Inhibition of the transport function of membrane proteins by some substituted phenothiazines in E. coli and multidrug resistant tumor cells.

Efflux-pumps mediated by P-glycoprotein increase the level of resistance to antibiotics in bacteria and to cytostatics in tumor cells due to decreased drug accumulation, and are also involved in the operation of blood brain barrier. Different compounds are able to enhance drug retention in the cells by inhibiting the efflux-pump mechanism of multidrug resistant (mdr) cancer cells and bacteria. The effects of substituted chlorpromazines were studied on a hemolysin producing and antibiotic resistant plasmid carrying E coli, and rhodamine uptake of multidrug resistant (mdr 1 gene expressing) mouse lymphoma cells. Hemolysin transporter protein encoding plasmids were eliminated from E. coli by a representative phenothiazine namely promethazine. Minimal inhibitory concentrations of tetracyclin and promethazine were lower for plasmidless bacteria as compared to the parent, plasmid carrying strains. The antibiotic resistance plasmid was cured of the R-plasmid of E. coli JE 2571, however, the ring substituted derivatives were less effective then parent compounds. The effect of some substituted phenothiazines on P-glycoprotein efflux-pump of mouse lymphoma cells were studied. The majority of ring substituted derivatives reversed the mdr of tumor cells. The 3,7,8-trihydroxy- and 7,8-dihydroxy derivatives of chlorpromazine were effective as P-glycoprotein blockers, however, 7,8-diacetoxy-, 7,8dimetoxy-, 7-semicarbazone-, and 5-oxo-chlorpromazine derivatives had only moderate effect. A tomato lectin, specific for blood brain capillary endothelium was able to modify the activity of P-glycoprotein in tumor cells. Phenothiazine and tomato lectin had some antagonism in tumor cells. Our results suggest that the inhibition of P-glycoprotein function in murine tumor cells and inhibition of transporter protein in E. coli bacteria may depend on pi-electron superdelocalizibility and electrophile binding of the compounds to the transporter proteins. The intracellular accumulation of antibiotics or chemotherapeutics increased as a consequence of decreased drug efflux in both bacterial and tumor cell systems. The inhibition of the drug effux-pump is the same for all individual cells of the population. These results can be realized by combination chemotherapy, however, antiplasmid effect itself cannot be exploited in this respect because the resistance was reversed in a part of the population only. The similarity with mdr P-glycoprotein in tumor cells and brain capillary endothels provides a good model for molecules opening the blood brain barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Mapping of Papillon-Lefevre syndrome to the chromosome 11q14 region.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease which belongs to the palmo-plantar keratoderma (PPK) group. It is characterized by a premature loss of primary and permanent teeth and early onset periodontitis. High consanguinity has been observed in over one-third of PLS families. No candidate genes or gene localizations have been described to date for this disorder. A primary genome-wide search by homozygosity mapping using samples from a large consanguineous family in which 4 siblings were affected by the disease showed homozygosity and linkage in the region of 11q14. Linkage was confirmed in 4 additional families with diverse ethnic and geographic backgrounds, 2 of which were consanguineous. A maximum two-point lod score of 8.19 was obtained for the marker AFM063yg1 (D11S901= for theta = 0. Analysis of recombination events places the gene within a 7-cM interval between AFM063yg1 and AFM269yg9 (D11S4175). No shared haplotype was found for the 5 families analysed.

Chromosome Mapping↗
PubMedDate not supplied

A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine thymocytes.

A galactoside-specific plant lectin, Viscum album agglutinin-I (VAA-I) with protein synthesis-inhibiting properties, has been shown to be cytotoxic in various eukaryotic cells, in vitro above a 10 ng/ml concentration. Noncytotoxic concentrations of VAA-I induced mRNA expression and enhanced secretion of proinflammatory cytokines in cultures of human peripheral blood mononuclear cells. In an animal model VAA-I has been shown to stimulate natural killer cells and granulocytes. In this study, human peripheral blood lymphocytes (PBL), human peripheral blood monocytes (PBM), murine thymocytes and human monocytic THP-1 cells were incubated for 24 h in the presence of various concentrations of VAA-I. The apoptotic effect of VAA-I was analyzed by flow cytometry following staining of the apoptotic nuclei in the cells with PI in hypotonic buffer and quantitative detection of DNA breaks were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. In cultures of all types of investigated cells, a dose-dependent VAA-I concentrations above 10 ng/ml in PBL and at 1 ng/ml VAA-I concentration in PBM, thymocytes and THP-1 cells, a lectin-induced increase of the apoptotic nuclei was observed. In 24-hour cultures of PBL and thymocytes, the ratios between apoptotic and nonapoptotic cells were enhanced 10 times and 8 times, respectively, by 100 ng/ml VAA-I compared to the negative control. The concentration of 100 micrograms/ml VAA-I only caused necrosis. The isolated A chain of the VAA-I induced apoptosis in PBL and thymocytes. In the culture of PBL the isolated B chain of the VAA-I was not effective indicating that cytokine induction by VAA-I is probably not involved in its apoptotic effect. On CD4+8+ thymocytes, VAA-I resulted in a reduced expression of CD8+ molecules that could be related to a loss of volume and increase of density, both characteristic features of apoptosis.

Animals↗
PubMedDate not supplied

Multidrug resistance reversal in mouse lymphoma cells by heterocyclic compounds.

Due to the close homology between bacterial and tumor cell transporter proteins, some antiplasmid and anticancer compounds were tested for their ability to reserve the multidrug resistance (mdr) of lymphoma cells. Some known anticancer medicines such as platidiam, novantron, fluorouracil, bleomycin and methotrexate were ineffective/while vinca alkaloids exerted a strong reversal effect on the mdr of lymphoma cells. The structurally related reserpine and yohimbine do not affect the activity of efflux pump. Some selected antitumor phenothiazines and benzo[a]phenothiazines, including trifluoperazine inhibit the P-glycoprotein (pgp) function. This fact is independent from the antiproliferative- or differentiation inducing effects. Since the polylactosamine specific tomato lectin prevents the action of the chemosensitizers tested, it is supposed that the site of action of phenothiazines can be at the 1st loop in the transmembrane glycoprotein. The efflux pump activity of the pgp in brain capillary endothel which is responsible for blood brain barrier (BBB) was also inhibited by some phenothiazines. However, the tomato lectin sensitivity of pgp was different in mouse lymphoma and human brain capillary endothelial cells. The mdr-gene expression of the mouse lymphoma cells (which were transfected with the human mdr-1 gene) could be reduced by phenothiazines such as promethazine and trifluoperazine, when the cells were cultured in the presence of 0.5 microgram/mL phenothiazines. Further synergism was found between two resistance modifiers i.e. verapamil and trifluoperazine on the inhibition of mdr-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Tomato lectin labels the 180 kD glycoform of P-glycoprotein in rat brain capillary endothelia and mdr tumor cells.

Two main isoforms of P-glycoproteins can be distinguished according to their solubility in ionic and non-ionic detergents. Studies on mdr cell lines and brain capillary vessels support the evidence that tomato lectin reveals high affinity binding to the oligosaccharide chains of the SDS soluble isoform of P-glycoprotein, but not to the non-ionic detergent soluble isoform. Thus the SDS-soluble isoform represents a glycoform having polylactosamines in its oligosaccharide chains. The function of these oligosaccharides is still unknown, although the carbohydrate chains of P-glycoprotein were believed to take part in correct protein folding only. We also demonstrated that lectin binding to the extracellular lactosamine sequences of drug efflux pump does not change its efficiency on mdr cell lines, but interferes with the inhibitory action of some drugs, such as verapamil and promethazine. In accordance with earlier findings we assume that carbohydrate chains might be involved in stabilization of the active conformation of efflux pump. The possible role of lectin treatment in maintaining P-glycoprotein mediated blood-brain barrier functions has to be proved in further investigations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗