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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 451 records · Page 25Linked to original sources

Number of synaptic vesicles in rat cortex immediately after cessation of the self-sustained afterdischarge during kindling.

The sensorimotor area of rat cerebral cortex was subjected to repetitive electrical stimulation at 10-min intervals; this led to progressive lengthening of self-sustained afterdischarges (SSADs). At 50-60 s after cessation of the third SSAD the brains of the animals were perfused transaortally with fixing fluid, and a quantitative electron microscopic analysis of type I synapses in the second cortical layer of the sensorimotor area of the contralateral hemisphere was carried out. In a zone 0.1 micron wide adjacent to the presynaptic membrane in the active zone, the number of synaptic vesicles (converted to the number per 0.01 micron2 area) in the experimental animals fell by 64.6%. In a zone of the same width 0.1 micron distant from the presynaptic membrane, it fell by 67.6%. The mean absolute synaptic vesicle count per presynaptic bag section fell by 66.6%. The number of synapses showing signs of exocytosis rose in the experimental animals from 3.8 to 5.9%, while the number with clearly demonstrable exocytosis rose from 0.7 to 11.4%. The proportion of synapses with signs of (clearly demonstrable) endocytosis rose from 2.8% (2.1%) in the controls to 7.1% (3.7%) in the experimental rats. In the experimental and control animals we demonstrated complex vesicle formation in 4.3 and 3.8%, respectively, of the synapses and dense-cored vesicles in 7.7 and 2.8%, respectively, of the synapses. We consider changes in the number and formation of synaptic vesicles to be signs of exhaustion of the synapses caused by the previous epileptic seizure, which simultaneously activates mechanisms of vesicle formation.

Animals↗

Mucociliary clearance in patients with chronic bronchitis and bronchial carcinoma.

We measured the mucociliary clearance rates and lung function data of 40 normal subjects, of 30 smokers with chronic bronchitis and of 64 patients with bronchial carcinoma. The mucociliary clearance rate of cancer patients was significantly lower than that of normal subjects and of patients with chronic bronchitis who smoked the same amount of cigarettes. The fast clearing phase of the central bronchial tree is more delayed than the peripheral mucociliary clearance rate in smokers with and without carcinoma. With our mucociliary clearance measurement we assessed the self-cleaning filter function of about the first 10 generations of the branching bronchial tree where also most bronchial carcinomas develop. The correlation between lung function data (MMEF) and smoking habits is much better (r = 0.73) than with the measured mucociliary clearance rates (r = 0.3), suggesting that inborn errors of mucociliary transport are nearly as important as external lung damage due to smoking and infection in the development of chronic bronchitis and bronchial carcinoma.

Adenocarcinoma↗

Histochemical tumor markers for evaluation of hormone dependence in breast cancer.

Lectin from the peanut (peanut agglutinin = PNA) possesses a high affinity for D-galactosyl-(1-3)-N-acetyl-D-galactosamine, used for histochemical investigations on formalin-fixed tissue sections of normal mammary gland as well as of benign and malignant breast diseases. Thereby, a lectin-binding pattern was found that partly exhibited secretory malfunction. Additional studies with a labeled antibody directed against a milk fat globule membrane glycoprotein, which was isolated by PNA affinity chromatography from human milk, confirmed the PNA receptor as a marker of a milk protein in breast carcinomas. The most important clinicopathological finding, however, was that in accordance with the secretory activity about 77% of PNA-positive tumors responded to endocrine treatment, whereas PNA-negative mammary carcinomas usually failed to show any response to hormonal therapy. These results also correlated with the hormone receptor content of tumor tissue.

Breast Neoplasms↗

Peanut agglutinin (PNA) binding sites: a useful marker for hormonal dependence in experimental breast cancer.

Histochemical studies were performed with the labeled lectin from Arachis hypogaea (peanut agglutinin, PNA) to detect the occurrence, distribution, and amount of this lectin receptor in N-nitrosomethylurea-induced rat mammary carcinomas. Since in normal rat mammary tissue, the formation and secretion of PNA binding sites are controlled by the combined action of estrogen and prolactin, the amount of secretion-associated PNA binding sites was correlated with tumor response to either ovariectomy or antiestrogenic treatment with tamoxifen. Free as well as sialic acid-substituted PNA binding sites which were represented by the disaccharide beta-D-Gal(1-3)NAcGal occurred in the apical cytoplasm of tumor cells and within the secretions of acinar and tubular structures. In contrast the whole tumor cell membrane contained predominantly sialic acid-substituted PNA binding sites. All of the tumors investigated contained some secretion-associated PNA binding sites. The values showed a continuum from very low to very high amounts. The number of PNA binding sites associated with secretory activity was lower in hormone-independent than in hormone-dependent tumors. Furthermore, there was an inverse relationship between mitotic and secretory activities with positive PNA staining. In conclusion, these studies revealed that the secretory PNA index, mitotic index, and especially the ratio of secretory PNA index to mitotic index represent useful parameters to select tumors for endocrine therapy in this experimental model.

Animals↗

Influence of clonazepam on thalamocortical phenomena in rats.

The influence of clonazepam on thalamo-cortical phenomena was studied in acute experiments in 20 rats. Early components of cortical responses to electrical stimulation of either LA or VDM thalamic nuclei remained unchanged. Only the latency of the late N2 component was significantly shortened after CZP. CZP did not change the incidence of rhythmic after-discharge ("thalamo-cortical spindles") and tended to prolong them. Two types of self-sustained after-discharges of an epileptic nature which could appear after the end of rhythmic thalamic stimulation were influenced differently: Spike-and-wave type was invariably suppressed, serrated wave type of SSAD was generally unchanged by CZP. This last finding speaks in favour of the hypothesis that these two types of SSADs could serve as models of two different epileptic seizures.

Animals↗

Lectin binding properties of glycoproteins in cells of normal gastric mucosa and gastric cancers: a comparative histochemical and biochemical study.

The different binding of labeled lectins to the individual cell types of the normal mucosa indicates differences in glycoprotein composition of the: a) surface epithelial cells showing various degrees of differentiation; b) cell types lying above and below the generative cell zone; c) specific membrane systems of the parietal and chief cells. The enhanced peanut agglutinin (PNA) binding of activated, hyperplastic isthmus cells, of goblet cells in intestinal metaplasia, and even of the majority of gastric cancer cells may be indicative for their common origin and for their similar functional states in glycoprotein synthesis. Lectins demonstrate differences also in the mucus structure of the main types of gastric cancers. Adenocarcinomas show similar lectin binding patterns to activated isthmus cells, but the subtypes of signet ring cells resemble mucus neck cells or intestinal and colonic goblet cells, respectively. Glycoproteins which can be isolated by the lectins in a pure form allow further detailed studies in these fields.

Binding Sites↗

Identification and quantitation of methotrexate and methotrexate metabolites in clinical high-dose therapy by high pressure liquid chromatography and field desorption mass spectrometry.

High-pressure liquid chromatography in combination with field desorption mass spectrometry as techniques of high specificity and sensitivity have been applied to the identification and quantitation of the anticancer drug methotrexate and its metabolites which occur in clinical high-dose therapy. Field desorption mass spectra of methotrexate and several methotrexate and folic acid derivatives, when investigated as free acids or ammonium salts, yield abundant protonated molecular ions and a consistent pattern of structurally significant fragments. High-pressure liquid chromatographic separation of methotrexate metabolites was performed on reverse-phase, C-18 columns using a volatile, ammonium bicarbonate/acetate containing mobile phase that was especially suited for the field desorption mass spectral analysis of isolated metabolites, and provided the definite identification of 7-hydroxymethotrexate and 4-[[2,4-diamino-6-pteridinyl]methyl]methylamino]-benzoic acid in serum and urine of patients treated with high-dose methotrexate. The high intensity and stability of the [MH]+ ions was found suitable for the quantitation of methotrexate and related folate analogues by field desorption mass spectrometry. A synthetic methotrexate derivative, methotrexate-gamma-(2-hydroxy)ethyl-amide was used as internal standard for the quantitative determination of methotrexate in serum and urine. In a study to comparatively assess the potential of specific quantitation methods, serum and urine levels of methotrexate and its major metabolite, 7-hydroxymethotrexate were determined by (i) an enzyme immunoassay, (ii) reverse phase high-pressure liquid chromatography and (iii) field desorption mass spectrometry. Results obtained from four patients with osteogenic sarcoma receiving high-dose methotrexate/leucovorin rescue therapy consistently show the sustained elimination of 7-hydroxymethotrexate over several days, thus indicating the utility of specifically monitoring this nephrotoxic metabolite, at massive methotrexate doses.

Adult↗