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Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 343 records · Page 19Linked to original sources

[Validity of cytologic examination of voided urine in patients with urologic cancer].

Predictive tests for tumour cells in voided urine, compared with cytological and bioptic specimens taken by cystoscopy are quite similar (80-87%) but compared with the degree of malignancy, the sensitivity is least for grade I (62-77%) and greatest for grades II-III (91-94%). The low sensitivity is primarily an expression of the much greater certainty of biopsy investigations. Whereas the choice of the type of sample is not so decisive in experienced hands, the sensitivity in PV-positive test is least in cases of grade I malignant changes and least for grade II cases in PV-negative test.

Evaluation Studies as Topic↗

[Malignant cells in voided urine from elderly men contacted by mail].

Urine cytological examination among elderly men in an urban region will increase the number of current cases of cancer of the bladder in the first year in which this form of investigation is offered from 1.7 to 3.7 per 1,000 men examined. In order to achieve this result, an overdiagnosing occurs in the 1,045 participants as five men were offered cystoscopy without confirmation of malignancy during the follow-up period. Among seven men who defaulted for one reason or another, three had degrees of malignancy of II and III. The newly discovered cases of cancer of the bladder, only three in number, do not, however, represent any particular health benefit as regards degree of malignancy or tumour stage. The cytological validity for the entire group of participants revealed a nosographic sensitivity of 0.5, a predictive positive value of 0.14 and a nosographic specificity of 0.96 but, in the particular group with positive cytology, the predictive positive value was 0.54. The prevalence proportion was calculated to 7.3 per 1,000 men per annum.

Aged↗

High pp60c-src level in human platelet dense bodies.

Phosphoproteins phosphorylated in vivo were examined in resting and thrombin-activated human blood platelets. Thrombin-stimulation resulted in an overall increase in labeled proteins containing phosphotyrosine. The most prominent was a protein of 60 Kd. By electroblotting, the 60 Kd protein was identified as the pp60c-src, the normal cellular homolog of the transforming protein of Rous sarcoma virus. We have examined the intracellular distribution of the pp60c-src within platelets. Use of immunoprecipitation and electrotransfer to study isolated membranes, alpha-granules, lysosomes, and dense granules (also termed dense bodies) revealed that pp60c-src was highly enriched in dense bodies. In view of the prominent role of these granules in platelet function, We postulate that protein phosphorylation by activated pp60c-src is involved in early steps of platelet activation.

Blood Platelets↗

The lymphocyte-specific protein tyrosine kinase p56lck is hyperphosphorylated on serine and tyrosine residues within minutes after activation via T cell receptor or CD2.

Human T cells can be activated and induced to proliferate through either the antigen-specific receptor complex (TcR-CD3) or the CD2 surface molecule. Following stimulation, both serine and tyrosine phosphorylation of cellular protein have been demonstrated to occur. p56lck, a protein tyrosine kinase associated to the inner face of the plasma membrane, is almost exclusively expressed in lymphoid cells, especially T cells. Within minutes after activation of a human T cell-derived line (Jurkat) via stimulation of either the TcR-CD3 complex or the CD2 glycoprotein, we observed a hyperphorphosylation of p56lck. A concomitant shift to a higher molecular weight in sodium dodecyl sulfate-polyacrylamide gel was also observed. Similar changes were obtained with phorbol 12-myristate 13-acetate. Tryptic phosphopeptide analysis of the hyperphosphorylated form of p56lck yielded new phosphorylated sites in serine residues and an increased tyrosine phosphorylation. These results suggest that p56lck may be intimately connected to the signaling pathway in T cell activation.

Antigens, Differentiation, T-Lymphocyte↗

Resetting of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors in conscious dogs.

We investigated the influence of a stimulation of intrarenal alpha 1-adrenoceptors on the relationship between renin release and renal artery pressure in 8 conscious, chronically instrumented dogs receiving a normal salt diet. Renin stimulus-response curves were determined by a stepwise reduction of renal artery pressure down to 70 mm Hg (1) under control conditions, (2) during a bilateral common carotid occlusion combined with an intrarenal prazosin infusion, and (3) during an intrarenal methoxamine infusion. Both drug infusions did not alter resting renal blood flow. (1) The control renin stimulus-response curve revealed a flat portion (plateau-level) around and above the resting blood pressure and a very steep portion (slope) below a well-defined threshold pressure 10-15 mm Hg below the resting blood pressure. (2) An intrarenal alpha 1-adrenoceptor blockade by prazosin prevented the resetting of the threshold pressure which is regularly observed during bilateral common carotid occlusion. (3) An intrarenal infusion of the alpha 1-adrenoceptor agonist methoxamine increased the threshold pressure. We suggest that the neural control of renin release within the autoregulatory range of renal blood flow involves two independent mechanisms: the direct release of renin from juxtaglomerular granular cells by beta 1-adrenoceptors, and the modulation of the threshold pressure of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors. The small changes in renal nerve activity necessary to reset the threshold pressure and the close relationship between the threshold pressure and resting blood pressure imply an important function of intrarenal alpha 1-adrenoceptors in the regulation of renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urinary excretion of PGI2/3-M and recent N-6/3 fatty acid intake.

Epidemiological studies were performed in a Japanese fishing village when catches of fish were highest and in a Japanese farming village with usual fish consumption. Intake of eicosapentaenoic, docosahexaenoic and also arachidonic acid were significantly higher in the fishing village during the 3 days of the study than in the farming village. The correlation between eicosapentaenoic acid intake on the day when urine was collected and excretion of delta 17-2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I3, was highly significant, whereas there was no correlation between arachidonic or linoleic acid intake and excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I2. We suggest that the arachidonic acid pool for prostaglandin I2 production is not quickly influenced by dietary linoleic or arachidonic acid because of a large pool size of arachidonic acid and a slow conversion of linoleic acid to arachidonic acid, while prostaglandin I3 formation is directly related to the intake of eicosapentaenoic acid.

6-Ketoprostaglandin F1 alpha↗

alpha-Linolenic acid and long-chain omega-3 fatty acid supplementation in three patients with omega-3 fatty acid deficiency: effect on lymphocyte function, plasma and red cell lipids, and prostanoid formation.

alpha-Linolenic acid deficiency is described in three patients. Observed clinical symptoms were hemorrhagic dermatitis, hemorrhagic folliculitis, skin atrophy, and scaly dermatitis. Supplementation with ethyl alpha-linolenate followed by a purified fish oil (EPA-oil) began to normalize symptoms within 10 d. The mitogenic response in isolated lymphocytes was reduced whereas the number of T lymphocytes increased significantly. Serum thromboxanes, urinary excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (PGI2-M), and bleeding time were unaffected. The results indicate that omega-3 fatty acids are essential for normal accumulation of erythrocyte omega-6 acids. The dietary intake of long-chain omega-3 acids required to obtain midnormal concentrations of omega-3 acids in plasma and erythrocyte lipids was estimated to be 350-400 mg/d (0.4% of calories), whereas the corresponding mean intake of alpha-linolenic acid was 990 mg/d (1.0% of calories). It is suggested that essential fatty acid requirement should be stated as grams or milligrams per day, similarly to other essential nutrients.

Dermatitis↗

Tobacco-specific nitrosamines in mainstream smoke of West German cigarettes--tar alone is not a sufficient index for the carcinogenic potential of cigarette smoke.

Fifty-five types of commercial cigarettes on the West German market were analyzed for tobacco-specific nitrosamines (TSNA) in mainstream smoke. The cigarettes included filter and nonfilter cigarettes with very high, high, medium, low and ultra-low tar and nicotine yields. The observed range for N'-nitrosonornicotine was from 5 to 625 ng/cigarette and for 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone from not detected (less than 4 ng/cigarette) to 432 ng/cigarette. The highest TSNA values were obtained for nonfilter cigarettes made of dark tobaccos and the lowest values for nonfilter Oriental-type cigarettes. Relatively high TSNA yields were also observed in filter cigarettes with moderate and lower tar deliveries. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstrain smoke. The TSNA deliveries in mainstream smoke depended on the actual tobacco composition. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke.

Filtration↗

Influence of smoking parameters on the delivery of tobacco-specific nitrosamines in cigarette smoke--a contribution to relative risk evaluation.

The influence of the smoking parameters (puff profile, puff duration, puff volume, puff frequency) on the delivery of tobacco-specific nitrosamines (TSNAs) in mainstream smoke was investigated for six different cigarette brands, including filter cigarettes with very low to medium smoke yields and non-filter cigarettes with high and very high smoke yields. The puff profile did not influence the TSNA yields. The puff duration also had no remarkable influence on the TSNA delivery with the exception of a non-filter cigarette made of dark tobaccos. The puff volume and the puff frequency significantly influenced the TSNA yields. Increasing puff volume and frequency resulted in increasing TSNA values. The total volume drawn through a cigarette was calculated. The dependency of the TSNA delivery on the total volume was almost linear at least up to a total volume of approximately 500 ml/cigarette. The TSNA yield was the same for the same total volume no matter whether the total volume was due to a changing puff volume or a changing puff frequency. The total volume drawn through a cigarette is the main responsible factor for the TSNA delivery in mainstream smoke. Total volume data from smokers of low- and medium-tar cigarettes are used to calculate TSNA intake. The different smoking behaviour observed for smokers of low-tar and low-nicotine cigarettes as compared to standard smoking conditions is discussed with respect to the TSNA dependency on smoke parameters.

Humans↗

Preformed tobacco-specific nitrosamines in tobacco--role of nitrate and influence of tobacco type.

Fifty-five types of commercial cigarettes on the open market in the FRG and several samples of pure tobacco types were analyzed for preformed tobacco-specific nitrosamines (TSNA) and nitrate in the tobacco. For the cigarette tobaccos the observed range for N'-nitrosonornicotine (NNN) was 50-5316 ng/cigarette and for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) from not detected (less than 50 ng/cigarette) to 1120 ng/cigarette. Nitrate levels ranged from 0.6 to 14.4 mg/cigarette. The highest TSNA values were obtained for cigarettes made of dark tobaccos and the lowest for Oriental type cigarettes. The results demonstrated that there is a correlation between TSNA and nitrate levels. The tobacco type is another important influencing factor, especially for NNK. In Virginia tobaccos unexpectedly high NNK values were observed. For the samples of the pure tobacco types, NNN levels ranged from 20 to 8850 p.p.b. and NNK levels from not detected (less than 50 p.p.b.) to 1400 p.p.b. The observed range for nitrate was from traces (less than 0.005%) to 4.1%. Pure Oriental tobaccos which are low in nitrate showed the lowest TSNA concentrations. In the high nitrate Burley tobaccos the highest TSNA concentrations could be determined. Virginia tobaccos which show a low nitrate content are low in NNN but rather high NNK concentrations were found. The results from these pure tobacco types demonstrate that the nitrate content of the tobacco has a great influence on the TSNA level. However, Virginia tobaccos show higher NNK concentrations than expected according to their low nitrate content.

Chromatography, Gas↗

Over fifty support group for patients in a rehabilitation hospital. Commentary.

The psychosocial needs of newly disabled 50- to 85-year-old individuals are often neglected in rehabilitation. The Rehabilitation Hospital of the Medical College of Ohio has addressed these needs with the establishment of an over 50 support group. Topics chosen by the group focused on common fears and concerns. The group has been valuable in offering opportunities for peer reinforcement, problem solving, and ventilation of feelings in a safe and supportive setting which had not before existed.

Aged↗

How should we measure n-3 polyunsaturated fatty acids and their metabolites in humans?

Growing interest in nutritional intervention with n-3 polyunsaturated fatty acids demands reliable analyses of these fatty acids and their corresponding eicosanoids in vivo or ex vivo. n-3 polyunsaturated fatty acids are preferably assayed by capillary gas-liquid chromatography after extraction of the lipid classes, their separation by chromatographic methods and conversion of the fatty acids to methylesters. n-3 eicosanoids have to be separated from their arachidonic acid analogues by HPLC or by gas-liquid chromatography and are then quantified by UV-spectroscopy or mass-spectrometry. Structure elucidation has to be performed by chemical reactions and by mass spectrometry. Antibodies for radioimmunoassays against n-3 eicosanoids are not yet available.

Body Fluids↗

Vascular protein deposits in temporal arteritis with special reference to failure of histological findings.

The object of an immunohistochemical search for vascular protein deposits in temporal arteritis is to assess the diagnostic possibilities in cases which are clinically typical but unconfirmed by biopsy results. In a group of older patients with arteritis, however, vascular aging may give rise to intimal thickening and a broad-spectrum deposition of protein. In an inter- and intra-individual comparison of vascular segments with and without arteritis we, however, found a few protein markers in arteritis which are essentially different from those in vascular aging. The intimal thickening and immune reaction in 9 selected marker proteins were graded 0-2, using the tunica media as reference for both properties. Of the nine proteins studied, alpha-2-macroglobulin was significantly increased, not only in segments affected with arteritis, but also in unaffected segments from the same biopsy as compared with biopsies from patients not suffering from this disease. 79% of patients with biopsy-confirmed arteritis also showed a significantly elevated serum alpha-2-macroglobulin as compared to 27% of those having only changes attributed to aging. In conclusion, immunohistochemical demonstration of deposits in the arterial wall and elevated serum levels of alpha-2-macroglobulin substantiate the clinical suspicion of arteritis in the absence of histological and inflammatory changes.

Aged↗

Favorable effects of fish oil concentrate on risk factors for thrombosis in renal allograft recipients.

The incidence of thromboembolic complications in renal allograft recipients is very high. Since fish oil has antithrombotic properties, we administered 18 capsules of fish oil concentrate (1.5 g of eicosapentaenoic acid, EPA, and 0.7 g of docosahexaenoic acid) per day to 14 renal allograft recipients for 6 months. Another group of recipients served as controls. In the treated group the levels of EPA and docosahexaenoic acid in erythrocyte membrane lipids increased significantly after the fish oil treatment. Red blood cell filterability significantly increased in the treated group compared with the case of the control group. Epinephrine-induced platelet aggregation increased significantly in the control group, and this change was significantly different from that of the treated group (almost a null change). At the end of the study, the ratio of the main urinary metabolite of prostacyclin I2/3 to the metabolite of thromboxane A2/3 was significantly higher in the treated group than in the control group. In conclusion, we suggest that fish oil concentrate may favorably affect risk factors for thromboembolic complications in renal allograft recipients.

Adult↗

Pharmacokinetics of rioprostil in human plasma as assayed by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry.

To investigate the pharmacokinetics of rioprostil in man an assay is developed to analyse levels of rioprostil in plasma. After extraction and purification by solid-phase cartridges rioprostil is measured by negative ion chemical ionization mass spectrometry using a deuterated internal standard. The method is validated by a recovery experiment. Levels of rioprostil in the plasma of four volunteers following a single oral dose of 600 micrograms rioprostil are found as always below 100 pg/ml. The data presented here suggest that rioprostil is transformed rapidly in man to its more polar metabolites.

Adult↗

Elevated level of p60c-src in virus-transformed murine megakaryocytic cell lines.

Megakaryocytic cell lines derived from mouse bone marrow cells transformed by the Myeloproliferative Leukemia Virus (MPLV) contain elevated levels of p60c-src. Northern blot analysis revealed the presence of a 4 kb normal sized c-src transcript only in MPLV-transformed megakaryocytic cell lines containing a high percentage of acetylcholinesterase positive cells (AChE+ greater than 10%), but not in MPLV-transformed erythroblastic or myeloblastic cell lines. The p60c-src protein was identified in lysates from in vivo labelled cells and in in vitro labelled membrane extracts by immunoblotting analysis and by immunoprecipitations with specific anti-src antibodies. In dimethylsulfoxide (DMSO) treated cells, the number of AChE+ cells increased together with p60c-src kinase activity indicating a possible correlation between p60c-src expression/activity and megakaryocytic differentiation.

Acetylcholinesterase↗