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Biomedical subjects

G Tyler

Publications and source records attributed to G Tyler.

At least 19 recordsLinked to original sources
PubMed1993

Improvement of Clostridium difficile isolation by heat-shock and typing of the isolated strains by SDS-PAGE.

Clostridium difficile plays an essential role in causing pseudomembranous colitis. We looked for the presence of these bacteria in the stools of 169 hospitalized patients and 38 nurses from wards with cases of diarrhea (207 subjects). The study was divided into three parts. In the first part, we compared three methods for isolating Clostridium difficile from stool samples: pre-selection with heat-shock, direct plating on Cycloserine-Cefotaxime-Fructose Agar (CCFA) and culturing in a selective broth medium. Final identification of Clostridium difficile was achieved by gas-chromatography and ApiZym. From the 207 consecutively obtained stool specimens, Clostridium difficile was isolated in 108 (52%) when pre-treated by heat-shock compared to only 26 (13%) when plated on modified CCFA and 23 (11%) when cultured in selective broth medium. Pre-selection significantly increases the isolation rate for Clostridium difficile and should be used in further epidemiological research. In the second part of our study, a retrospective review of subjects' records showed that the heat-shock method detected Clostridium difficile in all age groups at a higher rate than the other methods. In the third part of our study, we typed the 157 isolates of Clostridium difficile strains by protein patterns using SDS-PAGE, and 16 distinct groups were identified. In 19 cases different Clostridium difficile strains were found in the same subject by SDS-PAGE. Finally, the isolated strains were compared with strains from Brussels and Freiburg. Matching patterns were noted in only three cases.

Adolescent↗
PubMed1992

Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines.

The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5-day cultures. Bryostatin 1 inhibited growth of only MCF-7 cells and only at a high dose (100 nM). However, bryostatin 1 completely antagonized the growth inhibition and morphological changes induced by TPA in MCF-7 cells. The divergent effects of these two agents are associated with differing effects on PKC activity and isoform expression in MCF-7 cells. TPA induced rapid translocation of the PKC-alpha isozyme and PKC activity to the membrane fraction of MCF-7 cells. In contrast, bryostatin 1 treatment resulted in the loss of the PKC-alpha isozyme and PKC activity from both cytosolic and membrane compartments within 10 min of treatment. In coincubation assays the bryostatin 1 effect was dominant over that of TPA. Similar effects on PKC-alpha isozyme and PKC activity were seen in a second cell line whose growth was inhibited by TPA but not by bryostatin 1, MDA-MB-468. In contrast, in the T47D cell line, where TPA was not growth inhibitory, TPA failed to induce translocation of PKC-alpha to the cell membrane. Bryostatin, however, still caused loss of PKC-alpha isozyme and PKC activity from cytosolic and membrane fractions. Thus, differential actions of bryostatin 1 and TPA on PKC activity and alpha-isoform level in the membrane-associated fraction of MCF-7 and MDA-MB-468 cells may account for the divergent effects of these two agents on cell growth and morphology. These results suggest that the PKC-alpha isoform may specifically play a role in inhibiting growth of human breast cancer cells.

Breast Neoplasms↗
PubMed1991

c-myc gene-induced alterations in protein kinase C expression: a possible mechanism facilitating myc-ras gene complementation.

The mechanism(s) by which the c-myc nuclear protein and the membrane-associated ras protein interact to mediate phenotypic changes is unknown. We now find that c-mcy gene expression is associated with alterations in the principal signal transduction pathway through which the ras protein is thought to function. We studied the transcript and protein expression of protein kinase C (PKC) isoforms in a culture line of human small cell lung cancer cells (NCI H209) in which expression of inserted c-myc and Ha-ras genes together, but not alone, causes a transition to a large cell phenotype. In control H209 cells, at the transcript and cell membrane protein levels, PKC-alpha is the dominant PKC species. In this cell line, the expression of an exogenous c-myc gene, but not of a viral Ha-ras gene, causes a 5- to 10-fold increase in the PKC-beta isoform transcript and protein. The insertion of ras into the exogenous myc-expressing 209 cells, in addition to causing phenotypic transition, results in the translocation of the PKC-beta protein from the cytosol to the membrane fraction and a decrease in membrane-associated PKC-alpha. Concomitant with these changes, the increased PKC isoform transcript levels induced by myc alone are completely reversed. These observations suggest that a complex set of PKC transcript and protein alterations, most prominently involving an increased PKC-beta protein level in the cell membrane, a decrease in PKC-alpha protein, and a decrease in all PKC isoform transcripts, may represent a fundamental event(s) for c-myc collaboration with Ha-ras to alter cell phenotype.

Carcinoma, Small Cell↗
PubMed1990

Role of nuclear protein kinase C in the mitogenic response to platelet-derived growth factor.

We have assessed the involvement of nuclear envelope protein phosphorylation in the mitogenic response to platelet-derived growth factor (PDGF) in NIH/3T3 fibroblasts. We find that stimulation of quiescent NIH/3T3 cells with PDGF or with the mitogenic protein kinase C (PKC) activators phorbol 12-myristate 13-acetate (PMA) or bryostatin 1 (bryo) leads to rapid, dose-dependent phosphorylation of several nuclear envelope polypeptides. The predominant nuclear envelope targets for mitogen-induced phosphorylation are immunologically identified as the nuclear envelope lamins. All three lamin species (A, B and C) are phosphorylated in response to PMA or bryo, while lamins A and C are preferentially phosphorylated in response to PDGF. Phosphopeptide mapping and phosphoamino acid analysis indicate that similar serine sites on the lamins are phosphorylated in response to PDGF, PMA and bryo. Both mitogenicity and lamina phosphorylation induced by these mitogens can be inhibited by the selective PKC inhibitor staurosporine at 2 nM. Treatment of quiescent NIH/3T3 cells with PDGF, PMA or bryo leads to rapid translocation of PKC to the nuclear envelope. These data indicate that rapid nuclear events, including translocation of cytosolic PKC to the nuclear membrane and lamina phosphorylation, may play a role in the transduction of the mitogenic signals of PDGF from the cytoplasm to the nucleus in NIH/3T3 fibroblasts.

Animals↗
PubMed1989

Growth-related changes of oxygen consumption rates of tumor cells grown in vitro and in vivo.

Growth-related changes of oxygen consumption rates of tumor cells, grown in vitro or in vivo, were investigated. For in vitro investigations, L929 and DS-carcinosarcoma cells were cultured in artificial media. For in vivo studies, DS-carcinosarcoma cells were implanted into the abdominal cavity of Sprague-Dawley rats (ascites tumor, containing malignant cells, leukocytes, lymphocytes, and macrophages). Oxygen uptake was measured photometrically. Parameters of the extracellular medium judged to possibly influence the respiratory activity of tumor cells were monitored at different growth stages (glucose, lactate, and amino acid levels, oxygen and carbon dioxide partial pressures, and pH values). The results obtained clearly show that the oxygen uptake of tumor cells grown in vitro decreased as quiescence developed. In contrast, the respiratory activity of in vivo DS-carcinosarcoma ascites cells increased as tumor growth reached plateau phase. The differences observed cannot be attributed solely to changes of the environmental conditions monitored. It is likely that an increased respiration rate of activated host cells might profoundly contribute to the elevation of the respiratory capacity of DS-carcinosarcoma ascites tumors grown in vivo. These data provide evidence that solid tumors in vivo can increase their O2 uptake at an enhanced O2 availability not only due to an enlarged tumor volume with adequate O2 supply but also due to an elevation of the respiratory activity of different cell populations within a tumor.

Amino Acids↗
PubMed1989

In vivo targets of recombinant human tumour necrosis factor-alpha: blood flow, oxygen consumption and growth of isotransplanted rat tumours.

The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.

Animals↗
PubMed1989

[The effect of recombinant human tumor necrosis factor alpha on malignant tumors in vivo. Physiopathologic basis for clinical oncology].

Effects of Recombinant Human Tumor Necrosis Factor-alpha on Malignant Tumors in vivo/Pathophysiological fundamentals for clinical oncology. The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha; 6.6.10(6) U/mg protein) on growth, metabolism and perfusion of isotransplanted rat tumors (DS-carcinosarcomas) was investigated. Tumor growth was stimulated at low TNF doses (1 and 10 micrograms/kg), and significantly retarded at higher TNF dose levels (0.1 and 1.0 mg/kg). Growth changes were paralleled by variations in perfusion and metabolism. A reduced tumor blood flow enhanced the efficacy of a subsequent heat treatment. From these results, important implications for the clinical use of rhTNF-alpha are obvious (e.g., possible growth stimulation, timing of a combination therapy with other tumor treatment modalities).

Animals↗
PubMed1988

Aneurysm of a common digital artery: resection and vein graft.

A 57-year-old woman developed an aneurysm of a common digital artery and its branches, which caused pain from pressure on digital nerves. There was also evidence of median nerve compression at the wrist. Treatment included resection and vein graft connecting three vessels, and carpal tunnel release. Three years later, the graft is patent, and the patient's hand has excellent function with no recurrence of symptoms.

Aneurysm↗
PubMed1988

An unusual presentation of splenic rupture.

A case is described of rupture of the spleen with a hemoperitoneum which was forced through two abdominal wall hernias to produce potentially misleading ecchymosis of the upper midline and the thigh. The diagnostic significance of the entire clinical presentation is discussed.

Hemoperitoneum↗
PubMed1987

Phosphorylation of the surface transferrin receptor stimulates receptor internalization in HL60 leukemic cells.

The transferrin receptor is a target protein for phosphorylation by activated intracellular protein kinase C (May, W. S., Sahyoun, N., Jacobs, S., Wolf, M., and Cuatrecasas, P. (1985) J. Biol. Chem. 260, 9419-9426). Recently we reported that the potent tumor-promoting agent phorbol diester or a synthetic diacylglycerol could mediate rapid down-regulation of the surface transferrin receptor in association with receptor phosphorylation in HL60 leukemic cells and suggested that this phosphorylation may provide a signal for receptor internalization. In this communication we have tested experimentally the predictions generated by the hypothesis that receptor phosphorylation may play such a role in the intracellular cycling of the transferrin receptor. Results indicate that phorbol diester-stimulated phosphorylation occurs stoichiometrically only on the surface-oriented receptor and precedes internalization. Using a specific inhibitor of protein kinase C, it was found that both phorbol diester-mediated receptor phosphorylation and down-regulation could be antagonized. While the mechanism of internalization of the phosphorylated receptor is not clear, phorbol diester treatment significantly increases the rate constant for endocytosis from 0.183 to 0.462 min-1, while inhibiting only slightly the rate constant for exocytosis of the internalized receptor from 0.113 to 0.079 min-1. Thus, we conclude that phorbol diester treatment affects intracellular cycling of receptors and establishes a new steady state distribution of surface and intracellular receptors. These data support a role for receptor phosphorylation as a trigger for internalization primarily by stimulating the process of transferrin receptor endocytosis while affecting the subsequent exocytosis of the receptor cycling only slightly.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1983

Established hand infections: a controlled, prospective study.

A randomized, prospective study of 200 consecutive established hand infections was designed to compare the efficacy of two antibiotics, cefamandole and nafcillin. Bacteriologic data revealed 63.5% of the patients grew multiple organisms (2.3 organisms per culture) and 26% of the patients had anaerobic infections. Complications were noted in 13% of all patients--26% in patients who grew aerobes and anaerobes and 9.8% in patients who grew aerobes alone (p less than 0.05). Despite the fact that 95% of all organisms were sensitive in vitro to cefamandole whereas only 67% of organisms were sensitive to nafcillin (p less than 0.01), complications occurred more frequently in patients treated with cefamandole. We conclude that the empirical selection of a broad-spectrum antibiotic is reasonable based on in vitro sensitivity studies; however, other factors such as treatment delay, initial extent of infection, anatomic location of infection, cause of infection, and extent of surgical debridement are important in the development of complications.

Adolescent↗
PubMed1983

Sonographic and scintigraphic detection of a bile leak in a post-cholecystectomy patient. Recognition of the tail sign.

Hepatobiliary scintigraphy using Tc-99m HIDA derivates is used primarily for the diagnosis of acute cholecystitis and for demonstration of biliary tract patency. Ultrasound is usually employed for diagnosing cholelithiasis and biliary tree dilatation, as well as identifying focal lesions in the liver. These two complementary modalities are also useful in the evaluation of post-cholecystectomy patients. We present a case of a bile leak, diagnosed by these two modalities.

Adult↗
PubMed1982

Nonocclusive intestinal ischemia treated with intraarterial infusion of prostaglandin E1.

An elderly woman with a history of cardiac failure treated with digitalis had both abdominal pain and dehydration. Parenteral fluid and electrolyte support failed to alleviate abdominal pain. Superior mesenteric arteriography combined with "spillover" method of estimating blood flow revealed an intestinal nonocclusive ischemic state which was treated successfully with 44-hour intraarterial infusion of prostaglandin E1. Laparotomy performed during the drug infusion revealed viable intestine.

Aged↗
PubMed1980

Melanin containing clear cell sarcoma in a fingertip. Case report and review of the literature.

A case is described of a clear cell sarcoma with ultrastructural evidence of melanin production. The tumour appeared on the distal portion of the index finger of a thirteen-year-old girl and showed little change in size over seven years of observation by the patient. At age twenty she required hospital admission at which time clinical evidence of metastases to axillary nodes, lungs and bone was found and the patient died within two months. The previous cases reported in the literature are discussed.

Adolescent↗
PubMed1980

Superior mesenteric angiography and blood flow measurement following intra-arterial injection of prostaglandin E1.

The hemodynamic effects of intra-material prostaglandin E1 (PE1) administered via the angiographic catheter were evaluated in 14 patients. Blood flow in the superior mesenteric artery (SMA) after PGE1 infusion was compared with control SMA blood flow as measured by the "spillover" angiographic reflux method, using a specially designed injector/film-changer system. In all patients, SMA blood flow increased by more than 50% and visualization of the SMA and portal vein was enhanced.

Adult↗
PubMed1980

Pancreatic trauma.

The early diagnosis of pancreatic injuries depends on a high degree of clinical suspicion. During laparotomy, exploration of the pancreas and duodenum for suspected injury should be thorough and orderly. In managing these injuries, one should select the simplest procedure that will re-establish the integrity of the upper gastrointestinal tract and control the free escape of pancreatic juices into the surrounding tissue. In general, resection of the distal portion of the body and tail of the pancreas for severe injuries in that area and duodenal diverticularization for injuries involving the pancreatic head are the procedures of choice for preservation of functioning pancreatic tissue.

Accidents, Traffic↗