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  • 11
    ISSN: 1573-7241
    Keywords: cerivastatin sodium ; BAY w6228 ; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ; plasma cholesterol concentration ; LDL receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0 and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations, were increased in a dose-dependent manner (0.01–1.0 μM) by exposure of Hep G2 cells to cerivastatin. The results suggest that cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors, but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin, therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-2013
    Keywords: Phosphorylation ; Mg-ATP ; AMP-PNP AMP-PCP ; ATP[γS] ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ca2+-activated K+ channels in the basolateral plasma membrane of bullfrog oxynticopeptic cells are intimately involved in the regulation of acid secretion. Patch-clamp techniques were applied to study the regulating mechanism of these channels. In the excised inside-out configuration, intracellular Mg2+ decreased channel activity in a dose-dependent manner. In the absence of Mg2+, administration of adenosine 5′ triphosphate (ATP) to the cytoplasmic side also inhibited channel activity. On the other hand, in the presence of Mg2+, addition of ATP markedly increased channel activity. At a fixed concentration of free Mg2+ the Mg-ATP complex caused channel activation and shifted the dose response relationship between channel activity and the intracellular Ca2+ concentration to the left. A nonhydrolysable ATP analogue, adenosine 5′-[β,γ-imido]triphosphate (AMP-PNP) adenylyl [β,γ-methylene]diphosphate (AMP-PCP), could not substitute for ATP in channel activation, but a hydrolysable ATP analogue, adenosine 5′-O-(3-thiotriphosphate) (ATP[γS]) could do so. Furthermore, application of alkaline phosphatase to the cytoplasmic side inhibited channel activity. These results demonstrate that Ca2+-activated K+ channels are regulated by Mg2+ and ATP, and suggest that a phosphorylation reaction may be involved in the regulation mechanism of these channels.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-2307
    Keywords: Key words Human telomerase RNA ; In situ mRNA hybridization ; Oesophageal carcinoma ; Oesophageal dysplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumour progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human oesophageal dysplasia and cancer by using in situ mRNA hybridization (ISH) with avidin–biotin staining. Ki-67 immunoreactivity was also examined. We analysed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of the mRNA in each sample was verified by using a poly d(T)20 probe. Seventy-six samples (63%) showed no mRNA degradation; these included 30 carcinomas, 7 dysplasias and 39 normal mucosae. At the single-cell level, high levels of hTR expression were found in the cytoplasm and especially in the nucleus. Most (〉90%) cancer cells demonstrated high levels of hTR expression in 29 (97%) of the 30 tumours. Most dysplastic cells also showed high levels of hTR in all 7 dysplastic cases. In all 39 normal mucosae, most basal cells indicated high levels of hTR expression, which were also seen in infiltrating lymphocytes. The distribution of hTR-expressing cells was similar to that of Ki-67-positive cells. These data suggest that overexpression of hTR may be correlated with the proliferative activity that defined by Ki-67 immunoreactivity and is an early event in carcinogenesis of the oesophagus.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-2013
    Keywords: Key words Phosphorylation ; Mg-ATP ; AMP-PNP ; AMP-PCP ; ATP[γS] ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ca2+-activated K+ channels in the basolateral plasma membrane of bullfrog oxynticopeptic cells are intimately involved in the regulation of acid secretion. Patch-clamp techniques were applied to study the regulating mechanism of these channels. In the excised inside-out configuration, intracellular Mg2+ decreased channel activity in a dose-dependent manner. In the absence of Mg2+, administration of adenosine 5′-triphosphate (ATP) to the cytoplasmic side also inhibited channel activity. On the other hand, in the presence of Mg2+, addition of ATP markedly increased channel activity. At a fixed concentration of free Mg2+, the Mg-ATP complex caused channel activation and shifted the dose response relationship between channel activity and the intracellular Ca2+ concentration to the left. A nonhydrolysable ATP analogue, adenosine 5′-[β,γ-imido]triphosphate (AMP-PNP) adenylyl [β,γ-methylene]diphosphate (AMP-PCP), could not substitute for ATP in channel activation, but a hydrolysable ATP analogue, adenosine 5′-O-(3-thiotriphosphate) (ATP[γS]) could do so. Furthermore, application of alkaline phosphatase to the cytoplasmic side inhibited channel activity. These results demonstrate that Ca2+-activated K+ channels are regulated by Mg2+ and ATP, and suggest that a phosphorylation reaction may be involved in the regulation mechanism of these channels.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1435-5922
    Keywords: bile acid dissolution ; extracorporeal shockwave lithotripsy ; gallbladder stones ; pulverization ; ursodeoxycholic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of bile acid dissolution therapy in extracorporeal shockwave lithotripsy of gallstones, remains controversial. Our study examined whether chemolitholysis after sufficient disintegration enhanced stone clearance within 6 months of the first lithotripsy. A total of 143 patients who developed one to three radiolucent stones measuring⪯30 mm in diameter were randomly separated into two treatment groups: 47% were given lithotripsy alone, and 53% lithotripsy plus ursodeoxycholic acid (UDCA). Repeated piezoelectric lithotripsy was given, with no limit on the total number of treatment sessions, to pulverize or disintegrate stones into fragments〈3 mm. Stones were disintegrated in 97% of all patients, and the fragments were ⪯2 mm in 50% of these patients. According to an intention-to-treat analysis, 52% in the lithotripsy alone group and 58% in the UDCA group were free of stones 6 months after the first lithotripsy (P=0.61). Of the patients with fragments⪯2 mm, 71% in the former and 86% in the latter group were free of stones 6 months after the first lithotripsy, with no significant difference between the groups. Biliary pain occurred in 25% of all patients, including 3 with acute cholecystitis. We concluded that the sufficient disintegration of gallstones achieved with repeated lithotripsy enhanced the early clearance of fragments, regardless of whether chemolitholysis was employed.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1435-5922
    Keywords: hypergastrinemia ; omeprazole ; pirenzepine ; gastric acid secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Journal of gastroenterology 30 (1995), S. 452-460 
    ISSN: 1435-5922
    Keywords: pepsinogen ; gastric cancer ; gastric mass survey ; cut-off point
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To establish a sensitive and efficient screening method for gastric cancer using serum pepsinogen, we investigated the characteristics of serum pepsinogen I and II levels and the I/II ratio and their cut-off points. We found that the pepsinogen I level and the I/II ratio were significantly lower in patients with gastric cancer than in control subjects, especially in patients with cancers of the differentiated type, the elevated type, and the depressed type without ulceration. However, sex, depth of invasion, and location of tumor did not correlate with the pepsinogen levels. A suitable cut-off point in screening for gastric cancer was a pepsinogen I level of less than 50 ng/ml and a I/II ratio of less than 3.0, as determined by receiver operator characteristics curves. The sensitivity, the specificity, and the accuracy of detection for all types of gastric cancer were approximately 55%, 75%, and 72%, respectively. If restricted to cancers of the elevated and the depressed type without ulceration, the sensitivity was approximately 85%, and the specificity and accuracy were approximately 76% and 77%, respectively. These results suggest that, in screening for gastric cancer when using pepsinogen levels and morphological examinations, the suitable cut-off point in regard to specificity is as stated above. However, regarding sensitivity, when the pepsinogen method is used alone, a pepsinogen I level of less than 70 ng/ml and a I/II ratio of less than 3.0 is acceptable.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1435-5922
    Keywords: cholesterol gallstone ; concanavalin A ; glycoprotein ; calcium ion ; nucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The concanavalin A-bound glycoproteins in human gallbladder bile have recently been demonstrated to be strong promoters of cholesterol crystal nucleation. In the present study, we investigated the mechanism(s) whereby such promoters affect cholesterol crystal nucleation and/or growth, and compared these mechanisms with those of another promoter, calcium ion. Concanavalin A-bound glycoproteins were isolated from theHelix pomatia-unbound fraction of gallbladder bile from stone-free patients, and determined by electrohoresis to consist of six subclasses (MW 143, 98, 80, 58, 50, and 40 kDa). A cholesterol crystal growth assay showed that concanavalin A-bound glycoproteins both accelerated nucleation time and increased growth rate, whereas calcium ion affected nucleation time only. In the presence of both concanavalin A-bound glycoproteins and calcium ion, both cholesterol nucleation and growth were markedly enhanced. A gel permeation chromatographic study revealed that concanavalin A-bound glycoproteins shifted a considerable amount of cholesterol from micelles to vesicles, whereas calcium ion did not. These results suggest that concanavalin A-bound glycoproteins promote cholesterol crystal nucleation and growth, partly by shifting cholesterol from stable micelles to metastable nonmicellar fractions in bile. In contrast, calcium ion promotes these processes by other mechanisms and, therefore, enhances the effect of concanavalin A-bound glycoproteins.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1435-5922
    Keywords: HCV ; core region ; nucleotide sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1435-5922
    Keywords: submucosal invasive colon cancer ; lymph node metastasis ; endoscopic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderatelypoorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa+IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invastion and lymphatic invasion (ly) were also significantly correlated with incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(−) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.
    Type of Medium: Electronic Resource
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