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Biomedical subjects

K Kashima

Publications and source records attributed to K Kashima.

At least 109 records · Page 6Linked to original sources
PubMed1998

Pathophysiologic studies of experimental chronic pancreatitis in rats induced by injection of zein-oleic acid-linoleic acid solution into the pancreatic duct.

An experimental model of chronic pancreatitis was induced by a retrograde injection of a viscous solution consisting of zein-oleic acid-linoleic acid (0.05 ml/100 g body weight) into the rat pancreatic duct. Histologic and biochemical changes were investigated over a period of 6 months after induction of this model. The treated rats gained weight, but pancreatic weight decreased with time. Histologically, the widening of acinar lumen and cellular vacuolization occurred within 24 h at the parenchyma neighboring the small ducts filled with the injected solution. Degenerative parenchyma, interstitial edema, and inflammatory cell infiltration were pronounced 1 week later. Thereafter, duct-like tubular complex formation progressed, and the exocrine tissue exhibited marked atrophy of the gland with irregular fibrosis and fat replacement over a period of 6 months. Pancreatic contents of protein, amylase, DNA, and RNA markedly decreased, as did pancreatic weight, whereas hydroxyproline content increased. Oral administration of camostat did not affect pancreatic weight and contents of enzyme in this model. Urinary para-aminobenzoic acid (PABA) excretion in the BT-PABA test decreased to 54% at 6 weeks and 22% at 6 months. Although three quarters of pancreatic immunoreactive insulin (IRI) content was lost after 6 months, overt diabetes did not occur. The results suggest that an obstructive mechanism in the small ducts plays an important role in the genesis and development of chronic pancreatitis.

Amylases↗
PubMed1998

Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats.

The aim of the present study was to clarify whether bile acids influence chemiluminescence (CL) in the liver in vivo. Hepatic CL was determined on the surface of the liver of anaesthetized rats by using a photon counter. In normal rats, hepatic CL was significantly decreased 30 min after enteral administration of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA), but returned to its initial level 3 h later, after part of the CDCA administered was metabolized. Ursodeoxycholic acid (UDCA) and cholic acid had no effect on CL. In contrast, hepatic CL was markedly increased 30 min after CDCA or DCA administration in rats given either buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, or diethyldithiocarbamate (DDC), an inhibitor of both superoxide dismutase and glutathione peroxidase. Chenodeoxycholic acid further increased the CL of BSO- or DDC-treated rats during inhalation of oxygen via a tracheal cannula. Coadministration of UDCA eliminated the effects of CDCA on the hepatic CL of normal and BSO- or DDC-treated rats with or without oxygen inhalation. We conclude that cytotoxic bile acids, such as CDCA, increase CL in the antioxidants-depleted or oxidative-stressed liver in vivo, but that UDCA prevents CDCA from developing CL.

Animals↗
PubMed1998

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of delta-13CO2 using laser spectroscopy.

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified 13C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The 13C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of 13C-urea administration. The ratio of 13CO2 to 12CO2 was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of 13C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of delta-13CO2. In 32 H. pylori-negative patients (without therapy), the mean +/- 2SD of delta-13CO2 was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean +/- SD delta-13CO2 was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5-3.0 per mil (%0) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, and 94.1%, respectively. In conclusion, 13C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific 13C-UBT results.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Expression of splice variants of CD44 in thyroid neoplasms derived from follicular cells.

Isoform expression of CD44 in follicular carcinoma (FC) of the thyroid was analyzed by immunohistochemical staining and compared to the isoforms in follicular adenoma (FA) and papillary carcinoma (PC) of the thyroid. Variant isoforms of CD44 (CD44v) were detected in these neoplastic cells but not in non-neoplastic cells. CD44v6 was expressed in PC with nodal metastasis and also in FC at significantly higher frequencies than those in PC without metastasis and FA. The frequency of expression of CD44v3 was significantly higher in PC with nodal metastasis than in PC without metastasis. The reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blotting analysis revealed the presence of a transcript for a variant of CD44 that contained variant exon 6 in FA, FC and PC. DNA sequencing of the products of RT-PCR yielded three species of cDNA for CD44v. One of the cDNA corresponded to a transcript that contained variant exon 6. These results suggest that immunohistochemical staining and RT-PCR with Southern blotting analysis for CD44v6 might be a useful diagnostic tool for the differentiation of FC from FA and that the expression of CD44v3 and CD44v6 might be important for the development of nodal metastasis in cases of PC.

Adenoma↗
PubMed1998

Life-threatening hemorrhage in a patient with gastric cancer and acquired hemophilia.

We report a case of a patient with life-threatening hemorrhage caused by the presence of acquired factor VIII inhibitors after gastrectomy for signet-ring cell carcinoma of the stomach. Acquired factor VIII inhibitors should be taken into consideration as a cause of acquired bleeding tendency among patients with gastrointestinal malignancies especially when the coagulation tests are unusual.

Aged↗
PubMed1998

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry.

To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.

Adenoma↗
PubMed1998

Comparison of four serological tests to determine the CagA or VacA status of Helicobacter pylori strains.

We compared four tests for antibodies to CagA or VacA, HelicoBlot 2. 0, RIDA Blot Helicobacter, CHIRON RIBA H. pylori SIA, and an enzyme-linked immunosorbent assay using recombinant CagA. Immunoblot assays were accurate for determining Helicobacter pylori status but poor for determining CagA or VacA status (accuracy, 66 to 80% for CagA status and 34 to 67% for VacA status). None can be recommended for determining CagA or VacA status.

Antigens, Bacterial↗
PubMed1998

Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases.

The CagA protein of Helicobacter pylori is an immunogenic antigen of variable size and unknown function that has been associated with increased virulence as well as two mutually exclusive diseases, duodenal ulcer and gastric carcinoma. The 3' region of the cagA gene contains repeated sequences. To determine whether there are structural changes in the 3' region of cagA that predict outcome of H. pylori infection, we examined 155 cagA gene-positive H. pylori isolates from Japanese patients including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA proteins were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The sequence of the 3' region of the cagA gene in Japan differs markedly from the primary sequence of cagA genes from Western isolates. Sequence analysis of the PCR products showed four types of primary gene structure (designated types A, B, C, and D) depending on the type and number of repeats. Six of the seven type C strains were found in patients with gastric cancer (P < 0.01 in comparison to noncancer patients). Comparison of type A and type C strains from patients with gastric cancer showed that type C was associated with higher levels of CagA antibody and more severe degrees of atrophy. Differences in cagA genotype may be useful for molecular epidemiology and may provide a marker for differences in virulence among cagA-positive H. pylori strains.

Adult↗
PubMed1998

Chemokines in the gastric mucosa in Helicobacter pylori infection.

BACKGROUND: Although chemokines have been suggested to play an important role in Helicobacter pylori associated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa. AIMS: To investigate the expression and production patterns of various chemokines using gastric biopsy specimens. METHODS: In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated alpha (GRO alpha)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). cagA gene was identified using PCR. RESULTS: H pylori infection was associated with increased rates of expression of mRNA for IL-8, GRO alpha, RANTES, and MIP-1 alpha and with increased levels of mucosal IL-8 and GRO alpha. IL-8 and GRO alpha levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pylori infection was associated with increased rates of expression of mRNA for IL-8 and GRO alpha and with increased levels of these chemokines. CONCLUSION: H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GRO alpha), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.

Adult↗
PubMed1998

Rare alteration of genomic structure or expression of the DPC4 gene in myelogenous leukemias.

We examined homozygous deletion, point mutation and expression of DPC4 gene, a recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of chronic myelogenous leukemia including 22 in the chronic phase, 3 in the accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous leukemia including 9 at the initial presentation and 10 at relapse. Polymerase chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single strand conformation polymorphism study for the entire coding region were carried out. Homozygous deletion or subtle mutation was not detected in any of the samples examined. However, 3 patients with various clinical phases showed a decrease of DPC4 expression. These results suggest that DPC4 alteration is not a crucial event in the development or the progression of myelogenous leukemias.

DNA-Binding Proteins↗
PubMed1998

Effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals in neutrophils from streptozotocin-induced diabetic rats.

Neutrophil function is impaired by a known mechanism in diabetic patients, thus increasing susceptibility to infections. We studied the effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals and cytosolic sorbitol concentration in neutrophils from streptozotocin-induced diabetic rats. There were four groups: treated and untreated control and diabetic rats. Treated groups were given 0.075% epalrestat in their diet for 4 weeks from the induction of diabetes and were untreated for the subsequent 4 weeks. Oxygen radicals were measured as chemiluminescence amplified by a luciferin analog [Cypridina luciferin analog-dependent chemiluminescence (CLA-DCL), which is dependent on O2- generation] and luminol (L)-DCL, which is highly dependent on OCl- generation) in response to formyl-methonyl-leucyl-phenylalanine. Diabetes resulted in a significant decrease in CLA/L-DCL and a significant increase in sorbitol (P < 0.01); there was a negative correlation between sorbitol and CLA-DCL (P < 0.05) in diabetic groups. The 4-week treatment with epalrestat in the diabetic group completely prevented the increase in sorbitol and partially improved the CLA-DCL, although L-DCL was not significantly affected. After 4 weeks off treatment, CLA-DCL decreased and sorbitol increased. Treatment had no effect on serum insulin or glucose concentration. We conclude that an increase in sorbitol in neutrophils causes, in part, an impaired generation of O2-. Epalrestat improves the impaired O2- generation by preventing the sorbitol increase in streptozotocin-induced diabetic rats.

Aldehyde Reductase↗
PubMed1998

Treatment with bovine gallstones exacerbates liver damage, but enhances hepatoprotection by bear gall powder in carbon tetrachloride-intoxicated rats.

The interactions between bovine gallstones (Goou) and bear gall powder (Yutan) in decreases in serum transaminase levels were investigated in rats intoxicated with carbon tetrachloride (CCl4). The p.o. administration of Goou significantly increased both serum transaminase levels and hepatic lipid peroxidation following i.p. administration of CCl4. Concomitant administration of both Goou and Yutan resulted in decreases of serum transaminase levels and hepatic lipid peroxidation, which were more remarkable than with administration of Yutan alone. Goou significantly increased the estimated hepatic blood flow in the indocyanine green clearance test and enhanced the delivery of CCl4 to the liver from the peritoneal cavity. These findings suggest that Goou exacerbates CCl4-induced hepatic damage because of the accelerated delivery of CCl4 to the liver and that Goou might have a hemodynamic drug interaction with Yutan in the liver, possibly enhancing the hepatoprotective effect of Yutan.

Alanine Transaminase↗
PubMed1998

Irsogladine maleate may preserve gastric mucosal hydrophobicity against ethanol in phospholipids independent way in rats.

Irsogladine maleate (IM) has been used as a mucosal protective agent, whose action is partially explained as enhancement of mucosal blood flow, increase of cellular cyclic AMP and facilitation of gap-junctional intercellular communication. Effect of IM on rat gastric mucosal hydrophobicity, one of the mucosal barrier properties, was investigated, in comparison with that of 16,16-dimethyl prostaglandin E2 (dmPGE2). IM alone had no effect on mucosal hydrophobicity and mucosal phospholipids content. dmPGE2 alone did not change mucosal hydrophobicity significantly, but remarkably increased mucosal surface-active phospholipids. Intragastric administration of absolute ethanol significantly decreased gastric mucosal hydrophobicity and mucosal phospholipids content. IM could prevent the decrease in mucosal hydrophobicity by ethanol, maintaining the surface mucus gel layer and mucosal surface phospholipids almost as non-damaged control levels, whereas dmPGE2 also prevented the decrease in mucosal hydrophobicity by ethanol, with the surface epithelium being partially exfoliated and mucosal surface-active phospholipids showing remarkable enhancement. These results suggest that IM may preserve gastric mucosal hydrophobicity against ethanol, not through enhancement of mucosal phospholipids content like prostaglandin, but possibly through its reported stabilization action to the epithelial cell lining, which may preserve the surface epithelium with the mucous gel layer containing surface-active phospholipids, a possible origin of mucosal hydrophobicity.

Animals↗
PubMed1998

Frequency of chromosome 7 gain in human breast cancer cells: correlation with the number of metastatic lymph nodes and prognosis.

Trisomy 7 has been reported in various malignant neoplasms, but there are no reports in breast cancer. In order to evaluate the contribution of chromosome 7 gain to breast cancer, we investigated the relationship of numerical abberation of chromosome 7 with clinicopathological variables and prognosis in seventy-nine breast cancer cases (invasive carcinomas) using the technique of fluorescence in situ hybridization (FISH) on paraffin-embedded sections. A significant correlation of the frequency of cells with extra copies of chromosome 7 (percent polysomy 7 cell score) was found with tumor size, regional lymph node status, tnm stage, histological extension, estrogen receptor (ER), and DNA ploidy. The number of metastatic lymph nodes was positively correlated with percent polysomy 7 cell score (correlation coefficient=0.623, p < 0.01). Furthermore, cases with a high percent polysomy 7 cell score had a shorter disease-free survival and overall survival times, especially in the lymph node-positive group. It was demonstrated that percent polysomy 7 cell value was closely associated with lymph node metastasis and prognosis and might be a useful prognostic predictor of breast cancer patients.

Adenocarcinoma↗
PubMed1998

Acute liver damage with characteristic apoptotic hepatocytes by ingestion of Aplysia kurodai, a sea hare.

A case of acute liver damage by ingestion of Aplysia kurodai, a sea hare is reported. A 40-year-old man, complaining of vomiting and pyrexia after eating a sea hare, was admitted. Laboratory data showed mild liver damage with sustained elevations of aminotransferases. Microscopic findings in the liver biopsy specimen revealed characteristic apoptotic hepatocytes accompanied by mitotic hepatocytes. It is suggested that bioactive substances in the sea hare might induce such apoptosis of hepatocytes in the liver.

Adult↗
PubMed1998

[Clinical study on the inhibitory effect of a 5-HT3 antagonist, granisetron, for nausea and vomiting induced by chemotherapy (CHOP, VEPA, high-dose ETP) for non-Hodgkin's lymphoma].

The antiemetic effect of granisetron on nausea and vomiting induced by cancer chemotherapy (CHOP, VEPA, VEPA-B, massive dose of ETP) was studied in fifty patients with non-Hodgkin's lymphoma. There was almost no difference in the inhibitory effect by regimen, with the rates of perfect inhibition of nausea and vomiting standing at 55.6% to 60%. Nausea and vomiting was perfectly controlled in 60% of 35 patients receiving CHOP therapy. As a part of this study, a comparison was made of perfect inhibitory effect on nausea and vomiting by potency of chemotherapy under the potency scale of 750 mg/m2 of CPA as 1, revealing no significant difference in the rates of complete inhibition as 71.4% for a drug potency of less than 0.8 vs 52.4% for 0.8 or above (p = 0.26). However, it was clear that the higher the dose of chemotherapy, the lower the rate of complete inhibition. The results confirmed the high efficacy and safety of granisetron in the treatment of nausea and vomiting induced by cancer chemotherapy.

Adult↗
PubMed1998

Blockage by terfenadine of the adenosine triphosphate (ATP)-sensitive K+ current in rabbit ventricular myocytes.

We examined the blocking effects of terfenadine, an antihistaminic agent, on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells. IK,ATP was induced by cromakalim or NaCN. Terfenadine blocked the IK,ATP with an IC50 of 1.7 microM at -10 mV. This blockage was voltage dependent; depolarization induced a stronger blockage. According to the transmembrane electrical field model, terfenadine interacts with the site located 15 to 18% from the cytoplasmic membrane surface. In line with the assumption that the binding site is near the cytoplasmic surface, terfenadine applied to the cytoplasmic solution potently inhibited the single-channel activity for IK,ATP in the inside-out configuration (IC50 0.19 microM). In contrast, terfenadine applied to the external solution did not affect the channel activity in the cell-attached configuration, but inhibited it when applied into the pipette. The inhibition of the single channels by terfenadine was accompanied by flickering of the channels. These findings suggest that 1) terfenadine blocks the ATP-sensitive K+ channel in the open state, 2) the binding site is near the internal membrane surface and 3) terfenadine is poorly diffusible into the lipid biomembrane and accesses the binding site via the hydrophilic pathway. Terfenadine also inhibited the transient outward K+ current, inward rectifier K+ current and E4031-sensitive rectifier K+ current. However, the inhibition of these repolarization currents by terfenadine at 1 microM was not sufficient to prolong the action potential duration significantly. Whereas, terfenadine (1 microM) prolonged the action potential duration which had been shortened by cromakalim. Terfenadine may modify the ischemia-induced arrhythmias by blocking IK,ATP.

Action Potentials↗