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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 343 records · Page 19Linked to original sources
PubMed1999

Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats.

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.

Allylglycine↗
PubMed1999

[Epidemiological study on association of periodontal disease and total and differential leukocyte counts].

Periodontal disease is defined as inflammation that is caused by bacteria in dental plaque. This disease is liable to be a factor contributing to the high leukocyte count over an extended period. Furthermore, a number of prospective epidemiologic studies have shown that the leukocyte count is a good predictor of ischemic heart disease (IHD). However there have been few epidemiological studies of the relationship between periodontal disease and the leukocyte count. The purpose of this study was to investigate the relationship between the total and differential leukocyte counts and oral conditions of Japanese factory workers who were classified according to their smoking habits. The 1,167 subjects were male factory workers employed with a chemical factory in Osaka, Japan. The oral conditions recorded were periodontal status (Community Periodontal Index of Treatment Needs, CPITN). The relationship between the total and differential leukocyte counts and the CPITN score of subjects who were classified according to their smoking habits was investigated in 1996 and 1997. In both the current smokers and nonsmokers, the subjects with severe periodontal disease, in contrast to the normal subjects, exhibited total leukocyte, neutrophil and monocyte counts that were significantly high for 1 year during follow-up studies. The periodontal disease is shown that causes the total leukocyte and neutrophil counts related to the development of IHD to remain at a high level.

Adult↗
PubMed1999

Prediction of life expectancy in patients with primary pulmonary hypertension. A retrospective nationwide survey from 1980-1990.

Primary pulmonary hypertension (PPH) is a progressive disease of unknown etiology usually followed by death within 5 years after diagnosis. Although heart-lung or lung transplantation is now offered to patients with advanced PPH, adequate criteria assessing an accurate prediction of life expectancy in PPH has been difficult to establish. The aims of this study were to identify the characteristic features associated with a poor prognosis in patients with PPH, and to attempt to establish an individual prognostic index that predicts with great accuracy survival or death of PPH after one year, thereby helping to define criteria for patient selection for transplantation. In 1991, a retrospective nation-wide survey on PPH was conducted in Japan, and the clinical and cardiorespiratory variables of 223 PPH cases (female; 144, male; 79) in the period from 1980-1990 were obtained. The mean pulmonary arterial pressure (PPA) was 57.5+/-17.2 mm Hg (mean+/-SD), and the overall median survival time was 32.5 months since the first diagnostic catheterization. The characteristic features of 61 patients who died within one year of catheterization (Nonsurvivors group) were compared to 141 patients who survived one year or more from the time of catheterization (Survivors group). Among several clinical and cardiorespiratory variables, heart rate, PPA, right atrial pressure (PRA), stroke volume index (SI), pulmonary vascular resistance, and partial pressure of carbon dioxide (PaCO2) were significantly different between the two groups. As the independent factors, PPA, PRA, SI, and PaCO2 were selected for the multiple logistic analysis. Using a 0.7 probability cut-point to separate Nonsurvivors from Survivors, 84.6% of Nonsurvivors and Survivors could be correctly predicted from this logistic regression equation. Predictive equations like the present preliminary one can be used in the future to better assess life expectancy in patients with PPH in whom transplantation will be considered.

Adolescent↗
PubMed1999

Adenosine and neopterin levels in cerebrospinal fluid of patients with neurological disorders.

We determined the cerebrospinal fluid (CSF) levels of adenosine, a mediator of cerebral blood flow regulation, and neopterin, a macrophage-producing compound, in patients with neurological disorders. Compared to control subjects, the adenosine levels were significantly increased in the patients with acute-stage cerebral infarction (n=12, p<0.0001), acute meningitis (n=10, p<0.0001), or amyotrophic lateral sclerosis (ALS, n=12, p<0.05) (Mann-Whitney U-test). The neopterin levels were significantly increased in the 41 patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP, p<0.0001), acute meningitis (p<0.0001), ALS (p<0.05) (Mann-Whitney U-test), or acute-stage cerebral infarction (p<0.005, Student's t-test). In the analysis of 41 HAM/TSP patients, the neopterin levels were significantly correlated with the cell number and glucose levels in the CSF, and were a sensitive marker of inflammation. Several of the HAM/TSP patients with increased adenosine levels were probably complicated with other diseases. The increased neopterin levels in the HAM/TSP group persisted, suggesting that the mononuclear cellular infiltration remained for a long time.

Adenosine↗
PubMed1999

Histological changes in the rat common carotid artery induced by aneurysmal wrapping and coating materials.

Histological changes in and around the arterial walls of rats were investigated following topical application of aneurysmal wrapping and coating materials, including a fibrin glue, a cyanoacrylate glue (Biobond), and cotton fibers (Bemsheet). Bilateral common carotid arteries were exposed using sterile techniques, and one of the test materials was applied to the right artery. The left artery was used as the control. Changes in arterial histology were evaluated at 2 weeks, 1 month, 2 months, and 3 months after surgery. The fibrin glue was surrounded by intense inflammation at 2 weeks after surgery. Both the fibrin glue and inflammation had disappeared at 2 months, but the glue had induced mild inflammation in the adventitia. Biobond caused chronic inflammation, necrosis of the media, and thickening of the arterial wall due to fibrosis in both the media and adventitia. Bemsheet produced chronic inflammation, progressive fibrosis, and granuloma. Connective tissue increased in the adventitia, but no major changes were observed in the media. The Bemsheet fibers remained unchanged, and adhered to the arterial wall. Although arterial stenoses were not observed in the present study, the results suggest that cyanoacrylate glue can cause the arterial occlusive lesions observed following aneurysm surgery.

Animals↗
PubMed1999

Histological changes in the rat common carotid artery following simultaneous topical application of cotton sheet and cyanoacrylate glue.

Histological changes in and around the arterial walls of rats were investigated following simultaneous topical application of cotton sheet and cyanoacrylate glue. The bilateral common carotid arteries were exposed using sterile techniques, and the test materials were applied to the right artery. The left artery served as a control. Changes in arterial histology were evaluated at 2 weeks, 1 month, 2 months, and 3 months after surgery. Extensive inflammation consisting primarily of histiocytes and multinuclear giant cells was observed around the materials, but tended to decrease by 3 months. Necrosis in the media and fibrosis in the adventitia initially appeared around 2 weeks, and became advanced by 2-3 months. At 2-3 months, disruption of elastic fibers and marked fibrosis in the media were seen, and endothelial proliferation in the intima appeared. Intimal proliferation was observed at both the experimental and other sites of the vessels. The present results suggest that simultaneous use of the test materials can cause the arterial occlusive lesions observed following aneurysmal surgery.

Animals↗
PubMed1999

Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2- imbalance in insulin-resistant rat aorta.

To investigate underlying mechanisms responsible for the impaired nitric oxide (NO)-dependent vascular relaxation in the insulin-resistant state, we examined production of both NO and superoxide anion radical (O2-) and those modulating factors in aortas obtained from normal (CTR), insulin-treated (INS), or high fructose-fed (FR) rats. FR rats showed insulin resistance with endogenous hyperinsulinemia, whereas INS rats showed normal insulin sensitivity. Only FR aortic strips with endothelium elicited impaired relaxation in response to either acetylcholine or calcium ionophore A23187. Endothelial NO synthase (eNOS) activity and its mRNA levels were increased only in vessels from INS rats (P < 0.001), whereas eNOS activity in FR rats was decreased by 58% (P < 0.05) when compared with CTR rats. NO production from aortic strips stimulated with A23187 was significantly lower in FR than CTR rats. In contrast, A23187-stimulated O2- production was higher (P < 0.01) in FR than CTR rats. These differences were abolished when aortic strips were preincubated in the media including (6R)-5,6,7,8-tetrahydrobiopterin (BH4), an active cofactor for eNOS. Furthermore, as compared with CTR rats, aortic BH4 contents in FR rats were decreased (P < 0.001), whereas the levels of 7,8-dihydrobiopterin, the oxidized form of BH4, were increased, with opposite results in INS rats. These results indicate that insulin resistance rather than hyperinsulinemia itself may be a pathogenic factor for decreased vascular relaxation through impaired eNOS activity and increased oxidative breakdown of NO due to enhanced formation of O2- (NO/O2- imbalance), which are caused by relative deficiency of BH4 in vascular endothelial cells.

Acetylcholine↗
PubMed1999

Signaling through Gp130: toward a general scenario of cytokine action.

Cytokines play roles in a wide range of responses such as immune response, hematopoiesis and inflammation. A large volume of studies revealed that cytokines show functional pleiotropy and redundancy. Gp130 is a receptor subunit shared by the interleukin-6 family of cytokines. We describe and discuss signaling through gp130 in relation to a general scenario for cytokine signaling regulating cell growth, differentiation and survival.

Animals↗
PubMed1999

Homozygous deletion of the p16/MTS-1/CDKN2 gene in malignant gliomas is infrequent among Japanese patients.

We have analyzed the status of the p16/MST-1/CDKN2 gene in 63 brain tumors from Japanese patients. With quantitative multiplex polymerase chain reaction (PCR) assay using the exon 2 primers of the p16 gene and control chromosome 9qSTS primers, we found homozygous deletion of the p16 gene in 7 cases; in 1 out of 10 cases of anaplastic astrocytomas (WHO grade III), 6 out of 35 cases of glioblastoma multiformes (grade IV) but in none of the tumors of grade I or II. We also found mobility-shifted PCR products in 8 cases using the single-strand conformation polymorphism technique. DNA sequencing of the aberrantly migrated products revealed that 5 cases of glioblastoma multiforme had mutations which caused amino acid substitutions. We found one case with silent mutations and two cases with nucleotide changes in the non-coding region. The frequency of the alteration of the p16 gene, either homozygous deletion or mutation accompanied with amino acid substitutions, increased in malignant brain tumors (grade III and IV) compared with that in low grade tumors (grade I and II) (p=0.0275), suggesting possible role(s) of the gene in the progression of brain tumors. In addition, the low frequency of homozygous deletions shown in this study is quite different from previous reports that demonstrated frequently deleted p16 gene in malignant gliomas from Caucasian patients. We have also shown the presence of heterogeneous cell populations within the glioblastoma masses based on the variety of the mutated p16 sequences. The present study, therefore, suggests a possible racial difference in the mechanism of the tumorigenesis and a heterogeneity of malignant gliomas developed during the tumor progression.

Adolescent↗
PubMed1999

Expression of angiostatic factors in colorectal cancer.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. We examined expression of genes encoding various angiostatic factors: thrombospondin 1 (TSP1), thrombospondin 2 (TSP2), brain-specific angiogenesis inhibitor 1 (BAI1) and angiopoietin 2 (AGP2) in 62 colorectal cancers and 40 samples of extraneoplastic colon mucosa. The expression of the angiostatic factors TSP2 and AGP2 were significantly increased in the cancerous mucosa as compared to these in extraneoplastic mucosa (o2 test; p<0. 0001, and Fisher's exact test; p<0.0001), while the increase in TSP1 expression was not significant. BAI1 expression was slightly decreased in the cancer tissue. These results suggested that specific types of angiostatic factors might have protective roles against cancer cell proliferation via dormancy due to hyponutrition caused by decreased vascularity.

Angiogenesis Inhibitors↗
PubMed1999

[Triple therapy regimens involving H2 blockaders for therapy of Helicobacter pylori infections].

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection. To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection, 99 patients with H. pylori infection were treated with either lansoprazole (LPZ) or ranitidine (RNT) used together with clarithromycin (CAM) and metrinidazole (MTZ). The drug combination and administration periods in the PPI group were LPZ 30 mg, CAM 400 mg, MTZ 500 mg (LCM group). The ranitidine group received RNT 300 mg, CAM 400 mg, MTZ 500 mg (RCM group). The cure rate of H. pylori infection was 88% in the LCM group; 95% CI 79-97 and 92% in the RCM group; 95% CI 84-99.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

A new Bennettitalean trunk with unilacunar five-trace nodal structure from the Upper Cretaceous of Hokkaido, Japan.

A new species of Bucklandia is described based on a permineralized fossil trunk that was obtained from sediments of Upper Cretaceous age from Hokkaido, Japan. The quality of preservation is exquisite, and anatomical and morphological features are preserved at the cellular level. The specimen is clearly bennettitalean because of the cycadeoidean-type arrangement of vascular bundles in the petiole. However, this specimen is unique among previously described progymnosperms and gymnosperms in possessing a unilacunar five-trace type of nodal structure. The fossil thus contributes to a more complete understanding of the variation of nodal structure in bennettitalean trunks.

Journal Article↗
PubMed1999

Stimulation of plasma membrane Ca2+ -pump ATPase of vascular smooth muscle by cGMP-dependent protein kinase: functional reconstitution with purified proteins.

A 240-kDa protein isolated from porcine aortic smooth muscle as a substrate for cGMP-dependent protein kinase (cGMP kinase) whose phosphorylation was in a close association with stimulation of partially purified plasma membrane Ca2+ -pump ATPase by the kinase was later shown to represent splicing variants of type 1 inositol 1,4,5-trisphosphate (IP3) receptor. To further clarify the role played by this protein in the stimulation of Ca2+ -pumpATPase, it was attempted in thepresent study to specifically remove the protein by immunoprecipitation with an antibody specific to type 1 IP3 receptor. Contrary to expectation, stimulation of the ATPase by cGMP kinase was still observed after removal of the IP3 receptor. Furthermore, cGMP kinase stimulated a highly purified preparation of Ca2+ -pump ATPase deprived of IP3 receptor when the concentrations of the ATPase were low enough (10-20 nM) to make it retain a monomeric form, while it did not produce stimulation when the concentration of the enzyme was increased to 40 nM at which the enzyme is known to take an oligomeric, fully activated form insensitive to activation by calmodulin. Heat-inactivated cGMP kinase and cGMP kinase without cGMP failed to stimulate the highly purified Ca2+ -pumpATPase. In addition, type Ialpha but not type Ibeta cGMP kinase was found to stimulate the ATPase. The stimulation of Ca2+ -pump ATPase by cGMP kinase occurs without any detectable phosphorylation of the ATPase. In conclusion, cGMP kinase can stimulate the plasma membrane Ca2+ -pump ATPase when it is in a monomeric form without phosphorylating the Ca2+ -pump ATPase and that of the two cGMP kinase isozymes found in the vascular smooth muscle, only type Ialpha cGMP kinase participates in the stimulation.

Animals↗
PubMed1999

Pharmacokinetics and safety of Z-321, a novel specific orally active prolyl endopeptidase inhibitor, in healthy male volunteers.

This study investigates the pharmacokinetics and safety profile of Z-321, (4R)-3-(indan-2-ylacetyl)-4-(1-pyrrolidinyl-carbonyl)-1,3-thiazoli dine, a novel specific orally active prolyl endopeptidase (PEP) inhibitor. Following a preliminary safety evaluation wherein 2 subjects received 3.75 and 15 mg doses and 2 other subjects received 7.5 and 30 mg doses, 16 subjects were assigned to two groups of 8 subjects each. In each group, 6 subjects were to receive active treatment, and 1 or 2 subjects were to receive placebo treatment. One group received 60 mg under fasted and fed conditions. A separate group of 8 subjects received 60 mg of Z-321 or a placebo in a bid regimen for 6 days and the morning dose on day 7. The concentrations of Z-321 and its main metabolites--R- and S-sulfoxide; RR-, SS-, and RS-indanol; and indanolsulfoxides in plasma and urine--were determined by the HPLC method. In the multiple-dose study, the cholinesterase activity was gradually increased and reached above the normal range on day 8 in 3 of 6 subjects given Z-321 and gradually returned to the normal range after completion of dosing. The elevation of plasma cholinesterase activity was considered to be an action of Z-321, but this remains to be verified. In a single-dose study at a dose of 30 mg, headache and vomiting were observed in 1 of 6 subjects. In the multiple-dose study, slight skin itching and eczema in 3 and 2 of 6 subjects, respectively, and headache in 2 of 6 subjects were observed, but all symptoms were not severe. There were no other abnormal findings in objective signs and laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis. The Cmax of Z-321 at 30, 60, and 120 mg in the fasting state were 63.7 +/- 23.9, 102.0 +/- 43.1, and 543.3 +/- 437.0 ng/ml (mean +/- SD), respectively, at 0.9 hours after administration, and the t1/2 was about 1.8 hours. There were no dramatic changes in the pharmacokinetics of Z-321 in the presence of food. In the multiple-dose study, there was no drug accumulation trend in plasma. These results indicate that Z-321 has acceptable pharmacodynamic and pharmacokinetics profiles for clinical use without any serious adverse events, as verified in healthy young male volunteers.

Adult↗
PubMed1999

The SHAP-HA complex in sera from patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To investigate serum derived hyaluronan (HA) associated protein-hyaluronan (SHAP-HA) complex in sera from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and determine levels of the complex in comparison with those of hyaluronan (HA), in order to assess the role of the complex as an indicator of joint inflammation. METHODS: ELISA and HA binding assays were used for quantitation of the SHAP-HA complex and HA levels in serum samples from 142 patients (114 with RA, 28 with OA) and 31 healthy controls. Clinical evaluations were also performed. RESULTS: In some RA sera, SHAP-HA complex levels were extremely high compared to control levels, but in OA sera no marked increase was observed compared to controls. This was also the case with the HA levels compared between RA and OA sera. However, in RA the levels of the SHAP-HA complex appear to be more related to clinical variables than are levels of HA, and the most significant correlations between levels of SHAP-HA complex and HA were found in the RA group. CONCLUSION: Quantitation of the SHAP-HA complex in sera may be useful as a joint marker that directly correlates to the degree of joint inflammation in RA, and offers new insight into the pathogenesis of arthritis. It may also serve as an independent criterion in the subsequent classification of RA and OA.

Adult↗