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Biomedical subjects

H Asakura

Publications and source records attributed to H Asakura.

At least 73 records · Page 4Linked to original sources
PubMed2001

Beneficial effect of the active form of vitamin D3 against LPS-induced DIC but not against tissue-factor-induced DIC in rat models.

1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes. The possibility exists that vitamin D3 prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in the pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin D3 is effective against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ dysfunction and pathological findings (assessment of glomelular fibrin deposition). Vitamin D3 was administered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; i.v.) was given 10 min before the injection of TF or LPS in each treatment group. Vitamin D3 was effective against DIC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIC effect of vitamin D3 was equal to (or more potent than) that of LMWH. The results suggested that vitamin D3 was useful for the treatment of LPS-induced DIC, and that the assessment of a drug's efficacy should be done carefully given the markedly different results obtained according to the agents used to induce DIC.

Administration, Oral↗
PubMed2001

[A point mutation at Arg169 (CGG-->TGG) in hereditary protein C deficiency].

We investigated a 56-year-old Japanese man with protein C deficiency, who was referred to our hospital because of venous sinus thrombosis and pulmonary thromboembolism. Protein C (PC) activity and the corresponding antigen level in plasma were 66% and 106% of the normal values, respectively. Both the activity and antigen levels of protein C were reduced by approximately 50% in plasma from the patient's mother. All exons and their flanking intron regions were amplified by PCR from genomic DNA. Sequencing analysis of the PCR fragments revealed that the patient was heterozygous for a C to T substitution at nucleotide position 6218, resulting in a single amino acid substitution of arginine (CGG) by tryptophan (TGG) at codon 169 of the heavy chain. We analyzed the patient, his mother, and normal controls by a Sac II digestion study of exon 7 and found that the patient and his mother had the same C to T point mutation at base 6218. This mutation could have been responsible for the defective activation of the molecule and the resulting thrombotic disorder. The patient is now being treated with warfarin, and so far no further clinical thrombotic episode has occurred.

DNA Mutational Analysis↗
PubMed2001

Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse transcriptase messenger RNA in pancreatic juice with sample qualification.

PURPOSE: We evaluated the diagnostic efficacy of detection of human telomerase reverse transcriptase (hTERT) message, a catalytic domain of human telomerase, in endoscopic retrograde pancreatography (ERP)-derived pancreatic juice. EXPERIMENTAL DESIGN: Both hTERT and CD25 expression were detected by reverse transcription-PCR (RT-PCR) in 17 patients with pancreatic adenocarcinoma (PC), 12 patients with chronic pancreatitis (CP), and 7 patients with no ERP abnormality (N). In the same patients, beta-actin message was semiquantified by competitive RT-PCR. K-ras codon 12 mutations were concomitantly analyzed by enriched PCR-SSCP in 11 and 7 PC and CP cases, respectively. RESULTS: Expression of hTERT was detected in 88% of PC cases and 17% of CP cases but not in the normal control (N). Alterations in K-ras were detected in 73% of PC cases and 57% of CP cases, respectively. beta-Actin mRNA was expressed in >3.0 x 10(1) copies/microl in all but two PC cases in which hTERT mRNA was not detected. CD25-positive and -negative peripheral lymphocytes were isolated from a normal volunteer using a fluorescent activating cell sorter. The hTERT message was detected in CD25-positive peripheral lymphocytes and in 18, 25, and 0% of the pancreatic juice samples from PC, CP, and N cases, respectively. All CP cases expressing hTERT message were also CD25 positive. CONCLUSIONS: These results suggest that detection of hTERT mRNA in pancreatic juice is a powerful tool to discriminate PC from CP, particularly when the samples are qualified against beta-actin mRNA levels and contaminating CD25-positive lymphocytes.

Actins↗
PubMed2000

Differential chromatin packaging of genomic imprinted regions between expressed and non-expressed alleles.

Chromosomal regions subject to genomic imprinting comprise a functional domain exhibiting parental-specific expression of genes and hence may take a unique chromatin structure. Here we have examined the chromatin packaging state of allelic sites in the Zfp127/Snrpn locus on mouse chromosome 7 and in the Igf2r locus on mouse chromosome 17 with an assay consisting of chromatin fractionation and allele-specific detection. The results showed that non-transcribed alleles of Igf2r are packaged more compactly than transcribed alleles in F(1) hybrid mice of both types of cross between C57BL/6 and MSM strains, whereas a non-imprinted gene, Sod-2, in the vicinity of Igf2r does not show such a difference. This indicates a close correlation between imprinting and the differential packaging of chromatin. On the other hand, the Zfp127/Snrpn locus showed such an allele-specific fractionation pattern only in F(1) hybrid mice of a cross but not in those of the reciprocal cross. Analysis of the congenic mice produced for this locus did not provide any difference. These results suggest that chromatin of imprinted domains in different compaction levels is affected by distinct blueprints in homologous chromosomes that are heritable through the germ line.

Alleles↗
PubMed2000

Prognostic value of alkaline phosphatase flare in patients with metastatic prostate cancer treated with endocrine therapy.

OBJECTIVES: To assess the prognostic significance of alkaline phosphatase (ALP) flare in 114 patients with metastatic prostate cancer treated with endocrine therapy. METHODS: ALP flare was defined as a transient increase of the serum ALP level to 120% or more of the pretreatment value after the initiation of endocrine therapy, followed by a subsequent decrease. RESULTS: Univariate analysis demonstrated that patients with poorly differentiated adenocarcinoma, an extent of disease of 2 or greater, a serum ALP level above twice the upper limit of normal, a serum prostate-specific antigen level greater than 100 ng/mL, an ALP flare, and a hemoglobin level of 12 g/dL or less had a significantly lower survival rate than their respective counterparts. Multivariate Cox's proportional hazards model analysis demonstrated that tumor histologic features and ALP flare were significant prognostic indicators for survival. CONCLUSIONS: The results of the present study suggest that the tumor histologic features and the ALP flare are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with endocrine therapy.

Adenocarcinoma↗
PubMed2000

Prostate specific antigen adjusted for transition zone volume: the most powerful method for detecting prostate carcinoma.

BACKGROUND: Several methods for the identification of patients with prostate carcinoma have been proposed to enhance the clinical usefulness of prostate specific antigen (PSA). However, it remains unclear which method is superior in practical use. The authors attempted prospectively to identify the most powerful method with which to detect prostate carcinoma, especially among patients with intermediate PSA levels. METHODS: Between October 1997 and August 1999, systematic sextant biopsies were performed on 281 patients, including 147 with PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA density of the transition zone (PSATZD) for the detection of prostate carcinoma were compared by using receiver operating characteristic (ROC) curves and logistic regression analyses. RESULTS: According to ROC curve analysis, PSATZD had the greatest area under the curve in the overall patient population and in patients with intermediate PSA levels. In patients with intermediate PSA levels, at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68 of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25 patients, respectively. Stepwise logistic regression analysis showed that PSATZD and findings on digital rectal examination were significant independent predictors. CONCLUSIONS: PSATZD had the most useful validity in the differentiation between prostate carcinoma and benign prostatic enlargement in the overall patient population and in patients with intermediate PSA levels.

Aged↗
PubMed2000

Surface antigen, SpaA, of erysipelothrix rhusiopathiae binds to Gram-positive bacterial cell surfaces.

In a previous study, we isolated the spaA gene encoding the surface protective antigen A, SpaA, of Erysipelothrix rhusiopathiae, and found that the N-terminal region of SpaA was responsible for protective immunity against erysipelas and that the C-terminal region contained eight repeat units consisting of 20 amino acids comprising the binding domain on the Erysipelothrix cell surface. In this study, using recombinant SpaA proteins, we showed that the repeat region bound to the cell surfaces of various Gram-positive bacterial cells, SpaA was a membrane-associated protein, this association depended on the interaction with choline residues in teichoic acid, and SpaA bound to lipoteichoic acid (LTA) of Bacillus subtilis and Staphylococcus aureus. These results showed that LTA was required for the surface association of SpaA in E. rhusiopathiae and that such an association might be common among Gram-positive bacterial cells. We suggested that an LTA-SpaA complex might have an important role in the E. rhusiopathiae infection process.

Antigens, Bacterial↗
PubMed2000

Developmental changes in mitochondrial activity and energy metabolism in fetal and neonatal rat brain.

Experiments were undertaken to investigate mitochondrial activity and energy metabolism in the developing rat brain from the late fetal stage to the neonatal stage. Samples of cerebral cortical tissue were obtained from fetuses at 14, 16, 18, and 20 days of gestation, and from pups at 1 h, 1 day and 7 days after birth. Mitochondrial respiration was measured polarographically using homogenates. Fetal and neonatal brains were frozen in situ and fluorometric enzymatic techniques were used for the analysis of ATP, ADP, AMP, and lactate. In the fetal brain, there was a gradual increase in stimulated (+ADP) and uncoupled respiratory rates using glutamate and malate as substrates, from 14 days to 20 days of gestation, together with a moderate increase in ATP concentration and in the sum total of adenine nucleotides, and a significant decrease in lactate. Since non-stimulated (-ADP) respiratory rates did not change with increasing gestational age, the respiratory control ratio appeared to increase over the same period. An increase in mitochondrial activity was more pronounced immediately after birth, together with a marked increase in ATP concentration and in the sum total of adenine nucleotides. The highest rate of mitochondrial respiration was observed in 1-hour-old pups. These results indicate that, in the rat brain, there is maturation of oxidative metabolism in mitochondria that is initiated in late gestation. Acceleration in mitochondrial respiration occurs immediately after birth in order to maintain high-energy phosphate levels, and this may be crucial for the successful outcome of the newborn.

Adenosine Diphosphate↗
PubMed2000

Analysis of cytokine production in the colon of nude mice with experimental colitis induced by adoptive transfer of immunocompetent cells from mice infected with a murine retrovirus.

LP-BM5 murine leukemia virus (MuLV) is known to induce murine AIDS (MAIDS). We have shown that Sjögren's syndrome (SjS)-like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of spleen cells from MAIDS mice can induce inflammatory bowel disease-like colitis as well as SjS-like exocrinopathy in nude mice. To assess the role of interferon (IFN)-gamma and interleukin (IL)-10 in the pathogenesis of our experimental model, we tried to identify the cells producing these cytokines and their localization in the colitis lesions in situ. Expression of mRNA for IFN-gamma and IL-10 was assessed by RT-PCR, and protein expression of these cytokines was also analyzed in frozen sections of colon by double-color-staining immunofluorescence (IF). An increase of IFN-gamma and IL-10 mRNA was detected in the colon of mice with colitis, but not in that of control mice. Double-color IF showed that Mac-1(+) cells were positive for IFN-gamma or IL-10 and that most CD4(+) T cells were positive for IL-10, although the population of IFN-gamma-positive CD4(+) T cells was low. In our experimental colitis model, Mac-1(+) macrophages that produce both IFN-gamma and IL-10 might play a crucial role in the pathogenesis of colitis in combination with CD4(+) T cells.

Adoptive Transfer↗
PubMed2000

First presentation of polymyositis postpartum following intrauterine fetal death.

We present a case of polymyositis (PM) following intrauterine fetal death. The first presentation of PM in the patient was during postpartum. The patient was referred to our hospital because of a fever of unknown cause 13 d after delivery of dead fetus at 32 weeks' gestation. PM was diagnosed based on the increased serum creatine phosphokinase level, typical electromyogram findings and characteristic muscle biopsy findings.

Adult↗
PubMed2000

Severity of hyperemesis gravidarum correlates with serum levels of reverse T3.

To investigate the possible physiological relevance of extra-thyroidal production of reverse T3 (rT3) in hyperemesis gravidarum, measurements of serum rT3, free T3 (FT3), free T4, (FT4), and nonesterified fatty acids (NEFA) were correlated with weight loss of hyperemetic women. All the thyroid hormones, NEFAs and weight loss were significantly higher in hyperemesis gravidarum than in control subjects, and also higher than in those with milder symptoms of morning sickness (p < 0.05). Elevations of FT3, FT4 and NEFAs correlated with the extent of weight loss, the latter taken as the index of the severity of hyperemesis gravidarum (p < 0.05). Only rT3 correlated with both weight loss and the rate of lipolysis, as reflected by elevations of NEFAs (p < 0.05). The data are consistent with a shift from T3 to rT3 as products of 5'-monodeiodination of thyroxine in hyperemesis gravidarum. Because reverse T3 is physiologically inactive a control mechanism may be postulated wherein T3 production is minimized, thereby reducing weight loss and lipolysis in patients with hyperemesis gravidarum.

Fatty Acids, Nonesterified↗
PubMed2000

Plasma fucosyltransferase activity in patients with hepatocellular carcinoma, with special reference to correlation with fucosylated species of alpha-fetoprotein.

BACKGROUND/AIMS: Our previous results showed that the percentage of fucosylated species of alpha-fetoprotein (AFP) in total AFP, fucosylation index, was a very useful diagnostic tool to distinguish AFP due to hepatocellular carcinoma from AFP due to non-neoplastic liver diseases. On the other hand, alpha1-6 fucosyl-transferase (alphaFT) catalyzes the addition of fucose from GDP-fucose through an alpha1-6 linkage to the reducing end of N-acetylglucosamine residue of N-linked oligosaccharides of glycoproteins. However, the biological and clinical significance of alphaFT in patients with hepatocellular carcinoma is not fully understood. In the present study, we measured alphaFT activity to elucidate the enzymatic background of fucosylated species of AFP in hepatocellular carcinoma. METHODS: Plasma samples from 84 cases of hepatocellular carcinoma, 40 of liver cirrhosis, 40 of chronic hepatitis and 30 of normal controls, and 26 paired samples of hepatocellular carcinoma and surrounding noncancerous tissues were enrolled in the present study. AlphaFT activity was measured by high performance liquid chromatography with a synthesized fluorescence-labeled glycopeptide with an asialoagalactobiantennary sugar chain as a substrate in the presence of GDP-fucose. RESULTS: Plasma alphaFT activities (mean+/-SD, pmol/ml/h) in patients with hepatocellular carcinoma, liver cirrhosis, chronic hepatitis and normal controls were 435+/-271, 490+/-290, 590+/-209 and 380+/-133, respectively. AlphaFT levels in hepatocellular carcinoma and chronic liver diseases were increased compared with that in normal controls. A statistically significant positive correlation was observed between plasma alphaFT activity and fucosylation index of AFP (r=0.34, p= 0.0032) in 60 patients with hepatocellular carcinoma, in which increments of serum AFP were observed. When the tentative cutoff value of fucosylation index was set at 18%, which corresponded to the cutoff value to discriminate between hepatocellular carcinoma and non-neoplastic liver diseases in our previous study, the plasma alphaFT activity in hepatocellular carcinoma patients whose fucosylation index was more than 18% (n=32, 523+/-324 pmol/ml/h) was higher than that in hepatocellular carcinoma patients whose fucosylation index was equal to or less than 18% (n=28, 383+/-229) (p=0.055). An increment of the plasma levels of alphaFT occurred in accordance with an advancement of hepatocellular carcinoma stages. Tissue aFT activity in hepatocellular carcinoma (175+/-178 pmol/mg/h) was higher than those in surrounding noncancerous liver (144+/-134) and in normal liver (79+/-19). The mean alphaFT activities in well-, moderately- and poorly-differentiated hepatocellular carcinoma were 38+/-0.7, 177+/-182 and 219+/-189, respectively, and they tended to increase with dedifferentiation in hepatocellular carcinoma tissues. CONCLUSIONS: The present study indicates that alphaFT is responsible for the formation of the fucosylated species of AFP in hepatocellular carcinoma and suggests that the measurement of alphaFT provides a possible aid in the evaluation of the degree of advancement in patients with hepatocellular carcinoma.

Aged↗
PubMed2000

Urinary steroid profile in adrenocortical tumors.

Determination of the urinary steroid profile has been proposed as a sensitive tool for diagnosing adrenocortical tumors. The urinary steroid profiles were determined for patients with adrenocortical tumors. Urinary steroids were extracted, derivatized to form methyloxime-trimethylsilyl ether and analyzed by gas chromatography/mass spectrometry. Patients with adrenal adenomas from primary hyperaldosteronism had increased metabolites of 18-hydroxycorticosterone and aldosterone, and those with Cushing's syndrome had elevated excretion of 11 -deoxycortisol, cortisol, 18-hydroxycortisol, and cortisone metabolites. In patients with adrenocortical carcinomas, increased levels of metabolites of 11-deoxycortisol or 33-hydroxy-5-ene steroids were observed. The urinary steroid profiles of adrenal adenomas and adrenocortical carcinomas were quite different, suggesting the diagnostic validity for discriminating malignant from benign diseases.

Adenoma↗
PubMed2000

Detection and characterization of Shiga toxin-producing Escherichia coli from seagulls.

Shiga toxin (Stx)-producing Escherichia coli (STEC) strains isolated from a seagull in Japan were examined. A total of 50 faecal samples was collected on a harbour bank in Hokkaido, Japan, in July 1998. Two different STEC strains, whose serotypes were O136:H16 and O153:H-, were isolated from the same individual by PCR screening; both of them were confirmed by ELISA and Vero cell cytotoxicity assay to be producing active Stx2 and Stx1, respectively. They harboured large plasmids, but did not carry the haemolysin or eaeA genes of STEC O157:H7. Based on their plasmid profiles, antibiotic resistance patterns, pulsed-field gel electrophoresis analysis (PFGE), and the stx genes sequences, the isolates were different. Phylogenic analysis of the deduced Stx amino acid sequences demonstrated that the Stx toxins of seagull-origin STEC were closely associated with those of the human-origin, but not those of other animal-origin STEC. In addition, Stx2phi-K7 phage purified from O136 STEC resembled Stx2phi-II from human-origin O157:H7, and was able to convert non-toxigenic E. coli to STEC. These results suggest that birds may be one of the important carriers in terms of the distribution of STEC.

Animals↗
PubMed2000

Liver-infiltrating CD56 positive T lymphocytes in hepatitis C virus infection.

AIM: Hepatitis C virus (HCV) is a major cause of post-transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus-specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV-infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56+ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH-C). MATERIAL AND METHODS: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH-C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. RESULTS: The CD56+ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly gamma delta-TCR. There was a correlation between the ratio of CH-C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. CONCLUSION: The correlation between CD56+ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver-infiltrating CD56+ T lymphocytes play an important pathologic role in hepatocellular injury in CH-C.

Adult↗