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Biomedical subjects

H Kanda

Publications and source records attributed to H Kanda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Influence of various hemodialysis membranes on the plasma (1-->3)-beta-D-glucan level.

BACKGROUND: Recently, invasive fungal infections have increased significantly because of the growing number of immunocompromised hosts. The measurement of plasma (1-->3)-beta-D-glucan has been proposed as a useful diagnostic tool for deep mycosis. In this study, we analyzed the alteration of the plasma (1-->3)-beta-D-glucan concentration by using different kinds of hemodialysis (HD) membranes in end-stage renal disease (ESRD) patients and estimated its half-life. METHODS: Twenty-seven patients with ESRD without known fungal infections (with a median age of 66 years old) were enrolled in this study. Cellulose triacetate (CTA) membrane, cellulose (Cu) membrane, and polymethyl methacrylate (PMMA) membrane were used in three consecutive initiations of HD and plasma (1-->3)-beta-D-glucan concentration was measured before and after each HD session. RESULTS: The level did not change between before and after HD when CTA and PMMA membranes were used. In contrast, the plasma (1-->3)-beta-D-glucan level increased greatly after HD using the Cu membrane (from 9.4 to 332 pg/mL in median). Hypothesizing that the plasma (1-->3)-beta-D-glucan level declines exponentially, its median half-life is estimated at 20 hours, which is not affected by hepatic or renal function. CONCLUSIONS: Because the plasma (1-->3)-beta-D-glucan level increases dramatically after HD using the Cu membrane, dialyzers with Cu membrane should be avoided for HD in patients with suspected deep mycosis. The measurement of plasma (1-->3)-beta-D-glucan is also useful for the patients with hepatic or renal failure.

Adult↗
PubMed2001

Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 18 cases.

Extraskeletal myxoid chondrosarcoma (EMCS) is an uncommon clinicopathologically well-defined tumor, but its pathogenesis and biologic behavior are poorly understood. We reviewed 18 cases of EMCS to verify clinicopathologic features and immunohistochemical profiles together with molecular detection of the tumor-specific fusion genes. The tumors were located mainly in the proximal extremities and limb girdles (72%). Two tumors arose at unusual anatomic sites: the finger and the hip joint. Nine of the 17 followed-up patients were alive and disease free, 4 were alive with recurrences and/or metastases, and 4 died of the tumor. Fifteen tumors showed typical features of EMCS, and 3 had hypercellular areas in addition to conventional EMCS areas. The tumors were variably immunoreactive for S-100 protein (50%), NSE (89%), peripherin (60%), and synaptophysin (22%). Chromogranin A and some epithelial markers (AE1/AE3, CAM5.2, and epithelial membrane antigen) were entirely negative. Frequent expressions of the neural/neuroendocrine markers suggest possible neural/neuroendocrine differentiation in at least some EMCSs, in addition to chondroid differentiation. In a reverse-transcription polymerase chain reaction (RT-PCR) assay using paraffin-embedded specimens, EWS-CHN or TAF2N-CHN fusion gene transcripts characteristic of EMCS could be detected in 15 (83%) of the 18 cases: EWS-CHN type 1 in 11 cases, EWS-CHN type 2 in 1, and TAF2N-CHN in 3. Three fusion-negative cases included 2 conventional EMCSs and 1 considered a "cellular" variant of the tumor. None of 30 other soft tissue and bone tumors with myxoid or chondroid morphology that we examined contained these fusion genes. Thus, RT-PCR detection of EWS-CHN or TAF2N-CHN fusion gene using archival paraffin-embedded tissue is a feasible and useful ancillary technique for the diagnosis of EMCS.

Adult↗
PubMed2001

Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes.

OBJECTIVE: To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy. RESEARCH DESIGN AND METHODS: Plasma tHcy levels were measured using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas. RESULTS: Plasma tHcy levels and their log-translormed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 +/- 0.7 [SE] vs. 8.7 +/- 0.3 micromol/l, P < 0.0001; log tHcy, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 micromol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy correlated with insulin sensitivity indexes (r = -0.319, P = 0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (beta = -0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHcy (beta = -0.438, R2 = 0.561, P < 0.001). CONCLUSION: Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.

Blood Glucose↗
PubMed2001

[Treatment of steroid-resistant polymyositis and dermatomyositis].

It is well known that a certain percentage of patients with polymyositis and dermatomyositis (PM/DM) is corticosteroid resistant. Established and novel approaches to steroid-resistant PM/DM are discussed in this review. Methotrexate (MTX) is a first-line treatment in the case that steroid therapy fails. Azathioprine and cyclophosphamide also fall into this category. Cyclosporine, a specific inhibitor of calcineurin, has been reported almost as effective as MTX. Tacrolimus, also a calcineurin inhibitor, and mycophenolate mofetil could be additional alternatives for the treatment. Several clinical trials have demonstrated that high-dose intravenous immunoglobulin is promising. Recently favorable data have been published using intravenous high-dose pulse cyclophosphamide or cyclosporine for the poorly prognostic interstitial pneumonitis or pulmonary fibrosis accompanied with PM/DM.

Animals↗
PubMed2000

Malignant transformation and EGFR activation of immortalized mouse liver epithelial cells caused by HBV enhancer-X from a human hepatocellular carcinoma.

We have previously observed that all human hepatocellular carcinomas (HCCs) from HBV carriers examined had the integrated X region. In this study, HBV DNA was isolated from an integration site in one HCC that had a single, very small integrated viral DNA including the X region, but it had no expression of X gene as poly(A)RNA. It was found that HBV DNA was present between alphoid repetitive sequences, and it included Enhancer and X regions, encompassing the adr sequence from 910 to 1811. Nucleotides for 8 amino acids at the 3' end, a stop codon of X gene and a poly(A) signal downstream of X gene were lost by integration, and nucleotides for 7 amino acids and a stop codon were substituted by a connected alphoid sequence. When this cloned HBV DNA was transfected with an expression vector to an immortalized mouse liver epithelial cell line, MLE-10, malignant transformation occurred. Transformants having expressed poly(A)RNA of the X gene showed anchorage-independent growth in soft agar and tumor formation in the subcutis of nude mice. The mRNA level of EGFR was found to be remarkably enhanced in X-transformed cells, in contrast with the absence of this mRNA in parental and ras-transformed MLE-10. Our data provide evidence that the Enhancer-X region alone is the key contributor to the malignant change of pre-malignant liver cells in HBV carriers through activation of some specific genes, such as EGFR.

Amino Acid Sequence↗
PubMed2000

A genetic linkage map of the MSM Japanese wild mouse strain with restriction landmark genomic scanning (RLGS).

A high-resolution genetic map of the Mus musculus molossinus (MSM) Japanese wild mouse strain was constructed with restriction landmark genomic scanning (RLGS) and compared with that of the laboratory strain C3H. MSM is phylogenetically 1 million years apart from common laboratory mouse strains and is distinctly resistant to chemical carcinogenesis. Since it exhibits frequent genetic polymorphisms with laboratory mice but can still be easily crossed with laboratory strains, hybrids between MSM and carcinogen-sensitive laboratory mouse strains provide excellent materials for analysis of modifier genes and genetic changes during carcinogenesis. We have generated MSM backcross progeny with the C3H strain, which is extremely sensitive to hepatocarcinogenesis, to construct the present map. RLGS profiles with two combinations of restriction enzymes (NotI-PvuII-PstI, NotI-PstI-PvuII) yielded more than 2000 spots each. The polymorphism rate was about 39.2%, and of a total of 1732 polymorphic spot loci identified, 1371 could be assigned to specific chromosomes by comparison with 79 microsatellite marker loci. Thus, 1450 loci, on all chromosomes except for Y, effectively mapped 90% of the genome (1431.7 cM length). Although some spots might be derived from the same NotI site, each NotI site potentially generating two fragments, the presence of at least 515 loci groups with different progeny distribution patterns dispersed through the genome with an average spacing of 3 cM, means that this genetic map should be useful for analysis of various biological phenomena, including carcinogenesis and ontogenesis, at the gene level.

Animals↗
PubMed2000

A nuclear complex containing PPARalpha/RXRalpha is markedly downregulated in the hypertrophied rat left ventricular myocardium with normal systolic function.

The expression of genes encoding fatty acid utilization enzymes is coordinately downregulated during the development of cardiac hypertrophy and failure. However, molecular mechanisms that mediate this downregulation are unknown. Peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) have been identified in promoters of many genes involved in fatty acid utilization, where they function as positive regulatory elements. PPARs bind to PPREs as heterodimers with retinoid X receptors (RXRs). Primary cardiac myocytes from neonatal rats were transfected with a reporter construct driven by the C promoter of rat acyl-coenzyme A synthetase (ACS) gene. Stimulation with phenylephrine, a potent inducer of hypertrophy, markedly downregulated the activity of this promoter. By use of electrophoretic mobility-shift assays (EMSAs) using PPRE in the rat ACS promoter as a probe, we found a sequence-specific protein-DNA complex in the nuclear extract from adult rat left ventricular (LV) myocardium. Supershift experiments revealed that this complex was immunoreactive for PPARalpha and RXRalpha. We compared the activity of this complex in LV nuclear extracts from Dahl salt-sensitive rats (DSs) with hypertension and control age-matched Dahl salt-resistant rats (DRs). Even at the stage of concentric LV hypertrophy with normal systolic function, the activity of the band was markedly diminished in DSs compared with DRs. However, immunoblot analyses showed no difference in LV expression levels of PPARalpha or RXRalpha between DSs and DRs. These findings indicate that a nuclear complex of PPARalpha/RXRalpha is present in adult rat LV and is markedly downregulated in the hypertrophied LV from DS rats, which may account for the loss of transcriptional activation. The downregulation of this complex precedes LV systolic dysfunction and is mediated at the posttranslational levels.

Analysis of Variance↗
PubMed2000

Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects.

Oxidized low density lipoprotein (oxLDL) has been implicated in the pathogenesis of atherosclerosis. Recent studies have shown that immunization of animals with oxLDL results in suppression of atherogenesis. Antibody against oxLDL (oxLDL Ab) is detectable in human sera, although its biological significance is not well established. We examined the relationship between oxLDL Ab titer and circulating oxLDL level in 130 healthy Japanese subjects. OxLDL was measured as apolipoprotein (apo) B-containing lipoproteins carrying oxidized phosphatidylcholines by a sensitive ELISA. IgG class oxLDL Ab titer was measured by ELISA. Plasma oxLDL concentration was very low and it corresponded on average to one to two out of 1000 apoB-containing lipoproteins in plasma. Plasma oxLDL correlated positively with LDL cholesterol and inversely with oxLDL Ab titer. These associations remained significant and independent in multiple regression analysis including age, gender, smoking, and high-density lipoprotein cholesterol. These data indicate that healthy subjects have a very low concentration of oxLDL in the circulation, and that oxLDL Ab titer is in an inverse relationship with plasma oxLDL concentration in this population. Although these results suggest that oxLDL Ab may play a role in maintaining the low level of plasma oxLDL, its role in atherogenesis awaits further studies.

Adult↗
PubMed2000

Spontaneously regressed Kaposi's sarcoma and human herpesvirus 8 infection in a human immunodeficiency virus-negative patient.

Kaposi's sarcoma occurring in a 78-year-old woman, with the absence of the human immunodeficiency virus infection, was correctly diagnosed by immunohistochemistry using anti-human herpesvirus 8 (HHV8) antibody (PA1-73N) for the first time. The patient suffered from chronic respiratory failure and was treated with a low dose of steroids for 2.5 years. After her medication dosage was increased for the exacerbation of the respiratory failure, multiple skin tumors in her feet and legs suddenly developed. Histopathologically, skin tumors were suspected as Kaposi's sarcoma at the first biopsy and reactive angiomatosis at the second biopsy. Polymerase chain reaction and immunohistochemistry, however, revealed the presence of HHV8 DNA fragment and positive staining in the majority of spindle cells in the skin tumors. Serological examination confirmed the positivity of anti-HHV8 antibodies. HHV8 infection and steroid-induced immunosuppression, as well as environmental factors played a role in the development of Kaposi's sarcoma in this patient, because she was born in Okinawa, which is a well-known endemic area of Kaposi's sarcoma in Japan. As her general condition improved, the skin lesions regressed without any specific treatment, and disappeared completely 8 months later, in which regression may be associated with evidence of numerous CD8 cell infiltration in the second biopsy tissues. No recurrence was observed during the following 6 month follow up.

Aged↗
PubMed2000

Impaired collagen gel contraction with cultured skin fibroblasts from patients with systemic sclerosis.

We investigated the capacity of skin fibroblasts, derived from 9 patients with systemic sclerosis (SSc), to contract collagen lattices in a three-dimensional culture system. In comparison with control fibroblasts (N = 8), more than 30% of SSc fibroblasts exhibited markedly impaired ability to contract collagen lattices. The expression of alpha2beta1 integrins and integrin-mediated signals were not significantly different between normal and SSc fibroblasts. Although the underlying mechanisms remain to be determined, our present data provide evidence that certain aspects of interaction with collagen are impaired in SSc fibroblasts.

Adolescent↗
PubMed2000

Quantitative analysis of fushi tarazu factor 1 homolog messenger ribonucleic acids in the pituitary of salmon at different prespawning stages.

Steroidogenic factor 1 (SF-1) or Ad4BP is a member of the fushi tarazu factor 1 (FTZ-F1) family and an orphan nuclear receptor that plays an important role in the hypothalamus-pituitary-gonadal axis and the adrenal cortex. Although its critical role in the differentiation of adrenals, gonads, and pituitary gonadotropes has been well demonstrated, regulatory function of SF-1 during sexual maturation is yet to be examined. To investigate the potential role of SF-1 in sexual maturation, expression of two salmon FTZ-F1 homolog genes, sFF1-I and sFF1-II, was examined in the pituitaries of chum and sockeye salmons, using specific and sensitive RNase protection assays. Only sFF1-I mRNA was found in the pituitary and other organs, such as the ovary, spleen, liver, brain, and skeletal muscle. In chum salmon during upstream migration from the bay to the hatchery, the level of sFF1-I mRNA in the male fish was increased on the midway in the river, where the levels of gonadotropin alpha- and II beta-subunit mRNAs were increased. In maturing sockeye salmon, the expression of the sFF1-I gene was elevated in the mature male fish, but the administration of GnRH analog did not further enhance the expression. These results indicate that sFF1-I gene expression in the pituitary is upregulated in maturing salmon, and this upregulation may not depend on GnRH.

Animals↗
PubMed2000

[Cyclophosphamide-induced renal pelvic tumor--a case report].

We report a case of transitional cell carcinoma in the left renal pelvis, which occurred in a 24-year-old man. He had been treated with cyclophosphamide (CPM) for a period of 27 months for retroperitoneal rhabdomyosarcoma diagnosed at the age of 10. At first 1.2 g CPM had been given twice intravenously for 3 months, followed by oral administration of 41 g CPM for 23 months. Drip infusion pyelography revealed a filling defect in the left renal pelvis. A left renal pelvic tumor was strongly suspected on computerized tomography and magnetic resonance imaging. Left nephroureterectomy was then performed. Histological diagnosis of the left renal pelvic tumor was transitional cell carcinoma, grade 2, pT1N0M0. No recurrence was defected 17 months later. This case seems to be the second case of cyclophosphamide-induced upper urothelial carcinoma reported in Japan.

Adult↗
PubMed1999

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104.

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.

Heptanoic Acids↗
PubMed1999

Antitumor mechanisms and metabolism of the novel antitumor nucleoside analogues, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil.

The antitumor ribonucleoside analogues 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd), first synthesized in 1995, have strong antitumor activity against human cancer xenografts without severe side effects. Here, we studied the antitumor mechanisms of ECyd and EUrd using mouse mammary tumor FM3A cells in vitro and the mechanism of selective cytotoxicity of ECyd using human tumor xenografts in nude rats in vivo. In FM3A cells, ECyd and EUrd were rapidly phosphorylated to ECyd 5'-triphosphate (ECTP) and EUrd 5'-triphosphate (EUTP), which strongly inhibiting RNA synthesis. Cells treated with EUrd were later found to contain both EUTP and ECTP, and ECTP accumulated as the final product. Probably the uracil moieties of EUrd derivatives were efficiently converted to cytosine moieties in the cells. EUrd and its derivatives were minor metabolites in the cells treated with ECyd, so cytidine forms probably were not converted to uridine forms at the nucleoside or nucleotide stage. The ultimate metabolite of ECyd and EUrd, ECTP, is stable in cultured cells with a half-life of at least 3 days, so ECyd and EUrd are on a "closed" metabolic pathway to ECTP. These characteristics of ECyd and EUrd may be important for their antitumor activity. ECyd had strong and selective antitumor activity against the human tumor xenografts. ECyd-phosphorylating activity (uridine/cytidine kinase) in the xenografts was higher than that in the organs of the rats. This finding may account for the strong activity with mild side effects. ECyd and EUrd may be a new kind of antitumor nucleoside analogue for clinical use.

Animals↗