Biomedical subjects

K Yamazaki

Publications and source records attributed to K Yamazaki.

At least 217 records · Page 12Linked to original sources

PubMed1999

cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse.

We subcloned human and mouse full-length cDNAs of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT), which was designated GFAT2 (the previously reported GFAT was named GFAT1). Both the human and the mouse GFAT2 proteins deduced from their open reading frame sequences are composed of 682 amino acids of approximately 77.0 kDa. At the amino acid level, homologies between the human GFAT1 and GFAT2, between the mouse GFAT1 and GFAT2, and between the human GFAT2 and the mouse GFAT2 were 75.6, 74.7, and 97. 2%, respectively. Northern blot analysis using probe specific to human GFAT1 or GFAT2 showed that major transcripts were approximately 3.0 kb in both the human GFAT subtypes. The analysis also revealed different tissue distribution between GFAT1 and GFAT2: GFAT1 was more highly expressed in the placenta, pancreas, and testis than GFAT2; GFAT2 was expressed throughout the central nervous system, especially in the spinal cord, but GFAT1 expression was weak. The locus was mapped to human chromosome 5q and mouse chromosome 11, where a synteny between the two species has been known. GFAT2 can provide insights into understanding the roles of the hexosamine pathway in various tissues, particularly with the development of glucose toxicity and diabetes complications.

Amino Acid Sequence↗

PubMed1999

Odortypes: their origin and composition.

Odors that distinguish one individual from another member of the species and are determined by polymorphic genes are called odortypes. Odortypes and their considerable societal significance have been studied intimately only in mice and mainly with respect to the genes of the major histocompatibility complex. Further understanding and the matter of human relevance have been hampered by the apparent restriction of odortype expression to urine. The present finding that odorants comprising prerenal odortypes are already present in blood, albeit in masked form, affords the basis of a comprehensive view of odortypes. Accordingly, major histocompatibility complex and other polymorphic genes of antiquity are seen inter alia as agents of normal variation, which entails quantitative variation in output of odorant metabolites. Relatively few such normal variations should suffice for a vast range of compound odors whose specificity is determined by combinative assortment of the same set of individual volatile compounds.

Animals↗

PubMed1999

Increase in oxidized NO products and reduction in oxidized glutathione in cerebrospinal fluid from patients with sporadic form of amyotrophic lateral sclerosis.

To determine the role of free radical mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS), cerebrospinal fluid concentrations of oxidized nitric oxide (NO) products (nitrite and nitrate) and reduced and oxidized forms of glutathione (GSH and GSSG, respectively) were compared between patients with the sporadic form of ALS (SALS) and controls. In the SALS patients, the nitrate levels were significantly higher (by 73%) in contrast to remarkably lower GSSG/GSH ratio, approximately 3-fold, compared to controls. These results suggest that NO production or oxidation is activated in SALS patients, leading to a decrease in superoxide radicals to oxidize GSH. The subsequent generation of a highly reactive anion, peroxynitrite, may play a causal role in the pathogenesis of SALS.

Aged↗

PubMed1999

Remarkable increase in cerebrospinal fluid 3-nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis.

To investigate the significance of peroxynitrite-mediated oxidative damage in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), the concentrations of 3-nitrotyrosine and tyrosine in the cerebrospinal fluid (CSF) of patients with SALS were determined. The concentration of 3-nitrotyrosine and the 3-nitrotyrosine/ tyrosine ratio in patients with SALS were approximately seven times those of controls. Thus, the present findings in living patients provide in vivo evidence for a possible role of peroxynitrite, a mediator of oxidative stress, and increased nitration of tyrosine residues in the pathogenesis of SALS.

Adult↗

PubMed1999

Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis.

Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), especially in its early stages. Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients with PBC. It remains unknown, however, whether eosinophils in PBC patients are functionally activated and whether UDCA inhibits eosinophil activation. In the present study, we systematically examined eosinophil dynamics in the blood and liver in patients with stage I to II PBC before and after UDCA treatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radioimmunoassay and quantitated eosinophil degranulation using computer-assisted morphometry after MBP immunohistochemistry. Before UDCA treatment, patients with PBC (n = 25) showed significantly higher circulating eosinophil counts (P <. 05) and serum concentrations of MBP (P <.0005) and EDN (P <.02) compared with patients with chronic viral hepatitis (n = 22), autoimmune hepatitis (n = 10), and obstructive jaundice (n = 12). Four-week UDCA treatment significantly reduced blood eosinophil counts (P <.0001) and serum MBP (P <.0001) and EDN (P <.0001) levels in PBC patients. MBP immunohistochemistry and computer-assisted quantitative morphometry showed infiltration and degranulation of eosinophils in the portal tract in patients with PBC and significant reductions in the number of sites and the area occupied by extracellular MBP deposits after UDCA treatment for 2 years (P <.02) but not in placebo-treated patients. Our results suggest that eosinophils in patients with PBC are not only increased in number, but also release granule proteins, and that UDCA treatment inhibits this eosinophil activation/degranulation.

Blood Proteins↗

PubMed1999

Calcaneus bone mineral density using single x-ray absorptiometry in Japanese women.

Calcaneus bone mineral density (BMD) of 738 Japanese women (605 healthy and 133 with osteoporosis) was measured using single X-ray absorptiometry (SXA). A reference range of calcaneus BMD values for healthy Japanese women was established and the usefulness of this method for screening and diagnosis of osteoporosis was evaluated. There was no significant age change of calcaneus BMD prior to menopause, though values decreased significantly thereafter. BMD loss ratio was 1.7%/year in the 10 years after menopause. The reference range of calcaneus BMD was 410 +/- 43 mg/cm(2), calculated from the mean BMD value of subjects whose ages ranged from 25 to 50 years old. The fracture threshold for the spine was established as 294 mg/cm(2), which corresponded to -2.67 SD from the average BMD of the young healthy women, and the odds ratio for spine fracture in the subjects with BMD lower than this threshold was 3.52 [95% CI (confidence interval) 1.34-9.26]. The spine fracture group showed statistically lower calcaneus BMD than the nonfracture group when subjects with adjusted age and body size were analyzed. There were no significant differences in the ROC analysis for spine fracture between calcaneus BMD and spine BMD. Therefore, calcaneus BMD is not readily affected by degenerative change or soft tissue, and the annual decrement rate (1.7%/year) can be detected easily and with low precision error (0.8%). These indices may prove useful for the screening and diagnosis of osteoporosis.

Absorptiometry, Photon↗

PubMed1999

An epidemic of acute haemorrhagic conjunctivitis caused by enterovirus 70 in Okinawa, Japan, in 1994.

BACKGROUND: Although enterovirus 70 (EV70) has been identified as the major aetiological agent of acute haemorrhagic conjunctivities (ACH),no EV70 strain has been isolated by cell culture method since 1988. Therefore, recent clinical and epidemiological characteristics of AHC caused by EV70 have not been clarified. METHODS: Clinical and serological studies were carried out on patients during the AHC epidemic in Okinawa, Japan, in 1994 in which 7509 cases were reported by national epidemiological surveillance. EV70 was confirmed as the causative agent by reverse-transcription polymerase chain reaction. RESULTS: The 11-15 years age group contained the highest number of cases (62% of the total). Conjunctival hyperaemia was present in all patients, and subconjunctival haemorrhage, superficial punctate keratitis and preauricular lymphadenopathy were present in 24.0%, 11.7% and 9.3% of AHC cases, respectively. No neurological complication was observed in this epidemic. Out of 31 paired serum samples, 10 pairs showed a fourfold rise in antibody level to EV70. None of the paired serum samples showed a fourfold rise in antibody level to Coxsackie A24 variant virus. CONCLUSION: These findings demonstrate that the clinical features of AHC observed in this study were milder than those reported previously, in contrast to the high transmission rate during an epidemic. Changes in clinical features of AHC, such as a low incidence of subconjunctival haemorrhage and disappearance of neurological complications, might be due to biological transformation of EV70. It should be noted that EV70 is still an important aetiological agent of explosive epidemics of AHC.

Adolescent↗

PubMed1999

Evaluation of magnetic resonance angiography in detection of gastric varices.

We evaluated the detection of gastric varices, inflowing blood vessels to gastric varices, and outflowing blood vessels from gastric varices via magnetic resonance (MR) angiography in 31 patients with gastric varices. Twenty-four patients had F2 type varices and 7 had F3 type, classified according to the Japanese Research Society for Portal Hypertension. Seventeen patients had cardiofornical varices, and 14 had fundal varices. All patients were examined with an MR system operating at 1.5T. MR angiography was performed using the two-dimensional time-of-flight method. With MR angiography, the imaging of gastric varices was clearly delineated in 28 of the 31 patients (90.3%). From the images of MR angiography, flow direction itself cannot be determined. The outflowing blood vessels of gastric varices were reported to be the gastro-renal shunt and the subphrenic vein, and angiographic findings have shown the inflowing blood vessels to be the left gastric vein (LGV), the short gastric vein (SGV), and the posterior gastric vein (PGV). In 25 of the 31 patients (80.7%), the outflowing blood vessels from gastric varices were detected (gastro-renal shunt in 24; subphrenic vein in 1). MR angiography provided clear images of the inflowing blood vessels to gastric varices in 18 of the 31 patients (58.1%). These inflowing vessels were categorized as SGV in 7 patients, LGV in 5, LGV and SGV in 4, and LGV and PGV in 2. We suggest that MR angiography be used as a routine method for detecting and diagnosing collateral veins in patients with gastric varices.

Adult↗

PubMed1999

Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia.

HMG-CoA reductase inhibitors reduce serum total cholesterol concentrations and the risk of coronary heart disease in patients with hypercholesterolemia. Recently, it has been reported that patients with combined hyperlipidemia are also at risk of coronary heart disease. However, HMG-CoA reductase inhibitor therapy alone does not sufficiently reduce serum triglyceride concentrations. Epidemiological and clinical evidence has shown that fish oil can lower plasma lipid levels, especially triglycerides. Consequently, we investigated the effects of the combination of HMG-CoA reductase inhibitors and eicosapentaenoic acid, a major component of fish oil, on hyperlipidemia. We administered 900-1,800 mg/day of the ethyl ester of eicosapentaenoic acid to patients with hyperlipidemia who had been treated with HMG-CoA reductase inhibitors for 30 +/- 6 months (means +/- SE). Serum total cholesterol and triglyceride concentrations were significantly decreased 3 months after the administration of eicosapentaenoic acid (from 5.63 +/- 0.23 mmol/l to 5.02 +/- 0.20 mmol/l, P < 0.05; from 2.07 +/- 0.41 mmol/l to 1.08 +/- 0.17 mmol/l, P < 0.01, respectively). Serum high-density lipoprotein-cholesterol concentrations were significantly increased after the treatment (from 1.23 +/- 0.12 mmol/l to 1.34 +/- 0.13 mmol/l, P < 0.05). Plasma eicosapentaenoic acid concentrations and the ratio to arachidonic acid in plasma were also significantly increased 3 months after the treatment (from 101.9 +/- 8.1 mg/l to 181.8 +/- 23.9 mg/l, P < 0.001; from 0.640 +/- 0.075 to 1.211 +/- 0.170, P < 0.001, respectively). These results suggested that the combination therapy of HMG-CoA reductase inhibitors and eicosapentaenoic acid was effective for patients with hyperlipidemia.

Aged↗

PubMed1999

A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997-1998 season in Tokyo.

We analyzed the hemagglutinin (HA) genes of influenza A viruses consisting of 6 strains isolated from cerebrospinal fluids of patients with encephalopathy and 3 isolates from throat washes of patients without central nervous system symptoms during the 1997-1998 season in Tokyo. Aligned 9 amino acid sequences showed 7 common substitutions compared with A/Wuhan/359/95 (vaccine strain used in the season in Japan), which were allocated to three different antigenic sites on the H3 HA molecule. It is noted that a novel substitution at the receptor-binding site (Tyr-137 to Phe) was found exclusively in the isolates from the patients with encephalopathy.

Amino Acid Sequence↗

PubMed1999

Distribution of parathyroid hormone-related protein (PTHrP) and type I parathyroid hormone (PTH) PTHrP receptor in developing mouse mandibular condylar cartilage.

The mandibular condylar cartilage undergoes endochondral bone formation and is an important growth site in the mandible. Parathyroid hormone-related protein (PTHrP) has received attention as a physiological regulator attenuating chondrocytic differentiation and preventing apoptotic cell death. In order to examine the localization of PTHrP and its receptor during fetal development of the condylar cartilage, an immunohistochemical study of PTHrP and the type I PTH/PTHrP receptor was carried out. At day 15 of gestation, the condylar cartilage was evident and some chondrocytes showed positive staining for PTHrP. At day 16, the cartilage was increasing in length and width, and PTHrP was localized in the flattened and hypertrophic cell layers. After day 17, when endochondral bone formation had already started, PTHrP was mainly observed in the flattened cell layer and in a few layers of the hypertrophic chondrocytes. The localization of the type I PTH/PTHrP receptor was similar to that of PTHrP on days 15 and 16, and was broadly distributed at day 18. Apoptotic chondrocytes were scarcely observed on days 15 and 16, and only a few cells were present in the erosion front at day 18. This temporal and spatial localization of PTHrP and the type I PTH/PTHrP receptor suggests that PTHrP is a possible autocrine/ paracrine factor regulating condylar chondrocytic differentiation during development.

Animals↗

PubMed1999

T-cell antigen specificity in humans following stimulation with Porphyromonas gingivalis.

The effects of Porphyromonas gingivalis stimulation on T-cell clonality and cytokine mRNA expression in peripheral blood mononuclear cells from individuals with gingivitis and periodontitis were investigated. Clonality of T cells was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and single-strand conformation polymorphism analysis. Cytokine mRNA expression was investigated by RT-PCR. Whereas unstimulated mononuclear cells did not demonstrate obvious clonality, clonal expansion was found in most Vbeta families after stimulation. However, there was no relation between clonal change and disease category or the presence of P. gingivalis infection. Messenger RNA for interferon-gamma and interleukin-13 was upregulated whereas interleukin-4 and -10 were downregulated following P. gingivalis stimulation. Interleukin-12p35 demonstrated no consistent pattern. This study supports the concept that P. gingivalis stimulates T cells in an antigen-specific fashion. It further suggests that peripheral blood T cells may preferentially produce interferon-gamma and interleukin-13 in response to P. gingivalis stimulation irrespective of disease or P. gingivalis status.

Bacteroidaceae Infections↗

PubMed1999

Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer.

We conducted a clinical trial of adoptive immunotherapy with lymph node-lymphokine-activated killer (LN-LAK) cells and recombinant interleukin 2 (rIL-2) for a surgical adjuvant therapy of pathologic stage I non-small cell lung cancer. The regimen consisted of the subcutaneous administration of low-dose rIL-2 for 6 consecutive days and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. A group of 19 patients with primary lung cancer received the immunotherapy about 2 weeks after surgery (pulmonary lobectomy). The regimen was postoperatively well tolerated by the patients. In peripheral blood lymphocytes (PBL) obtained after the treatment, the proportion of CD3+ T cells predominantly increased with the increase of CD4+ T cell subsets. On the other hand, the proportion of CD20+ B cells decreased. Both NK and LAK activity of PBL significantly increased. However, the immunomodulatory effects did not result in a prolongation of the postoperative survival time in comparison to the postoperative survival of patients (n = 21) with surgery alone during the same period. These results suggested that the treatment with low-dose LN-LAK cells and concurrent low-dose IL-2 could, therefore, neither reduce nor eradicate minimal micrometastatic diseases.

Aged↗

PubMed1999

Risk factors for vertebral fractures in renal osteodystrophy.

We determined the prevalence of vertebral fractures in hemodialysis (HD) patients, investigated whether low bone mineral density (BMD) is predictive of vertebral fracture, and evaluated the effect of serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) levels on vertebral fracture. One hundred eighty-seven male HD patients were assessed for vertebral fractures, and lumbar-spine and total-body BMD were measured by dual-energy x-ray absorptiometory. Thirty-nine patients (20.9%) had vertebral fractures. Each standard deviation (SD) decrease in lumbar-spine BMD increased the age-adjusted odds ratio of vertebral fracture 2.0 times (95% confidence interval [CI], 1.4 to 2.0) and 1.6 times (95% CI, 1.1 to 1.6) for total-body BMD. The area under the receiver operating characteristic curve for lumbar-spine BMD was significantly greater than that for total-body BMD (P < 0.05). Patients with serum iPTH levels in the lowest tertile had a 2.4-fold greater risk for vertebral fracture than those in the middle tertile and a 1.6-fold greater risk than those in the highest tertile (P < 0.05). When the two criteria of lowest tertile of serum iPTH level and highest tertile of serum ALP level were combined, the prevalence of vertebral fractures was the greatest. Similarly, when the lowest tertile of serum iPTH level and lowest tertile of serum ALP level were combined, the prevalence was the second greatest among the combined groups according to tertiles of serum iPTH and ALP levels. We conclude that low lumbar-spine BMD might be a sensitive predictor of vertebral fracture in HD patients, and patients with relatively low iPTH levels would have a greater risk for vertebral fracture than those with hyperparathyroidism.

Absorptiometry, Photon↗

PubMed1999

Identification of a 21 kDa laminin-binding component of Candida albicans.

Binding of Candida albicans strain JCM0239 to radiolabelled laminin was studied to identify possible receptors. When two forms of the organism were examined, laminin was found to bind to germinating blastoconidia. There was only weak binding to blastoconidia without germ tubes. Laminin-binding to germinating blastoconidia was inhibited by non-labelled laminin or fibrinogen but not by fibronectin, a fibronectin peptide (Gly-Arg-Gly-Asp-Ser), or a laminin peptide (Tyr-Ile-Gly-Ser-Arg). A cell extract from germinating blastoconidia was analyzed by using SDS-PAGE and Western blotting, and 125I-labelled laminin was shown to bind to a 21 kDa component.

Animals↗

PubMed1999

Native heart complications after heterotopic heart transplantation: insight into the potential risk of left ventricular assist device.

BACKGROUND: In heterotopic heart transplantation, the donor heart is connected parallel to the recipient's diseased heart. Recipients continue to have risks, such as arrhythmia, thromboembolism, valvular heart disease, and ischemic heart disease which can develop in the native heart. It may serve as a clinical model to study long-term pathophysiologic processes in the native heart of patients with a left ventricular assist device. METHOD: We analyzed the prevalence of long-term complications related to the native heart in the heterotopic heart transplant and attempted to gain insight into the potential risk to a native heart after receiving a left ventricular assist device. RESULTS: Between December 1984 and December 1994, 16 patients (13 men, 3 women, ranging in age from 37 to 60 years) underwent heterotopic heart transplant at the University of Pittsburgh. The 1- and 5-year survival rate after the transplant was 81% and 44%, respectively. Actuarial freedom from complications related to the native heart after 1 year and 4 years was ventricular arrhythmia: 85%, 75%; ischemic disease: 85%, 64%; valvular disease: 100%, 88%; and thromboembolism: 85%, 58%. Of these complications, thromboembolism was not considered in determining actuarial freedom from complications because thromboembolism should be regarded as a device-related complication rather than as a native-heart-related complication for left ventricular assist device recipients. Consequently, actuarial freedom from all complications excluding thromboembolism was 70% after 1 year and 50% after 4 years. In addition, the hazard function curve remains constant up to 80 months after the operation without significant differences among the yearly ratios. CONCLUSIONS: This analysis suggests that cautious observation of the native heart's long-term performance is necessary for the left ventricular assist device recipient.

Adult↗

PubMed1999

Differential expression of costimulatory molecules in chronic inflammatory periodontal disease tissue.

Although B cell activation and subsequent immunoglobulin production are the immunopathological features of chronic inflammatory periodontal disease, in situ expression of costimulatory molecules in humoral immunity has not been investigated. In the present study we examined the expression of CD40, CD40 ligand (CD40L), CD80, CD86, CD28 and cytolytic T lymphocyte-associated antigen-4 (CTLA-4) on lymphocytes immunohistochemically. Cryostat sections were prepared from the gingival tissue samples of 14 patients with moderate to advanced adult periodontitis. In vitro kinetics of the expression of CD40L and CTLA-4 by peripheral blood T cells and that of CD80 and CD86 by peripheral blood B cells were also investigated by flow cytometry. Positive percentage expression of CD40L, CD28 and CTLA-4, and CD40, CD80 and CD86 was calculated for the number of CD3+ and CD19+ cells, respectively. Flow cytometric analysis demonstrated that the expression of CD40L and CTLA-4 on T cells, and CD80 and CD86 on B cells of peripheral blood was up-regulated upon activation. While most T cells and B cells expressed CD28, and CD80 and CD86, respectively, in gingival tissues, the expression of CD40L and CTLA-4 was lower but highly variable between specimens. Furthermore, these two molecules seemed to be expressed reciprocally in the lesion. As both CD40L and CTLA-4 expression are induced transiently by stimulation, variability in the expression of the molecules may reflect immunological activities and participation in the regulation of B cell activation of the lesion.

Abatacept↗

PubMed1999

Animal model of sclerotic skin. I: Local injections of bleomycin induce sclerotic skin mimicking scleroderma.

We have established a mouse model for scleroderma induced by repeated local injections of bleomycin (BLM). Daily injection of BLM at a dose of >10 microg per ml for 4 wk induced histologic changes of dermal sclerosis, but not fibrosis, with thickened and homogenous collagen bundles and cellular infiltrates in BALB/C mice, whereas clinical signs of scleroderma were not apparent. In addition, lung fibrosis was also induced preceding the cutaneous changes. Sclerotic changes were not found in other sites of the skin distant from the injection site. Dermal sclerosis could also be induced by injecting BLM only every other day. The sclerotic changes of the dermis were sustained after ceasing BLM applications for at least 6 wk. Mast cells gradually increased in number as the sclerotic changes developed. Marked degranulation of mast cells was observed with elevated histamine release. The amount of hydroxyproline in skin was significantly increased at 4 wk of BLM treatment as compared with that in untreated or phosphate-buffered saline-treated mice. Anti-nuclear antibody was detected in serum of BLM-treated mice. Transforming growth factor-beta1 mRNA was detected at an early phase, while transforming growth factor-beta2 mRNA was strongly expressed at 4 wk when the sclerotic features were prominent. These results suggest that dermal sclerosis induced by BLM closely resembles systemic sclerosis both histologically and biochemically. Our mouse model can provide a powerful tool of inducing dermal sclerosis to examine the pathogenesis and the therapeutic approach of scleroderma.

Animals↗