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Biomedical subjects

S Yamazaki

Publications and source records attributed to S Yamazaki.

At least 37 records · Page 2Linked to original sources

Association of the HLA-DRB1 gene locus with gastric adenocarcinoma in Japan.

BACKGROUND AND AIM: Helicobacter pylori infection is associated with gastric adenocarcinoma, however, the odds ratio is relatively low. The aim of the present study was to investigate host genetic factors that increase the risk of gastric adenocarcinoma among H. pylori-infected individuals. METHODS: A total of 70 patients with early gastric adenocarcinoma and 121 unrelated healthy controls were examined for H. pylori infection and HLA-DRB1 genotyping. The frequencies of HLA-DRB1 alleles were compared among groups. RESULTS: The allele frequency of DRB1*04051 was significantly higher in patients with gastric adenocarcinoma (17.9%) than in controls (7.9%) (P(correct) = 0.045). The odds ratio of gastric adenocarcinoma associated with the presence of the HLA-DRB1*04051 allele compared with its absence was 2.55 (95% confidence limits, 1.35-4.83). This genetic risk was not associated with H. pylori infection. There was no significant difference in the HLA-DRB1 allele frequency between H. pylori-positive and H. pylori-negative controls. The frequency of genotypes that possessed the DRB1*04051 allele in gastric adenocarcinoma patients (34.3%) was significantly higher than that in H. pylori-negative controls (11.9%) (p = 0.0089) and H. pylori-positive controls (15.2%) (p = 0.0066). CONCLUSION: These findings suggest that immunogenetic factors for susceptibility to gastric adenocarcinoma are present in the host, the HLA-DRB1*04051 allele is a host genetic risk factor for gastric adenocarcinoma, and that this genetic risk is independent of H. pylori infection.

Adenocarcinoma↗

Is the food-entrainable circadian oscillator in the digestive system?

Food-anticipatory activity (FAA) is the increase in locomotion and core body temperature that precedes a daily scheduled meal. It is driven by a circadian oscillator but is independent of the suprachiasmatic nuclei. Recent results that reveal meal-entrained clock gene expression in rat and mouse peripheral organs raise the intriguing possibility that the digestive system is the site of the feeding-entrained oscillator (FEO) that underlies FAA. We tested this possibility by comparing FAA and Per1 rhythmicity in the digestive system of the Per1-luciferase transgenic rat. First, rats were entrained to daytime restricted feeding (RF, 10 days), then fed ad libitum (AL, 10 days), then food deprived (FD, 2 days). As expected FAA was evident during RF and disappeared during subsequent AL feeding, but returned at the correct phase during deprivation. The phase of Per1 in liver, stomach and colon shifted from a nocturnal to a diurnal peak during RF, but shifted back to nocturnal phase during the subsequent AL and remained nocturnal during food deprivation periods. Second, rats were entrained to two daily meals at zeitgeber time (ZT) 0400 and ZT 1600. FAA to both meals emerged after about 10days of dual RF. However, all tissues studied (all five liver lobes, esophagus, antral stomach, body of stomach, colon) showed entrainment consistent with only the night-time meal. These two results are inconsistent with the hypothesis that FAA arises as an output of rhythms in the gastrointestinal (GI) system. The results also highlight an interesting diversity among peripheral oscillators in their ability to entrain to meals and the direction of the phase shift after RF ends.

Animals↗

Split chimerism after allogeneic bone marrow transplantation in Chediak-Higashi syndrome.

Chediak-Higashi Syndrome (CHS) is a hereditary multiorgan disease associated with a lymphoproliferative disorder termed 'accelerated phase' (AP). As AP is often life-threatening, hematopoietic stem cell transplantation has been proposed as the only curative treatment for CHS. Here, we report a 1-year-old Japanese boy with CHS who received an HLA-matched unrelated BMT at the AP stage, which resulted in split chimerism. We evaluated the chimerism status of isolated leukocytes and found that only a limited population of T and NK cells was of donor origin and the majority of these and other hematopoietic cells was of host origin. Clinical outcome was successful, and the patient is currently alive and well, free of AP and serious infections more than 18 months after BMT.

Anemia↗

The effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells.

BACKGROUND: The CagA protein of Helicobacter pylori is directly injected from the bacteria into cells via the bacterial type IV secretion system and undergoes tyrosine phosphorylation in the gastric epithelial cells. Translocated CagA forms a physical complex with the SRC homology 2 domain (SH2)-containing tyrosine phosphatase SHP-2, which plays an important role in mitogenic signal transduction in the host cells. AIM: We examined the effect of eradication therapy on the signal transduction pathway of gastric epithelial cells induced by the CagA protein of H. pylori. METHODS: Gastric biopsy samples were obtained from 20 H. pylori-positive atrophic gastritis patients before, and 3 months after, H. pylori infection eradication therapy, and subjected to immunoblot analysis to detect tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2. RESULTS: Tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2 were detected in the gastric mucosa from H. pylori-positive atrophic gastritis patients. All H. pylori strains from these patients were cagA-positive type I strains. After curing H. pylori infection, the tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2 disappeared from the gastric mucosa. CONCLUSION: The cure of infection reduces the stimulated signal transduction of gastric epithelial cells by the translocated CagA protein of H. pylori, and may confer a beneficial effect on the reduction of cancer risk.

Bacterial Proteins↗

[Esophageal perforation after an anterior cervical fixation; report of a case].

We report 1 case of esophageal complications after anterior plate fixation of the cervical spine. A 62-year-old man underwent anterior cervical fusion in August 1996, and he did well after the operation. In January 1998, he was hospitalized for cardiac failure and was incubated twice for 10 days to cure. In March 1998, he suffered from dysphagia and continuous fever. Gastric fiberscopy showed the internal defect of esophagus and the plate to fix the cervical spine. He underwent immediate neck exploration via the cervical fusion incision, however he died of sepsis and respiratory failure. An esophageal perforation after an anterior cervical operation is an uncommon but well-recognized complication of the approach.

Cervical Vertebrae↗

Simulated annealing structure solution of a new phase of dicalcium silicate Ca(2)SiO(4) and the mechanism of structural changes from alpha-dicalcium silicate hydrate to alpha(L)'-dicalcium silicate via the new phase.

A new phase of dicalcium silicate (Ca(2)SiO(4)) was formed by heating alpha-dicalcium silicate hydrate [alpha-Ca(2)(SiO(4)H)OH = alpha-C(2)SH] at temperatures of approximately 663-763 K, and it was transformed into alpha(L)'-Ca(2)SiO(4) (= alpha(L)'-C(2)S) above approximately 1193 K. The crystal structure of the new phase (hereafter called x-C(2)S) has been determined by simulated annealing and refined by the Rietveld method using synchrotron radiation powder diffraction data. The structure consists of isolated SiO(4) tetrahedra and a three-dimensional CaO(n) polyhedral network, forming a new structural type of dicalcium silicate. A structural change from alpha-C(2)SH to x-C(2)S is compelled by large displacements of SiO(4) tetrahedra, accompanied by dehydration, in the direction perpendicular to the two-dimensional Ca(O,OH)(n) polyhedral network in alpha-C(2)SH. With increasing temperature, sizes of CaO(n) polyhedra in x-C(2)S become too large to confine Ca atoms at the sixfold to eightfold coordination sites. Then the structure of x-C(2)S is transformed into alpha(L)'-C(2)S, having eightfold to tenfold coordination sites for the Ca atoms.

Journal Article↗

2-Amino-3-carboxy-1,4-naphthoquinone affects the end-product profile of bifidobacteria through the mediated oxidation of NAD(P)H.

Glucose metabolism of bifidobacteria in the presence of 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ), a specific growth stimulator for bifidobacteria, and ferricyanide (Fe(CN)(6)(3-)) as an extracellular electron acceptor was examined using resting cells of Bifidobacterium longum and Bifidobacterium breve. NAD(P)H in the cells is oxidized by ACNQ with the aid of diaphorase activity, and reduced ACNQ donates the electron to Fe(CN)(6)(3-). Exogenous oxidation of NADH by the ACNQ/Fe(CN)(6)(3-) system suppresses the endogenous lactate dehydrogenase reaction competitively, which results in the remarkable generation of pyruvate and a decrease in lactate production. In addition, a decrease in acetate generation is also observed in the presence of ACNQ and Fe(CN)(6)(3-). This phenomenon could not be explained in terms of the fructose-6-phosphate phosphoketolase pathway, but suggests rather that glucose is partially metabolized via the hexose monophosphate pathway. This was verified by NADP(+)-induced reduction of Fe(CN)(6)(3-) in cell-free extracts in the presence of ACNQ. Effects of the ACNQ/Fe(CN)(6)(3-) system on anaerobically harvested cells were also examined. Stoichiometric analysis of the metabolites from the pyruvate-formate lyase pathway suggests that exogenous oxidation of NADH is an efficient method to produce ATP in this pathway.

Acetyltransferases↗

The polymorphism of telomerase RNA component gene in patients with systemic sclerosis.

BACKGROUND: The molecular basis of senescence and immortalization is not still understood, but one hypothesis for which there has recently been much evidence involves the shortening of telomeres. It can be hypothesized that abnormalities of telomerase contribute to the emergence of abnormal fibroblast clones in systemic sclerosis (SSc). OBJECTIVES: To study possible telomere abnormalities with respect to polymorphism of the telomerase RNA component gene. METHODS: Fifty-three patients with SSc and 98 normal controls were studied. Polymerase chain reaction was used to amplify 598 bp of the telomerase RNA component gene. Amplified fragments were digested with restriction enzyme BsrDI. RESULTS: The frequency of the A allele in SSc (41.5%) showed no significant difference from that in the normal controls (32.1%). The frequency of the A/A alleles in SSc (18.9%) was significantly higher than in normal controls (5.1%), compared with G/G (35.8% and 40.8%, respectively; P < 0.02), G/A (45.3% and 54.1%, respectively; P < 0.01) and G/G plus G/A (81.1% and 94.9%, respectively; P < 0.01). CONCLUSIONS: These results showed the possible involvement of a telomerase abnormality in the emergence of abnormal fibroblast clones in SSc skin-derived fibroblasts.

Adolescent↗

The polymorphism of transforming growth factor-beta1 gene in Japanese patients with systemic sclerosis.

BACKGROUND: Transforming growth factor (TGF)-beta has been shown to be a potent stimulator of collagen production by fibroblasts, and could play a role in the pathogenesis of systemic sclerosis (SSc). OBJECTIVE: To study the possible involvement of TGF-beta1 gene polymorphism in Japanese patients with SSc. METHODS: Fifty-nine patients with SSc and 110 normal subjects were studied. Genomic DNA was extracted from skin tissues, and was amplified in a thermal cycler, generating a TGF-beta1 gene fragment with a size of 294 bp. The T to C transition at T869C (Leu10Pro) and the G to C transition at G915C (Arg25Pro) were identified by digestion with MspA1I and BglI, respectively. RESULTS: At T869C (Leu10Pro), the frequency of the C allele in SSc (65.3%) was significantly higher than in normal controls (50.5%) (P < 0.01). SSc showed C/C allele 42.4%, C/T 45.8% and T/T 11.2%. Normal controls showed C/C allele 26.4%, C/T 48.2% and T/T 25.5%. The frequency of the C/C allele in SSc was significantly higher than in normal controls, in comparison with the T/T allele (P < 0.02), but no significant difference was found between the frequency of the C/C allele vs. the C/T allele. The frequency of the C/C allele showed no significant difference between diffuse and limited SSc. At G915C (Arg25Pro), all the normal controls and SSc patients showed only the G/G allele. These results are different from a previous study in which the frequency of the T/T allele was high in SSc at T869C (Leu10Pro). CONCLUSIONS: This discrepancy may indicate that Japanese patients with SSc show a different genetic predisposition to TGF-beta1.

Adolescent↗

Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog.

1. Linezolid (ZYVOX), the first of a new class of antibiotics, the oxazolidinones, is approved for treatment of Gram-positive bacterial infections. 2. The aim was to determine the absorption, distribution, metabolism and excretion (ADME) of linezolid in mouse, rat and dog in support of preclinical safety studies and clinical development. 3. Conventional replicate study designs were employed in animal experiments, and biofluids were assayed by HPLC or HPLC-MS. 4. Linezolid was rapidly absorbed after p.o. dosing with an p.o. bioavailability of > 95% in rat and dog, and > 70% in mouse. Twenty-eight-day i.v./p.o. toxicokinetic studies in rat (20-200mg kg(-1) day(-1)) and dog (10-80 mg kg(-1) day(-1)) revealed neither a meaningful increase in clearance nor accumulation upon multiple dosing. 5. Linezolid had limited protein binding (<35%) and was very well distributed to most extravascular sites, with a volume of distribution at steady-state (V(ss)) approximately equal to total body water. 6. Linezolid circulated mainly as parent drug and was excreted mainly as parent drug and two inactive carboxylic acids, PNU-142586 and PNU-142300. Minor secondary metabolites were also characterized. In all species, the clearance rate was determined by metabolism. 7. Radioactivity recovery was essentially complete within 24-48 h. Renal excretion of parent drug and metabolites was a major elimination route. Parent drug underwent renal tubular reabsorption, significantly slowing parent drug excretion and allowing a slow metabolic process to become rate-limiting in overall clearance. 8. It is concluded that ADME data were relatively consistent across species and supported the rat and dog as the principal non-clinical safety species.

Acetamides↗

[Delayed hydrothorax induced by a pericutaneous central venous catheter; report of a case].

We report herein a case of 53-year-old woman who suffered a hydrothorax induced by a central venous catheter which had been placed to facilitate total parenteral nutrition. The central venous catheter was inserted into the superior vena cava through the right subclavian vein. Chest X-ray film after insertion revealed proper position of the tip. She suddenly developed dyspnea and tachycardia due to right-sided hydrothorax 21 days after the insertion of the catheter. Chest X-ray showed massive pleural effusion in the right thorax, and the catheter tip inadvertently turned upward. The continuous mechanical force of the catheter tip against the SVC wall was considered to be the cause of this life-threatening delayed hydrothorax.

Catheterization, Central Venous↗

Cross-clade neutralizing antibody production against human immunodeficiency virus type 1 clade E and B' strains by recombinant Mycobacterium bovis BCG-based candidate vaccine.

The recombinant Mycobacterium bovis BCG (rBCG) vector-based vaccine secreting the V3 principal neutralizing epitope of human immunodeficiency virus type 1 (HIV-1) Japanese strain was reported to induce both humoral and cellular immune responses effectively [Proc. Natl. Acad. Sci. USA. 92 (1995) 10693]. The antigen-secreting rBCG system was applied to the V3 epitope of clade E HIV-1 in this study. The V3 sequence of 19 amino acids (aa) and 15aa fused with mycobacterial alpha-antigen was not secreted while 12aa and 11aa sequences were successfully secreted from BCG cells. Serum IgG from guinea pig which was immunized with 12aa epitope-secreting recombinant BCG neutralized the WHO reference strain as well as primary field isolates of clade E virus. The serum IgG could also neutralize Thai B (clade B') strains which possessed a conserved GPGQ motif in their V3 sequences. These data suggest that the rBCG construct secreting the 12aa epitope is implicated in the development of a prophylactic vaccine in Thailand in which both clade E and B' viruses are prevalent.

AIDS Vaccines↗

A novel IkappaB protein, IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei.

The transcription factor nuclear factor-kappaB (NF-kappaB) plays crucial roles in a wide variety of cellular functions and its activity is strictly regulated by cytosolic inhibitors known as IkappaBs. We here report a new member of the IkappaB protein family, IkappaB-zeta, harboring six ankyrin repeats at its carboxyl terminus. IkappaB-zeta mRNA is strongly induced after stimulation by lipopolysaccharide. The induction of IkappaB-zeta is also observed by stimulation with interleukin-1beta but not by tumor necrosis factor-alpha. In contrast to cytosolic IkappaB-alpha, -beta, and -epsilon, the induced IkappaB-zeta localizes in the nucleus via its amino-terminal region, which shows no homology with other proteins. Transiently expressed IkappaB-zeta inhibits the NF-kappaB activity without affecting the nuclear translocation of NF-kappaB upon stimulation. The expressed IkappaB-zeta preferentially associates with the NF-kappaB subunit p50 rather than p65 and recombinant IkappaB-zeta proteins inhibit the DNA binding of the p65/p50 heterodimer and the p50/p50 homodimer. Thus, IkappaB-zeta negatively regulates NF-kappaB activity in the nucleus, possibly in order to prevent excessive inflammation. Moreover, transfection of IkappaB-zeta renders cells more susceptible to apoptosis induced by tumor necrosis factor-alpha. The proapoptotic activity of IkappaB-zeta further suggests that it might be one of key regulators for inflammation and other biologically relevant processes.

Amino Acid Sequence↗

Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.

We have previously identified 204 partial cDNA fragments (ADRG1-204) as antidepressant related genes/expressed sequence tags. Then, we developed our original cDNA microarrays, on which the 194 clones out of ADRG1-204 were spotted. With this ADRG microarray, we found that the expression of a spot, ADRG55, which representing cysteine string protein (CSP), was significantly increased in rat brain after chronic treatment with a selective serotonin reuptake inhibitor, sertraline. In the present study, reverse transcription-polymerase chain reaction analysis confirmed the induction of CSP at mRNA levels in rat frontal cortex after chronic treatment with two different classes of antidepressants, imipramine or sertraline. Western blot analysis also revealed that CSP-immunoreactivity was increased after antidepressant treatment. In conclusion, our data suggest that CSP is one of the common functional molecules induced after chronic antidepressant treatment.

Animals↗

Entrainment of the circadian clock in the liver by feeding.

Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.

Animals↗