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Hiroshi Yamasaki

Publications and source records attributed to Hiroshi Yamasaki.

At least 19 recordsLinked to original sources
PubMed2007

Connexin 32 potentiates vinblastine-induced cytotoxicity in renal cell carcinoma cells.

We have reported that connexin (Cx) 32 gene, a member of gap junction protein family, acts as a tumor suppressor gene in human renal cell carcinoma (RCC). Of solid tumors, RCC is one of the most chemoresistant cancers, and there is no effective cancer chemotherapy against RCC at present. In this study, we examined if the combination of Cx32-dependent tumor-suppressive effect and vinblastine (VBL), a chemotherapeutic agent which has been utilized for clinical RCC treatment, could be effective in enhancing the sensitivity of RCC to VBL treatment. Cx32 expression in a human metastatic RCC cell (Caki-1 cell) significantly enhanced in vitro and in vivo VBL-induced cytotoxicity on the cell. Cx32 expression in the RCC cells potentiated VBL-induced apoptosis compared to the Cx32-negative RCC cells in vitro as well as in vivo. The enhancing apoptosis in the RCC cells by Cx32 mainly depended on the decrease of P-glycoprotein (P-gp), a multidrug resistance gene-1 (MDR-1) product responsible for reduction of VBL accumulation into the cells. We also observed that silencing of Cx32 by short interfering RNA (siRNA) treatment elevated the level of P-gp in Caki-1 cells and that inhibition of P-gp function enhanced VBL-induced apoptosis in the RCC cells. These results suggest that Cx32 is effective to enhance VBL-induced cytotoxicity in Caki-1 cells via the reduction of P-gp. Overall, it seems that the combination of Cx32-dependent tumor-suppressive effect and VBL is promising as a new cancer therapy against RCC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2007

Depletion of endothelial progenitor cells in the peripheral blood of patients with ulcerative colitis.

There is strong evidence to suggest that endothelial progenitor cells (EPCs) play a significant role in re-endothelialization and subsequent tissue repair. This study examined the role of EPCs in inflammatory bowel disease, a disease in which impairment of mucosal healing has been implicated. Peripheral blood mononuclear cells obtained from 50 patients with ulcerative colitis (UC), 29 patients with Crohn's disease (CD), 14 patients with infectious colitis, and 35 normal control subjects were cultured in EPC medium, harvested after 7 days, and characterized by immunocytochemistry and flow cytometry. Colony assay for hematopoietic progenitor cells was also performed. Patients with active UC had a significantly decreased number of circulating EPCs as compared with healthy controls (p=0.0013), patients with inactive UC (p=0.0099), patients with active CD (p=0.0235) and patients with infectious colitis (p=0.0002). On the other hand, patients with infectious colitis had a significantly increased number of circulating EPCs as compared with healthy controls (p=0.0406), patients with active UC (p=0.0002), and patients with active CD (p=0.0316). In patients with UC, the number of circulating EPCs was correlated with the serum hemoglobin levels (r=0.485, p=0.007) and inversely with the platelet count (r=-0.372, p=0.0382). The number of hematopoietic progenitor cell colonies was comparable among patients with UC, patients with CD, patients with infectious colitis, and healthy controls. Our observations indicate that the number of circulating EPCs in patients with UC is significantly reduced. Further studies are needed to define the mechanisms that underlie the reduction in the number of circulating EPCs and to better understand the pathophysiological consequences of this event in patients with UC.

Adult↗
PubMed2006

Evaluation of purified Taenia solium glycoproteins and recombinant antigens in the serologic detection of human and swine cysticercosis.

Cysticercosis caused by infection with embryonated eggs of Taenia solium is an important cause of neurological disease worldwide. On the basis of mitochondrial DNA analysis, T. solium is divided into 2 (African/American and Asian) genotypes. Glycoproteins (GPs) in cyst fluid purified from the 2 genotypes of T. solium were characterized and compared with the recombinant chimeric T. solium-Ag1V1/Ag2 protein (Rec-Ag1V1/Ag2) as serodiagnostic antigens. Immunoblot analysis revealed that banding patterns of GPs differed between the 2 genotypes because of posttranslation modification, especially glycosylation. The comparison of native GPs with Rec-Ag1V1/Ag2 by enzyme-linked immunosorbent assay demonstrated that there was no statistical difference in sensitivity. In addition, the conservation of the genes encoding Ag1V1 and Ag2 in T. solium worldwide was verified. These results indicate that Rec-Ag1V1/Ag2 has great potential for usefulness in serodiagnosis as an alternative to native antigens.

Africa↗
PubMed2006

Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor.

Gap junction (GJ) channels are formed by two hemichannels (connexons), each contributed by the cells taking part in this direct cell-cell communication conduit. Hemichannels that do not interact with their counterparts on neighboring cells feature as a release pathway for small paracrine messengers such as nucleotides, glutamate, and prostaglandins. Connexins are phosphorylated by various kinases, and we compared the effect of various kinase-activating stimuli on GJ channels and hemichannels. Using peptides identical to a short connexin (Cx) amino acid sequence to specifically block hemichannels, we found that protein kinase C, Src, and lysophosphatidic acid (LPA) inhibited GJs and hemichannel-mediated ATP release in Cx43-expressing C6 glioma cells (C6-Cx43). Lipopolysaccharide (LPS) and basic fibroblast growth factor (bFGF) inhibited GJs, but they stimulated ATP release via hemichannels in C6-Cx43. LPS and bFGF inhibited hemichannel-mediated ATP release in HeLa-Cx43 cells, but they stimulated it in HeLa-Cx43 with a truncated carboxy-terminal (CT) domain or in HeLa-Cx26, which has a very short CT. Hemichannel potentiation by LPS was inhibited by blockers of the arachidonic acid metabolism, and arachidonic acid had a potentiating effect like LPS and bFGF. We conclude that GJ channels and hemichannels display similar or oppositely directed responses to modulatory influences, depending on the balance between kinase activity and the activity of the arachidonic acid pathway. Distinctive hemichannel responses to pathological stimulation with LPS or bFGF may serve to optimize the cell response, directed at strictly controlling cellular ATP release, switching from direct GJ communication to indirect paracrine signaling, or maximizing cell-protective strategies.

Adenosine Triphosphate↗
PubMed2006

Complete resolution of acute renal failure after left renal artery angioplasty and stent placement for total renal artery occlusion.

A 25-year-old female, 17 weeks pregnant presented to our hospital with complaints of progressively increasing dyspnea. She was hypertensive with creatine of 1.0; she was transferred to ICU with multiple medications to control her blood pressure, without success. The patient continued to decompensate, which required intubation. The patient developed acute renal failure, part of her work-up suggested bilateral renal artery stenosis. She was taken to the catheterization lab and was found to have bilateral total renal artery occlusion. The left renal artery was successfully opened. The patient recovered and her blood pressure was controlled after the procedure. In the past, surgery was the preferred treatment in cases of acute renal artery occlusion. This approach has been replaced increasingly by renal artery angioplasty, which is less invasive and is at least as effective as surgical reconstruction. Our case demonstrates a percutaneous approach can be tried for totally occluded renal artery with a successful outcome.

Abortion, Therapeutic↗
PubMed2006

Altered expression of connexins in urethane-induced mouse lung adenomas.

Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.

Adenoma↗
PubMed2006

Echinococcus multilocularis: developmental stage-specific expression of Antigen B 8-kDa-subunits.

Antigen B (AgB) initially found in hydatid cyst fluid of Echinococcus granulosus is a polymeric lipoprotein of 160 kDa, and is an aggregate of several different but homologous small proteins with approximately 8 kDa. Four genes encoding these 8-kDa-subunits have been identified from E. granulosus. In this study we isolated five genes encoding 8-kDa-subunits of AgB from Echinococcus multilocularis. Sequence comparison of isolated cDNA clones demonstrated that one of these five clones was completely identical to EmAgB8/1 which had been isolated previously by our group, and three of them were 94.5, 90.8, and 91.9% homologous to E. granulosus antigen B 8-kDa subunit genes, EgAgB8/2, EgAgB8/3, and EgAgB8/4, respectively. The remaining clone shared 51-58% homology with the nucleotide sequences of AgB genes. Gene-specific RT-PCR and Western blot analyses revealed that these genes were expressed in a developmentally regulated manner in E. multilocularis vesicles, protoscoleces, and immature adult worms. Possible functions of different expression manners are also discussed.

Amino Acid Sequence↗
PubMed2006

A case of intramuscular cysticercosis diagnosed definitively by mitochondrial DNA analysis of extremely calcified cysts.

A case of obsolete intramuscular cysticercosis diagnosed definitively by mitochondrial DNA analysis of extremely calcified cysts was reported. X-ray and computed tomography findings highly suggested cysticercosis due to Taenia solium; however, no direct evidence of cysticercosis was obtained through serological or histopathological examinations. Mitochondrial DNA analysis of a histopathological specimen confirmed the causative agent to be the Asian genotype of T. solium.

Aged, 80 and over↗
PubMed2006

Increased circulating concentrations of growth-related oncogene (GRO)-alpha in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with increased risk of intestinal cancers. The aim of this study is to examine serum concentrations of growth-related oncogene (GRO)-alpha, a cytokine with inflammatory and growth-regulatory properties, in patients with IBD. We measured serum concentrations of GRO-alpha in 60 patients with ulcerative colitis, 42 patients with Crohn's disease, 16 patients with other colitides, 12 patients with colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent assay. We then analyzed how the cytokine was related to clinical and laboratory variables. Serum GRO-alpha concentrations in patients with active IBD were significantly higher than those in patients with quiescent disease, which in turn were higher than those in normal controls. Concentrations in patients with active ulcerative colitis were higher than in patients with active Crohn's disease. Analysis of paired serum samples showed a decrease in GRO-alpha after initiation of therapy. Furthermore, serum GRO-alpha correlated well with laboratory markers of IBD activity. We conclude that GRO-alpha may have an important role in development of IBD, and might itself be used as a marker of activity. Manipulation of GRO-alpha function might prove therapeutically useful.

Adolescent↗
PubMed2006

Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma.

Cellular homeostasis in many organs is maintained via gap junctions composed of connexin (Cx), a large protein family with a number of isoforms. In fact, gap junctional intercellular communication (GJIC) is actively involved in all aspects of the cellular life cycle, ranging from cell growth to cell death. It has been well known that Cx gene acts as a tumor suppressor gene due to the maintenance of cellular homeostasis via GJIC. On the other hand, recent data show that GJIC-independent function for Cx gene contributes to tumor-suppressive effect of the gene with cell certain specificity. However, the mechanistic aspect of the GJIC-independent function remains largely unknown. In this review, we briefly summarize the tumor-suppressive effects of Cx genes, refer to a new aspect of Cx32 as an anti-invasive and anti-metastatic gene against renal cell carcinoma in a GJIC-independent function and establishment of a new cancer therapy based on the new function of Cx32.

Carcinoma, Renal Cell↗
PubMed2006

Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve dysfunction in Japanese type 2 diabetic patients.

OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.

Alleles↗
PubMed2006

Inhibition of Src activity enhances the tumor-suppressive effect of the connexin 32 gene in Caki-1 renal cancer cells.

Connexin (Cx) genes exert negative growth effects on tumor cells with certain cell specificity. We have recently reported that Cx32 acts as a tumor suppressor gene in a metastatic renal cancer cell line (Caki-1) due to the inactivation of Src. In line with the previous study, here we investigated if an Src family inhibitor (PP1) could enhance the tumor-suppressive effect of Cx32 in Caki-1 cells from human metastatic renal cell carcinoma. We examined the difference in the cytotoxic effect of PP1 on two cell clones, Cx32-transfected Caki-1 cells (Caki-1T) and mock-transfected Caki-1 cells (Caki-1W), in vitro as well as in vivo. PP1 showed more cytotoxic effect on Caki-1T than on Caki-1W at lower doses. This reinforcement was also observed in a xenograft model of nude mice. The in vitro reinforcement of the cytotoxic effect depended not only on control of cell-cycle transition but also on the induction of apoptosis, and the occurrence of the event was mostly caused by potential inhibition of Src activity in Caki-1T. Also, under a hypoxic condition, which is a typical environment of tumor tissue, Cx32 suppressed hypoxia-induced Src activation, and PP1 enhanced cytotoxicity in Caki-1T. These results suggest that, in addition to the Cx32-dependent tumor-suppressive effect, the concomitant inhibition of Src by PP1 is an effective procedure to induce a cytotoxic effect in Caki-1 cells.

Animals↗
PubMed2006

[A case of sarcoidosis with diabetes insipidus].

A 23-year-old man was admitted because of polydipsia and polyuria. As chest radiographs and computed tomography showed mediastinal and bilateral hilary lymph node swelling, and diffuse small nodules in bilateral lung fields, we suspected sarcoidosis. Sarcoidosis was diagnosed by biopsy of a cervical lymph node, and central diabetes insipidus was diagnosed by fluid restriction test and vasopressin load test. A pituitary mass was also revealed by magnetic resonance imaging. Prednisolone therapy improved all of his clinical findings except diabetes insipidus. He had to continue intranasal 1-desamino-8-D-arginine vasopressin (DDAVP) therapy.

Adult↗
PubMed2006

[A case of liver cysts with Em18-WB was useful for differential diagnosis].

A 72-year-old woman with multilocular liver cysts was admitted. This lesions seemed to be an alveolar hydatid disease. Two methods of Western blotting were used for serologic diagnosis. One method recognizes antigens of crude extracts of Echinococcus multilocularis (EM). The other method recognizes a purified antigen (Em18) of EM. Her serum only reacted with the former method and never reacted with Em18 antigen. Eighteen months after first admission, she had an operation. The resected specimen was diagnosed with simple cysts. Western blotting using Em18 antigen could greatly facilitate the differential diagnosis of simple liver cyst and alveolar hydatid disease.

Aged↗
PubMed2006

Short report: Evidence and potential for transmission of human and swine Taenia solium cysticercosis in the Piracuruca region, Piauí, Brazil.

The study conducted in the Cocal dos Alves municipality, located in the Piracuruca region of Piauí State, Brazil in November of 2003 was based on both a socio-behavioral survey and analysis of serum antibodies and parasitic materials. Pig raising is the main economic activity with 91.4% using extensive farming. On the studied population, 54.3% of people did not apply any sanitary measures to wastewater, 45.7% used septic tanks, and 69.1% consumed water without treatment. The data collected indicated the occurrence and active transmission of the taeniasis-cysticercosis complex in the region. One of seven voluntary persons was positive in antibody-ELISA tests using both native and recombinant antigens. Multiplex PCR and DNA sequencing of cyst samples obtained from a pig revealed the presence of the Afro-American genotype of Taenia solium. This study revealed the occurrence of human and porcine cysticercosis in the Piracuruca region of Piauí State, middle-north of Brazil.

Animals↗
PubMed2006

[Adult case of acute encephalopathy associated with bilateral thalamic lesions and peripheral neuropathy].

A 76-year-old woman developed fever and consciousness disturbance. The next day, she became delirious and was brought to our hospital. On arrival, she was unconscious and showed hypopnea and hypotension. She was immediately intubated and placed on a respirator. CSF protein was 65.8 mg/dl with 1 cell/microl, and no oligoclonal bands were present. An electroencephalogram showed diffuse theta background activity without epileptic discharges. A nerve conduction study showed damaged motor and sensory peripheral nerve functions in the upper and lower limbs. The neurological findings showed no improvement after methylprednisolone pulse therapy and administration of intravenous immunoglobulin. Magnetic resonance imaging of the brain, including diffusion-weighted images showed bilateral symmetric lesions in the thalamus, globus pallidus and pontine tegmentum. These radiologic findings are not typically, but are similar to those of acute necrotizing encephalopathy (ANE) of childhood as proposed by Mizuguchi et al. After 10 months, brain MRI showed bilateral brain atrophy and a reduction of the abnormal thalamic lesions. There are very few reports of adult cases of ANE, in which, pathologically, local breakdown of the blood-brain-barrier causes acute edema and necrosis involving both gray and white matter. ANE is thought a proinflammatory cytokine-related disease. In our case, the concentrations of some cytokines (IL-6, IL-10) were elevated in serum and cerebrospinal fluid, which might suggest a relationship with them and local breakdown of the blood-brain-barrier in the thalamus.

Acute Disease↗