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Biomedical subjects

K Miyagi

Publications and source records attributed to K Miyagi.

At least 19 recordsLinked to original sources
PubMed2005

Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with Mycobacterium tuberculosis.

Diabetes mellitus is an important predisposing factor for tuberculosis. The aim of this study was to investigate the mechanism underlying this association using a murine model. Mice with streptozotocin-induced diabetes mellitus were prone to Mycobacterium tuberculosis infection, as indicated by increased numbers of live bacteria in lung, liver and spleen. In diabetic mice, the levels of IL-12 and IFN-gamma in the lung, liver and spleen were lower than those in control animals on day 14 postinfection, while the opposite was true for IL-4 levels in the lung and liver. The expression pattern of inducible nitric oxide synthase (iNOS), in the two mice types was as for IL-12 and IFN-gamma. In addition, peritoneal exudate cells obtained from diabetic mice produced lower amounts of IL-12 and NO than those from control mice, when stimulated in vitro with M. bovis BCG. Spleen cells from diabetic mice infected with M. tuberculosis produced a significantly lower amount of IFN-gamma upon restimulation with purified protein derivatives (PPD) than those from infected nondiabetic mice. Interestingly, addition of high glucose levels (33 mM) to the cultures of PPD-restimulated spleen cells reduced the synthesis of IFN-gamma only in diabetic mice, and not in nondiabetic mice. Finally, control of blood glucose levels by insulin therapy resulted in improvement of the impaired host protection and Th1-related cytokine synthesis. Our results suggest that the reduced production of Th1-related cytokines and NO account for the hampered host defense against M. tuberculosis infection under diabetic conditions.

Animals↗
PubMed2005

CpG oligodeoxynucleotides promote the host protective response against infection with Cryptococcus neoformans through induction of interferon-gamma production by CD4+ T cells.

In the present study, we elucidated the effect of synthetic CpG-containing oligodeoxynucleotides (ODN) on pulmonary and disseminated infection caused by Cryptococcus neoformans. CDF-1 mice were inoculated intratracheally with a highly virulent strain of this pathogen, which resulted in massive bacterial growth in the lung, dissemination to the brain and death. Administration of CpG-ODN promoted the clearance of C. neoformans in the lungs, decreased their dissemination to brain and prolonged the survival of infected mice. These effects correlated well with the enhanced production of interleukin (IL)-12 and interferon (IFN)-gamma and attenuated secretion of IL-4 in bronchoalveolar lavage fluids (BALF) and promoted development of Th1 cells, as indicated by the increased production of IFN-gamma by paratracheal lymph node cells upon restimulation with cryptococcal antigens. The IFN-gamma synthesis in BALF was inhibited by depletion of CD8(+) and CD4(+) T cells on days 7 and 14 after infection, respectively, but not by depletion of NK and gammadelta T cells. Consistent with these data, intracellular expression of IFN-gamma was detected predominantly in CD8(+) and CD4(+) T cells in the lung on days 7 and 14, respectively. The protective effect of CpG-ODN, as shown by the prolonged survival, was completely and partially inhibited by depletion of CD4(+) or CD8(+) T cells, respectively, but not by depletion of other cells. Finally, TNF-alpha was markedly induced by CpG-ODN, and the protective effect of this agent was strongly inhibited by neutralizing anti-TNF-alpha MoAb. Our results indicate that CpG-ODN alters the Th1-Th2 cytokine balance and promotes host resistance against infection with C. neoformans.

Animals↗
PubMed2004

[Spinal cord protection during thoracoabdominal aortic aneurysm repair; efficacy of distal aortic perfusion and segmental aortic clamping].

Despite improvement in adjuncts for thoracoabdominal aortic aneurysms (TAAA) repairs, many devastating complications remains after the surgery. Our experience with these aneurysms has been reviewed in order to identify those methods at risk of major morbidity, as well as which further improvements required. During last 16 years, 53 consecutive patients were operated on TAAA. The mean age was 58 years. Twenty patients had dissecting aneurysms and 13 patients had had prior aortic surgery. A femoro-femoral bypass was used to maintain distal aortic perfusion in most patients. Reimplantation of intercostal or lumbar arteries under the multi-segmental aortic clamping is consistent in our technique. Motor evoked potentials (MEP) were measured to monitor spinal cord protection since 2000. The hospital mortality was 9.4% (5/53), 22.2% (2/9) for emergency operation and 15.4% (2/13) for patients with prior aortic surgery. The mortality for the first and elective operations was 3.2% (1/31). No any neurologic dysfunction was observed in all patients including the hospital deaths. In view of clinical results, our adjuncts and techniques are useful for prevention of spinal cord ischemia during the TAAA surgery.

Adult↗
PubMed2003

Survey of Vibrio cholerae O1 and its survival over the winter in marine water of Port of Osaka.

The survey of Vibrio cholerae O1 in marine area was carried out in the Port of Osaka, Japan in 1987-2001, and 51 V. cholerae O1 strains were isolated. All strains were identified to be of El Tor biotype, Ogawa serotype and classic Ubon Kappa-phage type, and were cholera toxin (CT)-negative and CT gene-negative. In order to clarify certain ecological aspects of V. cholerae O1 in the marine environment of the temperate zone, we performed molecular analysis of the isolated strains using pulsed-field gel electrophoresis (PFGE) with NotI and SfiI restriction enzymes. We found the indistinguishable strains by DNA analysis using PFGE with strains passed for 1 year, and also found the closely related strains with that passed for 3 and 12 years. Those results indicated that V. cholerae O1 can survive over one winter at least, and that it survives in marine water for a long time by undergoing continuous mutation.

Adaptation, Physiological↗
PubMed2003

An efficient linkage analysis strategy for autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited renal disorders in the world. Mutations in PKD1 are responsible for 80-95% of all autosomal dominant polycystic kidney disease (ADPKD). Although the need for linkage analysis of ADPKD is decreasing after the success of mutation detection at whole exons of PKD1, linkage analysis still has some advantages in detecting non-PKD1 families, thereby avoiding hopeless mutation analysis. METHODS: We evaluated ten microsatellite markers beside or inside PKD1 on chromosome 16p. Allele frequency and heterozygosity of each marker were calculated based on the 100 genotypes obtained from 50 normal Japanese. Automated microsatellite genotyping using ABI Prism 377 and GeneScan software was applied. Markers were mapped using radiation hybrid mapping. Finally, this strategy was applied in the linkage analysis of 6 independent Japanese ADPKD families. RESULTS: D16S3024, D16S3082, D16S3027 and D16S423 showed high heterozygosity (> 0.80) in a normal Japanese population and sufficient proximity to the PKD1 gene for linkage analysis. We could successfully analyze 144 genotypes within 7 hours. This strategy produced theoretically near-maximum LOD scores in 4 independent Japanese families inheriting ADPKD. CONCLUSIONS: Automated genotyping using microsatellite markers, D16S3024, D16S3082, D16S3027 and D16S423 are very useful in the linkage analysis of ADPKD.

Chromosome Mapping↗
PubMed2003

Blood distribution to the anterior spinal artery from each segment of intercostal and lumbar arteries.

AIM: Prevention of paraplegia, a serious complication of surgery for thoracoabdominal aortic aneurysm, has been well documented. However no assured prophylaxis against this complication has yet been found. Spinal ischemia is believed to be the major cause of paraplegia. We conducted an experimental study to define the development of paraplegia with regard to the blood supply to the spinal cord. METHODS: A porcine model was used to evaluate blood distribution to the anterior spinal artery. Colored silastic agent was selectively injected into the intercostal and lumbar arteries, and distribution to the anterior spinal artery was evaluated on 50 animals. The intercostal and lumbar arteries were ligated in the segments where the blood supply to the anterior spinal artery would be interrupted. Whether or not paraplegia developed was checked 2 days later. RESULTS: Colored silastic agent arrived at the anterior spinal artery from all segments of the 8th intercostal to 4th lumbar arteries. Two of 9 pigs (22.2%) that underwent ligation of the segments from the 9th intercostal to 2(nd) lumbar artery suffered paraplegia. In 3 non-paraplegic pigs, colored silastic agent injected into the preserved arteries was found to have covered a wider range. CONCLUSION: All the intercostal and lumbar arteries supplied blood to the anterior spinal artery. When large segments of intercostal and lumbar arteries were ligated, the blood flow from the preserved segments acquired increased dominance. The possibility exists that any intercostal and lumbar artery can supply blood to the spinal cord and become collateral circulation to the anterior spinal artery.

Animals↗
PubMed2002

[Impact of multi-segmental aortic clamping and distal aortic perfusion on the prevention of postoperative paraplegia during thoracoabdominal aortic graft replacement].

OBJECTIVE: We present the impact of multisegmental aortic clamping under distal aortic perfusion and segmental artery reimplantation on the prevention of postoperative paraplegia during thoracoabdominal aortic graft replacement. PATIENTS: During the last 14 years in 47 patients (age range: 22 to 82 years; average: 57,9 +/- 13,2 years; 16 females and 31 males) with thoracoabdominal aortic aneurysm a graft replacement was performed with adjuncts of normothermic partial bypass and multisegmental aortic clamping. As many patent segmental arteries as possible were reimplanted. RESULTS: Five patients died during hospitalization, for an in-hospital mortality rate of 10,6 %. In the elective patients (n = 40), the hospital mortality rate was 7,5 %. The average number of segmental aortic clampings per patient was 2,83 +/- 1,19 times. In 39 patients (82,9 %), 117 segmental arteries were reimplanted or preserved by beveled anastomosis. Eighty-three out of 117 segmental arteries (70,9 %) were located between TH9 and L2. Postoperative paraplegia/paraparesis did not occur in any patient. CONCLUSION: In view of our results reimplantation of as many segmental arteries as possible under multisegmental aortic clamping with adequate distal aortic perfusion can be recommended for effective prevention of spinal cord ischemia in TAAA surgery.

Adult↗
PubMed2001

Monocyte chemoattractant protein-1-dependent increase of V alpha 14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection.

To elucidate the role of NKT cells in the host defense to cryptococcal infection, we examined the proportion of these cells, identified by the expression of CD3 and NK1.1, in lungs after intratracheal infection with Cryptococcus neoformans. This population increased on day 3 after infection, reached a peak level on days 6-7, and decreased thereafter. In Valpha14 NKT cell-deficient mice, such increase was significantly attenuated. The proportion of Valpha14 NKT cells, detected by binding to alpha-galactosylceramide-loaded CD1d tetramer, and the expression of Valpha14 mRNA increased after infection with a similar kinetics. The delayed-type hypersensitivity response and differentiation of the fungus-specific Th1 cells was reduced in Valpha14 NKT cell-deficient mice, compared with control mice. Additionally, elimination of this fungal pathogen from lungs was significantly delayed in Valpha14 NKT cell-deficient mice. Production of monocyte chemoattractant protein (MCP)-1 in lungs, detected at both mRNA and protein levels, increased on day 1, reached a peak level on day 3, and decreased thereafter, which preceded the increase in NKT cells. Finally, the increase of total and Valpha14(+) subset of NKT cells after infection was significantly reduced in MCP-1-deficient mice. Our results demonstrated that NKT cells, especially Valpha14(+) subset, accumulated in a MCP-1-dependent manner in the lungs after infection with C. neoformans and played an important role in the development of Th1 response and host resistance to this fungal pathogen.

Animals↗
PubMed2001

Changes in the composition of serum bile acid as a predictor of small bowel allograft rejection in rats.

Composition of bile acid was studied as a noninvasive rejection marker after small bowel transplantation (SBT). Orthotopic SBT were performed in rats, and they were divided into four groups: group 1, sham-operated rats; group 2, recipients with isografts; group 3, recipients with allografts treated with FK506; and group 4, recipients with untreated allografts. On postoperative days (POD) 5 and 7, the graft histology, intraluminal bacterial overgrowth, individual bile acids concentration of the recipient serum and bile were examined. On POD 5, early histological findings of acute rejection were observed in group 4, and the ratio of secondary bile acids of this group were significantly higher than the other groups. The bile acid changes were enhanced by bacterial overgrowth on POD 7. The ratio of secondary bile acids changed in relation to acute rejection after SBT, suggesting that they can be useful for early diagnosis of acute SBT allograft rejection.

Animals↗
PubMed2001

Application of hypothermia to autologous stem cell purging.

Autologous stem cell transplantation is used widely after high-dose chemotherapy for treating hematological and other malignancies. Bone marrow harvested for autologous bone marrow transplantation may contain residual malignant cells even when the cancer is judged to be in remission. Attempts to purge marrow of its putative residual malignant cells may delay hemopoietic reconstitution and are of uncertain efficacy. In this report, we demonstrate the possibility of applying hypothermia to autologous stem cell purging. Using clonogenic assay, we compared the surviving fraction of human leukemia (HL60, K562) and human small cell lung cancer (H69) cell lines with that of normal human bone marrow CFU-GM and BFU-E cells after incubation at 4 +/- 0.1 degrees C for 24 and 48 h. Hypothermia decreased the surviving fraction of HL60, H69, and K562 cells. In contrast, the surviving fractions of stem cells were not affected by the temperature shift. The surviving fraction of HL60 cells at 4 degrees C cooling was significantly lower than that at 22 degrees C cooling. These findings suggest that in vitro hypothermia may selectively purge residual malignant cells in stored remission bone marrow and may be applicable before autologous bone marrow transplantation. In addition, the method is very simple and cost effective.

Bone Marrow Purging↗
PubMed2001

Frequency of failure to isolate Shigella spp. by the direct plating technique and improvement of isolation by enrichment in selenite broth.

In order to clarify the failure to isolate Shigella spp. by direct plating, we compared frequencies of Shigella spp. isolation by direct plating and by plating after enrichment in selenite broth. A total 67 strains were isolated in this study. The strains of 38 (56.7%) were isolated only by direct plating, and 25 (37.3%) strains were isolated by both direct plating and after enrichment. Four strains (6.0%) were isolated after enrichment but not by direct plating. Since 6% of isolated Shigella spp. were not isolated by direct plating, we recommend that direct plating and additional isolations from selenite broth should be performed. The significance concerning reduction of concentration of sodium selenite in enrichment broth is discussed.

Bacteriological Techniques↗
PubMed2001

Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits.

Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. Rabbits were given with EPO (400 iu kg(-1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I2 were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(-1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(-1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I2 were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase.

Acetylcholine↗
PubMed2001

Basaloid-squamous cell carcinoma of the esophagus: diagnosis based on immunohistochemical analysis.

Basaloid-squamous cell carcinoma of the esophagus (BSCC) is an extremely rare tumor. Histologically, this tumor should be differentiated from adenoid cystic carcinoma (ACC) and small cell undifferentiated carcinoma (SCUC). Biologically, this tumor is very aggressive, with a propensity for distant metastasis. We report a 64-year-old male with esophageal BSCC. The patient complained of dysphagia and was found to have a torous lesion in the esophagus on radiological examination. Upper gastrointestinal fiberscopy showed a localized ulcerative type tumor, which was diagnosed as squamous cell carcinoma (SCC) on biopsy. Surgery resulted in curative resection. A histological examination of the resected tumor showed features of BSCC. Immunohistochemical examination demonstrated AE3/1- and CAM 5.2-positive tumor cells, and laminin-positive cells in the periphery of the nests. These data were useful in differentiating this tumor from ACC and SCUC. Six months after surgery, the patient developed hepatic metastases, which were successfully treated by regional chemotherapy via the hepatic artery by using fluorouracil. The patient is currently being followed up at the outpatient clinic and shows no signs of any recurrence.

Biomarkers↗
PubMed2001

Effect of ACE gene polymorphism on age at renal death in polycystic kidney disease in Japan.

Polycystic kidney disease (PKD) is one of the most common genetic disorders and a major cause of renal death or end-stage renal disease (ESRD) requiring regular hemodialysis. The responsible genes recently have been cloned; however, genetic factors influencing the rate of progression to ESRD in patients with PKD have yet to be defined. Several studies have shown increased activity of the renin-angiotensin system (RAS) in patients with PKD. In addition, genetic polymorphisms of the RAS have been associated with the development of cardiovascular diseases. Therefore, these polymorphisms are good candidates for disease-modifying genetic factors or markers in PKD. In two previous reports of white subjects with a cumulative survival analysis, it was suggested that patients with P:KD1 homozygous for the deletion allele of the angiotensin-converting enzyme (ACE) gene are at increased risk for early renal death. To confirm this hypothesis in Japanese subjects, 103 individuals with PKD were genotyped for several components of the RAS, ie, ACE insertion/deletion (I/D) polymorphism, angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1) A1166C. Seventy-six of the 103 patients (73.8%) reached ESRD at an average age of 52.1 +/- 11.3 years. The frequencies of each genotype of the genes were similar to those expected from Hardy-Weinberg equilibrium. There was a tendency to an excess of patients homozygous for the D allele in patients with ESRD (DD in patients with ESRD, 11.8%; DD in patients without ESRD, 3.7%; chi-square, 1.505; P: = 0.22). Cumulative renal survival was significantly less in those with the DD genotype compared with ID/II genotypes. Estimated mean renal survival was 46.4 years (95% confidence interval, 39.5 to 53.3) in subjects with the DD genotype and 57.2 years (95% confidence interval, 54.2 to 60.2) in ID/II genotypes (chi-square, 7.76; P: = 0.0053). There was no association between age at onset of ESRD and either M235T or A1166C polymorphism. These findings suggest that Japanese patients with PKD homozygous for the D allele of the ACE gene are at increased risk for developing ESRD at an early age.

Adult↗
PubMed2001

Successful living donor liver transplantation for polycystic liver in a patient with autosomal-dominant polycystic kidney disease.

Orthotopic liver transplantation has been recommended for patients with disabling polycystic liver disease (PCLD). Because of the shortage of cadaveric donors, living donor liver transplantation (LDLT) has been developed as an alternative. We describe the case of a woman with PCLD as an extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD) who was successfully palliated by LDLT. The patient was a 48-year-old woman with abdominal distention. Computed tomography showed a massively enlarged liver containing innumerable cysts, as well as bilateral kidney cysts. Hepatic and renal functions were well preserved. Genetic analysis of the family did not exclude linkage to the PKD1 locus. Two and a half years after the first examination, the patient reported severely disabling symptoms caused by the PCLD. Living donor liver transplantation was performed using a right-lobe graft. The recipient and donor were both well 8 months after the transplantation. The excised liver weighed 7.4 kg, and the histopathology revealed multiple cysts and von Meyenburg complexes in the portal areas.

Cysts↗
PubMed2001

Survival of Shiga toxin-producing Escherichia coli O157 in marine water and frequent detection of the Shiga toxin gene in marine water samples from an estuary port.

Shiga toxin-producing Escherichia coli (STEC) O157 was investigated with respect to its halotolerance and whether it can survive in marine water. STEC O157 could multiply in a medium containing 5% NaCl and in sterilized marine water, and could survive in unsterilized marine water for at least 15 days. On the basis of these results, we postulated that STEC O157 may survive in natural marine water, and attempted to isolate the bacterium and Shiga toxin gene (stx) from marine water in Japan. The stx, comprising stx1 and stx2, was detected from marine water samples by PCR. STEC and other stx-positive bacteria, however, could not be isolated from these samples in this study. These results indicate that stx-positive bacteria may survive in marine water and suggest the necessity of a survey.

Escherichia coli O157↗
PubMed2001

One-stage operation for descending thoracic aortic aneurysm and left lung cancer: a case report.

We performed concomitant graft replacement for descending thoracic aortic aneurysm and pulmonary resection for squamous cell carcinoma of the left upper lobe in a 79-year-old man. The tumor reached the parietal pleura. No distance metastasis was found, and the tumor was diagnosed preoperatively as a stage IIB (N0, M0, T3) tumor. The descending thoracic aortic aneurysm was saccular, with greatest diameter being 55 mm, and extending from TH5 to TH8. A left upper lobectomy was performed, and after irrigation with a large volume of saline diluted with povidone iodine, graft replacement for the aortic aneurysm was performed under femoro-femoral partial bypass. To prevent postoperative graft infection, the greater omentum was dissected and placed over the resected pulmonary hilum and the graft. The patient's postoperative course was uneventful. There was no sign of infection, and the patient was discharged 1 month after surgery. Artificial graft wrapping with the greater omentum was useful for the prevention of the postoperative graft infection in this case of surgical treatment of lung cancer and descending thoracic aortic aneurysm.

Aged↗