Search PubMed⌕ Search

Biomedical subjects

N Kobayashi

Publications and source records attributed to N Kobayashi.

At least 19 recordsLinked to original sources
PubMed2007

Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet transplantation and prevention of islet graft loss by intraportal injection of JNK inhibitor.

AIMS/HYPOTHESIS: Although application of the Edmonton protocol has markedly improved the outcome for pancreatic islet transplantation, the insulin independence rate after islet transplantation from one donor pancreas has remained low. During the isolation process and subsequent clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. The aim of this study was to map the c-Jun NH2-terminal kinase (JNK) pathway that mediates islet loss during islet transplantation and to clarify whether intraportal injection with JNK inhibitor during islet transplantation can prevent islet graft loss. METHODS: We measured JNK activity in the liver, fat and muscle of diabetic mice and in the liver immediately after islet transplantation. We examined the effect of intraportal injection of JNK inhibitory peptide at islet transplantation. RESULTS: JNK activity became progressively higher at least until 24 h after transplantation. The cell-permeable peptide of JNK inhibitor was delivered not only in the liver but also in other insulin target organs, preventing JNK activation in the liver at least until 24 h after transplantation and reducing JNK activity in these insulin target organs. Moreover, the peptide inhibitor prevented islet graft loss immediately after transplantation and improved islet transplant outcome. CONCLUSIONS/INTERPRETATION: These findings suggest that control of the JNK pathway is extremely important in islet transplantation and that intraportal injection of JNK inhibitor during islet transplantation (addition of JNK inhibitor to transplant media) could prevent the impairment of islet cells, leading to improved outcome for pancreatic islet transplantation.

Adipose Tissue↗
PubMed2007

Molecular epidemiologic analysis of group A rotaviruses in adults and children with diarrhea in Wuhan city, China, 2000-2006.

To compare epidemiologic features and genetic characteristics of group A rotaviruses causing diarrhea in children and adults, a survey was conducted in Wuhan, China, during the period of Dec. 2000-May 2006. A total of 3839 stool specimens from diarrheal patients from eight hospitals were analyzed. Winter seasonality was observed for rotavirus diarrhea in both adults and children, showing overall rotavirus-positive rates of 9.0 and 23.9%, respectively. Throughout the study period, G3 was the most frequent G serotype in both adults and children (detection rates 86.2 and 87.8%, respectively), and was mostly associated with VP4 genotype P[8], VP 6 genotype II (subgroup II), and NSP4 genotype B. G3 rotaviruses were differentiated into eight electropherotypes, among which seven types were found in specimens from both adults and children. VP7 gene sequences of G3 rotaviruses from adults and children (6 and 4 strains, respectively), detected in different years and different hospitals, showed extremely high sequence identities (99-100%) to each other and to a few G3 rotavirus strains reported in Asia. However, lower sequence identities (82-96%) were observed to most of the human and animal G3 rotaviruses reported so far, including some Chinese strains. These findings indicate that in Wuhan, China, epidemic and genetic features of rotaviruses are similar in adults and children, and it has been suggested that G3 rotaviruses that might have originated from the same rotavirus were circulating among children and adults as prevailing viruses. In this study, two rotavirus strains, G9P[8] strain L169, derived from an adult, and G4P[6] strain R479, derived from a child, were isolated and genetically analyzed. The VP7 gene of L169 belongs to a major lineage of G9 rotaviruses that are globally widespread, but is distinct from G9 rotaviruses reported previously in China. The strain R479 had a VP7 gene which was divergent from most G4 human rotaviruses and showed an unusual dual subgroup specificity, I + II. The R479 VP6 gene does not belong to the main clusters of subgroup I and II rotaviruses phylogenetically, but is related to those of the porcine rotaviruses and some unusual human rotaviruses represented by the RMC321 strain isolated in eastern India.

Adolescent↗
PubMed2006

Evidence for independent segregation of the VP6- and NSP4- encoding genes in porcine group A rotavirus G6P[13] strains.

Molecular characterization of two porcine group A rotavirus strains (HP113 and HP140), detected from eastern India, revealed a VP7 closely related to those of human G6P[14] strains, VP4 with a borderline P[13] genotype, and VP6 related to bovine and human SGI strains rather than porcine SGI and/or SGII group A rotaviruses. Both strains had NSP4 and NSP5 of porcine origin. Therefore, to our knowledge, the present study is the first report of detection of group A rotavirus strains with G6P[13] genotype specificities and provides evidence for independent segregation of the VP6- and NSP4-encoding genes in porcine group A rotaviruses.

Amino Acid Sequence↗
PubMed2006

Genetic analysis of an ADRV-N-like novel rotavirus strain B219 detected in a sporadic case of adult diarrhea in Bangladesh.

An unusual human rotavirus strain B219 was detected in a stool specimen from a 65-year old patient with diarrhea in Bangladesh during April 2002. Cloning and sequence analysis of five genes of the B219 strain indicated that this virus is genetically closely related to the ADRV-N strain, which caused an adult diarrhea outbreak in China, but distinct from groups A, B, and C rotaviruses known to cause diarrheal diseases in humans. Accordingly, rotavirus strains B219 and ADRV-N were considered to belong to a novel group of human rotavirus, and the ADRV-N-like novel human rotaviruses were suggested to be distributed to a geographically wider area.

Aged↗
PubMed2006

Subtype IV of the BK polyomavirus is prevalent in East Asia.

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney. Using either serological or genotyping methods, BKV isolates have been classified into four subtypes (I-IV), with subtype I mainly detected in all countries studied so far. To elucidate the subtype of BKV prevalent in East Asia, we examined BKV-positive urine samples collected from immunocompetent elderly patients in Mongolia, Northeast China, Northwest China, Southeast China, Southwest China, Vietnam and Japan. The 287-bp typing region of the viral genome in each of these samples was PCR-amplified and sequenced, and a phylogenetic tree was constructed. According to the tree, BKV isolates in East Asia were unambiguously classified into subtype I or IV (subtypes II and III were not detected). In Japan, subtype I was mainly detected and subtype IV was rare, whereas in the other regions subtype IV was detected frequently, at rates ranging from 24 to 100%. Thus, East Asia (excluding Japan) is a region in which subtype-IV BKV is prevalent, a finding that requires the view of the geographic distribution of BKV subtypes to be revised. Furthermore, we present evidence that the immunological states of urine donors do not affect the pattern of BKV subtypes.

BK Virus↗
PubMed2006

Analysis of genetic factors related to preferential selection of the NSP1 gene segment observed in mixed infection and multiple passage of rotaviruses.

Reassortment is one of the major evolutionary mechanisms of the rotavirus genome. Preferential selection (assortment) of the NSP1 gene segment from either of the parental viruses after coinfection of these viruses has been reported as a notable finding in reassortment. To analyze genetic factors which are associated with preferential selection of the rotavirus NSP1 gene segment into progeny viruses, mixed infection and multiple passages were performed using two panels of rotaviruses, i.e., bovine rotavirus A5 clones, and simian rotavirus SA11 and five strains of SA11-based single NSP1 gene-substitution reassortants. In the first experiment, three A5 clones (A5-10, A5-13, and A5-16) that had genetically distinct NSP1 genes in the same genetic background were used. In coinfection of these A5 clones, it was noted that the A5-10 NSP1 gene, which encodes an incomplete protein product due to presence of a nonsense codon at an unusual position, was selected more preferentially than the A5-13 NSP1 gene with intact length and structure. The A5-16 NSP1 gene, with a deletion of 500 bp, was least efficiently selected. In the second experiment, we prepared two reassortants, SOF and SRF, which have NSP1 genes from rotavirus strains OSU and RRV, respectively, in the genetic background of SA11, which were used together with previously prepared reassortants SKF, SDF, and SNF, which had NSP1 genes from strains KU, DS1, and K9, respectively. Among the 6 NSP1 genes analyzed, the NSP1 gene from SKF was most preferentially selected, followed by SNF, SOF, SDF, SA11, and SRF, in that order. Although SOF exhibited less growth efficacy than SA11, the growth rates of other reassortants were similar to that of SA11. These findings suggest that for the occurrence of preferential selection of the NSP1 gene, production of the intact NSP1 protein may not be involved, but the presence of intact length of the NSP1 gene may be required. Furthermore, it was also found that genetic similarity based on primary structure of this gene is not related to the selectivity of the NSP1 gene.

Animals↗
PubMed2006

RT-PCR based diagnosis revealed importance of human group B rotavirus infection in childhood diarrhoea.

BACKGROUND: Human group B rotavirus was first identified as causative agent of a large outbreak of severe gastroenteritis affecting more than 1 million people, predominantly adults in China in 1982-1983. In spite of serological evidences for the presence of group B rotavirus in many countries of the world, the virus has been detected only from China, India and Bangladesh, where most of the cases were from adults. OBJECTIVES: To ascertain the role of group B rotavirus as an aetiological agent of diarrhoea among children in Kolkata, India. STUDY DESIGN: An active surveillance was conducted for rotavirus infection in children in a leading referral paediatric hospital and a few samples were also collected from adults of another hospital in Kolkata, India over a period of 3 years (2002-2004). After primary screening of rotaviruses by RNA electrophoresis in polyacrylamide gel, 200 of 412 samples negative by PAGE were screened by reverse transcription polymerase chain reaction for group B rotaviruses. The group B rotavirus positives samples were also confirmed by dot-blot hybridization. RESULT: During the study period, we detected 37 (18.5%) sporadic cases of human group B rotavirus infection in children below 3 years of age of which 15 (7.5%) showed mixed infection with group A rotaviruses by RT-PCR. In dot-blot hybridization studies the RNA of all rotavirus positive samples hybridized with the nonisotopic psoralen-biotin labeled total RNA probe generated from a human group B rotavirus CAL-1 strain confirming the samples as group B rotaviruses. CONCLUSION: The shift in age preference of group B rotavirus infection from adult to children and mixed infection of group B and group A rotaviruses reveals the importance of group B rotavirus as an etiological agent of childhood diarrhoea. Therefore, future vaccination strategy should include both group A and B rotaviruses to control rotavirus diarrhoea.

Child, Preschool↗
PubMed2006

Changing pattern of human group A rotaviruses: emergence of G12 as an important pathogen among children in eastern India.

BACKGROUND: Rotavirus genotypes, G1-G4 and G9 are associated with childhood diarrhoea throughout the world. In our previous study, we detected G1, G2, G4 and three G12 strains from Kolkata, India. OBJECTIVES: To study the prevalence of G- and P-genotypes of rotaviruses associated with dehydrating diarrhoea in children admitted to two leading hospitals in eastern India. STUDY DESIGN: An active surveillance was conducted for elucidation of rotavirus infection in two leading hospitals in Kolkata, West Bengal and Berhampur (GM), Orissa, India, separated by 603km from January 2003 to April 2005. The rotaviruses were detected by RNA electrophoresis in polyacrylamide gels. G- and P-typing of the positive samples were accomplished by amplifying VP7 and VP4 genes by RT-PCR and genotyped by seminested multiplex PCR methods. Sequencing, sequence analysis and phylogenetic analysis of VP7 genes of G12 strains were carried out to understand the variations between the strains isolated from different parts of the world. RESULTS: The genotypic distribution varied remarkably from our earlier study period (1998-2001) with G1 (53.8%) being the most predominant strain followed by G2 (22.5%), G12 (17.1%), G9 (2.1%) and not a single G3 or G4 isolate was detected separately. 35.2% samples exhibited mixed P-types followed by P[4] (31.7%), P[8] (21.8%) and P[6] (9.8%). The phylogenetic analysis of G12 strains revealed that the G12 strains detected from different parts of the world clustered into three different lineages. Though VP7 sequences of G12 strains isolated from Kolkata and Berhampur are conserved, their P-types were different. CONCLUSION: During this study period we reported emergence of G12 strains as an important pathogen among children in eastern India, thus necessitating its inclusion in future polyvalent vaccine to control rotavirus diarrhoea.

Antigens, Viral↗
PubMed2006

An optical spectrum of the afterglow of a gamma-ray burst at a redshift of z = 6.295.

The prompt gamma-ray emission from gamma-ray bursts (GRBs) should be detectable out to distances of z > 10 (ref. 1), and should therefore provide an excellent probe of the evolution of cosmic star formation, reionization of the intergalactic medium, and the metal enrichment history of the Universe. Hitherto, the highest measured redshift for a GRB has been z = 4.50 (ref. 5). Here we report the optical spectrum of the afterglow of GRB 050904 obtained 3.4 days after the burst; the spectrum shows a clear continuum at the long-wavelength end of the spectrum with a sharp cut-off at around 9,000 A due to Lyman alpha absorption at z approximately 6.3 (with a damping wing). A system of absorption lines of heavy elements at z = 6.295 +/- 0.002 was also detected, yielding the precise measurement of the redshift. The Si ii fine-structure lines suggest a dense, metal-enriched environment around the progenitor of the GRB.

Journal Article↗
PubMed2006

Molecular characterization of a porcine Group A rotavirus strain with G12 genotype specificity.

A porcine Group A rotavirus strain (RU172) was detected and molecularly characterized during a surveillance study conducted for rotavirus infection in a pig farm located in a suburban area of Kolkata City, India. The G12 genotype specificity of RU172 was revealed by PCR-based genotyping assays following addition of a G12 type-specific primer (designed in our laboratory to pick up G12 isolates from field samples) and was confirmed by sequence analysis of the VP7-encoding gene. The RU172 strain exhibited maximum VP7 identities of 93.6% to 94.5% with human G12 strains at the deduced amino acid level. In spite of its G12 genotype nature, RU172 appeared to be distinct from human G12 rotaviruses and, on phylogenetic analysis, formed a separate lineage with human G12 strains. Among the other gene segments analyzed, RU172 belonged to NSP4 genotype B, had a NSP5 and VP6 of porcine origin, and shared maximum VP4 identities with porcine P[7] rotaviruses (94.3%-95.4% at the deduced amino acid level). Therefore, to the best of our knowledge, this is the first report of detection of an animal rotavirus strain with G12 genotype specificity. Detection of strains like RU172 provides vital insights into the genomic diversity of Group A rotaviruses of man and animals.

Amino Acid Sequence↗
PubMed2006

Superconductivity in entirely end-bonded multiwalled carbon nanotubes.

We report that entirely end-bonded multiwalled carbon nanotubes (MWNTs) can exhibit superconductivity with a transition temperature (T(c)) as high as 12 K, which is approximately 30 times greater than T(c) reported for ropes of single-walled nanotubes. We find that the emergence of this superconductivity is highly sensitive to the junction structures of the Au electrode/MWNTs. This reveals that only MWNTs with optimal numbers of electrically activated shells, which are realized by end bonding, can allow superconductivity due to intershell effects.

Journal Article↗
PubMed2006

Execution of BMP-4-induced apoptosis by p53-dependent ER dysfunction in myeloma and B-cell hybridoma cells.

Bone morphogenic protein (BMP)-4 inhibits proliferation and induces the apoptosis of myeloma cells. However, little is known about the molecular mechanisms of how BMP-4 executes this apoptosis. In this report, we investigated the roles of p53 and the endoplasmic reticulum (ER) in BMP-4-induced apoptosis of mouse hybridoma HS-72 cells. We found that 3 ng/ml of BMP-4 is sufficient to induce the expression of proapoptotic proteins, puma and bax, in a p53-dependent mechanism, and facilitate Ca(2+) release from the ER to the cytosol, resulting in the activation of caspase-12 and ER dysfunction. Similarly to HS-72 cells, multiple myeloma cells with wild-type p53 genes show much higher sensitivity to BMP-4-induced apoptosis than cells without wild-type p53 genes, suggesting that wild-type p53 status is required for dysfunction of the ER during BMP-4-induced apoptosis in ER-enriched cells, such as hybridoma and myeloma cells. These findings demonstrate that the presence of wild-type p53 genes and enrichment of the ER determines the sensitivity to effective apoptosis by BMP-4, and suggest that ER stress-inducing agents would be valuable in the treatment of multiple myeloma.

Animals↗
PubMed2006

Coincidence of a right retroaortic circumflex coronary artery and a right-sided aortic arch with a retroesophageal course of the left subclavian artery (arteria lusoria).

An anomalous branch of the right coronary artery was found in a 71-year-old male cadaver with a right-sided aortic arch. The anomalous artery arose from the proximal portion of the right coronary artery and ran in a retroaortic course, before reaching the posterior wall of the heart. It was recognized as the right-sided variation of the circumflex coronary artery. The aortic arch had as branches the left common carotid, right common carotid, right subclavian, and left subclavian arteries, in that order, and the descending aorta was located in the right thorax. The left subclavian artery arose from a Kommerell's diverticulum and ran behind the esophagus, and the left-sided ligamentum arteriosum was also connected at the diverticulum. Therefore, the right aortic arch was classified as type N according to Adachi-Williams-Nakagawa and type III-B1 in accordance with Stewart-Edwards. The Kommerell's diverticulum in this case seemed to press on the posterior wall of the esophagus.

Aged↗
PubMed2006

Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic renal insufficiency (CRI). We proposed that changes in serum PTH and FGF23 levels might be associated with changes in serum phosphorus levels caused by the phosphate binder sevelamer hydrochloride (sevelamer, i.e. crosslinked poly[allylamine hydrochloride]). Rats were fed a diet containing adenine for 4 weeks to establish CRI. Animals were then offered either a normal diet or a diet containing 1 or 3% sevelamer for 8 weeks continuously, or intermittently with sevelamer diet or a normal diet offered for alternating 2-week periods. Changes in the serum levels of phosphorus, calcium, PTH, FGF23, and 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) were monitored over time. Adenine-treated rats developed severe CRI, with markedly elevated serum levels of phosphorus, PTH and FGF23, and reduced levels of serum 1,25(OH)(2)D(3). Continuous treatment with sevelamer suppressed these increases throughout the study period. Serum phosphorus, PTH, and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, the changes in serum FGF23 levels began after the onset of changes in serum phosphorus and PTH levels. In conclusion, circulating PTH, and FGF23 levels can be promptly manipulated through the control of serum phosphorus levels. Moreover, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CRI.

Adenine↗
PubMed2006

Modified two-layer preservation method (M-Kyoto/PFC) improves islet yields in islet isolation.

Islet allotransplantation can achieve insulin independence in patients with type I diabetes. Recent reports show that the two-layer method (TLM), which employs oxygenated perfluorochemical (PFC) and UW solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. However, UW solution has several disadvantages, including the inhibition of Liberase activity. In this study, we investigated the features of a new solution, designated M-Kyoto solution. M-Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M-Kyoto/PFC group compared with the UW/PFC group. There was no significant difference in ATP content in the pancreas between the two groups, suggesting that different islet yields are not due to their differences as energy sources. Compared with UW solution, M-Kyoto solution significantly inhibited trypsin activity in the digestion step; moreover, M-Kyoto solution inhibited collagenase digestion less than UW solution. In conclusion, the advantages of M-Kyoto solution are trypsin inhibition and less collagenase inhibition. Based on these data, we now use M-Kyoto solution for clinical islet transplantation from nonheart-beating donor pancreata.

Adenosine↗