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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 199 records · Page 11Linked to original sources
PubMed2000

An improved method for avulsion of lumbar nerve roots as an experimental model of nitric oxide-mediated neuronal degeneration.

A root avulsion lesion on the spinal nerve of adult animals is a useful technique to make a model for axotomy-induced motoneuronal degeneration, which is thought to be mediated by nitric oxide (NO). Here, we show a simplified version of extravertebral avulsion in the young adult rat. The L4 nerve always runs under the transverse process of the L5 vertebra, which is located just rostral to the delineation of the iliac crest. We used the iliac crest as a clue for the identification of the L4 nerve during surgery, including before skin incision. In almost all animals the L4 nerve was successfully avulsed at the exit point from the spinal cord. This experimental result was similar to that shown in the previous literature; the number of either Nissl-stained or ChAT-immunoreactive (-ir) motoneurons (MN) gradually decreased, while NOS immunoreactivity was induced in the MN after avulsion. Furthermore, a combined method of confocal laser scanning microscopy and double fluorescent procedures carried out in this model suggested the existence of cellular interaction between NOS-ir MN and OX42-ir or ED1-ir microglia. It is concluded that this simple and fast method of spinal root avulsion is very useful for making a reproducible model of NO-mediated MN cell death, with which the mechanism of neuronal cell death, including neuron-glia interaction, can be further explored.

Animals↗
PubMed2000

Is Campylobacter lipopolysaccharide bearing a GD3 epitope essential for the pathogenesis of Guillain-Barré syndrome?

The hypothesis has been proposed that the GD3 ganglioside-like lipopolysaccharide (LPS) is essential for and functions in the development of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) subsequent to Campylobacter jejuni enteritis. Our study showed that patients with GBS or MFS who had previously suffered diarrhea had anti-GD3 antibodies less often than those who had not had diarrhea. Sera from patients who showed GBS or MFS with the serologic evidence of prior C. jejuni infection had anti-GD3 antibodies less frequently than sera from those without evidence of infection. Statistical analysis showed that anti-GD3 antibodies were less frequent in patients with GBS or MFS from whom C. jejuni had been isolated than were other antiganglioside antibodies, such as anti-GM1 antibodies. These results could not support the above hypothesis.

Acute Disease↗
PubMed2000

A prospective study of interferon therapy modified by pre-treatment viral load in cirrhotic patients. Tokyo-Chiba Hepatitis Research Group.

BACKGROUND/AIMS: The relative role of hepatitis C virus (HCV) load and subtype as predictors of the efficacy of interferon therapy has been clarified in patients with chronic hepatitis C, but the effectiveness of interferon therapy in cirrhotic patients is still unclear. METHODS: To resolve this issue, we undertook a multicenter, randomized, and prospective study of 114 cirrhotic patients with hepatitis C virus infection. The patients were selected to undergo two different periods (6 or 12 months) of IFN therapy according to viral load. Patients with "low" viral load (< or = 10(5.8) copies/ml serum) were randomly divided into three groups, receiving 6 or 9 million units (MU) interferon three times a week for 6 months (total dose: 468 or 702 MU), or of a modified regimen using 6MU of IFN over 6 months (total dose 564 MU), while patients with "high" viral load (< or = 10(6.3) copies/ml serum) were also randomly divided into two groups of 6 or 9 MU of IFN three times a week for 12 months (total dose: 936 or 1,404 MU). RESULTS: HCV-RNA negativity rate at the completion of treatment with 6 or 9 MU IFN was 65% in patients with "low" viral load, in contrast to 14% in patients with "high" viral load. Sustained virological response was found in 40% of patients with "low" viral load irrespective of the three different regimens, in contrast to only 1 out of 35 patients (3%) with "high" viral load. Viral eradication was found in approximately 50% of patients having a low virus load (< or = 10(4.3) copies/ml) and with HCV subtype 2a. Univariate and multivariate analysis revealed that pretreatment viral load was a significant factor contributing to efficacy of IFN therapy. CONCLUSIONS: Sustained response was scarcely achieved in cirrhotic patients with high viral loads even after a 12-month course of intensive IFN therapy. This result indicates that there is a certain cut-off level of HCV RNA load which can not be eradicated.

Adult↗
PubMed2000

Possible mechanism of bronchoprotection by SIN-1 in anaesthetized guinea pigs: roles of nitric oxide and peroxynitrite.

BACKGROUND: S-morpholinosydnonimine (SIN-1) is thought to generate peroxynitrite. Recent reports suggested that peroxynitrite possessed a potent vascular relaxant activity via guanylate cyclase activation. However, no previous studies have examined the relaxant effect of peroxynitrite on airway smooth muscle. OBJECTIVE: To determine the mechanism of bronchoprotection by SIN-1, considering in particular the involvement of nitric oxide (NO) and peroxynitrite. METHODS: Peroxynitrite formation was assayed by monitoring the oxidizing activity of dihydrorhodamine 123, and NO was measured polarographically as a redox current in vitro. We examined the effect of SIN-1 delivered to the airway by ultrasonic nebulization against bronchoconstriction induced by acetylcholine in anaesthetized guinea pigs. RESULTS: SIN-1 produced peroxynitrite in a time- and concentration-dependent manner, but did not produce NO in vitro. However, when mixed with glutathione (GSH) and bronchoalveolar lavage fluid (BALF), peroxynitrite formation by SIN-1 was inhibited and SIN-1 induced the release of NO. SNAP (S-nitroso-N-acetyl-penicillamine) and SIN-1 each inhibited acetylcholine-induced bronchoconstriction in a dose-dependent manner in vivo. Though GSH alone did not have any effect on baseline airway resistance and acetylcholine-induced bronchoconstriction, pretreatment with GSH significantly enhanced SNAP- and SIN-1-induced bronchoprotection. In addition, pretreatment with carboxy-PTIO, a NO scavenger, completely inhibited bronchoprotective effect of SNAP on acetylcholine-induced bronchoconstriction, but partially inhibited SIN-1-induced bronchoprotection. CONCLUSION: These findings demonstrated that SIN-1 is a potent peroxynitrite-releasing compound and caused significant bronchoprotection against acetylcholine. The mechanism of bronchoprotection by SIN-1 appears to be mediated by peroxynitrite but also at least in part through NO regeneration, which may involve GSH and airway thiols as a consequence of exposure to peroxynitrite.

Acetylcholine↗
PubMed2000

Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS).

Brainstem function was evaluated by proton magnetic resonance (MR) spectroscopy (1H-MRS) in a 69-year-old man with idiopathic rapid eye movement (REM) sleep behavior disorder. An analysis of spectral peak area ratios revealed an increase in the choline/creatine ratio. This change suggests that brainstem neurons have functional impairment at the cell membrane level. Further, our results suggest that 1H-MRS may provide for non-invasive, metabolic evaluation of brainstem neuronal function in REM sleep behavior disorder and find application in the differentiation of secondary REM sleep behavior disorders with neurodegenerative disorders from idiopathic disorders.

Aged↗
PubMed2000

Heme oxygenase1 (HSP-32) is induced in myelin-phagocytosing Schwann cells of injured sciatic nerves in the rat.

Schwann cells participate in myelin phagocytosis in the early stage of Wallerian degeneration, prior to the recruitment of macrophages. This is the first report that Schwann cells induce heme oxygenase-1 (HO-1), a 32-kDa heat shock protein, only when they have transformed into myelin-phagocytosing cells from myelinating cells (days 2-3) immediately after crush injury of rat sciatic nerves. Double immunofluorescent labelling for HO-1 and transferrin receptors revealed that HO-1-immunoreactive Schwann cells also expressed transferrin receptors suggesting activation of iron metabolism. The transient induction of HO-1 in Schwann cells may contribute to the adaptive function in an altered environment when the cells have lost contact with axons, and may play a crucial role in the ensuing regeneration.

Animals↗
PubMed2000

Paper is a compatible bed for rat hepatocytes.

To develop an effective hybrid bioartificial liver (BAL) device, the material of the scaffold is very important to support hepatocytes that have both growth ability and hepatic differentiated functions. In this study we used paper (Kimwipe, Kimberly-Clark Corp., Roswell, GA, U.S.A.) as a scaffold. Primary hepatocytes isolated from a normal adult rat liver could proliferate on the paper. The secretion of albumin into culture medium by the cells on the paper increased with time in culture and, compared to the cells on dishes, the amount of 48 h albumin secretion at Day 10 was two times larger. Perpendicular sections of hepatocytes on the paper revealed that the cells fell into cavities made by intersecting fibers, piled up, and formed three to four layers. The piled-up cells changed their shape from flat to cuboidal and enlarged their cytoplasm, which was rich in organelles such as mitochondria and peroxisomes with a nucleoid. In addition, they formed bile canalicular structures between the cells. Their morphological appearance was similar to in vivo hepatocytes. Paper (Kimwipe) may be a good candidate as a scaffold to make a BAL device.

Albumins↗
PubMed2000

Role of endogenous nitric oxide in exercise-induced airway narrowing in patients with bronchial asthma.

BACKGROUND: Increased amounts of nitric oxide (NO) in expired air and induced sputum have been found in asthmatic patients, and the role of excessively produced NO in the pathogenesis of bronchial asthma is under active investigation. OBJECTIVE: This study was designed to investigate the involvement of endogenous NO in exercise-induced bronchoconstriction (EIB) in asthmatic patients by using the sputum induction method. METHODS: The concentration of NO derivatives and inflammatory indices in induced sputum were examined in 18 asthmatic subjects and 10 normal control subjects. All asthmatic subjects performed an exercise test for 6 minutes. For 8 weeks after the first exercise testing, 400 microg of beclomethasone dipropionate twice daily was administered for asthmatic subjects with EIB, and the exercise testing and sputum induction were repeated in these patients. RESULTS: The concentration of NO derivatives in induced sputum was significantly higher in 9 asthmatic subjects with EIB (1580 +/- 280 micromol/L) than in 9 asthmatic subjects without EIB (1130 +/- 210 micromol/L) and normal control subjects (510 +/- 150 micromol/L). Moreover, there was a significant correlation between the concentration of NO derivatives and the percentage of maximal fall in FEV(1) (r = 0.569, P =.019). The concentration of NO derivatives was also more closely correlated with the area under the curve of the percentage fall in FEV(1) plotted against time for 30 minutes (AUC(0-30); r = 0.812, P <.001). After treatment with inhaled beclomethasone dipropionate in asthmatic subjects with EIB, there was a significant decrease in the concentration of NO derivatives in induced sputum. The change in the concentration of NO derivatives was significantly correlated with the change in the AUC(0-30) (r = 0.896, P =.0114) but not with the change in the percentage of maximal fall in FEV(1). CONCLUSION: These findings suggest that excessive production of NO is associated with EIB in patients with asthma and contributes to the prolonged airway narrowing phase rather than to the maximal airway narrowing evoked by exercise.

Adult↗
PubMed2000

Delayed-feedback control of spatial bifurcations and chaos in open-flow models

A delayed-feedback control scheme is presented for suppressing spatial bifurcation and chaotic behavior in open-flow models. It is shown that spatial bifurcation and chaotic behavior never occur when the delayed-feedback controller is designed such that the following two conditions are satisfied: all the poles of the transfer function of each site are inside a unit circle and the H(infinity) norm of the transfer function is less than 1. We provide a simple systematic procedure for design of the delayed-feedback controller. It is confirmed that our theoretical results agree well with the numerical simulations.

Journal Article↗
PubMed2000

Spatiotemporal stability of one-way open coupled nonlinear systems

The present paper investigates the spatiotemporal stability of homogeneous solutions in one-way open coupled nonlinear systems. We show that the H(infinity) norm concept, which has been used as an important index in the field of robust control theory, allows us to grasp the mechanism of spatial instability in coupled systems. Spatial instability occurs only when the H(infinity) norm of the transfer function of each site is greater than 1. It is shown that numerical simulations for one-way open coupled double scroll circuits are in good agreement with our theoretical results.

Journal Article↗
PubMed2000

Mutations in zinc-binding domains of p53 as a prognostic marker of esophageal-cancer patients.

Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 (P=0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others (P=0.0105). Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.

Adult↗
PubMed2000

A novel experimental mouse model of peritoneal dissemination of human gastric cancer cells: different mechanisms in peritoneal dissemination and hematogenous metastasis.

We established a new cell line, AZ-P7a, with high peritoneal-metastatic potential in nude mice. AZ-P7a cells were derived from the human gastric carcinoma line AZ-521, which has low capacity for peritoneal dissemination. AZ-P7a cells developed peritoneal metastasis in 11 / 14 (78.6%) mice, whereas the parental AZ-521 cells developed metastasis in 2 / 6 (33.3%) mice. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. The tumorigenicity and the motile activity of AZ-P7a cells were stronger than those of the parental AZ-521 cells; in contrast, adhesion to the extracellular matrix and the production of vascular endothelial growth factor by AZ-P7a cells were decreased. In fluorescence-activated cell sorter (FACS) analysis, AZ-P7a cells expressed significantly greater levels of integrins alpha2, alpha3, alpha5, alpha6 and alphavbeta5, as compared with AZ-521 cells. However, alpha1, alpha4, alphavbeta3, hCD44H, hCD44v3, hCD44v6 and hCD44v10 were not expressed in either cell line. AZ-P7a cells developed no liver metastasis when administered by the intrasplenic injection method, though the highly liver metastatic cell line AZ-H5c showed the same rate of peritoneal dissemination as that exhibited by AZ-P7a cells after intraabdominal injection. These findings suggested that the mechanism of peritoneal dissemination differed from that of hematogenous metastasis. Moreover, the latter appears to be controlled by more complex mechanisms than the former. Thus, this cell line might be useful for investigating the mechanism of peritoneal dissemination of human gastric cancer.

Adenocarcinoma↗
PubMed2000

[A clinical investigation of infective endocarditis at a community hospital in Japan].

There have been few reports on the clinical features of infective endocarditis (IE) in Japan. We clinically investigates 45 episodes (36 cases) of definite IE that were experienced from January 1985 to March 1997 at a community hospital, Okinawa Chubu Hospital, Okinawa, Japan. Regarding age, prior dental procedure, causative organisms and sites of infection, analyses and comparison were performed on a total of 94 episodes, by adding another 49 episodes of IE that were experienced between 1977 and 1984 at our hospital. The mean age was 47 years and majority of patients in the recent 12 years were older than 50 years of age. Mortality of all 94 episodes was 20%, while that of recent 45 cases was 13%. Eight % of all episodes had history of recent dental treatment but significance of the finding remains unclear. Alpha streptococci were most common (33%) and Staphylococcus aureus was the second most common organism (17%). Eleven % of all episodes were culture-negative and there was a statistically significant difference in the histories of prior antibiotic therapy between culture-negative and culture-positive episodes. Regarding sites of infection, 27% of all episodes involved mitral valves, while 24% involved aortic valves. Prosthetic valves were involved in 12%. Ninety-eight % of the recent episodes had fever, 98% had cardiac murmurs and 27% had characteristic mucocutaneous lesions. Heart failure was the most common complication (27%) and half of the cases with prosthetic valve infection had heart failure. Cerebral embolism was most frequently seen among the major arterial embolic complications. Our results were similar to those which were previously reported from other countries. We should have a high index of suspicion for endocarditis whenever we see patients who present various clinical manifestations and fever of which origin remains unclear. Willingness to obtain blood culture before starting antibiotics is most important.

Adolescent↗
PubMed2000

Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract.

BACKGROUND: Little is known about the genetic alterations in multiple primary cancers of the gastrointestinal tract. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and multiple primary cancers is a feature of this syndrome. AIMS: To identify MSI incidence, target gene mutation, and mismatch repair (MMR) protein status in patients with multiple primary cancers of the gastrointestinal tract. SUBJECTS: Fifty seven cancers from 22 Japanese patients with multiple primary cancers of the stomach, duodenum, colon, and rectum. METHODS: MSI was examined at 5-7 microsatellite loci. Mutation analysis for TGFbetaRII, IGFIIR, and BAX was performed in cancers with MSI. MMR protein status was examined by immunohistochemical analysis using a monoclonal antibody against hMSH2 and hMLH1. RESULTS: MSI was observed in 16 of 22 patients (73%) and in 29 of 57 lesions (51%). High frequency MSI (MSI-H) was found often in patients with multiple cancers in the same organ (p = 0.042), especially in multiple gastric cancer patients (p = 0.038). In contrast, patients with multiple cancers in different organs had a tendency to show low frequency MSI (MSI-L) or microsatellite stable (MSS) phenotype. Both target gene mutation and decreased expression of MMR protein were found only in seven lesions of three patients with MSI at more than four microsatellite loci. CONCLUSIONS: These results suggest that genetic instability may play an important role in the development of multiple gastrointestinal cancers but there may be different genetic alterations between multiple gastrointestinal cancers of the same and different organs.

Aged↗