Search PubMed⌕ Search

Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 289 records · Page 16Linked to original sources
PubMed1998

Functional recovery of vision in regenerated optic nerve fibers.

Retinal ganglion cells (RGCs) of adult mammals normally suffer from retrograde cell death after optic nerve section. However, with transplantation of a segment of peripheral nerve (PN), their axons can regenerate and regrow through the graft. When properly guided, the regenerated axons make functional synapses with the target cells in the superior colliculus. Two months after PN graft we studied the number and morphology of RGCs with regenerated axons in adult cats. Number of regenerated RGCs was a few percent of the total population and, among various RGC types, alpha cells revealed the greatest ability for axonal regeneration and ON-center RGCs tended to regenerate better than OFF-center cells. While dendritic field dimension of RGCs with regenerated axons was mostly preserved, their regenerated axons were thinner than normal optic axons and mostly unmyelinated. The RGCs with regenerated axons revealed normal physiological properties in response to visual stimuli, and were classifiable into Y, X or W cells. In accordance with morphological results, Y cells (morphological alpha cells) were most frequently sampled. In hamsters and rats it has been shown that the animals with reconstructed retinocollicular pathway by the PN graft reveal behavioral recovery of visual function. However, in the cat, trials are still in progress to reconstruct the retinogeniculate pathway. The present status of researches on optic nerve regeneration of adult mammals using the PN graft is reviewed, and some future directions discussed.

Action Potentials↗
PubMed1998

Construction and expression of a mouse-human chimeric antibody against human tumor necrosis factor-alpha.

A mouse anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (MoAb), designated as 3B10, has previously been produced and characterized by our laboratory. We report here the construction and the expression of mouse-human chimeric antibody derived from the MoAb. cDNAs encoding variable regions of heavy and light chains were prepared from 3B10 cells by polymerase chain reaction, and introduced to mammalian expression vectors containing cDNA for human gamma1 and kappa constant regions, respectively. Cotransfection of the vectors into CHO cells resulted in production of antibody reacting with human TNF-alpha. In SDS-PAGE analysis, the chimeric antibody, c3B10, migrated at 170 kDa under a nonreducing condition, whereas two bands with 58 and 28 kDa appeared following treatment with 2-mercaptoethanol. Both c3B10 and mouse 3B10 neutralized the cytotoxic activity of human TNF-alpha to the same level, indicating that c3B10 holds the binding activity of its original MoAb. These findings suggest that the introduced genes for chimeric heavy and light chains are transcribed and translated to produce the chimeric heavy and light chain peptides, and that the peptides are assembled to form native IgG molecule. The chimeric anti-TNF-alpha antibody described in this study is expected to be less immunogenic and thus more suitable for possible clinical use.

Animals↗
PubMed1998

An analysis of the prognostic significance of p53 status for squamous cell carcinoma of the oral cavity treated by radiotherapy.

The status of the p53 gene in biopsy specimens was analyzed to determine whether it is predictive of the outcome of radiotherapy of squamous cell carcinomas of the oral cavity. Biopsy materials were obtained from 45 patients, and the p53 status of each patient was determined using a single-strand conformation polymorphism analysis. Fourteen of the patients were treated with radiation therapy alone; the other 31 patients underwent radiotherapy in combination with surgery or chemotherapy. Twenty-seven patients had tumors with wild-type p53 and 18 patients had a tumor with mutant p53. The initial tumor response was not significantly different between these two groups. Kaplan-Meier survival plots (log-rank test) showed that the probability of survival was not significantly different between two groups although the patients with mutant p53 had a tendency for longer survival (P = 0.2941). However, among the patients with stage III/IV tumors (n = 24), those with a wild-type p53 status tended to have longer survivals.

Adult↗
PubMed1998

Nitric oxide-induced cytotoxicity attenuation by thiopentone sodium but not pentobarbitone sodium in primary brain cultures.

1. We describe the effects of barbiturates on the neurotoxicity induced by nitric oxide (NO) on foetal rat cultured cortical and hippocampal neurones. Cessation of cerebral blood flow leads to an initiation of a neurotoxic cascade including NO and peroxynitrite. Barbiturates are often used to protect neurones against cerebrovascular disorders clinically. However, its neuroprotective mechanism remains unclear. 2. In the present experiment, we established a new in vitro model of brain injury mediated by NO with an NO-donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5) on grid tissue culture wells. We also investigated the mechanisms of protection of CNS neurones from NO-induced neurotoxicity by thiopentone sodium, which contains a sulphydryl group (SH-) in the medium, and pentobarbitone sodium, which does not contain SH-. 3. Primary cultures of cortical and hippocampal neurones (prepared from 16-day gestational rat foetuses) were used after 13-14 days in culture. The cells were exposed to NOC-5 at the various concentrations for 24 h in the culture to evaluate a dose-dependent effect of NOC-5. 4. To evaluate the role of the barbiturates, neurones were exposed to 4, 40 and 400 microM of thiopentone sodium or pentobarbitone sodium with or without 30 microM NOC-5. In addition, superoxide dismutase (SOD) at 1000 u ml(-1) and 30 microM NOC-5 were co-administered for 24 h to evaluate the role of SOD. 5. Exposure to NOC-5 induced neural cell death in a dose-dependent manner in both cortical and hippocampal cultured neurones. Approximately 90% of the cultured neurones were killed by 100 microM NOC-5. 6. This NOC-5-induced neurotoxicity was significantly attenuated by high concentrations of thiopentone sodium (40 and 400 microM) as well as SOD, but not by pentobarbitone sodium. The survival rates of the cortical neurones and hippocampal neurones that were exposed to 30 microM NOC-5 were 11.2+/-4.2% and 37.2+/-3.0%, respectively, and in the presence of 400 microM thiopentone sodium, the survival rate increased to 65.3+/-3.5% in the cortical neurones and 74.6+/-2.2% in the hippocampal neurones. 7. These findings demonstrate that thiopentone sodium, which acts as a free radical scavenger, protects the CNS neurones against NO-mediated cytotoxicity in vitro. In conclusion, thiopentone sodium is one of the best of the currently available pharmacological agents for protection of neurones against intraoperative cerebral ischaemia.

Animals↗
PubMed1998

Assessment and treatment of liver disease in Japanese haemophilia patients.

We studied the prevalence of the hepatitis C virus (HCV), human immunodeficiency virus (HIV) and GB virus C or hepatitis G virus (GBV-C/HGV), and characteristics of infections in Japanese haemophilia patients. Haemophilia patients were highly infected with HCV (88.2%) because of frequent use of unheated blood concentrates. Analysis for HCV genotypes revealed characteristics of HCV infection in haemophilia patients. Japanese haemophilia patients were highly infected with rare genotypes in Japan: genotype 1a (26.5%), genotype 3 (14.5%) and genotype 4 (2.4%). HIV infection was observed in 32.3% of haemophilia patients. HCV quasispecies (clones) and direct sequencing were investigated in patients with a single HCV genotype in the hypervariable region 1 of HCV, which resulted in a high degree of diversity. This indicates that even a single genotype of HCV might have multiple origins. GBV-C/HGV infection was noted in 20.9% of Japanese haemophilia patients. Over 40 haemophilia patients with chronic hepatitis C have been treated with interferon alpha for 6 months at total doses of 480-720 million units. About 38% showed clearance of HCV RNA from serum. Six patients with HIV infection were included in the study and they did not show eradication of HCV from the serum. This might derive from that they had high serum HCV RNA titers and genotype 1a or 1b. Histologic assessment was performed in 36 haemophilia patients with HCV. No case showed a histologically normal liver. Hepatic fibrosis in the biopsy specimens was classified into five stages of fibrosis and compared with serum hepatic fibrosis markers. Serum hyaluronic acid mostly correlated with hepatic fibrosis (r = 0.78, P < 0.0001) followed by type IV collagen (r = 0.38, P < 0.05). This suggests that estimation of serum fibrosis markers might be substituted for liver biopsy in haemophilia patients.

HIV Infections↗
PubMed1998

The outcome of liver transplantation at various times (70, 120, and 134 days) after the initiation of carcinogenesis in rats.

The therapeutic results of liver transplantation for primary liver cancer have not been satisfactory. The high rate of recurrence appears to be due to the inadequate care taken in selecting the most appropriate candidates for orthotopic liver transplantation (OLT), the presence of circulating hepatocellular carcinoma (HCC) cells and micrometastases at the time of liver transplantation, and the tumor growth-promoting effects of immunosuppressive agents. We believe that HCC patients must be carefully staged in order to identify those most suitable for OLT. We therefore induced HCC in pure-strain rats by the oral administration of diethylnitrosamine (DEN) and studied the outcomes of liver transplantation at various time points (70, 120, and 134 days) after the initiation of carcinogenesis. The mean survival time (MST +/- SD) of the non-OLT control group (N = 14) was 18.2 +/- 5 days after Day 120. The survival time of the four rats in the OLT Day 120 group was 81.3 +/- 20.6 days after transplantation. One rat showing full weight recovery soon after transplantation survived for 97 days after transplantation and then succumbed to recurrence. The survival time of the four rats in the OLT Day 134 group was 7.3 +/- 5.0 days after transplantation. The survival time of the three rats in the OLT Day 70 group was 145.3 +/- 70.0 days after transplantation, with a maximum survival of 221 days until death. Significantly prolonged survival, as compared with that in the non-OLT group, was observed in the OLT Day 70 and OLT Day 120 groups (p < 0.01), while there was no significant prolongation in the OLT Day 134 group (NS). The timing of liver transplantation is a very important factor. Preoperative assessment of factors potentially affecting recurrence in HCC patients is imperative for selecting the most appropriate candidates for OLT. Careful selection of candidates for OLT should always be considered the key to successful liver transplantation (i.e., long-term survival) for patients with liver cancer.

Animals↗
PubMed1998

Characteristics of patients with chronic infection due to hepatitis C virus of mixed subtype: prevalence, viral RNA concentrations, and response to interferon therapy.

We studied 349 patients with chronic infection due to hepatitis C virus (HCV), including 83 with coagulopathy, 122 with community-acquired infection, 20 with chronic posttransfusion hepatitis C, and 124 for whom the transmission mode was unknown. The prevalence of mixed-subtype HCV infection was investigated in each group of patients. The serum HCV RNA concentration and the response to interferon (IFN) therapy were evaluated. HCV infection with mixed subtypes was more frequent in patients who had been at high risk for exposure to HCV, such as those with coagulopathy or community-acquired infection. HCV RNA concentrations were lower in patients infected with mixed subtypes, except for those with subtypes 1a and 1b. Ten of 11 patients with mixed subtypes (not including those with 1a and 1b) achieved complete clearance of HCV RNA with IFN therapy.

Adolescent↗
PubMed1998

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayama's method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Animals↗
PubMed1998

Prophylactic endoscopic ligation of high-risk oesophageal varices in a cirrhotic patient with severe haemophilia A.

One of the main complications in cirrhosis is haemorrhage from oesophageal varices. It is serious and often fatal, especially in cirrhotic patients with haemophilia. We describe the use of endoscopic variceal ligation (EVL) for prophylaxis of oesophageal variceal bleeding in a high-risk patient, a 40-year-old Japanese man, with severe haemophilia A and liver cirrhosis caused by hepatitis C virus. He had large, coil-shaped varices with a red colour sign, predicting the likelihood of haemorrhage. Administration of omeprazole and factor VIII concentrate achieved rapid healing of the post-EVL ulcers and prevented bleeding from them. Four EVL sessions eradicated oesophageal varices completely, and he has had no recurrence of varices for 2 years, indicating that the procedure was of considerable benefit.

Adult↗
PubMed1998

Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis.

The role of various matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2), and the gelatinolytic activities of MMP involved in the process of bleomycin-induced pulmonary fibrosis in rabbits were investigated. Male Japanese white rabbits were intubated with tracheal tubes under anesthesia, and bleomycin hydrochloride in sterile saline or only sterile saline was administered through the tracheal tubes. The animals were killed 1, 3, 7, 14 and 28 days after the administration of bleomycin (n = 3) or saline (n = 2). Light microscopic immunohistochemistry for MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-9 (gelatinase B) and TIMP-2 was performed. The gelatinolytic activities of lung tissue homogenates were studied by gelatin zymography. In the early stages, the gelatinolytic activity of MMP-9 was predominant. MMP-9 localized in the infiltrating neutrophils, macrophages, bronchial and bronchiolar epithelial cells. The alveolar epithelial basement membrane was frequently disrupted in the early stages, where MMP-9 possibly contributed to the disruption. In the late stages, the gelatinolytic activities of the latent and active forms of MMP-2 were predominant, and MMP-2 localized in the regenerated alveolar epithelial cells in addition to the bronchial epithelial cells. MMP-2, especially its active form, possibly plays a role in alveolar epithelial cell regeneration. The localization of MMP-1 was similar to that of MMP-9. TIMP-2 localized in the epithelial cells and in some fibroblasts in fibrotic lesions. TIMP-2 possibly plays a role in extracellular matrix deposition in balance with MMP.

Animals↗
PubMed1998

Serum hyaluronan as a marker of liver fibrosis in hemophiliacs with hepatitis C virus-associated chronic liver disease.

We measured serum type III procollagen peptide, type IV collagen (IV-C), and hyaluronan (HA) in 36 hemophiliacs with hepatitis C virus (HCV)-related chronic liver disease. We also measured these markers in 19 interferon (IFN)-treated patients before and after a 6-month course of IFN-alpha. The serum concentrations of IV-C and HA were correlated with the stage of fibrosis (IV-C r = 0.38; HA r = 0.78). These markers fell only in complete responders showing sustained clearance of serum HCV RNA by IFN. These results suggest that, in hemophiliacs with chronic liver disease, serum HA measurement might be an alternative to liver biopsy and reflect the response to IFN.

Adolescent↗
PubMed1998

Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in asymptomatic carriers of hepatitis C virus.

High levels of serum-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have been noted in patients with chronic hepatitis C. This study aimed to measure serum levels of sICAM-1 and sVCAM-1 in asymptomatic hepatitis C virus carriers and clarify the clinical significance of measuring soluble forms. Serum levels of sICAM-1 were significantly higher than in healthy controls but serum sVCAM-1 levels did not differ statistically from those in healthy controls. Liver biopsy obtained from 12 asymptomatic hepatitis C virus carriers showed evidence of hepatitis. Estimating sICAM-1 and sVCAM-1 in asymptomatic carriers may be helpful, especially in cases in which liver biopsy is not possible.

Adult↗
PubMed1998

Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial agent in intravenous use. II. Dermovascular permeability-increasing effect and action on peritoneal mast cells.

To predict the actions of T-3762, a newly developed fluoroquinolone antimicrobial agent, as well as ciprofloxacin (CPFX) and ofloxacin (OFLX), on injection sites when dosed parenterally, their ability to increase cutaneous vascular permeability in dogs and to release histamine from rat peritoneal mast cells was examined. CPFX and OFLX increased cutaneous vascular permeability in concentrations ranging from 16 to 32 microg/ml, while T-3762 was inactive at 2000 microg/ml. The vascular permeability-increasing activities of these drugs were inhibited efficiently by pretreatment with a combined dose of diphenhydramine and cimetidine. CPFX induced histamine release from rat mast cells in a dose-dependent manner, whereas T-3762 was ineffective. Therefore, it is concluded that fluoroquinolone antimicrobial agents may have the ability to cause an increase in cutaneous vascular permeability by releasing histamine from mast cells at the injection site when administered parenterally, and that T-3762 has minimum activity among the agents tested in this study.

Animals↗