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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 451 records · Page 25Linked to original sources
PubMed1995

Significance of early intra-alveolar fibrotic lesions and integrin expression in lung biopsy specimens from patients with idiopathic pulmonary fibrosis.

To study the pulmonary structural remodeling in idiopathic pulmonary fibrosis (IPF), ultrastructural, immunohistochemical, and light microscopic morphometric observations were made on 11 pulmonary biopsy specimens from patients with IPF. The morphometric study was done using sequentially cut tissue sections stained for keratin-alcian blue periodic acid-Schiff (PAS), fibronectin, and type IV collagen-alcian blue PAS. Most of the early fibrotic lesions, which were alcian blue- and fibronectin-positive, were intra-alveolar in location. Intra-alveolar fibrosis is considered to be essential for the fusion of alveolar walls in IPF. A strong reaction for integrin alpha 5 beta 1 and vinculin was found in epithelial cells and mesenchymal cells in areas of intra-alveolar fibrosis. These findings show that these cells are active in adhesion to fibronectin in areas of early intra-alveolar fibrosis. Some of the epithelial cells, including cytoplasmic hyaline-laden cells, showed evidence of inadequate adhesion to the extracellular matrix, and this may constitute one of the mechanisms of progression of fibrosis in IPF.

Adult↗
PubMed1995

Epitope mapping of monoclonal antibodies to tumor necrosis factor-alpha by synthetic peptide approach.

A monoclonal antibody (mAb) against human tumor necrosis factor-alpha (TNF-alpha), designated 3B10, neutralizes biological activity of TNF-alpha, while another anti-TNF-alpha mAb 10F10 does not. In Western blot analysis, both mAbs bound to SDS-denatured TNF-alpha, indicating that the epitopes recognized by the mAbs are sequential but not conformational. To map precisely the epitopes of the mAbs, 76 overlapping octapeptides corresponding to an entire sequence of TNF-alpha were synthesized and their abilities to react with the mAbs were examined by enzyme-linked immunosorbent assay (ELISA). 3B10 bound to only one peptide at position 81-88 of TNF-alpha, SRIAVSYQ, whereas 10F10 was reactive with three overlapping peptides, ANALLANG (33-40), ALLANGVE (35-42), and LANGVELR (37-44). These results demonstrate that the 81-88 and 37-40 regions are important for the recognition of TNF-alpha by 3B10 and by 10F10, respectively. In solid-phase ELISA, 3B10 inhibited the binding of TNF-alpha to soluble TNF receptors, sTNF-RI and sTNF-RII. In contrast, 10F10 exerted little effect on the binding. TNF-alpha was detected by sandwich-type ELISA where 3B10 alone was used for both capture and detection, suggesting that 3B10 did not interfere with the trimer formation of TNF-alpha. The results obtained in this study suggest that the 81-88 region of TNF-alpha may participate in the receptor binding and that 3B10 neutralizes the activities of TNF-alpha by blocking the region.

Amino Acid Sequence↗
PubMed1995

Production and characterization of monoclonal antibodies against human natriuretic peptide receptor-A or -B.

Monoclonal antibodies (mAbs) against human natriuretic peptide receptor-A (NPR-A) or NPR-B were produced using NPR-expressing Chinese hamster ovary (CHO) cells and soluble chimeric NPRs consisting of the extracellular domain of each receptor fused to Fc region of human IgG. Three anti-NPR-A mAbs, designated as A144, A397 and A416, bound to human NPR-A but not to NPR-B, while an anti-NPR-B mAb B136 reacted with human NPR-B but not with NPR-A. Competition analysis with the anti-NPR-A mAbs revealed that two mAbs, A144 and A416, recognize an identical or the adjacent site of the receptor and that A397 is directed against another epitope. No anti-NPR-A mAb affected binding of atrial natriuretic peptide (ANP) to NPR-A, while the anti-NPR-B mAb B136 inhibited binding of C-type natriuretic peptide (CNP) to NPR-B. Inhibition of the ligand-binding by B136 is specific in that the mAb showed no effect on the binding of ANP to NPR-A. B136 also blocked CNP-mediated intracellular cGMP accumulation in NPR-B-expressing cells. These results suggest that the region recognized by B136 may be related to the ligand-binding region of NPR-B. NPR-A- and NPR-B-expressing cells were selectively detected by immunostaining using the mAbs. These findings demonstrate that the mAbs will be useful to elucidate the role of the natriuretic peptides and their receptors in normal and disease states in humans [correction of human].

Animals↗
PubMed1995

Monitoring for engraftment following rat orthotopic liver transplantation by in vitro amplification of Y-chromosome gene using polymerase chain reaction.

The polymerase chain reaction (PCR) using primers specific for the rat Y-chromosome gene made it possible to distinguish a very small number of male rat cells from a large excess of female rat cells. In nonimmunosuppressed LEW recipients of ACI liver allografts, the donor cells in the bloodstream disappeared rapidly by day 3, earlier than the biochemical changes indicative of liver dysfunction. In immunosuppressed LEW recipients of ACI liver allografts, the donor cells were detected for a longer time. Moreover, in LEW recipients surviving for long period, the PCR revealed mixed-microchimerism. Our results indicated that this Y chromosomal gene-specific PCR method is useful for assessing engraftment following rat liver transplantation.

Animals↗
PubMed1995

Development of a rat model for orthotopic liver transplantation for hepatocellular carcinoma.

BACKGROUND: Surgical resection is of limited benefit in hepatocellular carcinoma accompanied by severe liver cirrhosis or multicentric hepatic cancer. The long-term survival of patients with advanced hepatocellular carcinoma after transplantation is quite poor. We have studied the characteristics, natural course, and cause of diethylnitrosamine-induced liver cancer in rats and have shown it to be a good model of liver cancer in human beings. Therefore we performed orthotopic liver transplantation (OLT) in rats with diethylnitrosamine-induced liver cancer to study the patterns of recurrence. METHODS: Diethylnitrosamine 100 parts per million in drinking water was administered daily for 4 months to male inbred LEW rats. A laparotomy was performed 120 or 134 days after commencing the oral diethylnitrosamine to confirm the induction of cancer confined grossly to the liver. The livers were resected, and orthotopic transplantation with livers of normal LEW rats was performed. RESULTS: By day 150 all the rats in the non-OLT group died of intraabdominal hemorrhage caused by spontaneous rupture of liver cancer (mean survival time +/- SD, 138.2 +/- 5.3 days; n = 14). However, the OLT (day 120) group recovered their body weight comparatively early after transplantation and survived a maximum of 218 days until death from recurrence (203.8 +/- 21.3 days; n = 4). A significant extension in survival time was observed (p < 0.01). In autopsies performed at the time of death, metastatic liver cancer was observed in the transplanted livers with two showing metastases to the lung. The cause of death was cancer in all the rats. However, the OLT (day 134) group all died of major complications of severe pneumonia and disseminated intravascular coagulation within 2 weeks of OLT (141.3 +/- 5.0 days; n = 4). CONCLUSIONS: After liver transplantation to rats with hepatocellular cancer confined to the liver, recurrence was observed at a comparatively early stage in all transplant recipients. Although a significant prolongation of survival was noted, they all died of cancer. The timing of transplantation is also an important factor. This experimental liver transplantation model of progressive rat liver cancer will be useful in the study of primary liver cancer in human beings.

Animals↗
PubMed1995

Cytotoxicity of anti-c-erbB-2 immunoliposomes containing doxorubicin on human cancer cells.

We have examined the selective cytotoxicity of immunoliposomes containing doxorubicin (chemoimmunoliposomes, CILs) targeting the c-erbB-2 gene product (gp185) or gp125. Anti-gp185 and anti-gp125 CILs were prepared by conjugation of doxorubicin-containing liposomes with monoclonal antibodies SER4 (IgG) and HBJ127 (IgG) respectively. Both CILs bound to human SKBr-3 breast cancer cells and MKN-7 human gastric cancer cells, which express both antigens in high density. The IC50 of anti-gp185 CILs on protein synthesis by SKBr-3 cells was respectively 2- and 25-fold lower than that of anti-gp125 CILs and unmodified liposomes. Furthermore, anti-gp185 CILs significantly inhibited neither the phytohaemagglutin response of normal lymphocytes nor protein synthesis of gp185-negative T24 bladder cancer. Quantitative analysis of cell-associated doxorubicin revealed that, compared with anti-gp125 CILs, anti-gp185 CILs required, respectively 4.5 and 4.3 times less doxorubicin association in SKBR-3 and MKN-7 cells, for 50% cytotoxicity. In addition, flow cytometric analysis showed that both SKBr-3 and MKN-7 internalised more anti-gp185 CILs and processed them more efficiently than anti-gp125 CILs. These results suggest that anti-gp185 CILs act selectively against gp185-expressing cancer cells and that gp185 is a more sensitive antigen for CIL cytotoxicity associated with endocytosis activity.

Animals↗
PubMed1995

Adult T-cell leukemia with multiple lymphomatous polyposis of the gastrointestinal tract.

A rare case of adult T-cell leukemia (ATL) in which multiple lymphomatous polyposis (MLP) was revealed throughout the entire gastrointestinal tract is reported here. The polypectomy specimens taken from the rectum revealed infiltration of neoplastic T-cells, the integration of HTLV-1 proviral DNA, and increased CD4 (OKT4) and CD25 (IL-2R) cells. The analysis of surface markers of the lymphocytes from polypoid lesions may be useful for elucidating cell tropism and homing properties in the gastrointestinal tract. Although MLP has always been associated with B-cell lymphoma in the Western world, it is important for clinicians and pathologists to be aware that MLP may be caused by the infiltration of ATL cells.

Adult↗
PubMed1995

Proton pump inhibitors for Helicobacter pylori eradication in patients with peptic ulcer.

We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n = 86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Combination therapies with a proton pump inhibitor for Helicobacter pylori-infected gastric ulcer patients.

We investigated the eradication and recurrence rate of Helicobacter pylori-infected gastric ulcer patients by combination therapies. Eighty-six H. pylori-positive gastric ulcer patients were assigned randomly to one of seven groups: I, omeprazole 20 mg (n = 9); II, lansoprazole (LPZ) 30 mg (n = 16); III, LPZ 30 mg plus plaunotol 480 mg (n = 13); IV, LPZ 30 mg plus ecabet sodium 2 g (n = 11); V, LPZ 30 mg plus clarithromycin 600 mg (the first 2 weeks; n = 11); VI, LPZ 30 mg plus plaunotol 480 mg plus clarithromycin 600 mg (the first 2 weeks; n = 13); and VII, LPZ 30 mg plus ecabet sodium 2 g plus amoxicillin 1,500 mg (the first 2 weeks; n = 13). All therapy was for 8 weeks except where otherwise noted. H. pylori eradication rates as diagnosed by culture, histology, urease test, and [13C]urea breath test 4 weeks after stopping therapy were 0, 0, 8, 45, 6, 46, and 62%, respectively, in groups I-VII. No patient achieving H. pylori eradication suffered recurrence. The combination therapies with proton pump inhibitors in addition to antibiotics and antiulcer agents are safe and effective in H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Significance of the HLA-DQB matching in one-haplotype identical kidney transplant pairs and the matching analysis by the polymerase chain reaction (PCR)--heteroduplex--polymorphism method.

Sixty-five living related kidney transplant pairs were analyzed for matching at HLA class II loci by the polymerase chain reaction (PCR)--sequence specific oligonucleotide probe (SSOP) method. The retrospective HLA matching study revealed that there were many early graft loss cases despite the DQB compatibility, contrary to our expectation. There were 54 DRB1 one-mismatched cases, in which 7 of the 11 (64%) DQB zero-mismatched cases had lost their grafts, while the graft loss cases were only 10 of the 43 (23%) DQB one-mismatched pairs (P value = 0.0006). The DQB matching of these cases was studied in detail, because the PCR-SSOP methods are based on the detection of sequence polymorphisms in a relatively narrow range, i.e., recognized sequences by SSOPs. The PCR--heteroduplex--polymorphism analysis method was developed to analyze the polymorphism in exon 2 of the DQB1 gene. However, all the pairs proved to be compatible for the DQB, demonstrating that the DQB compatibility was associated with a harmful influence on the graft outcome. These observations suggested that the DQB1 incompatibility might exert the low responsiveness to HLA haplo-identical allogeneic transplants.

Base Sequence↗
PubMed1995

Sebaceous carcinoma of the vulva.

Extraocular sebaceous carcinoma (SC) is a rare tumor usually found on the head and neck. A 78 year old Japanese female who had an asymptomatic vulvar tumor is reported here. The excised specimen showed SC with metastasis to the inguinal lymph nodes. This is the fourth reported case of SC arising from female genitalia, and the second case that apparently arose from the labia minora. Contrary to the previously reported cases, tumor cells in the present case had abundant glycogen. Thus, differential diagnosis of SC from metastatic renal cell carcinoma is difficult morphologically because both of them have glycogen and lipid. Intraepidermal invasion of tumor cells has been reported in SC, but a suspected lesion of this phenomenon in the present case was proved to be histiocytic infiltration by immunohistochemistry using anti-CD 68 antibody.

Adenocarcinoma, Sebaceous↗
PubMed1995

Evolution of three patterns of intra-alveolar fibrosis produced by bleomycin in rats.

In pulmonary fibrosis, it is known that fibrotic changes develop in the intra-alveolar spaces and that intra-alveolar fibrosis can be classified into three patterns, namely intra-alveolar buds, mural incorporation and obliterative changes. In order to clarify the evolution of intra-alveolar fibrosis, immunohistochemical studies of extracellular matrix proteins and electron microscopic observations were made of the lungs of rats given a single intratracheal instillation of bleomycin. All three patterns of fibrosis developed in this model. Intra-alveolar buds changed into globular lesions with dense collagen deposition, the surface of which was covered by alveolar epithelium. Electron microscopy revealed that the buds often contained spiraling collagen fibrils and numerous microfibrils, but not mature elastic fibres, beneath the regenerating epithelial lining cells; the epithelial basement membranes were discontinuous. In contrast, mural incorporation and obliterative changes were associated with alveolar structural remodeling. Electron microscopically, these lesions had bundles of normal collagen fibrils, small elastic fibers, and continuous epithelial basement membranes. These results indicate that: (i) intra-alveolar buds, that become intra-alveolar collagen globules, with an unusual extracellular matrix, do not contribute to alveolar structural remodelling; and (ii) areas of mural incorporation and obliterative changes have the usual type of extracellular matrix and are essential for alveolar structural remodelling.

Animals↗
PubMed1995

Hepatitis C virus infection and genotypes in Japanese hemophiliacs.

Liver function and antibodies to hepatitis C virus and to human immunodeficiency virus-1 were examined in 195 Japanese patients with hemophilia. One hundred and seventy-three were positive for antibody to HCV and 61 for antibody to human immunodeficiency virus-1. In 63 patients, we examined HCV genotypes according to the double polymerase chain reaction method. Forty cases (63%) were infected with hepatitis C virus with a single genotype, including type 1a in five, type 1b in 21, type 2a in seven and type 2b in seven; 16 (25%) were infected with double genotypes, including types 1a + 1b in 14, types 1b + 2a in one and types 1b+2b in one; and four (6%) were infected with triple genotypes, including types 1a + 1b + 2b in two. Genotype could not be determined in three patients by this method. In the 191 nonhemophiliac patients with chronic hepatitis C, HCV genotyping was as follows: type 1a in 0, type 1b in 121, type 2a in 40 and type 2b in 10 of 171 cases (89.5%) with single infection and types 1b + 2a in five and types 2a + 2b in one of six (5.5%) with double infection. In the remaining 14 patients, genotype could not be determined. Frequent transfusion of domestic and/or imported coagulation factor concentrates probably caused the high incidence of HCV infection with rare or mixed genotypes in Japanese hemophiliacs.

Adolescent↗
PubMed1995

Susceptibility of insulin to proteolysis in rat lung homogenate and its protection from proteolysis by various protease inhibitors.

The objective of this study was to determine the stability of insulin in rat lung homogenate and to confirm the effectiveness of various protease inhibitors for insulin delivery from the lung. The stability of insulin in rat lung homogenate was compared with that in the small intestine. Insulin was rapidly degraded in lung homogenate similarly to degradation in the small intestinal homogenate. The effects of various protease inhibitors on the degradation of insulin were studied in the lung. Protease inhibitors such as Na-glycocholate (Na-GC; 10 mM), aprotinin (10 mg/ml), soybean trypsin inhibitor (STI; 10 mg/ml) and bacitracin (20 mM) effectively reduced insulin degradation in lung homogenate. The rank order of effectiveness for decreasing the insulin hydrolysis in lung homogenate was bacitracin > aprotinin > STI > Na-GC. In addition, a slight correlation was observed between the in situ pulmonary absorption of insulin and its stability in vitro in the lung homogenate in the presence of various protease inhibitors. These findings suggest that the coadministration of protease inhibitors would be useful for improving the stability of insulin in the lung.

Absorption↗
PubMed1995

[Chemical studies on crude drug processing. X. On the constituents of rehmanniae radix (4): comparison of the constituents of various rehmanniae radixes originating in China, Korea, and Japan].

In order to characterize the chemical change of their constituents during the processing of various Rehmanniae Radixes, we have investigated the constituents by comparing with those of Chinese Juku-jio (variously processed root of Chinese Rehmannia sp.), Korean Kan-jio (dried root of Korean Rehmannia sp.) and each two species of Japanese Sho-jio (fresh root), Japanese Kan-jio (dried root), and Japanese Juku-jio (steamed root), prepared from Rehmannia glutinosa Libosch. var. purpurea Makino (Akaya-jio in Japanese) and Rehmannia glutinosa Libosch. forma hueichingensis Hsiao (Kaikei-jio in Japanese). It was found that, during the processing for preparing Kan-jio and Juku-jio from Sho-jio, jio-serebroside (9) and acteoside (10) were provided, and that the iridoid glycosides were completely degradated or their contents decreased remarkably. Quantitative analysis by means of gas liquid chromatography (GLC) has confirmed that the contents of monosaccharides and oligosaccharides in Kan-jio and Juku-jio increased more than those in Sho-jio. During the course of these studies, a new iridoid glycoside named 6'-O-acetylcatalpol (2) was isolated from Japanese Sho-jio and the structure has been determined.

Chromatography, Gas↗
PubMed1995

[Vasodilating effects of NY-008 in ring preparation of rat aorta].

Vasodilating effects of NY-008 were compared to those of verapamil in isolated rat aorta. NY-008 at the dose of 3 x 10(-5) M relaxed 10-70 mM potassium chloride (KCl)-induced contraction. NY-008 relaxed preparations precontracted with 60 mM KCl concentration-dependently with an IC50 of (6.17 +/- 1.75) x 10(-6) M, and those precontracted with norepinephrine (NE) (10(-6) M) concentration-dependently, maximally by 90.0 +/- 2.86%, with an IC50 of (2.06 +/- 0.38) x 10(-5) M. At 10(-8)-3 x 10(-6) M, verapamil relaxed preparations precontracted with NE (10(-6) M) concentration-dependently, maximally by 55.9 +/- 5.56%. At 3 x 10(-5) M and 10(-4) M, NY-008 relaxed (10(-6) M)-induced phasic contractions in a Ca(2+)-free 1 mM EGTA-containing buffer, by 22.4 +/- 3.69% and 35.4 +/- 5.74%, respectively. In contrast, 3 x 10(-7) M verapamil did not. NY-008 concentration-dependently decreased the maximal responses to calcium chloride (CaCl2) in 60 mM KCl-depolarized preparations, and it shifted the ED50 values of CaCl2 to the right, whereas verapamil shifted the ED50 values of CaCl2 to the right without decreasing the maximal responses to CaCl2. At 10(-5)-3 x 10(-4) M, NY-008 concentration-dependently relaxed preparations precontracted with prostaglandin F2 alpha (10(-5) M) in a Ca(2+)-free, 0.5 mM EGTA-containing buffer, whereas 10(-7)-10(-5) M verapamil did not. These results suggest that NY-008 antagonized Ca2+ and decreased the Ca(2+)-sensitivity of contractile elements or inhibited contractile proteins in rat aorta.

Animals↗
PubMed1995

Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung cancer patients.

To investigate the influence of thoracic irradiation on immunological competence in patients with lung cancer, we examined the changes in peripheral blood lymphocyte subsets in 15 patients before and after radiation therapy by two-color flow cytometry techniques. After radiation therapy, the percentage and the absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+ and/or CD16+ cells (NK cells) decreased. The percentage of CD4+human leukocyte antigen-DR(HLA-DR)+ cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells) increased, although the absolute number did not change significantly. Naive T cells may be more selectively damaged than memory T cells by thoracic irradiation, through their recirculation behavior. The reduction of natural killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of HLA-DR positive T lymphocytes was significantly increased, and thus the possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore, thoracic irradiation has numerous varied effects on the immunological system of lung cancer patients.

Adult↗