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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 505 records · Page 28Linked to original sources
PubMed1995

Cell viability of aortic allografts after long-term cryopreservation and clinical application to aortic root replacement in a patient with aortitis.

A key point in the establishment of a tissue cryopreservation system is to maintain cell viability for an extended period. The viability of the tissue cells in the authors' cryopreservation system was examined, and the first clinical application reported. The tissue culture method demonstrated 95% of rat aortas (21 of 22 specimens) and 88% of human cardiac valves (seven of eight) to be viable after 6.4 months and 5.8 months of cryopreservation, respectively. The first clinical case, a 54-year-old man with aortic valve replacement and complications of aortitis, underwent successful aortic root replacement. Whereas the use of allografts in aortitis cases is controversial, such an approach was assumed reasonable because the mechanical stress between the native aortic annulus and the inserted valve could be reduced by aortic root replacement with the allograft.

Adult↗
PubMed1995

Peptides with carboxyl-terminal sequence of alanine-proline: detection by a human monoclonal antibody.

A human B lymphoblastoid cell line JWCI-L94 secretes an IgM human monoclonal antibody (HuMAb) that reacts with human melanoma cell lines, M14 and M12. To identify the antigenic epitope of this antibody, we screened lambda gt11 expression libraries constructed from M14 and M12. A total of 12 immunoreactive clones were isolated, and their DNA sequences were determined. The only sequence shared by all these clones was alanine-proline (A-P) at the carboxyl (C) terminal. HuMAb L94 reacted not only with C-terminal A-P-containing fusion proteins, but also with the synthetic dipeptide A-P. None of the peptides containing A-P internally or amino terminally reacted to HuMAb L94. Proline or alanine alone had no ability to bind to HuMAb L94. When alanine was replaced by glycine (G-P) or proline (P-P), the binding activity of these peptides was similar to that of A-P. On the other hand, when alanine was replaced by serine, valine, leucine, glutamine, lysine, methionine, phenylalanine, or hydroxyl proline, the resulting peptide completely lost the antigenic activity of HuMAb L94. These results demonstrate that HuMAb L94 recognizes C-terminal A-P, G-P, or P-P, and that a human antibody can recognize peptides as small as a two-amino acid residue.

Amino Acid Sequence↗
PubMed1995

The rat intrinsic factor gene: its 5'-upstream region and chief cell-specific transcription.

A DNA segment containing the 5'-upstream region and amino terminal reading frame of the gastric intrinsic factor gene was cloned from rat and its nucleotide sequence was determined. S1 mapping demonstrated that the transcription initiation site is located downstream of the second TATA-box sequence. Similar sequence motifs to those in the pepsinogen genes transcribed in gastric chief cells were found in the deduced sequence, suggesting that the rat intrinsic factor gene is transcribed in these cells. The genes for the intrinsic factor and its homologous protein transcobalamin I were apparently derived from a common ancestoral gene, since the positions of their intron insertions as well as the amino acid residues are conserved. Northern blot hybridization showed that the gene for the intrinsic factor is transcribed in the stomach but not detectably in the intestine, kidney, testis, brain, heart, liver, lung, or spleen. In situ hybridization using radioactive complementary RNA clearly indicated that the major transcription site in gastric glands is chief cells. Different locations of expression of intrinsic factor proteins in various mammals were observed previously using antibodies: in rat parietal cells and chief cells, in mouse chief cells, and in human parietal cells. The present results clearly demonstrated the intrinsic factor mRNA mainly in chief cells of adult rats, as in mice, suggesting that transcriptional regulation of the intrinsic factor gene is essentially the same in rodents.

Animals↗
PubMed1995

Clonal and non-clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis.

We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein-Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV-associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease. Although HLH did not show histological and/or haematological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation.

Adolescent↗
PubMed1995

Increased S-100 protein-immunoreactivity of Kupffer cells is associated with lymphohematological malignancy.

The distribution of S-100 protein in normal tissue has been studied extensively. However, little is known about its expression in pathologic states. The aim of the present study was to investigate the expression of S-100 protein in diseased human liver, especially in Kupffer cells. One hundred cases of autopsy livers originating from patients with various diseases were examined. Increased S-100-immunoreactivity of Kupffer cells was observed in six cases. Of the six cases, four were derived from a lymphohematologic malignancy, such as B cell lymphoma, B cell lymphoblastic leukemia, multiple myeloma and chronic myelogenous leukemia with lymphoblastic crisis. Lymphohematologic malignancy accounted for 16 out of the 100 cases examined. Thus, increased S-100-positive Kupffer cells was significantly associated with lymphohematologic malignancy (P < 0.01); 25% (4/16) in cases with lymphohematologic malignancy versus 2.4% (2/84) in the remaining cases. Moreover, some of these S-100-positive Kupffer cells were positive for S-100 beta-subunit, which is not normally expressed by Kupffer cells. Although the reason for this increased S-100-immunoreactivity is speculative, the authors' hypothesis is that tumor cells may produce some factor(s) that induce the expression of S-100 protein in Kupffer cells.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1995

Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis.

A mesothelioma cell line, termed T-85, was established from a patient with malignant peritoneal mesothelioma and remarkable thrombocytosis (1.4 x 10(6)/mm3). Electron microscopically, two types of mesothelioma cells have been characterized; the major type of cells with dense-cored granules in the cytoplasm and the minor one with evenly dense granules. Immunologically, the cells showed staining for interleukin-6 (IL-6), cytokeratin, collagen type IV, vimentin, laminin, fibronectin and Factor VIII-related antigen. Quantitation by ELISA revealed a high concentration of IL-6 in T-85 cell culture supernatants. RT-polymerase chain reaction of T-85 cells showed two positive bands of cDNA at 628 and 251 base pairs indicating the constitutive expression of IL-6 and IL-6 receptor mRNA. Moreover, prominent pro-platelet process formation activity in T-85 cell culture supernatants indicated the presence of a thrombopoietic activity due mainly to IL-6 but not the c-Mpl ligand or erythropoietin. However, the fact that 15% of PPF activity remained in the supernatants treated with anti-IL-6 antibody indicated the presence of another thrombopoietic substance. T-85 is so far the first mesothelioma cell line derived from a case with remarkable thrombocytosis.

Base Sequence↗
PubMed1995

Clinical use of low porosity woven ultrafine polyester fiber grafts.

A woven fabric graft made of ultrafine polyester fibers (UFPF) (Toray Graft, water porosity: 100 ml/min/cm2:120 mm Hg H2O) was clinically applied in 81 cases (28 thoracic aortic aneurysms, 6 thoracoabdominal aortic aneurysms, 42 abdominal aortic aneurysms, and 5 atherosclerotic obstructions of the peripheral arteries). Eight patients died after surgery due to causes unrelated to the graft. The other 73 patients were in good condition after surgery. For operations requiring extracorporeal circulation, the graft was presealed with human albumin. For the abdominal aortic aneurysms, the graft was preclotted in situ with nonheparinized autoblood after the completion of the proximal anastomosis. It took about 2 min to complete the preclotting. A nonsealed graft was used for the reconstruction of peripheral arteries for the intraaortic balloon pumping procedure. The graft was easy to handle. There was no cut edge fraying problem with the graft in any direction of cutting. Even after presealing, the graft was soft and pliable enough to enable easy adaptation and anastomosis. Just after implantation, bleeding was minimal from the graft wall, anastomotic sites, and suture pores, and it stopped spontaneously. These clinical data showed that the woven UFPF graft exhibited both easy handling despite in spite of low porosity and safe application in the reconstruction of arterial systems even under totally heparinized conditions during extracorporeal circulation.

Aortic Aneurysm↗
PubMed1995

Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment.

Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperitoneally for 10 days, whereas saline vehicle was injected into control mice. Intra-alveolar fibrotic changes were observed in the lung tissue obtained from the mice at day 14 after the final BLM administration. Immunohistochemical studies using a polyclonal antibody to activin A revealed the presence of activin A in the bronchiolar epithelium and smooth muscle cells of veins in both control and BLM-treated mice. In the BLM-treated mice at days 7 and 14, the marked infiltration of immunoreactive alveolar macrophages was observed in the area of fibrotic changes. Bioactivity of activin A measured by erythroid differentiation factor assay in the conditioned medium of alveolar macrophages obtained from BLM-treated mice at day 14 was significantly increased. These findings indicate that alveolar macrophages are a potent source of activin A after BLM treatment. The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis.

Activins↗
PubMed1995

Colocalization of vascular endothelial growth factor (vascular permeability factor) and insulin in pancreatic islet cells.

Previously, we found that the islet of pancreas stained with a antibody against the vascular permeability factor (VPF; also known as vascular endothelial growth factor, VEGF) protein. To determine how common this reaction was and whether it was a specific reaction for the islet, we examined its expression and specific cellular localization. Two different antibodies directed against VPF/VEGF peptide revealed an intense reaction for beta-cells in the human islets of Langerhans, and several human beta-cell tumors (insulinomas), but no reaction, were detectable in the vascular endothelium. In the fetal pancreas (second and third trimesters), the VPF/VEGF peptide was detected in immature islets. Northern blot analysis of cell lines derived from rodent insulinomas revealed expression of VPF/VEGF messenger ribonucleic acid. Western blot analysis of conditioned medium from one of these cell lines showed the presence of the released VPF/VEGF protein. These findings indicate that beta-cells have a specific role other than endocrine function in the pancreas. VPF/VEGF in beta-cells may be involved in the maintenance and control of permeability within the islet capillary system.

Adult↗
PubMed1995

[Inhibitory effects of sepimostat mesilate (FUT-187) on the activities of trypsin-like serine proteases in vitro].

Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 microM for trypsin, 0.029 microM for pancreatic kallikrein, 0.61 microM for plasma kallikrein, 0.57 microM for plasmin, 2.5 microM for thrombin, 20.4 microM for factor Xa and 6.4 microM for C1r. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for C1s, and Ki values for these proteases were 0.021 and 0.18 microM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 microM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 microM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 microM, while camostat revealed no inhibition by concentrations up to 1 microM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 microM, respectively, the corresponding values for camostat being 350 and 150 microM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and C1s in complement pathway.

Animals↗
PubMed1995

Regional lung function following upper sleeve lobectomy for bronchogenic carcinoma.

Regional lung function of the operated side following upper sleeve lobectomy (n = 8) and simple upper lobectomy (n = 7) for lung cancer was evaluated. Regional ventilation was studied with Krypton 81m and regional pulmonary blood flow was studied with Technetium 99m. Measurements were taken from 12 to 24 months after operation. The ventilation rate of the operated side following right upper sleeve lobectomy (n = 5) was 42.9 +/- 6.7% and the perfusion rate was 37.4 +/- 4.6%. The regional ventilation rate of the operated side after simple right upper lobectomy (n = 3) was 45.9 +/- 10.5% and the perfusion rate was 46.2 +/- 5.2%. For the patients with left upper sleeve lobectomy (n = 3), these ratios were 29.9 +/- 11.1% and 19.2 +/- 3.6%, respectively. For the patients with simple left upper lobectomy (n = 4), these ratios were 27.3 +/- 4.5% and 22.3 +/- 3.3%. There were no statistical differences between the group with upper sleeve lobectomy and that with simple upper lobectomy. Regional function improved gradually with time. In conclusion, the regional lung function of the operated side following sleeve lobectomy was well preserved and showed no difference when compared with the regional function after simple lobectomy for lung cancer.

Aged↗
PubMed1995

How the developing septo-preoptic medical basal hypothalamus stimulates the development of placode-derived LHRH neurons.

We examined the effects of the developing cerebral cortex (CC) and septo-preoptic medial basal hypothalamus (S-MBH) on the development of LHRH neurons in vitro. The serum-free basal culture medium (BCM) was supplemented with CC or S-MBH extracts prepared from 18.5-day-old embryos or from 2-day-old newborns, and the olfactory placode (NAP) of 12-day-old embryos was cultured. The migration of LHRH neurons was found on Day 3 in the cultures supplemented with the embryonic S-MBH extract (Group 3), where the cell development proceeded showing a numerical increase of the cells and the elongation of neurites. In cultures supplemented with the newborn S-MBH extract (Group 5), the cell development was less intensive in comparison with that of Group 3, while in cultures which had no brain extracts (Group 1), the neurons failed to survive a long term culture. The effects of the CC were less than of S-MBH extracts. Analysis of the protein composition of the extracts by electrophoretic and immunoblotting examinations demonstrated a protein spot of 70-kD in the embryonic S-MBH extract. Because the protein spot was identified to be alpha-fetoprotein (AFP), we further examined the effects of AFP. When the anti-AFP immunoglobulin was added to the Group 3 culture, the stimulative effects of the embryonal extract were inhibited, and the addition of AFP to Group 1 cultures did not show stimulative effects. We conclude that the developing S-MBH, the migrating target of LHRH neurons, contains some essential factors for the development of LHRH neurons, but further analysis is needed to determine the chemical natures of these factors.

Animals↗
PubMed1995

Factors influencing nifedipine-induced gingival overgrowth in rats.

Factors such as age, the dose of nifedipine administered in the diet, serum drug level, duration of drug administration, and sex which may influence nifedipine-induced gingival overgrowth were examined in a rat model using 20-, 50-, and 90-days-old male and female rats. Oral administration of nifedipine (50 to 250 mg/kg diet) increased the serum level of the drug in a dose-dependent manner in both males and females. However, a higher serum level was required in females than males to attain the same degree of gingival overgrowth. The minimum dietary concentrations of the drug required to elicit gingival overgrowth in males and females were 150 and 100 mg/kg, respectively, which gave respective minimum serum levels of 800 and 1100 ng/ml. The degree of overgrowth depended on the serum concentration of the drug after it had reached the required minimum in male and female animals. Administration of nifedipine (250 mg/kg diet) for 20 days was enough to induce maximal overgrowth, but this induction occurred only in rats that started to receive the drug when they were 20 days old, not in those that started at 50 and 90 days of age for the same administration period of 55 days, and the overgrowth regressed and the gingiva were normal 40 days after ceasing drug administration. These results suggest that gingival overgrowth occurred in accordance with the drug concentration in the diet, as well as that in the serum, and was more likely to occur in males and younger individuals.

Age Factors↗
PubMed1995

[Single dose toxicity studies of metabolite, degradation product and impurity of montirelin hydrate (NS-3) in mice].

Montirelin hydrate (NS-3) is a new drug for the treatment of disturbance of consciousness. The single dose toxicity studies of its degradation product and impurity (CNK-603) and its metabolite (CNK-6004) were conducted in Slc: ddY mice. The compounds were administered intravenously to male and female mice. Deaths occurred in both sexes of mice receiving more than 125 mg/kg of CNK-603. There were no treatment-related effects on survival in both sexes of mice receiving doses up to 2,000 mg/kg of CNK-6004. Approximate lethal dose of CNK-603 was 125 mg/kg and lethal dose of CNK-6004 was more than 2,000 mg/kg. Decrease in locomotor activity was observed in mice receiving the two compounds. Tremor, prone position and dyspnea were seen in mice receiving CNK-603. The body weight showed no changes attributable to the dosing of the two compounds in mice. In autopsies, congestion and hemorrhage in the lung were observed in dead mice given CNK-603. There were no remarkable changes in mice given CNK-6004. These results show that the lethal dose of CNK-603 is over 4 times lower than that of montirelin hydrate, and that CNK-6004 is less toxic than montirelin hydrate.

Animals↗
PubMed1995

Neuroendocrine tumors of the liver and pancreas associated with elevated serum prostatic acid phosphatase.

A 58-year-old man was revealed to have multiple liver tumors with elevated prostatic acid phosphatase (PAP) during a medical examination. The tumors were of neuroendocrine nature, but no abnormal findings were obtained in other organs in which neuroendocrine tumors develop frequently. Repeated transarterial embolization was partially effective. However, the tumors became resistant to the therapy three years later, continued growing and ruptured. Autopsy disclosed neuroendocrine tumors in the pancreas, which were immunohistologically positive for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare; this case is reported with a review of literature.

Acid Phosphatase↗
PubMed1995

Proteolysis by calpain is an underlying mechanism for formation of sugar cataract in rat lens.

To confirm the effect of a new aldose reductase inhibitor (ARI), rat lenses were cultured with xylose. ARI prevented opacities and reduced lens hydration caused by xylose. Next, cataract was produced by feeding a diet containing 50% galactose. ARI was tested for amelioration of cataract. On day 19 after feeding of galactose, nuclear cataracts were visible in 75% of the animals receiving only galactose, while nuclear cataracts were not observed in animals treated with ARI. In galactose cataract, lens hydration and calcium were significantly increased. Calpain in soluble and insoluble fractions was decreased. Alpha- and beta-crystallins were proteolyzed. These changes were inhibited by administration of ARI. These results suggested that proteolysis by calpain is an underlying mechanism in formation of sugar cataract in rat lens.

Aldehyde Reductase↗
PubMed1995

Pyridoxal 5'-phosphate modulates expression of cytosolic aspartate aminotransferase gene by inactivation of glucocorticoid receptor.

The level of mRNA for cytosolic aspartate aminotransferase (cAST) in the liver of vitamin B6-deficient rats was found to be 7-fold higher than that of the control rats. The administration of hydrocortisone to adrenalectomized vitamin B6-deficient rats induced expression of hepatic cAST mRNA and the induction was suppressed by the simultaneous administration of pyridoxine. Since the 5' regulatory region of the rat cAST gene contains several sequences showing homology to glucocorticoid-responsive elements, we synthesized an oligonucleotide probe of glucocorticoid-responsive element sequence and assayed the binding activity of liver nuclear extract to the oligonucleotide by gel mobility shift analysis. We found that the binding activity of nuclear extract prepared from the liver of vitamin B6-deficient rats was far greater than that of the control rats, indicating that the DNA-binding activity of glucocorticoid receptor was enhanced by vitamin B6 deficiency. We further found that preincubation of the nuclear extract from the vitamin-deficient liver with pyridoxal 5'-phosphate brought about a rapid and extensive decrease in the binding of the extract to the glucocorticoid-responsive element. Congeners of pyridoxal phosphate, such as pyridoxamine 5'-phosphate, pyridoxal, pyridoxamine and pyridoxine, did not show an inhibitory effect. These observations suggest that pyridoxal 5'-phosphate modulates cAST gene expression by inactivating the binding activity of glucocorticoid receptor to glucocorticoid-responsive elements.

Adrenalectomy↗