Biomedical subjects

K Oda

Publications and source records attributed to K Oda.

At least 235 records · Page 13Linked to original sources

PubMed1996

Plasma cells composing plasmacytoma have phenotypes different from those of myeloma cells.

We describe one relapsed case of plasmacytoma of mandibular bone. The organs of relapse were liver and bone marrow. At relapse, monoclonal gammopathy (IgG-kappa) was observed without suppression of IgA and IgM. By immunostaining, the plasma cells of both the original mandibular bone and liver were positive for the same cytoplasmic immunoglobulin light chain kappa. The proliferative plasma cells in the bone marrow had the phenotype of CD38+, CD19+, and CD56- by flow cytometry and showed the presence of the rearranged IgH gene by Southern blotting. In addition, the zone of the Ig class of the patient's serum was not so sharply defined by zone electrophoresis. These results suggest that the characteristics of plasma cells of plasmacytoma are different from those of multiple myeloma.

ADP-ribosyl Cyclase↗

PubMed1996

Dispensability of Jak1 tyrosine kinase for interleukin-2-induced cell growth signaling in a human T cell line.

The tyrosine kinases Jak1 and Jak3 are known to be associated with the beta and gamma chains of interleukin-2 receptor (IL-2R). They are activated by stimulation with IL-2, IL-4, IL-7, IL-9, or IL-15, receptors of which share the gamma chain of the IL-2R. We have obtained direct evidence of Jak1 association with the alpha chains of receptors for IL-4, IL-7 and IL-9 and with the beta chain of IL-2R, which is also common to the IL-15R. Furthermore, we have prepared mutant IL-2R beta chains with a mutation in the box 1 region, which is conserved among the IL-2R beta chain and the alpha chains of the other cytokine receptors sharing the IL-2R gamma chain. Using MOLT-4 transfectants with the mutant beta chains, we found that two conserved proline residues within the box 1 region are essentially involved in association with Jak1. The MOLT-4 transfectants with the mutant beta chains lacking Jak1 association showed IL-2 responsiveness, in terms of activation of Jak3 and Stat5 and induction of cell growth, indicating that Jak1 is dispensable for IL-2-mediated cell growth signaling and that Jak1 activation is not required for activation of Jak3 and Stat5 in the MOLT-4 transfectants.

Antigens, CD↗

PubMed1996

Fine structural changes of muscle spindles in the gracile axonal dystrophy mutant mouse.

Fine structural changes of muscle spindles in the extensor digitorum longus of the gracile axonal dystrophy mutant mouse were studied from 20 to 120 postnatal days. Degenerative nerve endings in muscle spindles were first recognized at 20 postnatal days. The sensory nerve endings were usually swollen with decrease of cell organelles, and the cytoplasm was electron-lucent. At 50 postnatal days, atrophic nerve endings were frequently observed in the narrow spaces between the indented cell membrane of intrafusal muscle cells and the basement membrane. In addition to degenerative and atrophic changes, regenerative axons showing fine sprouts (with or without Schwann cell projections) appeared in the sensory nerve endings at this time. At 80 postnatal days, sensory nerve endings frequently showed dystrophic changes characterized by axonal dilatation with accumulations of neurofilaments, tubulovesicular structures, mitochondria and myelin-like figures. These findings suggest that axonal transport in the sensory nerve endings is impaired in this mutant mouse. Motor nerve endings were usually well preserved and normal structures even at 80 postnatal days. Intrafusal fibrosis, decrease in number of sensory nerve endings and atrophy of intrafusal muscle fibres were clearly recognized by 100 days of age.

Aging↗

PubMed1996

Myofibroblastoma of the breast: report of a case.

We report herein the case of a 36-year-old woman in whom a breast mass was diagnosed histologically and immunohistochemically as myofibroblastoma (MFB). The patient initially presented with a breast mass measuring 1.0 x 1.5 cm which was demonstrated by mammography as a well-circumscribed, round tumor with two coarse calcifications. On ultrasonography, the tumor showed slight shadowy internal echoes. Histological examination of an excisional biopsy specimen demonstrated a tumor consisting of spindle-shaped cells and broad bands of hyalinized collagen with cartilaginous and osseous components, but no epithelial components were observed. Immunohistochemically, the tumor cells were diffusely positive for alpha smooth muscle actin, and a diagnosis of MFB was made. A wide excision of the breast was performed as a secondary procedure, and the patient is well and free from recurrence 1 year after her operation. We present this case to stress the need for breast surgeons to be aware of the existence of MFB when considering the differential diagnosis of stromal lesions of the breast to avoid performing unnecessarily extensive procedures.

Adult↗

PubMed1996

Effect of the eradication of Helicobacter pylori on duodenal ulcer healing and ulcer relapse: randomized controlled study in Japan.

To investigate the effect of the eradication of Helicobacter pylori on the healing and relapse of duodenal ulcers. 50 patients with active duodenal ulcer and H. pylori infection were randomly allocated to two treatment groups. One group (cimetidine group) received cimetidine 400 mg twice daily for 6 weeks and the other group (double-therapy group) received 300 mg amoxicillin granules and 250 mg metronidazole thrice daily for 2 weeks, in addition to the same regimen of cimetidine as the cimetidine group. Forty-two patients completed the study. After confirmation of ulcer scar, all patients were followed up for 6 months while receiving treatment with teprenone, an agent that does not affect acid secretion or the eradication of H. pylori. The healing rates at 6 weeks were 90% in the cimetidine group and 95.5% in the double-therapy group. H. pylori eradication occurred in 0% of the cimetidine group and in 73.7% of the double-therapy group (P = 0.004). The cumulative relapse rates in the two groups at 6 months were 64.3% and 11.1%, respectively (P = 0.0007). In the double-therapy group, the cumulative relapse rate at 6 months in the patients in whom H. pylori persisted was 50% (2/4); the rate was 0% (0/14) in the patients in whom H. pylori had been eradicated (P = 0.005). Histological gastritis significantly improved compared with the baseline in the double-therapy group, but no such improvement was seen in the cimetidine group. White scarring was found in 7.1% of the cimetidine group and in 83.3% of the double-therapy group after 6 months (P < 0.0001). The eradication of H. pylori markedly decreased the relapse rate in duodenal ulcer patients, and it significantly improved both the grade of gastritis and the quality of the ulcer scar.

Adult↗

PubMed1996

Evaluation of the brain uptake properties of [1-11C]labeled hexanoate in anesthetized cats by means of positron emission tomography.

Positron emission tomography (PET) was performed on the cat brain to characterize [1-11C]hexanoate and other [1-11C]labeled short and medium-chain fatty acids as a tracer of fatty acid oxidative metabolism. After an intravenous injection the brain uptake of [1-11C]hexanoate reached a peak followed by rapid washout until 2 min (first phase). Subsequently the total brain uptake was again increased and reached to a peak 7-10 min after tracer injection (second phase). The blood radioactivity of unmetabolized [1-11C]hexanoate was rapidly decreased and almost eliminated within the first 2 min, whereas the blood radioactivity of [11C]CO2/HCO3- was gradually increased and reached a peak approximately 5 min after tracer injection. As the effect of circulating [11C]CO2/HCO3- was examined by a bolus intravenous injection of [11C]CO2/HCO3-, the brain uptake of [11C]CO2/HCO3- was rapidly increased right after the injection and changed parallel to the blood level of [11C]CO2/HCO3-. These results suggest that, in contrast to the previous mouse data, the time-activity curve in the cat brain following intravenous injection of [1-11C]hexanoate has a biphasic pattern, the second phase being determined by peripherally originating [11C]CO2/HCO3-, and therefore does not reflect the metabolism of 11C-labeled fatty acid in the brain.

Animals↗

PubMed1996

A distribution study of 11C platelet-activating factor (PAF) analogs in normal and tumor-bearing mice.

As a preliminary study to image platelet-activating factor (PAF) receptors in vivo, comparative study of biodistribution between 1-O-hexadecy1-2-O-N, N-dimethylcarbamoyl-sn-glycero-3-phosphocholine [choline-methyl-11C](L-[11C]dimethylcarbamoyl-PAF) and nonspecific PAF analog, 3-O-hexadecyl-2-O-N,N-dimethylcarbamoyl-sn-glycero-1-phosphocholine [choline-methyl-11C](D-[11C]-dimethylcarbamoyl-PAF) was carried out in both normal and tumor-bearing mice. Higher accumulation of L-[11C]dimethylcarbamoyl-PAF than D-[11C]dimethylcarbamoyl-PAF was observed in normal mice spleen. The co-administration of PAF antagonists dose-dependently reduced the radioactivity level of the L-isomer only in the spleen. In mice bearing Ehrlich tumors and Sarcoma 180, more L-than the D-[11C]-isomer was accumulated in the tumor and spleen. We found that specific accumulation sites for L-[11C]dimethylcarbamoyl-PAF exist in the spleen and tumors than in other tissues. Moreover, the comparison of accumulation between L- and D-[11C] dimethylcarbamoyl-PAF would be a useful procedure for estimation of PAF receptors in vivo.

Animals↗

PubMed1996

Blue light induced ADP ribosylation of 38 and 56 kDa proteins in the soluble fraction of mycelia of Neurospora crassa.

Soluble fractions prepared from the mycelia of wild type (74-OR23-1A) and band (bd) exhibited an increase in the rate of the ADP ribosylation of a 38 kDa protein from nicotinamide adenine [32P]dinucleotide ([32P]NAD) in the presence of 10(-7) M riboflavin caused by blue light irradiation in vitro. The soluble fraction was mixed with a reaction mixture containing 5 microCi [32P]NAD at 0 degree C for 20 s and then it was irradiated with blue light (420 nm, 42 mumol m-2 s-1) for 12.5, 25, 50, 100, 200 or 400 s at 0 degree C or for 100 s with photon irradiance of 0.42, 4.2, 6.4 or 42 mumol m-2 s-1. Immediately after irradiation, the reaction was stopped and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. An increase in the ADP ribosylation of the 38 kDa protein could be detected within 100 s of irradiation, and the enhancement in the rate of ADP ribosylation of the 38 kDa protein was proportional to the increase in the photon irradiance. By the irradiation with blue light for 200 or 400 s, the ADP ribosylation of a 56 kDa protein could also be detected. Analysis by two-dimensional gel electrophoresis of proteins after ADP ribosylation of them revealed that the 38 kDa proteins displayed at least four radioactive protein spots and the 56 kDa protein a single radioactive protein spot. Soluble fractions of mycelia prepared from blind mutants wc-1, wc-2, delta ps15-1, lis-1, lis-2 and lis-3 exhibited also the enhancement of the ADP ribosylation of the 38 kDa protein by blue light irradiation, and at least wc-1, delta ps15-1, lis-1 and lis-2 displayed a similar blue light response in the 56 kDa protein.

Adenosine Diphosphate Ribose↗

PubMed1996

Cloning and expression of an isovaleryl pepstatin-insensitive carboxyl proteinase gene from Xanthomonas sp. T-22.

Xanthomonas carboxyl proteinase (XCP), isolated from Xanthomonas sp. T-22, is the second example of the unique carboxyl proteinases [EC 3.4.23.33] which are insensitive to the classical aspartic proteinase inhibitor. The gene coding for XCP was cloned, sequenced, and expressed in Escherichia coli. The XCP gene contains an open reading frame of 2,481 base pairs encoding a protein of 827 amino acid residues with a M(r) of 83,677. The XCP was synthesized as a large precursor consisting of three regions: NH2-terminal prepro (N-Prepro) (237 amino acid residues); mature XCP (398 a.a.residues); and COOH-terminal pro (C-Pro) (192 a.a. residues). The N-Prepro and mature XCP regions had no sequence similarity to any other proteins reported so far, except the carboxyl proteinase from Pseudomonas sp. 101 [Oda, K., Takahashi, T., Tokuda, Y., Shibano, Y., and Takahashi, S. (1994) J. Biol. Chem. 269, 26518-26524]. The C-Pro region showed high similarity to COOH-terminal regions of other microbial proteinase precursors. E. coli carrying a plasmid containing the cloned wild-type XCP gene produced an 84-kDa protein. This protein was processed into a mature, active form under acidic conditions. This process was completely blocked by tyrostatin, an XCP-specific inhibitor from Kitasatosporia sp. 55, indicating an autocatalytic processing. The purified recombinant XCP had the same characteristics as authentic XCP except for the NH2-terminal amino acid sequence. When the mutant XCP gene truncated in the C-Pro region was expressed in E. coli, an expected 64-kDa protein was detected in the cells, and also processed into the 42-kDa active form under the acidic conditions. Thus, the C-Pro region was not essential for the formation of active mature XCP.

Amino Acid Sequence↗

PubMed1996

Substrate specificities of pepstatin-insensitive carboxyl proteinases from gram-negative bacteria.

Pseudomonas carboxyl proteinase (PCP), isolated from Pseudomonas sp. 101, and Xanthomonas carboxyl proteinase (XCP), isolated from Xanthomonas sp. T-22, are the first and second examples of unique carboxyl proteinases [EC 3.4.23.33] which are insensitive to aspartic proteinase inhibitors, such as pepstatin, diazoacetyl-DL-norleucine methylester, and 1,2-epoxy-3(p-nitrophenoxy)propane. The substrate specificities of PCP and XCP were studied using a series of synthetic chromogenic peptide substrates with the general structure, P5-P4-P3-P2-Phe-Nph-P2'-P3' (P5, P4, P3, P2, P2', P3': a variety of amino acids, Nph is p-nitro-L-phenylalanine, and the Phe-Nph bond is cleaved). PCP and XCP were shown to hydrolyze a synthetic substrate, Lys-Pro-Ala-Leu-Phe-Nph-Arg-Leu, most effectively among 28 substrates. The kinetic parameters of this peptide for PCP were Km = 6.3 microM, Kcat = 51.4 s-1, and kcat/Km = 8.16 microM-1.s-1. The kinetic parameters for XCP were Km = 3.6 microM, kcat = 52.2 s-1, and kcat/Km = 14.5 microM-1.s-1. PCP showed a stricter substrate specificity than XCP. That is, the specificity constant (kcat/Km) of each substrate for PCP was in general < 0.5 microM-1.s-1, but was drastically improved by the replacement of Lys by Leu at the P2 position. On the other hand, XCP showed a less stringent substrate specificity, with most of the peptides exhibiting reasonable kcat/Km values (> 1.0 microM-1.s-1). Thus it was found that the substrate specificities of PCP and XCP differ considerably, in spite of the high similarity in their primary structures. In addition, tyrostatin was found to be a competitive inhibitor for XCP, with a Ki value of 2.1 nM, as well as for PCP (Ki = 2.6 nM).

Aspartic Acid Endopeptidases↗

PubMed1996

Granulomatous cholangitis in chronic hepatitis C: a new diagnostic problem in liver pathology.

A case of chronic hepatitis C at the pre-cirrhotic stage complicated with hepatocellular carcinoma is reported. The patient, a 64 year old female, showed elevated levels of serum alkaline phosphatase and immunoglobulin M. Antimitochondrial antibodies were negative by indirect immunofluorescence. Western blotting using beef heart mitochondria and recombinant polypeptides coding for mitochondrial antigens revealed that the patient's serum was positive only for the E2-subunit of the branched chain ketoacid dehydrogenase complex. In the non-neoplastic liver, chronic non-suppurative cholangitis surrounded by epithelioid granuloma, resembling the granulomatous destructive cholangitis of primary biliary cirrhosis, was found. The damaged bile ducts were immunohistochemically minimally positive or ambiguous for HLA-DR, and their expression of the E2-subunit of the pyruvate dehydrogenase complex E2 (PDC-E2) was diffuse or granular, and not typical of primary biliary cirrhosis. There was no bile duct loss, and orcein-positive copper binding granules reflecting chronic cholestasis were negative in periportal hepatocytes. The overall features in this case were consistent with primary biliary cirrhosis presenting an infrequent profile of antimitochondrial antibodies and atypical expression of HLA-DR and PDC-E2 on biliary epithelial cells, with late superimposition on chronic hepatitis C. However, it is also possible that this is a case of chronic hepatitis C with hepatitis-associated bile duct damage accompanied by granulomatous reaction. Either way, this case raises new diagnostic issues in the differential diagnosis of chronic liver diseases presented with granulomatous cholangitis.

Aged↗

PubMed1996

The outbreak of mumps in a small island in Japan.

A major mumps outbreak occurred on a small island, Ikeshima. in Nagasaki Prefecture from August 1994 to February 1995. There were 236 patients with the mumps at Ikeshima Miners' Hospital during that period. The Measles-Mumps-Rubella (MMR, Toitsukabu) vaccination coverage in the 43 children at the nursery school was 65.1% and it was 61.9% in the 21 children aged 4-5 years not attending the nursery school. Coverage was 66.6% in the 63 kindergarten students and 53.7% in 56 first-graders. The overall MMR vaccination coverage among these children was 61.7% (113/183) from 1989 to 1992. Children from the second grade to junior high school received monovalent mumps vaccine, Torii strain. None received Zishakabu MMR. The age of the patients ranged from 1 to 43 years, with a mean of 9.1 years. The majority (77.5%) were primary school children. The attack rates for vaccinated and unvaccinated children in grades one to six were: 6.7% (2/30) and 88.5% (23/26), 25% (3/12) and 44.1% (30/68), 11.1% (1/9) and 64.4% (29/45), 25% (2/8) and 60% (45/79), 22.2% (2/9) and 35.9% (28/78). 0% (0/5) and 24.7% (18/73), respectively. The overall frequency in the primary school was 41.4% (183/442 children). The frequency in the nursery school for children aged 4-5 years was 14.0% (6/43). It was 17.5% (11/63) in children aged 5-6 years in the kindergarten, 5.2% (11/213) in children not attending school with an age range of 1-5 years, and 4.2% (10/237) in junior high school students. Although the frequencies of MMR coverage for the nursery school children and kindergarteners were not high enough to eradicate mumps outbreaks, the MMR vaccination program was thought to have influenced the low frequency of mumps among the children. Close physical interactions among the first-graders would have contributed to their high frequency of mumps. Some patients presented with suspected mumps parotitis several times, but no such serological confirmation of reinfection was obtained.

Adolescent↗

PubMed1996

Analysis of the region between amino acids 30 and 42 of intact UmuD by a monocysteine approach.

On the basis of characterizations of a set of UmuD monocysteine derivatives, we had suggested that positions 24, 34, and 44 are closer to the intact UmuD homodimer interface than other positions tested (M. H. Lee, T. Ohta, and G. C. Walker, J. Bacteriol. 176:4825-4837, 1994). Because this region of UmuD also appeared to be important for interactions with RecA, we followed up on our previous study by constructing a second set of monocysteine UmuD derivatives with single cysteine substitutions at positions 30 to 42. We found that like the VC34 mutant, UmuD derivatives with monocysteine substitutions at positions 32 and 35 showed deficiencies in in vivo and in vitro RecA-mediated cleavage as well as in UV mutagenesis, suggesting that the position 32 to 35 region may be important for RecA-mediated cleavage of UmuD. Interestingly, UmuD with monocysteine substitutions at residues 33 and 40 showed a reduction in UV mutagenesis while retaining the ability to be cleaved by RecA in vivo, suggesting a deficiency in the subsequent role of the UmuD' derivatives in mutagenesis. All of the UmuD monocysteine derivatives in the position 30 to 42 series purified indistinguishably from the wild-type protein. The observations that purified proteins of the UmuD derivatives RC37 and IC38 could be disulfide cross-linked quantitatively upon addition of iodine and yet were poorly modified with iodoacetate led us to suggest that the pairs of residues at positions 37 and 38 are extremely close to the UmuD2 homodimer interface. These observations indicate that the structure of the UmuD2 homodimer in solution is very different from the crystal structure of the UmuD'2 homodimer reported by Peat et al. (T. S. Peat, E. G. Frank, J. P. McDonald, A. S. Levine, R. Woodgate, and W. A. Hendrickson, Nature [London] 380:727-730, 1996).

Amino Acid Sequence↗

PubMed1996

The PB1 subunit alone can catalyze cRNA synthesis, and the PA subunit in addition to the PB1 subunit is required for viral RNA synthesis in replication of the influenza virus genome.

We indicated that the PB1 and PA subunits of RNA polymerase and nucleoprotein (NP) can support replication of the influenza virus genome as well as transcription to yield uncapped poly(A)(+)-RNA (Y. Nakagawa, N. Kimura, T. Toyoda, K. Mizumoto, A. Ishihama, K. Oda, and S. Nakada, J. Virol. 69:728-733, 1995). To analyze the functions of the PB1 and PA subunits in replication and transcription, YP1N clones in which the PB1 and NP genes can be expressed in response to dexamethasone were established. cRNA was transcribed from model viral RNA (vRNA), but vRNA synthesis from model cRNA was not detected in YP1N clones. Furthermore, poly(A)(+)-RNA directed from model vRNA was synthesized in YP1N clones. These results indicated that PB1 and NP can support the syntheses of cRNA and poly(A)(+)-RNA and that the PA subunit, in addition to that of PB1 and to NP, is required for vRNA synthesis. In summary, the PB1 subunit is involved in the catalytic activities of nucleotide elongation, and the PA subunit may act as an allosteric modulator and cause a conformational change from a cRNA-to a vRNA-synthesizing form of the PB1 subunit.

Animals↗

PubMed1996

ETA and ETB receptors cooperate in DNA synthesis via opposing regulations of cAMP in human lung cell line.

We investigated the contribution of endothelin type A (ETA) and ETB receptors on ET-induced DNA synthesis in CCD-18Lu cells, a human lung cell line possessing both ETA and ETB (ETA/ETB ratio: 9:1). ET-1 (0.05-2 nM) potently induced [3H]thymidine incorporation by 2- to 14-fold over the basal level. An ETA-selective antagonist, FR139317, inhibited 0.2 nM ET-1-induced DNA synthesis dose dependently, showing complete inhibition at 1 microM. ET-3 was inactive up to 2 nM. In contrast, ETB-selective antagonists, 100 nM of BQ-788 or IRL 2500, partially (30-60%) inhibited 0.2 nM ET-1-induced DNA synthesis. Stimulation of either ETA or ETB evoked the increases in intracellular Ca2+ concentration ([Ca2+]i). ETB-mediated but not ET-1-induced [Ca2+]i increase was pertussis toxin (PTX) sensitive. Adenosine 3',5'-cyclic monophosphate (cAMP) formation via ETA was observed in PTX-treated cells, whereas the inhibition of isoproterenol-stimulated cAMP formation via ETB was observed in PTX-untreated cells. Like the ETB-selective antagonists, PTX treatment or dibutyryl cAMP partially (50-70%) inhibited ET-1-induced DNA synthesis. These data suggest that 1) ET-1 induces DNA synthesis predominantly through ETA, via PTX-insensitive G protein; 2) ETA-mediated cAMP formation inhibits DNA synthesis; and 3) stimulation of ETB coupling to Gi protein modulates ETA-mediated DNA synthesis by inhibiting cAMP formation.

Cell Division↗

PubMed1996

Severe gastrointestinal complications of dialysis-related amyloidosis in two patients on long-term hemodialysis.

Two patients undergoing long-term hemodialysis developed severe gastrointestinal complications due to dialysis-related amyloidosis (DRA). Case 1, a 68-year-old male on hemodialysis for 18 years developed marked gastric dilatation and severe paralytic ileus. Five years later he died of peritonitis. Autopsy showed extensive amyloid deposits in the muscle layers and blood vessels throughout the gastrointestinal tract. Case 2, a 56-year-old male on hemodialysis for 19 years, developed panperitonitis due to perforation of the sigmoid colon. The resected colon showed massive amyloid deposits in the muscle layers. In both cases, immunological studies revealed positive staining for antihuman beta2-microglobulin antibody. In long-term hemodialysis patients with gastrointestinal symptoms, gastrointestinal complications of DRA should be considered.

Aged↗

PubMed1996

Endothelin-A receptor-mediated prostanoid secretion via autocrine and deoxyribonucleic acid synthesis via paracrine signaling in human bronchial epithelial cells.

It is known that serum promotes squamous differentiation of airway epithelial cell culture in vitro. We investigated which types of epithelial cells produce endothelins (ETs) and ET-evoked cellular responses in cultured human bronchial epithelial cells (HBECs). Squamous cells, not basal cells (nondifferentiated), secrete ET-1 actively. Specific binding of [125I]ET-1, not [125I]ET-3, was observed in squamous as well as basal cells, demonstrating the existence of only the ETA receptor. ET-1 together with epidermal growth factor stimulated synergistic DNA synthesis in basal cells, whereas ET-1 alone did not. Serum failed to induce DNA synthesis in HBECs, indicating terminal differentiation into squamous cells. ET-1 (1-100 nM) dose-dependently stimulated PGE2 (0.6-2.8 ng/10(5) cells) and thromboxane B2 release (4-30 pg/10(5) cells) from squamous HBECS, but not from basal cells. Western blot analysis showed that both squamous and basal HBECs expressed inducible and endothelial nitric oxide synthase, whereas ET-1 failed to stimulate nitric oxide synthase expression. Our findings suggest that secreted ET-1 from squamous cells evokes the release of prostanoids in an autocrine manner, and stimulates DNA synthesis in basal cells as a comitogen in a paracrine manner. Thus, it is likely that ET-1 secreted from HBECs plays an important role as a local, autocrine, and paracrine modulator in airway responses.

Azepines↗

PubMed1996

Synthesis and biological activity of O-alkyl-3-N-aminoacyloxymethyl-5-fluoro-2'-deoxyuridine derivatives.

In an attempt to improve the effectiveness of action of 5-fluoro-2'-deoxyuridine (FUdR), various kinds of O-alkylated water-soluble analogues were synthesized. Antitumor activities against sarcoma 180 (solid) were also evaluated. Some compounds exhibited potent activities. In particular, 3'-O-p-chlorobenzyl-3-N-aminoacyloxy-methylester derivatives were effective over a very wide range of dose and gave extremely large therapeutic ratios compared with known 5-fluorouracil (5-FU) derivations.

Animals↗