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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 397 records · Page 22Linked to original sources

[Trends for stroke incidence and prognosis in a rural community with a long-term stroke prevention program].

Trends for stroke incidence and prognosis were investigated in a southwest rural town in Japan, where a community-based stroke prevention program has been conducted since 1969. Four hundred forty-nine stroke patients aged 40 years and older were registered from 1969 to 1988. From among these, 405 (90%) were followed for 3 years to examine prognosis. 1. Age-adjusted stroke incidence in each 5 year interval decreased from 1969 to 1988 with stroke incidence decreasing in almost all age groups 40 years and older for both men and women. A small increase in incidence was observed for women aged 70 years and older between 1979-1983 and 1984-1988. 2. While there was a 46% increase in the population aged 40 years and older, the number of stroke patients decreased between 1969-1973 and 1984-1988. 3. Mortality rates between one week and three years after a stroke have shown a decrease from 1969-1978 to 1979-1988. The proportion of those not requiring nursing care between one week years after stroke has increased. The proportion of all patients requiring nursing care however did not change. 4. After adjusting for age, sex, type of stroke, and loss of consciousness, the blood pressure level within 5 years prior to the stroke was positively associated with death between one week and three years after the event, and was negatively associated with the proportion of those not requiring nursing care. 5. Despite a 31% increase in the census population of all ages between 1969-1978 and 1979-1988, the number of those requiring nursing care has increased only 6% at one year after stroke. If the population had remained constant, the number of those requiring nursing care would have decreased by 10% at one year after the event. These results suggest that a long-term community-based stroke prevention program can decrease both the number of those requiring nursing care and mortality after stroke, as well as stroke incidence and the number of stroke patients.

Adult↗

IgG-mediated anaphylactic contraction and 86Rb efflux from guinea pig tracheal smooth muscle.

Tracheal muscle strips isolated from guinea pigs passively sensitized with anti-egg albumin rabbit IgG were loaded with 86Rb as a K+ marker. The 86Rb efflux from the muscle tissue was measured after antigen exposure and the K(+)-channel subtypes involved in anaphylactic contraction were identified. The net 86Rb efflux was increased during antigen challenge. This increase was inhibited in Ca(2+)-free medium or in the medium of 40 mM of KCl, but not by 10 microM of glibenclamide or 20 mM of KCl. Decreased membrane potential and generation of action potentials were also observed during the anaphylactic contraction. As a comparison for antigen-induced 86Rb efflux changes, experiments using high concentrations of KCl were also performed. 86Rb efflux was increased depending on the KCl concentration. This increase was inhibited in Ca(2+)-free medium but not by 10 microM of glibenclamide. These results suggest that the K(+)-channel opening during IgG-mediated anaphylactic contraction was dependent on a decreased membrane potential due to 20-40 mM KCl. The subtype of the K(+)-channel involved is voltage-dependent K(+)-channel (Kv-channel), and Ca(2+)-activated K(+)-channel (KCa-channel) may also be involved in the 86Rb efflux change. The ATP-sensitive K(+)-channel (KATP-channel) was not involved in K(+)-channel opening during anaphylactic contraction.

Anaphylaxis↗

Effects of macrophage colony-stimulating factor (M-CSF) on the mobilization of peripheral blood stem cells.

We studied the effects of human urinary macrophage colony-stimulating factor (huM-CSF) on the mobilization of peripheral blood stem cells (PBSC) following cytotoxic chemotherapy in 6 patients with acute leukemia. After complete remission (CR) was achieved, two courses of consolidation chemotherapy consisting of an intermediate dose of cytosine arabinoside were administered to the patients. During a recovery phase after each course of consolidation chemotherapy, two successive cycles of leukapheresis were performed every other day. M-CSF was administered intravenously at a dose of 8 x 10(6) U/day during a recovery phase after the second course of consolidation chemotherapy (cytotoxic plus M-CSF mobilization). There was no significant difference in white blood cell (WBC) or platelet recovery between the first and second cycles, regardless of the administration of M-CSF. Furthermore, between cytotoxic and cytotoxic/M-CSF mobilization, significant differences were not observed in the harvest of mononuclear cells (average 1.43 x 10(8)/kg vs 1.62 x 10(8)/kg), granulocyte/macrophage progenitor cells (CFU-GM) (1.82 x 10(4)/kg vs 3.07 x 10(4)/kg) or erythroid progenitor cells (BFU-E) (2.86 x 10(4)/kg vs 2.66 x 10(4)/kg). Thus M-CSF is not effective for expanding a pool of circulating hematopoietic stem cells when administered at a conventional dose during hematologic recovery following chemotherapy.

Acute Disease↗

Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral arteries.

Nitric oxide synthase (NOS)-immunoreactive fibers innervating the dog arterial wall were histochemically determined by the use of NOS antiserum. NOS-immunoreactive fibers were consistently found in every arterial wall examined. In a whole-mount preparation, NOS-positive fibers were detectable in the small pial artery having a diameter of about 100 microns as well as the proximal middle cerebral artery. Further detailed analyses in thin cryostat sections indicated that in middle cerebral, basilar, temporal, mesenteric and femoral arteries, fine NOS-positive fibers were detected in outer zones of the media in addition to many thicker fibers in the adventitia. However, in the coronary artery, many thick fibers were situated in the adventitia, and fine NOS-positive fibers were not found in the media. Injection of ethanol to the pterygopalatine ganglion markedly decreased or abolished the NOS immunoreactivity in nerve cells and fibers and abolished the innervation of NOS-positive fibers in the wall of middle cerebral artery of the ipsilateral side. Together with findings in our previous publications concerning the functional role of nitroxidergic nerve in the control of arterial tone, we conclude that perivascular nerves containing NOS are crucial in eliciting the neurally induced, NO-mediated arterial relaxation.

Amino Acid Oxidoreductases↗

Factor IX Fukuoka. Substitution of ASN92 by His in the second epidermal growth factor-like domain results in defective interaction with factors VIIa/X.

Hemophilia B Fukuoka, a moderately severe bleeding disorder, is a naturally occurring mutant of factor IX. Plasma from our patient had 3% clotting activity even though 64% of factor IX antigen was present. The purified mutant protein was cleaved normally by factor Xla, factor VIIa-tissue factor complex, or RVV-X (factor X-activating enzyme from Russell's viper venom), yielding a two-chain factor IXa. Amino acid composition and sequence analyses of one of the lysyl endopeptidase peptides derived from factor IX Fukuoka revealed that Asn92 in the second epidermal growth factor (EGF)-like domain had been replaced by His. The active site of the factor IXa Fukuoka was normally competent for the incorporation of p-aminobenzamidine and for the hydrolysis of a synthetic substrate, N alpha-benzyloxycarbonyl-L-arginine p-nitrobenzyl ester. Factor Xa formation by factor IXa Fukuoka was only 8% of the normal factor IXa, even in the presence of polylysine, and only 0.2% of the normal in the system containing phospholipids, Ca2+, and factor VIIIa, thereby indicating a functional defect in interaction of the mutant with factors VIIIa/X. Furthermore, catalytic efficiency (kcat/Km) of factor IXa Fukuoka toward factor X in the presence of Ca2+, phospholipids, and factor VIIIa was only 2.3% of the normal factor IXa. These results suggest that an Asn-to-His substitution at position 92 in the second EGF-like domain of factor IX Fukuoka would have an untoward effect on the specific conformational state of factor IX for binding with factors VIIIa/X.

Adult↗

Hematopoietic progenitor cells from patients with adult T-cell leukemia-lymphoma are not infected with human T-cell leukemia virus type 1.

The in vivo host range of human T-cell leukemia virus type 1 (HTLV-1) has not been definitively established. To determine if hematopoietic stem cells from patients with adult T-cell leukemia-lymphoma (ATL) are infected with HTLV-1, we used a clonogenic progenitor assay followed by the polymerase chain reaction for the detection of HTLV-1 DNA. In vitro growth characteristics of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells among nonadherent T-cell-depleted bone marrow (BM) mononuclear cells (NA-T-MNCs) from 10 patients with ATL was not significantly different from those of HTLV-1-seronegative controls (P = .20); numbers of colonies per 1 x 10(5) NA-T-MNCs were 34.9 +/- 7.6 for CFU-GM and 39.0 +/- 12.5 for BFU-E in patients with ATL, whereas those were 32.1 +/- 9.5 for CFU-GM and 41.4 +/- 12.7 for BFU-E in normal controls. HTLV-1 DNA was not detected in individual colonies formed by CD34+ cells from any of the patients. Similarly HTLV-1 DNA was not detected in 1 x 10(3) CD34+ cells sorted on a fluorescence-activated cell sorter (FACS) from six patients with ATL studied. In contrast, HTLV-1 DNA was detected in BM mononuclear cells from all patients. These observations clearly indicate that hematopoietic progenitor cells from patients with ATL are normal in their colony-forming capacity and that CD34+ cells from patients with ATL are not infected with HTLV-1 in vivo.

Adult↗

Interactions of nitrovasodilators and atrial natriuretic peptide in isolated dog coronary arteries.

In helical strips of dog coronary arteries contracted with prostaglandin F2 alpha, relaxant responses to atrial natriuretic peptide (ANP), nitric oxide (NO), nitroglycerin and 8-bromo cyclic GMP were markedly inhibited or abolished by treatment with a high concentration of sodium nitroprusside, whereas the responses to beraprost and papaverine were not influenced. A similar suppression of the responses to ANP, NO, and sodium nitroprusside was observed after treatment with nitroglycerin. The relaxations induced by NO and nitroglycerin were abolished by methylene blue and oxyhemoglobin, whereas the response to ANP was not influenced. The sodium nitroprusside-induced relaxation was significantly potentiated by methylene blue but was abolished by oxyhemoglobin. The increase in cyclic GMP caused by ANP and nitroglycerin was not influenced by treatment with sodium nitroprusside, despite the fact that the responses to ANP and nitroglycerin were suppressed. It can be concluded that ANP and nitroglycerin or sodium nitroprusside share the same mechanism of action on intracellular processes occurring after the synthesis of cyclic GMP in dog coronary artery smooth muscle cells and that cross-tachyphylaxis between nitroglycerin, sodium nitroprusside, and ANP in the mechanical response is not associated with an impaired production of cyclic GMP.

8-Bromo Cyclic Adenosine Monophosphate↗

[An evaluation of prognostic factors in patients with esophageal carcinoma].

We evaluated the relationship between clinicopathological findings and the prognosis of 101 patients who underwent esophagectomy for primary esophageal cancers in our institution, from 1980 to 1991, and investigated the prognostic factors of esophageal carcinoma. There were significant relationships between the prognosis and the depth of cancer invasion (P < 0.05), lymph nodes involvement (P < 0.05), lymphatic invasion (P < 0.01), venous invasion (P < 0.05) and histological stages (P < 0.01). The stages were decided by the depth of invasion and the lymph nodes metastasis. There were also no positive relationships between the prognosis and lymphatic and venous invasion in the patients groups of both n (-) and n3 + 4. Therefore, we concluded that the most important prognostic factors were the depth of cancer invasion (invasion into the neighboring structures) and lymph nodes involvement. We suggest that lymphatic and venous invasion may play an important part in the prognosis of the patients in the n1 + 2 positive group.

Carcinoma, Squamous Cell↗

Diversity of primary structures of the carboxy-terminal regions of mammalian fibrinogen A alpha-chains. Characterization of the partial nucleotide and deduced amino acid sequences in five mammalian species; rhesus monkey, pig, dog, mouse and Syrian hamster.

The partial amino acid sequences of fibrinogen A alpha-chains from five mammalian species have been inferred by means of the polymerase chain reaction (PCR). From the genomic DNA of the rhesus monkey, pig, dog, mouse and Syrian hamster, the DNA fragments coding for alpha-C domains in the A alpha-chains were amplified and sequenced. In all species examined, four cysteine residues were always conserved at the homologous positions. The carboxy- and amino-terminal portions of the alpha-C domains showed a considerable homology among the species. However, the sizes of the middle portions, which corresponded to the internal repeat structures, showed an apparent variability because of several insertions and/or deletions. In the rhesus monkey, pig, mouse and Syrian hamster, 13 amino acid tandem repeats fundamentally similar to those in humans and the rat were identified. In the dog, however, tandem repeats were found to consist of 18 amino acids, suggesting an independent multiplication of the canine repeats. The sites of the alpha-chain cross-linking acceptor and alpha 2-plasmin inhibitor cross-linking donor were not always evolutionally conserved. The arginyl-glycyl-aspartic acid (RGD) sequence was not found in the amplified region of either the rhesus monkey or the pig. In the canine alpha-C domain, two RGD sequences were identified at the homologous positions to both rat and human RGDS. In the Syrian hamster, a single RGD sequence was found at the same position to that of the rat. Triplication of the RGD sequences was seen in the murine fibrinogen alpha-C domain around the homologous site to the rat RGDS sequence. These findings are of some interest from the point of view of structure-function and evolutionary relationships in the mammalian fibrinogen A alpha-chains.

Amino Acid Sequence↗

Effect of total parenteral nutrition on liver mitochondrial function in mature rats.

To evaluate the effects of TPN on the hepatic function, the changes in hepatic energy charge levels, oxidative and phosphorylative activities of mitochondria and serum transaminase were studied, using male Sprague-Dawley rats 240 to 250 g in weight. The rats were randomized into three groups. The first group (TPN-V group, n = 6) was infused with TPN solution via the right jugular vein. The number of calories of TPN solution infused daily was adjusted to provide each rat with 80 kcal/kg/day on the 1st day, 160 kcal/kg/day on the 2nd day and 240 kcal/kg/day on the 3rd day. After the 4th day, 240 kcal/kg/day was given to both groups. The second group (TPN-G group, n = 5) was infused with the same solution via an intragastric route and was given the same calories as the TPN-V group. The third group (control group, n = 6) was given a chow diet with the same calories as the TPN group. At the 13th day, all groups were sacrificed, and the hepatic energy charge (EC) and phosphorylation rate (PR) of hepatic mitochondria were measured, and liver function tests were done. PR was 101.2 +/- 5.0 nmol/mg protein/min in control group, 120.8 +/- 2.7 in TNP-G group and 136.5 +/- 6.2 in TPN-V group. EC was 0.906 +/- 0.006, 0.889 +/- 0.008, 0.831 +/- 0.010, respectively. The liver function tests of all group were normal. In both TPN groups, despite evidence that liver function tests were normal, enhanced mitochondrial phosphorylative activity was observed during the early stage of TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sequencing analysis of Ha-, Ki-, and N-ras genes in rat urinary bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and sodium saccharin.

Male F344 rats were fed N[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for up to 4 wk, then given the basal diet with or without 5% sodium saccharin for up to 100 wk. In a previous study, we demonstrated point mutations in codons 12 and 61 of Ha-ras gene among eleven transitional cell carcinomas (TCC), one undifferentiated carcinoma, and two sarcomas of the urinary bladder (Mol Carcinogen 3:210-215, 1990). In this study, Ha-ras, Ki-ras, and N-ras sequences were examined by polymerase chain reaction (PCR) and direct DNA sequencing. The results confirm the point mutation in codon 61 (CAA to CGA in 5 TCCs and to CTA in one TCC) of the Ha-ras gene. Mutation at codon 12 was not confirmed. No mutation was found in the Ki-ras gene. Sequences of the N-ras gene exons 1 and 2 were determined, and no mutations was detected. These results suggest the involvement of activated Ha-ras gene, but not Ki-N or N-ras gene, in rat urinary bladder carcinogenesis induced by FANFT. Subsequent sodium saccharin administration did not affect the changes in Ha-ras gene.

Amino Acid Sequence↗

Mechanisms of acetylcholine-induced relaxation in dog external and internal ophthalmic arteries.

Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in dog external (EOA) and internal ophthalmic arteries (IOA). Acetylcholine produced relaxation in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxations induced by ACh in these arteries were not inhibited by endothelium denudation. The ACh (10(-8)-10(-5) M)-induced relaxations in EOA and IOA were abolished by treatment with atropine or indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthesis inhibitor, but not influenced by hexamethonium. On the other hand, the relaxant response to the highest concentration used (10(-4) M) was partially attenuated but not abolished by treatment with atropine, indomethacin or hexamethonium. This relaxation under treatment with atropine was abolished by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, but not by indomethacin, whereas the response under treatment with hexamethonium was abolished by indomethacin, but not by L-NA. Combined treatment with indomethacin and L-NA or oxyhaemoglobin abolished the ACh (10(-4) M)-induced relaxation, or reversed it to a contraction. It may be concluded that relaxations induced by low concentrations of ACh in dog EOA and IOA are associated possibly with the release of PGI2 through activation of muscarinic receptors located in subendothelial tissues, including smooth muscle, and the relaxant response to the high concentration (10(-4) M) of ACh is mediated mainly by the release of nitric oxide through activation of nicotinic receptors in nitroxidergic nerves.

Acetylcholine↗

Detection of collagenase mRNA in odontoclasts of bovine root-resorbing tissue by in situ hybridization.

The odontoclast, which is morphologically similar to osteoclast, is thought to play a major role in root resorption of deciduous teeth. High collagenolytic activity has been detected in the root resorbing tissue. In order to identify collagenase-producing cells and the role of collagenase in root resorption of deciduous tooth, in situ hybridization of collagenase mRNA in bovine root-resorbing tissue sections was performed using a digoxigenin-labeled, nonradioactive RNA probe. Collagenase mRNA expression was clearly observed in odontoclasts in addition to the macrophages, fibroblasts, odontoblasts, and cementoblasts. Multinuclear odontoclasts showed intense tartrate-resistant acid phosphatase (TRAP) activity. We also examined interleukin-1 (IL-1) mRNA expression in the root-resorbing tissue by in situ hybridization. IL-1 transcripts were found to be expressed in odontoclasts, fibroblasts, and macrophages suggesting that IL-1 might be an important factor for promoting root resorption. These results suggest that the collagenase produced by odontoclasts may play a key role in dentin collagen degradation in root resorption.

Acid Phosphatase↗

Cytidine deaminase activity in abnormal pregnancy.

OBJECTIVE: To determine the usefulness of cytidine deaminase (CTD) activity in the prediction of abnormal pregnancy and the prognosis of fetal outcome. METHOD: The CTD activities in 367 pregnant women and 17 placentas and their cord sera were determined. The CTD activity was estimated to determine the amount of ammonia liberated during conversion of cytidine into uridine. The Kruskal-Wallis test and paired t-test were employed for statistical comparisons. RESULT: The placentas contained extremely high levels of CTD activity, but the cord serum did not. The mean value of CTD activity in abnormal pregnancy women was significantly higher than in normal pregnancy women. The two cases with a CTD activity of 40 U or more had the worst infant prognosis. CONCLUSION: The CTD activity in abnormal pregnancies was excessively elevated due to a damaged placenta under progressive deterioration. This CTD assay was simple and had predictive value for the prognosis of an infant of an abnormal pregnancy.

Abortion, Spontaneous↗