Effect of mitomycin-C upon gastric cancer (from follow-up study of gastrectomy). II.
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Biomedical subjects
Publications and source records attributed to T Okamura.
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BACKGROUND: Use of genetic analysis may improve the predictive value of risk factors for disease. A high plasma level of high-density lipoprotein (HDL) cholesterol is a strong negative risk factor for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) deficiency causes increased levels of HDL cholesterol. However, recent studies suggest that CETP deficiency is a risk factor for CHD despite elevated HDL cholesterol levels. METHODS: Plasma lipid levels, CHD prevalence, resting electrocardiograms, and common CETP gene mutations were analyzed cross-sectionally in a population of 19,044 male and 29,487 female Japanese subjects (ages 45-79 years). RESULTS: High HDL cholesterol levels (serum HDL cholesterol >/=80 mg/dl, >/=95th percentile) were found in 6 and 5% of Japanese men and women, respectively. In the group with HDL cholesterol >/=80 mg/dl, common CETP gene mutations were identified in 23-24% of men and 31-49% of women. The prevalence of CHD in the group with high HDL cholesterol (>/=80 mg/dl) was low among both men (1.0%) and women (1.3%). There was no difference in CHD prevalence between hyper-HDL-cholesterolemic subjects with and without CETP mutations. CONCLUSIONS: Subjects with very high HDL levels (HDL cholesterol >/=80 mg/dl) as well as mild-to-moderate HDL elevations (60-79 mg/dl) appear to be protected against CHD, whether or not they have CETP deficiency, a genetic cause of elevated HDL.
Acetylcholine applied extraluminally to isolated, perfused dog mesenteric artery segments produced an endothelium-dependent depressor response when the perfusion pressure was raised by continuous infusion of noradrenaline; the potency was 1/30 to 1/60 that of intraluminal acetylcholine. Contractions induced by transmural electrical stimulation were attenuated by treatment with intra- and extraluminal acetylcholine; the inhibitory effect of intraluminal acetylcholine was greater than that of extraluminal acetylcholine. Removal of endothelium did not significantly alter the inhibitory effect. In mesenteric artery strips with endothelium, treatment with oxyhaemoglobin suppressed the relaxant response to acetylcholine but did not influence the inhibitory effect of acetylcholine on stimulation-evoked contractions. Acetylcholine reduced the 3H-overflow and contraction of superfused mesenteric artery strips, preloaded with 3H-noradrenaline, response to transmural stimulation. By the use of bioassay (dog femoral artery segment with endothelium/coronary artery strip without endothelium), the release of EDRF was first determined in the perfusate, which was introduced to dog mesenteric artery strips loaded with 3H-noradrenaline. The 3H-overflow and contraction caused by the stimulation were not attenuated by EDRF and were also observed following treatment with superoxide dismutase. Inability of the perfusate to reduce the stimulation-evoked 3H-overflow was also observed when the donor and assay tissues were treated with superoxide dismutase. It may be concluded that the inhibition by acetylcholine of the release of neuronal noradrenaline is not dependent on endothelium. Extraluminally applied acetylcholine would reach the endothelium and release EDRF, and intraluminal acetylcholine is presumed to act directly on prejunctional muscarinic receptors; however, acetylcholine appears to cross the medial layer more efficiently from intima to adventitia than in the reverse direction.
Analysis of foot pressures in cases of reconstructed adactyly of the lateral toes is presented. Two cases with adactyly of the 4th and 5th toes in which new toes were created by cross-knee tubed pedicle flap were chosen and foot pressures of both the operated foot and the contralateral normal foot were measured postoperatively. The results did not indicate any functional disturbance after this method of reconstruction.
Endogenous cerebral vasoconstrictor mediators regulate vascular resistance and blood flow in the brain as a whole and in various regions and participate in the pathogenesis of cerebral circulatory disturbances. Vasoconstrictors are effective in the treatment of diseases associated with cerebral vasodilatation. There are variations in the response of cerebral arteries from primate and subprimate mammals; therefore, information as to similarities and differences in their response is quite important in evaluating the physiological role, involvement in pathogenesis and therapeutic usefulness of the mediators in healthy men and patients. In this review we described characteristics of the action of vasoconstrictors (amines, peptides, prostanoids, and others) on isolated cerebral arteries from mammals, including humans and monkeys.
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The preoperative diagnosis of uterine leiomyosarcoma (LMS) is very difficult. Magnetic resonance (MR) imaging is usually used for it; however, precise diagnosis by MR imaging is limited to typical LMS with coagulative tumor cell necrosis. We presented a case of LMS that was diagnosed preoperatively by positron emission tomography (PET) using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG).
Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of heart and lung injury after reperfusion and during cardiopulmonary bypass. This study was designed to determine whether leukocyte depletion prevents injury to the heart and lung during cardiopulmonary bypass. Twenty-eight open heart surgeries were performed in this study. In Group F, leukocyte depletion was performed with an LG-6 arterial line filter after aortic declamp (n = 14). Leukocyte depletion was not performed during cardiopulmonary bypass in Group C (n = 14). Thereafter, cardiac and lung function were assessed in the 24 hr after reperfusion. The total catecholamine dose used for 24 hr after reperfusion (r) was 61.9 +/- 13.4 in Group C and 43.9 +/- 19.2 in Group F (p < 0.05). CK-MB at 3 and 6 hr after reperfusion was 65.9 +/- 13.5 and 64.8 +/- 15.8 in Group C and 45 +/- 11.8 and 38 +/- 10.8 in Group F, respectively (p < 0.05). The pulmonary index after reperfusion at 3 and 6 hr was 1.7 +/- 0.5 and 1.3 +/- 0.4 in Group C and 0.7 +/- 0.3 and 0.6 +/- 0.4 in Group F, respectively (p < 0.05). There was significantly better preserved lung function in Group F. In conclusion, leukocyte depletion was significantly effective in preserving heart and lung function during cardiopulmonary bypass.
A 43-year-old woman was admitted with a tumor mass in her forehead. Two months previously, a lump in her breast had been diagnosed as mastopathy. Palpation revealed an elastically hard immobile tumor mass in her forehead. MRI detected a tumoral lesion of generally uniform contrast involving frontal subcutaneous, cranial, and intracranial regions. PET demonstrated more intensive and wider accumulation of [11C]methyl-L-methionine (Met) than of [18F]fluoro-2-deoxyglucose (FDG). Biopsy of the forehead mass was performed, which was diagnosed as B-cell-type malignant lymphoma. The tumor mass in the forehead then shrank spontaneously, as confirmed by palpation and MRI. The tumor mass in the left breast was totally extirpated and histologically diagnosed as B-cell-type malignant lymphoma, like the tumor mass in the forehead. Postoperatively, chemotherapy (VEPA) was performed. Although FDG accumulation had not been detected, postchemotherapy PET demonstrated slight Met accumulation, suggesting the presence of a residual tumor. PET served well to detect the lesion and evaluate therapeutic efficacy in malignant lymphoma. Met-PET was more sensitive to malignant lymphoma than FDG-PET.
Interactions of ONO3708, a thromboxane (TX) A2 analog, and epithio-methano-TXA2 (sTXA2) or prostaglandins (PGs) were investigated in helical strips of dog cerebral, coronary, renal, and mesenteric arteries. In these arterial strips sTXA2 (10(-10) to 10(-7) M) produced a dose-dependent contraction, whereas ONO3708 up to 10(-6) M failed to contract the arteries but antagonized the contractile response to sTXA2. The inhibition tended to be greater in renal arteries than in the other arteries. Contractions induced by PGF2 alpha, PGE2, and PGD2 were also suppressed by treatment with low concentrations (3 X 10(-9) and 10(-8) M) of ONO3708. The attenuations of the response to sTXA2, PGF2 alpha, PGE2, and PGD2 did not appreciably differ. Norepinephrine-induced contractions were not influenced by ONO3708 up to 2 X 10(-7) M. On the other hand, relaxant responses to PGI2 of cerebral and renal arteries were not reduced by ONO3708. Prostaglandin H2 produced a transient contraction followed by a relaxation in cerebral and renal arteries. The contractile response was abolished by 10(-7) M ONO3708, and the relaxation was potentiated. It may be concluded that ONO3708 selectively antagonizes the vasoconstrictor action of TXA2, its analogs, and PGs but does not alter the action of vasodilator PGs. At least in part, sTXA2, PGF2 alpha, PGE2, and PGD2 appear to share the same receptive site responsible for vascular contraction.
A case of hepatocellular carcinoma (HCC) in a cirrhotic liver which became detectable within a month is reported here. The patient was admitted for treatment of oesophageal varices due to Child's C grade liver cirrhosis. A hepatic angiogram was performed before the treatment and showed no neovascularture. After undergoing variceal treatment by injection sclerotherapy, the patient underwent another angiogram 28 days later in order to measure the efficacy of the treatment. The second angiogram revealed the emergence of small multiple neovasculatures throughout the entire liver. From the angiographic findings, those tumours were considered to be HCC. The present report suggests that small HCC latent in a cirrhotic liver can thus acquire neovasculature within a short period of time.
Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2 alpha, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation. The relaxations were not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adrenergic, non-cholinergic vasodilator nerve and liberates NO. The inhibitions were reversed by L- but not D-arginine. NO (acidified NaNO2)-induced relaxations were not reduced by L-NA. The inhibitory effect was greater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the peptides. Substance P increased the level of cyclic guanosine monophosphate (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Relaxations caused by adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothelium but did not alter the response of denuded strips.(ABSTRACT TRUNCATED AT 250 WORDS)
Arginine vasopressin (AVP) produced relaxations at low concentrations (10[-11] and 10[-10] M) and contractions at higher concentrations in canine ciliary arterial strips with endothelium, partially contracted with prostglandin F2alpha. The AVP-induced relaxation was abolished or reversed to a contraction by removal of the endothelium or treatment with NG-nitro-L-arginine. The effect of this antagonist was reversed by L-arginine. The relaxant response was inhibited dose-dependently by SR49059 (10[-10]-10[-9] M), [Pmp1,Tyr(Me)2]-Arg8-vasopressin (PMP-AVP) (10[-10]-10[-9] M), V1 receptor antagonists, and OPC31260 (3 x 10[-8] M), a reported V2 receptor antagonist, but not by OPC21268 (10[-7]-10[-6] M), a reported V1 antagonist. In the endothelium-denuded strips, the AVP-induced contraction was attenuated by SR49059, PMP-AVP and OPC31260, but not by OPC21268. It is concluded that AVP in low concentrations elicits intense relaxation of canine ciliary arteries, possibly due to nitric oxide synthesized in association with activation of the endothelial V1 receptor subtype. AVP-induced contractions appear to be mediated also by the V1 receptor in smooth muscle. Antagonistic selectivities of the OPC compounds to vasopressin receptor subtypes could not be seen in this particular material.
A case of hybrid phenotypic chronic myelomonocytic leukemia (CMMoL) transformed from a hematological remission state of severe aplastic anemia is reported. A 63-year-old woman was admitted to our hospital with complaints of easy fatigability and dizziness in December 1978. A diagnosis of aplastic anemia was made from findings of pancytopenia and hypoplastic marrow without dysplasia, and she was treated successfully with mepitiostane. Seven years later, anemia and thrombocytopenia reappeared with monocytosis. On the second admission, the peripheral blood showed a white blood cells count of 3.5 X 10(3)/microliters with 54% monocytes. The bone marrow was hypercellular with monocytosis, and dysplasia of three cell lineages was noted. A diagnosis of CMMoL was made. Cytogenetic analysis of bone marrow cells revealed a karyotype of 45 XX, -7, 11q-, and surface markers were polyphenotypic, including CD20+, CD14+ and CD13+. This is the first report of CMMoL with biphenotype which was transformed from aplastic anemia.
Danazol was administered to two patients with paroxysmal nocturnal hemoglobinuria (PNH) with a dramatic effect on the hematological findings. The patients, 31- and 41-year-old females, were initially diagnosed as having aplastic anemia, and were initially treated with anabolic steroid and immunosuppressive therapy, respectively. Sugar water and Ham tests turned positive at the start of danazol therapy in the former patient and after two months in the latter patient. This drug produced a dramatic improvement in the hemoglobin level and the platelet count and showed few side effects in the patients. A possible mechanism of action of danazol for PNH is briefly discussed.