Decreased eosinophil numbers in HTLV-I carriers.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Tsuda.
Explore the source record for details and available documents.
We describe the effects of Bay K 8644, a dihydropyridine-sensitive Ca2+ channel agonist, on [3H]norepinephrine (NE) release from the hypothalamus of spontaneously hypertensive rats (SHR). The electrical stimulation-evoked [3H]NE release was greater in hypothalamic slice of SHR than in those of Wistar Kyoto (WKY) rats. Bay K 8644 (10(-6) M) significantly increased the stimulation-evoked [3H]NE release in SHR. However, the agonist showed no significant effects in normotensive WKY rats. The results suggest that the dihydropyridine-sensitive Ca2+ channels might participate actively in the regulation of the central sympathetic tone of hypertension.
The microvasculature of the skin of the hand in primates, including man, was examined by means of scanning electron microscopy of corrosion casts. In this study, the microvascular patterns and structures in different areas of the hand, and the changes in vascular patterns that occur with age, have been described. The typical structure of the capillary loops in the hand can be observed in the ball of the finger of the young adult monkey. The capillary loops were formed out of not just one capillary vessel, but two or three vessels. Each capillary vessel arose and divided into several branches at the papillae, and these became descending limbs. After the loop passed a hairpin turn, the descending limbs were 1.5 times larger than the ascending limbs in the intrapapillary portion, and they became extrapapillary venules. The descending limbs connected with the postcapillary venules in the postpapillary portion and with the horizontal network. The postcapillary venules fused with each other to form the primary and secondary venous arcades. The secondary venous arcades anastomosed with each other and flowed into the subpapillary venules, which run along the dermal furrow in the fingerprint. Changes in vascular patterns with age could be observed. In the infant fingerprint, the vascular systems had not yet differentiated, especially the venous system in the dermis. In the old adult finger, the capillary loops presented complicated features deviating due to aging.
The ability of a beta-blocker to inhibit vascular sympathetic nerve activity associated with hypertension was studied in DOCA-salt hypertension in rats. A seven week treatment of DOCA and salt resulted in a significant increase in the systolic blood pressure of the uninephrectomized rats. The administration of propranolol (40 mg/L and 80 mg/L in drinking water) had little effect on the development of hypertension. After a three week administration of propranolol, perfused mesenteric vasculatures were prepared in vitro, and endogenous norepinephrine release as well as vascular responsiveness were examined. Endogenous norepinephrine and pressor responses during periarterial nerve stimulation were greater in the untreated DOCA-salt hypertensive rats than in the normotensive rats. In the DOCA-salt hypertensive rats treated with propranolol, the stimulation-evoked norepinephrine release and pressor responses were significantly attenuated, at both doses, compared with the untreated DOCA-salt hypertensive rats. These results demonstrate that propranolol inhibited the vascular sympathetic nerve activity in DOCA-salt hypertensive rats. This occurrence suggests a possible role of presynaptic beta-adrenoceptors in the regulation of sympathetic tone in DOCA-salt hypertension.
This study was performed to investigate the role of substance P in the vascular adrenergic transmission in hypertension. In perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR, 7 to 10 weeks old) and age-matched Wistar-Kyoto rats (WKY), we have examined the effects of substance P on vascular responsiveness as well as on norepinephrine release from the vascular adrenergic neurons. In preliminary studies with normotensive Wistar rats, pressor responses and endogenous norepinephrine release during electrical nerve stimulation were inhibited by substance P in a dose-dependent manner. However, vasoconstrictor responses to exogenous norepinephrine were not affected by the peptide. In SHR, the stimulation-evoked pressor responses and norepinephrine release were enhanced compared with WKY. Alternatively, the suppression of these responses by substance P was significantly less in SHR than in WKY. These results demonstrate that substance P could have a modulatory effect on noradrenergic activity and cause a decrease in stimulation-evoked norepinephrine release from the vascular adrenergic neurons. The attenuated reduction of pressor responses and norepinephrine release by substance P in SHR might suggest insufficient regulation of vascular adrenergic transmission by the peptide in hypertension.
In the present study, we have examined the effects of ouabain on membrane fluidity of erythrocytes by use of an electron spin resonance (ESR) and spin-labeling method, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects, and the ESR spectra for 5-nitroxy stearate incorporated into erythrocyte membranes were studied. The values of outer hyperfine splitting and order parameter (S) of the ESR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain loading to erythrocytes decreased the membrane fluidity (S value was increased). The alternative degree was significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.
Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.
Rat plasma glutathione peroxidase (GSH-Px) was purified 1,400-fold from rat serum by a combination of phenyl Sepharose, DEAE Sephacel, blue Sepharose and Sephacryl S-200 column chromatographies. The purified GSH-Px migrated as a single band corresponding to a molecular weight of 22,500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was used for the immunization of chickens to obtain a specific antibody and for determination of its amino acid sequence. Two overlapping cDNA clones for rat plasma GSH-Px were isolated from a placental cDNA library. The composite nucleotide sequence is 1,529 base-pairs long and encodes 226 amino acids. The deduced amino acid sequence completely coincided with the sequences of five individual peptide fragments derived from the purified plasma GSH-Px on digestion with lysyl endopeptidase. In order to identify the tissue(s) generating this plasma GSH-Px, immunoblot analysis was performed on homogenates prepared from 13 tissues. A single immunoreactive band of 22.5 kDa, corresponding to plasma GSH-Px, was detected for the kidney homogenate. A much fainter band was observed for the lung preparation, but liver, spleen, bone marrow, and other tissues examined were negative. Northern blot analysis further revealed that the expression level of the plasma GSH-Px gene was high in kidney and low in lung. No transcript was detected in liver or spleen. These results indicate that plasma GSH-Px is predominantly synthesized and secreted by renal cells.
1. The present review discusses evidence in support of the concept that alterations in sympathetic neurotransmitter release might contribute to the pathogenesis of hypertension. 2. Studies suggest that changes in sympathetic nervous activity in both the central and peripheral nervous systems participate in blood pressure control. 3. In the periphery increased release of norepinephrine from vascular adrenergic neurons might lead to the enhanced vasoconstrictor responses and thus to an elevation in systemic blood pressure. 4. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by autoregulatory systems by presynaptic receptors located on nerve terminals. 5. It has been proposed that alterations to sympathetic nervous activity of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release in central and peripheral tissues. 6. This article summarizes the results of studies to evaluate presynaptic receptor functions and sympathetic neurotransmitter release in hypertension.
The aim of the present study was to investigate alterations in catecholamine release in the central nervous system of spontaneously hypertensive rats. Slices of hypothalamus, medulla oblongata and striatum were prepared from spontaneously hypertensive rats (SHR: 9-10 weeks old) and age-matched Wistar Kyoto rats (WKY). The slices were incubated with (3H)norepinephrine (NE) or (3H)dopamine (DA), superfused with Krebs-solution in vitro, and the release of the catecholamines was compared between the two strains. The basal release of hypothalamic (3H)NE did not differ between SHR and WKY slices. However, stimulation (1 Hz)-evoked (3H)NE release was significantly greater in SHR than in WKY (percent fractional release of total tissue NE: WKY 0.494 +/- 0.019%, n = 6, SHR 0.730 +/- 0.053%, n = 6, p less than 0.05). The stimulation-evoked (3H)NE release from the medulla oblongata did not differ significantly between SHR and WKY slices. Finally stimulation-evoked release of striatal (3H)DA was significantly depressed in SHR (percent fractional release of total tissue DA: WKY 2.048 +/- 0.24%, n = 6, SHR 1.460 +/- 0.068%, n = 6, p less than 0.05). These results indicate that the release of hypothalamic NE and striatal DA are altered in SHR. It is suggested that enhanced hypothalamic noradrenergic activity and reduced striatal dopaminergic activity can increase sympathetic outflow to the periphery, which may play a role in the pathogenesis of this form of hypertension.
In cases of advanced ovarian cancer, intermittent CDDP therapy (ICDDPT) was applied after the first operation and induction chemotherapy, and its efficacy and limit were studied. One cycle of this therapy involved consecutive 5 day CDDP treatment (25-30mg/body/day). The therapy was repeated at intervals of 3 months. In many cases, ovarian cancer was histologically rated as epithelial adenocarcinoma. The study included 18 cases in total. ICDDPT was applied to 13 cases in which no tumor mass was detected by second look operation (SLO) or which showed clinical remission after operation. Only 3 of these 13 cases showed recurrence, and all these 13 are still living. Of the 5 cases in which SLO disclosed a tumor mass or which did not show remission after the first operation, 2 died. When the survival rate after ICDDPT was compared by the Kaplan-Meier method with that of controls without CDDP therapy, the effectiveness of ICDDPT was demonstrated. The survival rate could therefore be improved by ICDDPT. The therapy particularly improved the long term prognosis of SLO negative cases and cases in clinical remission. It seems necessary to repeat this therapy for a long period to achieve satisfactory results. In SLO positive cases and cases without clinical remission, the therapy had only a limited effect.
The effects of PGE1 on liver function tests in patients who underwent gastric cancer surgery were studied. PGE1 was administered in 13 patients at a rate of 20-100 ng.kg-1.min-1 (PGE1 group) during surgery. Fourteen patients served as the control group. On the first postoperative day, SGOT and SGPT increased in both groups. But on the first and the third postoperative days, SGPT of the PGE1 group was significantly lower (P less than 0.05) than that of the control group. Five patients in the control group showed transaminase above 100 IU.l-1 in the postoperative period. In contrast, no patient showed this increase in the PGE1 group. These findings indicate that continuous infusion of PGE1 during surgery is beneficial in attenuating hepatic injury.
A 39-year-old woman was first admitted to our hospital with increased white cell count on May, 1983. Physical examination showed only mild splenomegaly. Hematological examination revealed leukocytosis (14,600/microliters) with ATL cells (59%). Serum anti-HTLV-I antibody was positive. Examination of HTLV-I provirus in the abnormal T cells revealed the defective type. She was diagnosed as chronic type of ATL based on the clinical features. Cytogenetic study of the ATL cells revealed 47, xx, +4. For 12 months, she was followed without any therapy. WBC reduced to almost normal range and ATL cells decreased to 3 to 6% for 8 months. On May, 1985, she was readmitted to our hospital because of leukocytosis (32,200/microliters), and increased ATL cells (57%). She was diagnosed as crisis of ATL. Investigation of the proviral DNA and chromosome showed the same results as those of the chronic phase, indicating that ATL cells in both the chronic phase and the crisis phase originated from the same clone. She died after 3 months from massive diarrhea. Postmortem examination showed the extensive infiltration of leukemic cell in the small intestine.
Explore the source record for details and available documents.
We now describe the effects of calcitonin gene-related peptide (CGRP) on [3H]norepinephrine (NE) release in medulla oblongata of spontaneously hypertensive rats (SHR). CGRP inhibited stimulation-evoked [3H]NE release in a dose-dependent manner in Sprague-Dawley rats, although the basal release of [3H]NE was not affected by the peptide. In SHR, the inhibitory effect of CGRP on stimulation-evoked [3H]NE release was significantly attenuated compared with Wistar Kyoto rats. These results suggest that CGRP might be involved in the regulation of central sympathetic nervous activity in hypertension.
We describe the effects of neuropeptide Y (NPY) on [3H]norepinephrine (NE) release from hypothalamic slices of spontaneously hypertensive rats (SHR). The electrical stimulation (1 Hz)-evoked [3H]NE release was significantly greater in hypothalamic slices of SHR than in those of Wistar Kyoto rats (WKY). NPY inhibited the stimulation-evoked [3H]NE release in a dose-dependent manner. The inhibitory effect of NPY was significantly attenuated in SHR compared with WKY. The results may indicate that the less inhibitory effect of NPY on NE release induces increased sympathetic nerve activity in the hypothalamus of SHR.
The isolation and sequencing of a cDNA clone for the entire sequence of pig thymus non-histone protein HMG2 are described. cDNA the size of 1153 nucleotides contains an open reading frame of 627 nucleotides. The 5'-untranslated region of 146 nucleotides is extremely rich in GC residues whereas the 3'-untranslated region of 380 nucleotides is rich in AT residues. The open reading frame encodes 209 amino acids, which contain a unique continuous run of 23 acidic amino acids at the C-terminal. The deduced amino acid sequence is 79% homologous to that of HMG1 protein from the same source which we reported [Tsuda, K., Kikuchi, M., Mori, K., Waga, S., & Yoshida, M. (1988) Biochemistry 27, 6159-6163]. In addition, the hydropathy index profiles of both proteins are very similar, supporting that they have similar structural features. Northern analysis of poly(A+) RNA reveals that a single-sized mRNA codes for HMG2 protein. Southern analysis suggests that the HMG2 coding gene is homogeneous within the pig thymus genome.
alpha-Fetoprotein in sera from healthy subjects and patients with liver cirrhosis and hepatocellular carcinoma was fractionated into three peaks by affinity chromatography on a column of Lens culinaris agglutinin-Sepharose 4B. One peak (the first peak) was found in all the serum samples, but the other two peaks (the second and third peaks) were found only in patients with hepatocellular carcinoma. For alpha-fetoprotein in the second and third peaks, a specific enzyme immunoassay was developed. Lens culinaris agglutinin-coated polystyrene balls were incubated with alpha-fetoprotein and, after washing, with affinity-purified anti-alpha-fetoprotein Fab'-beta-D-galactosidase conjugate. beta-D-galactosidase activity bound to the polystyrene balls was assayed by fluorimetry. The maximal volume of serum that could be used without interference was 0.2 microliters, and the minimal detectable serum concentrations of alpha-fetoprotein in the second and third peaks were 3.5 mg/liter and 0.1 mg/liter, respectively. The maximal serum concentration of alpha-fetoprotein in the first peak that did not affect the detection limits of alpha-fetoprotein in the second and third peaks was 10 mg/liter. It was possible to confirm the presence of alpha-fetoprotein in the second and third peaks by a significant difference between bound beta-D-galactosidase activities in the absence and presence of alpha-methyl-D-mannoside or D-glucose. This assay may be useful for diagnosis of hepatocellular carcinoma, although further improvements remain to be made.