RERF scientific agenda and DOE.
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Foundations↗
Biomedical subjects
M Akahoshi
Publications and source records attributed to M Akahoshi.
Radiation studies.
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Government Agencies↗
Relation between cold pressor test and development of hypertension based on 28-year follow-up.
The present study examined the relation between blood pressure reactivity to cold stimulus and the subsequent development of hypertension based on a follow-up study from 1960 through 1988 of 824 normotensive participants (mean age, 35.8 +/- 10.8 years) in the Adult Health Study in Nagasaki, Japan. Hypertension developed in 343 individuals during the 28 years of follow-up, with a mean incidence rate of 24.6 per 10(3) person-years. Confounding variables, including attained age, resting systolic and diastolic blood pressures, and body mass index at baseline, were adjusted using a Poisson regression model. Systolic response was found to be an independent and significant predictor. The relative risk of hypertension for systolic hyperreactors was 1.37, with a 95% confidence interval of 1.10 to 1.71. Diastolic response was significant only when resting diastolic blood pressure was also considered. The cold pressor test appears to be useful if performed on middle-aged subjects older than 40 years at the time of examination, when hypertension is more prevalent. The current results support the hypothesis that hyperreactivity is a predictor of the development of hypertension.
Adolescent↗
Chronic hyperinsulinemia augments deoxycorticosterone acetate-salt hypertension.
To evaluate the effect of chronic hyperinsulinemia on blood pressure in salt-dependent hypertension, we infused insulin (1.0 IU/d, n = 15) or saline (n = 13) for 4 weeks into deoxycorticosterone acetate-salt hypertensive rats. The insulin infusion increased plasma insulin levels to 24 +/- 2 microU/mL, which was higher than in the saline-infused rats (9 +/- 1 microU/mL) but was still within the physiological range. Blood pressure was measured by the tail-cuff method twice a week, and daily sodium intake and urinary sodium excretion were calculated for 3 weeks. At week 4, arterial pressor responsiveness to norepinephrine, angiotensin II, and hexamethonium bromide was evaluated. After 14 days of chronic infusion, the insulin group showed a higher blood pressure than the saline group (on 21st day: 178 +/- 6 versus 156 +/- 5 mm Hg, P < .05 by tail-cuff method; 171 +/- 4 versus 149 +/- 3 mm Hg, P < .05 by direct intra-arterial measurement). This blood pressure difference was eliminated after ganglionic blockade with hexamethonium bromide (86 +/- 4 mm Hg in insulin-treated and 89 +/- 4 mm Hg in saline-treated rats by direct intra-arterial measurement). Throughout the experiment, neither sodium balance nor arterial pressor responsiveness to norepinephrine or angiotensin II differed between the two groups. In conclusion, chronic hyperinsulinemia in the physiological range augments the development of hypertension in salt-dependent hypertension, and this augmentation may be mediated by sympathetic stimulation independent of salt retention.
Analysis of Variance↗
The Multi-Scale 3D-1D compatibility scoring for inverse protein folding problem.
The applicability of the Multi-Scale Structure Description (MSSD) scheme to the inverse-folding problems was investigated. An MSSD represents a 3D protein structure with multiple symbolic sequences, where fine structures are represented with the sequence at low levels, the middle scale structural motifs at middle levels, and global topology at high levels. Each symbol in the symbolic sequence denotes a type of local structure of the level scale. The structure fragments are classified at each scale level respectively according to the shape and the environment around the fragments: how the structure is exposed to the solvent or buried in the molecule. I modeled the propensity of an amino-acid sequence to the structure fragment type (i.e., primary constraint) at each scale level. The local propensity is, therefore, modeled at small scale (low) levels, while the global propensity modeled at large scale (high) levels. Thus, superposing all the primary constraint, a 3D protein structure yields an amino-acid sequence profile. Evaluating the fit of an amino acid sequence to the profile derived from the known 3D protein structure, we can identify which 3D structure the given amino-acid sequence would fold into. I checked whether a sequence identifies its own structure over two hundred protein sequences. In many cases, an amino acid sequence identified its own 3D protein structure.
Animals↗
Autoantibodies and immunoglobulins among atomic bomb survivors.
The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.
Adult↗
Depressor effect of intraventricular administration of calcium on spontaneously hypertensive rats.
The role of central Ca2+ in the regulation of blood pressure (BP) was investigated in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Ten microliters of a high Ca2+ solution (Ca2+: 32.6 mM) administered intracerebroventricularly (i.c.v.) decreased the mean arterial pressure (MAP) for more than 20 min in SHR (n = 7, P < 0.005), while no change of MAP was observed in the WKY (n = 6). This depressor response to Ca2+ i.c.v. was dose-dependent at Ca2+ concentrations between 16.3 and 65.2 mM. We also investigated the effect of high Ca2+ i.c.v. in SHR after pretreatment with Ca2+ channel blockers, diltiazem (60 micrograms/10 microliters) or nisoldipine (4, 8, 16 and 32 micrograms/10 microliters), administered i.c.v., the autonomic ganglion blocker, hexamethonium (50 mg/kg), administered i.v. and alpha-methyl-p-tyrosine (100 and 400 micrograms/10 microliters) delivered i.c.v. Pretreatment with i.c.v. diltiazem (n = 8) or nisoldipine (n = 5 for 8 micrograms, n = 6 for 4, 16, 32 micrograms) abolished and/or blunted the decrease of MAP due to high Ca2+. Hexamethonium administered i.v. (n = 6) also canceled the depressor action of i.c.v. Ca2+. Pretreatment with 100 micrograms of i.c.v. alpha-methyl-p-tyrosine could not prevent the depressor action of i.c.v. Ca2+; however, 400 micrograms of alpha-methyl-p-tyrosine administered i.c.v. abolished the effect of i.c.v. Ca2+. Furthermore Ca2+ channel blockers administered i.c.v. in themselves increased MAP in SHR (P < 0.05). These results suggest that central Ca2+ is involved in the central regulation of BP in SHR. This effect may be mediated through changes in sympathetic activity.
Animals↗
A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells.
An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine-stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)-stimulated PBMC were assayed for their cytotoxicity against 51Cr-labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL-2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.
Antibodies, Monoclonal↗
Autophagolysosomes exhibiting lysosomophagy in the granular lymphocytes of patients with granular lymphocyte-proliferative disorders.
The ultrastructure of granular lymphocytes (GLs) in the peripheral blood of 12 patients with granular lymphocyte-proliferative disorders (GLPDs) was studied. Autophagolysosomes exhibiting so-called "lysosomophagy" were seen in the GLs of four of these patients but not in normal individuals. Because rod-shaped lysosomes beginning to enclose other lysosomes were seen, the autophagolysosomes exhibiting lysosomophagy in GLs were thought to be formed by the same wrapping mechanism. As far as we know, this is the first report of lysosomophagy in lymphocytes.
Adult↗
Augmented central pressor action of magnesium in SHR.
This study attempted to determine whether central magnesium (Mg) influences the regulation of blood pressure (BP). An intracerebroventricular (icv) injection of a high Mg2+ solution (190.0 mEq/L, 10 microL), made by adding MgC12 to artificial cerebrospinal fluid, increased the mean BP in both conscious spontaneously hypertensive rats (SHR; n = 17, p < 0.001) and Wistar Kyoto rats (WKY; n = 8, p < 0.005). Spontaneously hypertensive rats showed a greater pressor response than WKY (+11.7 +/- 0.9 mm Hg versus +3.5 +/- 1.1 mm Hg, p < 0.001). This pressor response to Mg2+ given icv was dose-dependent in the range of Mg2+ concentration between 47.5 and 190.0 mEq/L in SHR. A high Mg2+ solution (190.0 mEq/L), made by adding MgSO4 given icv, also increased the mean BP in SHR (n = 7, p < 0.001) and WKY (n = 6, p < 0.01), whereas the high osmolarity solution (340 mOsm/kg H2O) given icv did not change the mean BP in either SHR or WKY. Also administered was a high Mg2+ solution icv after either hexamethonium bromide (Hx; 50 mg/kg intravenously) or arginine vasopressin antagonist (aAVP, (CH2)5Tyr(Me)AVP, 30 micrograms/kg i.v.). The pressor response to the high Mg2+ solution was abolished by arginine vasopressin antagonist both in SHR and WKY, although it was not canceled by Hx. A high Mg2+ solution administered icv caused a 3.5-fold increase in plasma arginine vasopressin concentration in SHR (n = 5, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Contribution of the central interaction between calcium and sodium to hemodynamic regulation in spontaneously hypertensive rats.
The contribution of the central interaction between calcium and sodium to hemodynamic regulation was assessed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. The effect of a high calcium solution (Ca2+, 130 mg/dl, 10 microliters) infused into the cerebral ventricle (i.c.v.) on hemodynamic responses induced by a high sodium solution (Na+, 1,000 mEq/1, 10 microliters) i.c.v. and the mechanism by which high Ca2+ affects the hemodynamic responses induced by high Na+ i.c.v. were studied. High Na+ i.c.v. induced a pressor response with tachycardia in the SHRs, but induced a pressor response with reflex bradycardia in the WKYs. Prior treatment with high Ca2+ i.c.v. attenuated the pressor response induced by high Na+ i.c.v. (+55.6 +/- 4.4 to +33.1 +/- 3.2 mmHg, P < 0.01) and restored reflex bradycardia (+86.4 +/- 7.7 to -26.7 +/- 7.6 bpm, P < 0.01) in SHRs. Whereas prior treatment with high Ca2+ i.c.v. attenuated the pressor response (+35.7 +/- 2.0 to +22.2 +/- 4.0 mmHg, P < 0.05), it did not alter the degree of reflex bradycardia (-81.7 +/- 7.1 to -69.2 +/- 120 bpm, n.s.) in WKYs. Ganglionic blockade attenuated the pressor response (+56.9 +/- 3.5 to +42.9 +/- 2.3 mmHg, P < 0.05) and restored reflex bradycardia (+82.1 +/- 10.3 to -65.9 +/- 11.0 bpm, P < 0.01) in SHRs, whereas, inhibition of arginine vasopressin attenuated the pressor response without modification of the tachycardic response.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A case of transfusion-associated graft-versus-host disease not prevented by white cell-reduction filters.
A case of transfusion-associated graft-versus-host disease (TA-GVHD) in a patient with non-Hodgkin's lymphoma is reported. The patient, a 67-year-old woman, was diagnosed as having diffuse, mixed type non-Hodgkin's lymphoma, at clinical stage IIIA. She was treated with combination chemotherapy and received multiple blood transfusions for anemia and thrombocytopenia. Although white cells (WBCs) were reduced in the transfused components by WBC-reduction filters, the patient developed TA-GVHD that was confirmed by skin biopsy. It is suggested that the WBC reduction attained with these filters does not prevent TA-GVHD in immunocompromised patients. It is recommended that all blood components should be irradiated before transfusion to such patients.
Aged↗
Contrasuppressor T cell leukaemia: clonal proliferation of contrasuppressor T cells in a patient with granular lymphocyte-proliferative disorder.
In 12 patients with granular lymphocyte-proliferative disorders (GLPD), we studied the capacity of patient peripheral blood mononuclear cells (PBMC) to promote or suppress polyclonal IgG synthesis by normal non-T cells in pokeweed mitogen-containing medium using an enzyme-linked immunosorbent assay. During the experiments we found a patient whose PBMC possessed contrasuppressor function. The patient was a 27-year-old female with anaemia and lymphocytosis of CD3+CD8+ granular lymphocytes (GL). Reconstitution experiments using normal donor non-T cells and CD4+ and CD8+ T cells showed that addition of the patient's CD8+ cells abrogated the suppressor cell function of normal CD8+ T cells. The patient's PBMCs were CD3+, CD8+, Ia+, and Vicia villosa lectin-adherent characteristics which are consistent with those of normal blood contrasuppressor T cells. The T cell receptor beta and gamma genes were found to be monoclonally rearranged. Ultrastructurally, this patient's GLs exhibited clusters of dense cytoplasmic bodies, which were not detected in the GL of other patients with GLPDs. These results indicate that the clonal proliferation of contrasuppressor T lymphocytes had occurred in this patient.
Adult↗
Relationship between blood pressure and left ventricular mass in male patients with essential hypertension.
We performed retrospective study of the relationship between the severity and duration of hypertension and echocardiographically-detected left ventricular hypertrophy (echo-LVH) in patients with untreated essential hypertension. The subjects consisted of 92 untreated essential hypertensives who were observed for more than 5 years from the onset of diastolic hypertension (greater than or equal to 95 mmHg), and whose left ventricular (LV) mass index was measured at the end of the observation period. On the basis of the frequency of diastolic hypertension during the observation period, the population was categorized in 3 groups. In Group I (32 cases), diastolic hypertension was observed in more than 80% of blood pressures obtained throughout the entire observation period. In Group II (38 cases), diastolic hypertension was observed in 33 to 80% of the observation period. In Group III (22 cases), diastolic hypertension was observed in less than 33% of the observation period. The average diastolic blood pressure during the entire observation period in each group were 101.0, 96.0, and 90.7 mmHg in groups I, II, and III, respectively. The LV mass index was significantly higher in groups I (114.6 g/m2) and II (105.3 g/m2) than in group III (90.7 g/m2) (p less than 0.01). The prevalence of echo-LVH (more than 121 g/m2) was 34.4%, 18.4%, and 4.8% in groups I, II, and III, respectively. The average diastolic blood pressure in patients with echo-LVH (99.3 +/- 5.1 mmHg) was significantly higher than in patients without echo-LVH (95.7 +/- 4.7 mmHg). We concluded that the degree and duration of diastolic pressure elevation are closely correlated to the LV mass index.
Blood Pressure↗
Effects on blood pressure of intracerebroventricular administration of a kinin antagonist.
The components of the kallikrein kinin system are present in brain, and blood pressure is increased when kinins are injected into the brain cerebral ventricles. Therefore, brain kinins may play a role in the regulation of blood pressure. Kinin analogs which are effective as blockers of the vasodilatory and musculotropic activity of kinins have recently become available. Our objective in this study was to examine whether one of these kinin antagonists (K-ant) inhibits the pressor activity of intracerebroventricular (ICV) bradykinin, and whether ICV injections of this antagonist would alter basal mean blood pressure (BP). The analog used was DArg0-Hyp3-Thi5,8-DPhe7-bradykinin. All injections (10 microliters) were made into a lateral cerebral ventricle of restrained, conscious rats. The hypertensive response to 0.5 microgram bradykinin was partially blocked by simultaneous injections of either 5 or 10 micrograms of the K-ant: From (delta MBP = 36 +/- 7 to 17 +/- 5, p less than 0.05, and from 34 +/- 6 to 8 +/- 1 mmHg, p less than 0.01, respectively. Lower concentrations of K-ant were ineffective; the K-ant at doses up to 10 micrograms had no effect on BP. Doses of 25 and 50 micrograms increased BP (delta MBP = 32.5 +/- 5 and 59.0 +/- 5.5 mmHg, respectively, p less than 0.001). Both the 25 and the 50 micrograms doses of the K-ant induced barrel rotation in all rats. These data suggest that kinins present in circumventricular structures do not play a role in normal blood pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Central effect of aprotinin, a serine protease inhibitor, on blood pressure in spontaneously hypertensive and Wistar-Kyoto rats.
We examined the effect of centrally administered aprotinin, a serine protease inhibitor, on blood pressure (BP) in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Twenty-two gauge needles and polyethylene catheters were implanted into lateral cerebroventricle and femoral artery, respectively, at 48 hours before the experiments. In Group 1 (8 SHR, 6 WKY), rats received a bolus intracerebroventricular injection (i.c.v.) of aprotinin (1,000 KIU/kg/10 microliters). A prompt increase of BP was observed in SHR after aprotinin and this elevation of BP was persisted for over 30 minutes (mean BP: 158.8 +/- 2.9 mmHg at control to 168.7 +/- 3.2 at 15 min., p less than 0.01; to 168.3 +/- 3.4 at 30 min., p less than 0.01). On the other hand, BP of WKY decreased gradually after aprotinin (mean BP: 143.0 +/- 3.3 at control to 136.8 +/- 2.7 at 15 min., n.s.; to 134.2 +/- 5.1 at 30 min., p less than 0.05). The intravenous injection (i.v.) of aprotinin (Group 2: 7 SHR, 5 WKY) and the i.c.v. of artificial cerebrospinal fluid (CSF) (Group 3: 5 SHR, 6 WKY) did not affect BP in both SHR and WKY except for the minor transient increase of BP in WKY immediately after artificial CSF i.c.v.. We performed additional experiments to study the contributions of sympathetic nervous system and vasopressin to these changes in BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Body fluid volume and angiotensin II in maintenance of one-kidney, one clip hypertension.
To investigate the possible role of body fluid volume or the renin-angiotensin system in the maintenance of high blood pressure in chronic one-kidney, one clip (1K1C) hypertension, we studied whether blood pressure remained high after removal of the clip while the body fluid volume was kept constant or when angiotensin II (Ang II) was infused in conscious 1K1C rats. Blood pressure fell 58 +/- 13 mm Hg in 1K1C rats after removal of the clip. When body fluid volume was kept at the same level as before "unclipping," blood pressure fell only 9 +/- 2 mm Hg after removal of the clip; if body fluid volume was then allowed to decrease, blood pressure fell an additional 55 +/- 8 mm Hg. When Ang II was infused after removal of the clip, blood pressure fell 26 +/- 7 mm Hg despite the fact that plasma Ang II increased to nonphysiological concentrations (1,161 +/- 353 pg/ml). After Ang II infusion was stopped, blood pressure fell an additional 44 +/- 13 mm Hg. When Ang II was infused and body fluid volume kept constant, blood pressure still did not change after removal of the clip, although plasma Ang II concentrations increased to nonphysiological levels (618 +/- 98 pg/ml). After the Ang II infusion was discontinued and the body fluid volume was no longer kept constant, blood pressure fell 78 +/- 9 mm Hg. These data further support the hypothesis that a volume factor, not the renin-angiotensin system, is important in the maintenance of high blood pressure in 1K1C hypertension.
Angiotensin II↗
CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells.
Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.
Aged↗