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Biomedical subjects

M Akahoshi

Publications and source records attributed to M Akahoshi.

At least 55 records · Page 3Linked to original sources

Relationship between QRS duration and repolarization abnormalities in patients with Wolff-Parkinson-White syndrome.

Marked T wave abnormalities in 12-lead electrocardiograms often appear after radiofrequency ablation in patients with Wolff-Parkinson-White (WPW) syndrome. Durations of the QRS complex before ablation have been reported to be significantly greater in patients with repolarization abnormalities after ablation than in those with normal repolarization. However, there has been no report concerning the relationship between QRS duration and repolarization abnormalities before ablation. It has been reported that QRST isointegral maps are dependent on local cellular repolarization properties but largely independent of activation sequence, and that they provide quantitative information about repolarization abnormalities. Isointegral maps were constructed from data recorded in 34 patients with WPW syndrome and QRS durations of 0.1 second or longer (21 patients with left-sided accessory pathways and 13 with right-sided pathways) in order to investigate the relationship between QRS duration and abnormalities in repolarization properties during preexcitation. Body surface ECGs were recorded with an 87-lead system at a sampling interval of 1 ms. The QRST values (mean +/- 2SD) from 607 normal individuals were taken to represent the normal range. The area with abnormally low QRST values was designated as the -2SD area and the sum of the QRST values (sigma QRST) in this area was calculated. The QRS duration was found to be significantly related to sigma QRST. These results demonstrate that the patients with WPW syndrome had abnormalities in local repolarization properties that were significantly related to QRS duration during preexcitation. The degree of preexcitation may be important in producing these abnormalities in patients with manifest WPW syndrome. This may result in T wave abnormalities after ablation of the accessory pathway attributable to cardiac memory.

Adolescent↗

Autoantibodies and immunoglobulins in atomic bomb survivors with human T-lymphotropic virus type I.

The association of human T-lymphotropic virus type I (HTLV-I) with autoimmune disorders was investigated on the basis of prevalence of antinuclear antibody (ANA), rheumatoid factor and anti-thyroglobulin antibody as well as immunoglobulin (Ig) serum level (IgG, IgA, and IgM). The subjects, all atomic bomb survivors, were 59 HTLV-I-seropositive people without HTLV-I-associated myelopathy or adult T-cell leukemia and 149 HTLV-I-seronegative persons. The mean serum level of IgM was higher in HTLV-I-seropositive subjects than in HTLV-I-seronegative subjects, and a significant association with HTLV-I and sex was indicated in the IgM serum level. No association with HTLV-I was indicated in the prevalence of the autoantibodies except for ANA. These results suggest some clear humoral immunity differences between HTLV-I-infected and noninfected subjects, but whether HTLV-I infection can lead to autoimmune disorders remains uncertain.

Adult↗

Prevalence of skin neoplasms among the atomic bomb survivors.

About 7,000 atomic bomb (A-bomb) survivors from Hiroshima and Nagasaki who participate in the Radiation Effects Research Foundation (RERF) Adult Health Study (AHS) were examined to define the relationship between skin neoplasms and exposure to ionizing radiation. Careful clinical inspection of the skin was undertaken to detect not only skin cancer but precancerous lesions such as senile keratosis. Five cases of basal cell carcinoma, five cases of senile keratosis and one case of Bowen's disease were confirmed histologically among 5955 A-bomb survivors for whom Dosimetry System 1986 (DS86) dose estimates are available. The relationship between the combined prevalence of skin cancer and precancerous lesions and DS86 dose was examined together with other factors that might affect skin neoplasms including occupational exposure to ultraviolet (UV) rays, age, sex and city. The prevalence of basal cell carcinoma and senile keratosis increased as the DS86 dose increased. The prevalence of skin cancer and senile keratosis among persons engaged in work involving frequent exposure to UV rays was higher than among those who were not engaged in such work. Sex and city were not significantly related to those skin diseases. Odds ratios of skin neoplasm for a 1-Gy dose, occupational exposure to UV rays and age at time of examination (in 10-year increments) are 1.7, 5.9 and 1.9, respectively.

Adult↗

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↗