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Biomedical subjects

M Akahoshi

Publications and source records attributed to M Akahoshi.

At least 73 records · Page 4Linked to original sources

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↗

Role of T-cell antigens in the cytolytic activities of large granular lymphocytes (LGLs) in patients with LGL lymphocytosis.

By analyzing surface antigens and cytolytic functions of proliferating large granular lymphocytes (LGLs), three types of T cell LGL lymphocytosis were delineated. The first, most commonly encountered type exhibited CD3+4-8+16+, WT31+ phenotype, low or undetectable non-major histocompatibility complex (MHC)-restricted cytotoxicity, and moderate to strong antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). Because these LGLs carried T cell antigen receptor (Ti) recognized by WT31 monoclonal antibody (MoAb), and treatment with anti-Ti, anti-CD3 MoAbs and phytohemagglutinin elicited non-MHC-restricted cytotoxicity, they may have developed from populations of in vivo primed cytotoxic T lymphocytes with unknown antigen specificity. The second, rare type of LGL lymphocytosis exhibited CD3+4-8-16+, WT31 phenotype, and strong non-MHC-restricted, ADCC and LDCC cytotoxicities. These cells were probably derived from the lymphocytes of the same phenotype found in small numbers in normal peripheral blood. Because anti-CD3 MoAb inhibited non-MHC-restricted cytotoxicity of the LGLs, a Ti not detected by WT31 MoAb, but putatively present seemed to serve as a specific receptor for target tumor cell recognition. The third type of LGL lymphocytosis showed CD3+4+8-16+, WT31+ phenotype, and lacked cytolytic activities and parallel tubular arrays. These LGLs probably evolved from cells with the same characteristics selectively located in the germinal centers of lymphoid tissues. Taken together, in patients with LGL lymphocytosis, T cell-associated antigens expressed on LGLs were shown to be involved in the regulation of LGL-mediated cytolytic activities. In addition, studies of surface antigens and the effects of MoAbs and lectins on cytolytic activities may be useful in clarifying the normal counterpart of LGLs from which leukemic or reactively proliferating LGLs originate.

Adult↗

Ti (WT31)-negative, CD3-positive, large granular lymphocyte leukemia with nonspecific cytotoxicity.

A case of WT31-, CD3+ large granular lymphocyte leukemia is reported. On surface marker analysis, the proliferating cells were found to be CD3+4-8-16+ and WT31-. By two-color immunofluorescence staining, CD3+4-8- cells were found to be WT31-, and a small population of WT31+ cells expressed either CD4 or CD8. WT31-, CD3+ cells were also identified in a bulk culture of lymphocytes expanded in vitro. Because WT31 monoclonal antibody (MoAb) reacts with the nonpolymorphic epitope of the disulfide-linked heterodimer of the T cell antigen receptor (Ti), the absence of the WT31-reactive Ti determinant may represent an expression of different CD3-associated polypeptides. The rearrangement of the Ti-beta and Ti-gamma genes but not the immunoglobulin gene was demonstrated, and the single pattern of rearrangement indicated the monoclonal origin of the lymphocytes. When the lymphocytes were assayed for their cytotoxicity against K562, MOLT-4, Daudi, and Raji tumor cell lines, a broad spectrum of cytotoxicity for these tumor cells was observed, and the lymphocytes also exhibited antibody- and lectin-dependent cellular cytotoxicity and lymphokine-activated killer activity. Treatment with anti-CD2 and anti-CD3 MoAbs inhibited their nonspecific cytotoxicity. The anti-CD3-mediated inhibition of nonspecific cytotoxicity suggested that an as yet unidentified Ti, present in association with the CD3 molecule on these lymphocytes, serves as a specific receptor for target tumor cell recognition.

Antibodies, Monoclonal↗

Myeloproliferative disorders terminating in acute megakaryoblastic leukemia with chromosome 3q26 abnormality.

Two cases of myeloproliferative disorders terminating in acute megakaryoblastic leukemia are reported. One case began as primary myelofibrosis and the other as chronic myelogenous leukemia. Blast cells in the acute leukemic phase were identified as megakaryoblasts by the presence of platelet peroxidase. The clinical course is described, and the morphology, immunologic studies, and ultrastructure studies of the blast cells are reported. On cytogenetic analysis both cases had a translocation involving the No. 3 chromosome locus q26.2. The present data suggest that 3q26 may be associated with transformation of the megakaryocytic lineage.

Adult↗

[A resectable case of juvenile hepatocellular carcinoma in an asymptomatic HBV carrier].

A 28-year-old man was admitted to our hospital in October 1983 as he was found to have HBs-antigenemia at the time of blood donation. Since he had no symptoms and showed normal liver function, HBeAg(-), HBeAb (+) and HBcAb 87% (200x), he was diagnosed as an asymptomatic HBV-carrier. Unexpectedly, high serum AFP (13,500 ng/ml) was detected. Subsequently, computed tomography, angiography and ultrasonography demonstrated a tumor, 4.5 X 4.0 cm in diameter, in the left lobe of the liver. On Feb. 24, 1984, the tumor was radically resected. The postoperative course was excellent. This case suggested the relationship between hepatoma and asymptomatic HBV carriers and the importance of screening hepatoma patients to detect asymptomatic carriers.

Adult↗

A case of T-cell chronic lymphocytic leukemia with an unusual phenotype and central nervous system involvement.

A case of T-cell chronic lymphocytic leukemia is reported. The leukemic cells had the morphologic features of medium-sized, mature-looking lymphocytes, and had an affinity for the central nervous system. Cytochemically, they were positive for alpha-naphthyl acetate esterase and acid phosphatase. They formed E-rosettes (E+) and reacted with OKT11 but not with OKT3/Leu-4, OKT4/Leu-3, OKT8/Leu-2, or OKM1, and did not possess IgG-Fc receptors (Fc gamma R). Functionally, they did not respond to phytohemagglutinin or concanavalin A, were not natural killer cells or antibody-dependent as well as alloantigen-reactive killer cells. Furthermore, they did not possess a helper or suppressor T-cell function for immunoglobulin synthesis. Results of immunologic studies suggest that the leukemic cells were derived from a normal counterpart of a lymphocyte subset present as a minor component of the peripheral blood, namely an E+, OKT3-, OKM1-, Fc gamma R- subset, the function of which is not yet identified.

Adult↗

An epidemic of hepatitis A related to ingestion of raw oysters.

An epidemic of hepatitis A occurred around Hondo City, Kumamoto Prefecture in Japan during the first six months of 1982. Clinical, immunological and epidemiological studies were carried out in 225 cases. Cases were distributed over a relatively wide area, and in small numbers of young children and school children. More than half of the patients were in their twenties or thirties. The clinical course was generally favorable with rapid resolution. No episode lasted more than six months. There was only one fatality in a cure which was a carrier of HBs antigen with liver cirrhosis. Titers of IgM anti-HAV measured by radioimmunoassay (RIA) or enzyme immunoassay (EIA) reached a peak during the second week after onset, followed by a gradual decrease. Conversion to negative results was never experienced within two months. We found a good correlation between RIA and EIA in terms of detecting IgM anti-HAV. The route of infection was thought to be fecal-oral in nature, with ingestion of raw oysters the major etiologic factor.

Adolescent↗

Enzyme immunoassay for detection of total and IgM-specific antibodies to hepatitis A virus and its clinical application.

Antibody to hepatitis A virus (anti-HAV) and IgM class antibody to HAV (IgM anti-HAV) in sera from 73 patients with hepatitis A and from 550 normal subjects were measured by enzyme immunoassay (EIA) and the results were compared with those of radioimmunoassay (RIA). Since RIA has the disadvantage of requiring radioisotopes and special equipment, the clinical applicability of EIA and possible methodological problems were evaluated. The EIA for anti-HAV showed an excellent correlation with RIA, indicating its usefulness for the demonstration of the immune status in these subjects. Positive results of anti-HAV were obtained in the early stage after the onset of hepatitis A. However, pretreatment for inactivation of samples was required. False-positive reactions were found in sera to which sodium azide was added as preservative. In the measurement of IgM anti-HAV, a fundamental study revealed quite satisfactory results, correlation with the results of RIA was excellent. In patients with hepatitis A, the titers reached a peak in the second to third week, followed by a gradual decline. Changes to a negative reaction were never encountered within three months. We concluded that the EIA is an useful tool in the diagnosis of hepatitis A and can replace RIA.

Adolescent↗