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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 775 records · Page 43Linked to original sources
PubMed1992

The alpha beta complexes of ATP synthase: the alpha 3 beta 3 oligomer and alpha 1 beta 1 protomer.

The basic structures of the catalytic portion (F1, alpha 3 beta 3 gamma delta epsilon) of ATP synthase are the alpha 3 beta 3 hexamer (oligomer with cooperativity) and alpha 1 beta 1 heterodimer (protomer). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 hexamer was crystallized. On electrophoresis, both the dimer and hexamer showed bands with ATPase activity. Using the dimer and hexamer, we studied the nucleotide-dependent rapid molecular dynamics. The formation of the hexamer required neither nucleotide nor Mg. The hexamer was dissociated into the dimer in the presence of MgADP, while the dimer was associated into the hexamer in the presence of MgATP. The hexamer, like mitochondrial F1 and TF1, showed two kinds of ATPase activity: one was cooperative and was inhibited by only one BzADP per hexamer, and the other was inhibited by three BzADP per hexamer.

Nucleotides↗
PubMed1992

CD7-positive acute myeloid leukemia: further evidence of cellular immaturity.

Among 63 cases of acute myeloid leukemia (AML), 14 were found to express the CD7 antigen, a cell surface marker usually found at an early stage during T lineage differentiation. The CD7-positive AML cases consisted of 5 cases of M1, 3 cases of M2, 3 cases of M4, 1 case of M5, 1 case of M6 and 1 case of M7. Among these 63 cases, the proportion of blast cells expressing the CD34 antigen was examined. The proportion of CD34-stained cells among the CD7-positive AML cases, although varying, was significantly larger than that among the CD7-negative AML cases (P less than 0.05). As the CD34 antigen was expressed on hematopoietic progenitor cells and was considered to reflect an early hematopoietic stage, the high proportion of cells expressing CD34 among the CD7-positive AML cases may support the notion that CD7-positive AML cells are immature.

Adolescent↗
PubMed1992

Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation.

In two patients receiving L-asparaginase therapy, severe acute pancreatitis complicated by disseminated intravascular coagulation (DIC) developed. In both cases it was successfully treated with continuous infusion of a synthetic protease inhibitor, nafamostat mesilate. In this report, we briefly discuss the clinical efficacy of the synthetic protease inhibitor in treating such cases.

Acute Disease↗
PubMed1992

Circulating CD34+ hematopoietic progenitors in the harvesting peripheral blood stem cells; enhancement by recombinant human granulocyte colony-stimulating factor.

The number of circulating progenitor cells increases during the period of hematopoietic recovery following myeloablative therapy. These progenitor cells were used for autologous transplantation in order to reconstitute hematopoiesis. As an indicator of the circulating progenitor cells, the number of granulocyte-macrophage colony forming units (CFU-GM), which is measured by means of a long-term cell culture, has been widely used. Recently, a cell surface marker, CD34, which can easily be measured by means of flowcytometry, was found to represent immature hematopoietic progenitor cells, which are very close to stem cells. Therefore, the relationship between the number of CD34 positive cells (CD34+ cells) and the number of CFU-GM in the peripheral blood following chemotherapy was studied in 9 patients selected to undergo autotransplantation. The number of peripheral blood CD34+ cells was found to be significantly correlated with that of CFU-GM (r = 0.81). When four out of 9 patients received recombinant human granulocyte-colony stimulating factor (rG-CSF) administration, a significant increase in the release of peripheral blood CD34+ cells as well as peripheral blood CFU-GM was observed (P less than 0.01). Thus, the measurement of CD34+ cells is useful for predicting the number of circulating CFU-GM.

Adolescent↗
PubMed1992

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions.

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.

Adult↗
PubMed1992

Alloreactivity against IE-encoded antigens: evidence of the discrepancy between graft rejection and reactivity of IE-reactive T cells.

Participation of IE antigens (Ag) in immune response as the transplantation Ag was examined. IE- B10.A(4R)(4R; Kk, IAk, IE-, Db) mice could not reject skin graft from IE Ag alone-disparate B10.A(2R) (2R; Kk, IAk, IEk, Db) mice despite intravenous (iv) injection of 2R spleen cells (SC) before or after skin grafting, indicating that graft rejection could not be caused across IE Ag-barrier alone. Furthermore, 4R SC could not induce lethal graft-versus-host disease (GVHD) in supralethally (950 rad) irradiated 2R mice. On the other hand, infiltration of lymphoid cells was observed at the site of transplanted 2R skin in 4R mice. SC of 4R mice unprimed or primed with 2R skin or 2R SC showed the capability to proliferate in vitro in response to 2R Ag. In immunofluorescence analysis of lymph node cells (LNC) of 4R mice injected iv with 2R SC 7 days earlier, IE-reactive CD4+Vbeta 11+ T cells did not change in number, but slightly increased the expression of interleukin-2 receptor (IL-2R). In 2R mice irradiated with 670 rad and injected iv with 4R SC 7 days earlier, 4R-derived CD4+V beta 11+ T cells proliferated, changed to blastoid form, and showed a markedly increased expression of IL-2R. To further investigate the influence of IE alloantigens on transplantation immunity, IL-2 production and anti-class I CTL activity were assayed. The 4R SC capable of recognizing IEk and Dk Ag of B10.BR (Kk, IAk, IEk, Dk) generated levels of both IL-2 and CTL activities higher than those of 2R SC capable of recognizing Dk Ag alone. These results strongly suggest that IE alloantigens indirectly act as the transplantation Ag by the stimulation of IE-reactive CD4+ helper T cells resulting in the differentiation of class I-restricted CD8+ T cells.

Animals↗
PubMed1992

Development of hepatocellular carcinoma associated with increases in DNA synthesis in the surrounding cirrhosis.

The relationship between DNA synthesis activity in hepatocytes from cirrhotic tissue and development of hepatocellular carcinoma was studied in 33 posthepatitic patients with Child's grade A cirrhosis. DNA synthesis activity was measured by a bromodeoxyuridine (a thymidine analogue) labeling index, using the bromodeoxyuridine-antibromodeoxyuridine in vitro method, and the patients were followed up prospectively with frequent liver ultrasonography for 2 years. During the 2-year follow-up, 11 of the 33 cirrhotic patients developed hepatocellular carcinoma; they included 8 of the 15 patients (53%) in the high labeling index (greater than 1.5%) group compared with only 3 of the 18 patients (17%) in the low labeling index (less than 1.5) group (P less than 0.05). Five of the latter 18 subsequently had increased synthesis activity. Of these 20 patients who showed high synthesis activities either initially or subsequently, 10 (50%) developed hepatocellular carcinoma, in contrast to 1 of 13 (8%) with persistently low activities (P less than 0.05). Thus, hepatocellular carcinoma seems to develop or may become detectable when DNA synthesis in the background cirrhosis is increasing or remains high.

Adult↗
PubMed1992

Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys.

Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.

Animals↗
PubMed1992

Effects on cultured neonatal mouse calvaria of 1 alpha,25-dihydroxyvitamin D3, 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,26,26,27,27,27-hexafluoro-1 alpha,23S,25-trihydroxyvitamin D3.

The potency of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) to enhance bone calcium (Ca) mobilization in vitro was higher than that of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In a 48-h organ culture system using fetal rat limb bones, effects of 26,27-F6-1,25(OH)2D3 on bone resorption were similar to those of 1,25(OH)2D3. Thus, we attempted to clarify whether or not the potency of 26,27-F6-1,25(OH)2D3 in bone resorption in vitro would be higher than that of 1,25(OH)2D3. Calvarial bones from neonatal mice were used as explants and the culture period was extended to 144 from 48 h. In cultures of 0 to 48 h, both drugs increased the release of prelabeled 45Ca from cultured calvariae, in a dose-dependent manner. In cultures of 48 to 144 h, 26,27-F6-1,25(OH)2D3 was much more effective than 1,25(OH)2D3 regarding indices of bone resorption. 26,26,26,27,27,27-F6-1 alpha,23S,25-trihydroxyvitamin D3 (26,27-F6-1,23,25(OH)3D3), a main metabolite of 26,27-F6-1,25(OH)2D3 in rats, stimulated 45Ca release equipotently to 1,25(OH)2D3. In mouse bone marrow cells cultured for 7 days, the potency of 26,27-F6-1,25(OH)2D3 on osteoclast formation was much higher than 1,25(OH)2D3. These results suggest that the higher potency of 26,27-F6-1,25(OH)2D3 in bone resorption may be due at least in part to both the higher potency of 26,27-F6-1,25(OH)2D3 in osteoclast formation and the larger retention of 26,27-F6-1,23,25(OH)3D3 in calvariae.

Acid Phosphatase↗
PubMed1992

Identification of human blood in mosquitoes (Diptera: Culicidae) using nonradioactive DNA dot blot hybridization.

A dot blot hybridization procedure was developed to detect human blood meals in engorged mosquitoes. A biotinylated DNA probe allowed the detection of 10-100 ng of human DNA, discriminated well between human and nonhuman sources of blood, and cross-reacted only with monkey DNA. Results showed that this method was a specific and sensitive technique for the identification of blood meals up to 100 h after ingestion. The nonisotopic label offers easy handling without the problems inherent in the use of radioisotopes, and it can be adapted for use in routine field tests.

Animals↗
PubMed1992

Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose- and saline-infused rats.

To assess the effect of a glucose infusion on brain extracellular fluid (ECF) during systemic hypoxia, changes in glucose and lactate concentrations in cerebral ECF during and after moderate hypoxic hypoxia were measured in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were given either saline (n = 6) or 50% glucose solution (n = 6) for 3 h, starting 60 min before the onset of hypoxia. Hypoxia was produced by circulating 7% O2 gas in a plastic chamber for 90 min. In saline-infused animals, brain ECF glucose concentrations decreased slightly during hypoxia, although blood glucose concentrations did not change. Blood lactate concentrations increased to 6.28 +/- 0.91 mM, at 60 min after the onset of hypoxia (P less than 0.05). Brain ECF lactate concentrations increased to 3.53 +/- 0.20 mM and remained constant during 60 min of steady-state hypoxia (P less than 0.05) and decreased to the basal level within 60 min after the end of hypoxia. When sodium lactate solution was infused intravenously for 90 min (n = 4), blood lactate concentrations increased to a level as high as those found during hypoxia. However, the brain ECF lactate concentration increased only to 1.86 +/- 0.09 mM. In glucose-infused animals, the blood glucose concentration reached 339.1 +/- 32.3 mg/dl at the end of the glucose infusion, and the brain ECF glucose concentration increased to 54.7 +/- 7.3 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of glucose infusion on cerebral cortical glucose and lactate concentrations during endotoxemia in rats.

Hypoglycemia has been observed in several species before death from endotoxemia. Although several studies have emphasized the importance of maintaining brain glucose at normal concentration during endotoxemia, the effect of glucose infusion on cerebral glucose metabolism has not been studied. Accordingly, the effects of glucose infusion on interstitial glucose and lactate concentrations in the cerebral cortex during endotoxemia were studied in 22 Wistar rats. Cerebral glucose and lactate were measured at 30-min intervals for 4 h using microdialysis. Animals were divided into four groups: 1) saline-infused control (n = 5); 2) saline-infused endotoxemia (n = 7); 3) glucose-infused control (n = 5); and 4) glucose-infused endotoxemia (n = 5). In groups 2 and 4, endotoxemia was induced by intravenous injection with E. coli lipopolysaccharide B (5 mg.100 g-1). One hour after endotoxin administration, saline or 50% glucose was infused at a flow rate of 0.5 ml.100 g-1.h-1 for 3 h. Endotoxin induced a significant increase (P less than 0.05) in blood glucose in the saline-infused rats, which survived for 4 h (n = 5), from 91.6 +/- 15.4 mg.100 ml-1 at baseline to 136.3 +/- 23.3 mg.100 ml-1 (149%) at 1 h, followed by a gradual decrease (to 63% of the basal concentration at 4 h). Similar changes were observed in brain glucose (14.9 +/- 1.9 mg.100 ml-1 baseline, 175% of baseline at 2 h, and 57% of baseline at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Metabolism of tegafur in rat liver observed by in vivo 19F magnetic resonance spectroscopy and chromatography.

Metabolism of tegafur in the rat liver was observed by in-vivo 19F magnetic resonance spectroscopy (MRS). After MRS observation, tegafur and q-fluorouracil (5-FU) in the liver were determined by a chromatographic method for comparison with the results of 19F-MRS. Rats were divided into 3 groups: 1) CCl4-induced liver injury group, 2) uracil combined group, 3) control group. Catabolism to fluoro-beta-alanine was suppressed in both the liver injury group and the uracil combined group. Low peaks of 5-FU and fluoronucleotides could be found only in the uracil combined group. The result of 19F MRS observation of each group was in agreement with the result of determination of tegafur and 5-FU by chromatography. This showed that substances which could be observed by 19F-MRS were in proportion to all intracellular fluoro-containing substances. 19F-MRS can provide direct information on the metabolism of fluoropyimidines non-invasively and it might be a useful aid in choosing suitable chemotherapy for patients.

Alanine Transaminase↗
PubMed1992

Biological characteristics of CD7 positive acute myelogenous leukaemia.

We studied the biological characteristics of CD7+ acute myelogenous leukaemia (AML). We diagnosed nine out of 88 consecutive AML cases as CD7+ AML based on myeloperoxidase positivity and surface antigen expression. In eight of these nine cases more than 20% of leukaemic blasts were found to coexpress both CD7 and a myeloid-associated antigen, CD33, by a two-colour flow-cytometric assay, while in the remaining case more than 90% of blasts were positive for CD7 and myeloperoxidase. CD7+ AML was most frequently observed in M1 among AML subtypes according to the FAB classification. An early stage-specific antigen, CD34 was also expressed on leukaemic blasts from eight of these nine cases. Neither the T-cell receptor (TcR)-beta nor the TcR-gamma gene was clonally rearranged in any of the cases. We then studied the proliferative responses to stimulation by various growth factors. Among interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF), IL-3 showed the strongest stimulatory effect on DNA synthesis and leukaemic blast colony formation in 8/9 and 6/8 CD7+ AML cases examined, respectively. On the other hand, the strongest stimulatory effect exerted by IL-3 on blast colony formation was observed in only six out of the 33 CD7- AML cases examined. Furthermore, CD7+ AML blasts could proliferate in response to stem cell factor (SCF); SCF alone showed stimulatory effects on blast colony formation (7/8 cases), and in 5/7 SCF-responding cases, stimulatory effects of SCF were more potent than those of IL-3. In addition, SCF enhanced blast colony formation synergistically with IL-3 in four of these seven cases. These data suggest that progenitor cells of CD7+ AML may possess the biological properties characteristic of immature haematopoietic stem cells.

Adolescent↗
PubMed1992

Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia.

We report the biological characteristics of leukaemic blasts from two cases of acute leukaemia with an interstitial deletion of the long arm of chromosome 9 (9q-). Case 1 (FAB: M1) showed del(9)(q12q22) as the sole karyotypic anomaly, and case 2 (FAB: M1) presented del(9) (q12q22) in association with trisomy 10. In both cases, leukaemic blasts presented unique cytological features, such as prominent vacuoles on Giemsa staining, or strong localization of myeloperoxidase resembling 'pseudo-Chediak-Higashi' granules. Immunophenotyping of blasts revealed the biphenotypic expression of T-lymphoid/myeloid antigens (CD2, CD7/CD33) in addition to CD34. Neither T-cell receptor beta (TCRB), T-cell receptor gamma (TCRG) nor Ig heavy chain (IGH) genes were clonally rearranged. Furthermore, there was neither rearrangement nor expression of ABL, which is located at 9q34, indicating that the deletion involved bands centrometric to 9q34 did not induce the activation of ABL. DNA synthesis of the blasts was stimulated (stimulation index greater than 2.0) in the presence of interleukin (IL)-3, IL-4, granulocyte colony-stimulating factor or erythropoietin (Epo). IL-3 and IL-4 could also support the in vitro growth of leukaemic blast colonies, and the IL-3- or IL-4-dependent blast colony growth was synergistically enhanced by the addition of IL-6 or Epo. These observations imply that T-lymphoid/myeloid or pluripotent stem cells may be closely involved in the development of 9q- AML.

Adolescent↗
PubMed1992

Pulmonary mucormycosis with fatal massive hemoptysis.

A case of pulmonary mucormycosis in a 57-year-old woman with acute promyelocytic leukemia (APL) who died of massive hemoptysis is reported. Chest radiography revealed changes that began with a small focal infiltration and progressed to a large round nodule with cavity formation. Postmortem examination showed the nodule to be composed mainly of infarcted lung tissue with saprophytic growth of Mucor. An adjacent proximal branch of the left pulmonary artery was thrombosed with mucoraceous hyphae, and it had ruptured into the cavitary space around the necrotic tissue and then into a conducting bronchus. In general, both fatal massive hemoptysis and cavity formation are rare in pulmonary mucormycosis. In our present case, the histological findings suggested that both phenomena were closely related to the pulmonary infarction caused by Mucor invasion of the pulmonary artery.

Female↗