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Biomedical subjects

H Miwa

Publications and source records attributed to H Miwa.

At least 181 records · Page 10Linked to original sources

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation.

The response of atrial natriuretic peptide (ANP) release to haemodynamic influences after cardioversion of atrial fibrillation has not been fully examined. We measured plasma concentrations of ANP and assessed haemodynamic changes 60-120 min after DC cardioversion in 22 patients with non-valvular chronic atrial fibrillation. Passive leg elevation to enhance volume expansion was performed 60 min after DC cardioversion. Sinus rhythm was restored in 18 of the 22 patients (successful DC cardioversion group). The control group consisted of seven patients with non-valvular chronic atrial fibrillation who did not undergo DC cardioversion (atrial fibrillation control group). In the successful DC cardioversion group, the mean pulmonary artery wedge pressure decreased significantly 15 min after cardioversion (P < 0.05) and then remained unchanged. Plasma concentrations of ANP also decreased significantly 15 min after cardioversion (P < 0.05). Furthermore, there was an additional significant decrease in ANP levels for up to 60 min after cardioversion (P < 0.05 from 15 min). Passive leg elevation for 15 min led to an increase in the mean pulmonary artery wedge pressure (P < 0.01) and right atrial pressure (P < 0.05), but did not result in increased plasma concentrations of ANP (47.1 +/- 27.6 vs 43.9 +/- 34.4 pg.ml-1, mean +/- SD, P = ns). In the atrial fibrillation control group, passive leg elevation increased the mean pulmonary artery wedge pressure (P < 0.01), the mean right atrial pressure (P < 0.05) and plasma concentrations of ANP (139.9 +/- 85.8 vs 168.1 +/- 108.2, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Expression of interleukin-5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype.

Eosinophilia sometimes occurs in acute myeloid leukaemia (AML) and several laboratories have reported that cells with the t(8;21) or structural abnormalities of chromosome 16 can proliferate and differentiate to eosinophils in the presence of IL-5 in vitro. However, cases without these chromosomal abnormalities can also have eosinophilia. We investigated the association between the expression of IL-5 receptor (IL-5R) gene, karyotype and phenotype in 35 patients with AML. All cases expressed the IL-3R but the IL-5R gene was expressed predominantly in leukaemic cells with either t(8;21) or CD4-positive immunophenotype and was associated with the presence of eosinophilia.

Acute Disease↗

Somatosensory evoked blink response: findings in patients with Miller Fisher syndrome and in normal subjects.

Reflex blinking was elicited by the electrical stimulation of peripheral nerves and various parts of the body of seven of 11 patients with Miller Fisher syndrome. This reflex blinking disappeared during recovery. Reflex blinking was elicited in normal subjects only with specific stimulation of the peripheral nerves of their upper extremities. This response may be due to a release phenomenon transmitted via the brainstem reticular formation and may be useful in detecting latent CNS involvement in patients with Miller Fisher syndrome.

Adult↗

Western blot analysis of rat pituitary antigens recognized by human antipituitary antibodies.

Antipituitary antibodies have been reported to exist in sera of patients with autoimmune endocrine disorders. In order to investigate the pituitary antigens recognized by antipituitary antibodies, we studied the autoantigens in rat pituitary membrane and cytosolic fractions recognized by human antipituitary antibodies and anti-human pituitary hormone antibodies. Sera from 6 patients which showed positive antipituitary antibodies by immunofluorescence methods were studied. Each serum identified some proteins with 14.5, 22, 47, 49, 65, 84 and 97.5 kDa. Anti-GH antibodies and anti-PRL antibodies identified a positive band with 22 kDa, suggesting that anti-GH and anti-PRL antibodies may be present in patients' sera. These results indicate that Western blot analysis of rat pituitary antigens recognized by human antipituitary antibodies is a useful method to elucidate the pathophysiology of autoimmune endocrine disorders.

Animals↗

Glutamine supplementation prevents the decrease of mitogen response after a treadmill exercise in rats.

The effect of glutamine (Gln)-supplemented diet on mitogen response decreased immediately after a treadmill exercise was examined by measuring the proliferations of peripheral blood lymphocytes (PBL) with phytohemagglutinin (PHA) and concanavalin A (ConA) in male Fisher rats. Although the plasma Gln concentration was significantly decreased in the control group immediately after a treadmill exercise (20 m/min, 60 min) compared to rested rats, plasma Gln concentration of rats fed Gln-supplemented diet for 3 weeks was significantly higher than that of control group in resting and was not significantly decreased even immediately after a treadmill exercise. In addition, proliferation of PBL with PHA or ConA and interleukin 2 (IL2) production were also significantly decreased immediately after a treadmill exercise in control group. On the contrary, their functions were almost maintained in Gln-supplemented group even immediately after a treadmill exercise. PBL from rats fed Gln-supplemented diet showed a higher response to mitogens such as PHA and ConA compared to the control group. Furthermore, their PBL showed higher incorporation of [3H]Gln compared to that of the control group irrespective of treadmill exercise. These results indicate that the preventive effect of Gln-supplemented diet on mitogen response decreased after a treadmill exercise is due to an increased response to mitogen and increased uptake of Gln as sources of fuel and nucleotides to the immune cells.

Animals↗

Synthesis and antibacterial activity of 2-(isoxazolidinio-5-yl)carbapenem derivatives.

The synthesis and antibacterial activity of the title compounds having an isoxazolidine ring at the C-2 position are described. These derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of nitrone with 2-vinyl carbapenems. This 1,3-dipolar cycloaddition reaction proceeded regioselectively to give diastereomeric isomers of 2(-isoxazolidin-5-yl)carbapenems. It was ascertained that the antibacterial activity of 1 beta-methylcarbapenem derivatives was superior to that of the corresponding 1H-carbapenem derivatives, and between the 2-(isoxazolidin-5-yl)-1 beta-methylcarbapenems the antibacterial activity of the 5'R-isomer was slightly better than that of the 5' R-isomer slightly better than that of the 5' S-isomer.

Anti-Bacterial Agents↗

[A characteristic blink response observed in a patient with Lance-Adams syndrome--somatosensory-evoked blink response].

We report a patient with Lance-Adams syndrome, in whom a characteristic blinking response was observed. In this patient, the reflex blinking was elicited by electrical stimulations applied not only to the supraorbital nerve but also to peripheral nerves of both upper and lower extremities. The EMG discharges responsible for the blinking response were found to consist of some components. The pathophysiological mechanism underlying the characteristic blinking response was discussed. It is speculated that increased excitabilities of the brainstem reticular formation may play a role in generating this type of blinking response, namely the somatosensory-evoked blink response.

Adult↗

[P-glycoprotein expression in hematological malignancies].

To clarify the common characteristics among P-glycoprotein (P-gp)-expressing hematological malignancies and whether chemotherapies could or could not induce P-gp expression, we analyzed P-gp/MDR1 expression in tumor cells from 200 Japanese patients (104 with acute myeloblastic leukemia (AML); 30 with acute lymphoblastic leukemia (ALL); 66 with mature lymphoid malignancies). Functional P-gp expression was examined by Rhodamine-123 efflux test, and estimated with the data by RT-PCR method. In mature lymphoid malignancies, the cells of T or natural killer (NK) cell malignancies frequently expressed P-gp/MDR1. In AML, frequent P-gp/MDR1 expression was associated with the expression of CD7 or c-kit and with 8; 21 chromosomal translocation (p < 0.01), which were thought to be the characteristics of the hematopoietic stem cell. Though the expression of P-gp/MDR1 was more frequent at onset than at relapse phase, the increase is thought to result from the expansion of blastic fraction expressing P-gp/MDR1. In ALL, P-gp/MDR1 expression was not frequent in B-cell precursor lineage (three of eighteen patients), but the incidence was high in CD7(+) surface CD3(-) cases (seven of the cases). These results indicate P-gp/MDR1 expression is more frequently in the tumor of T, NK cell and stem cell, reflecting the characteristics of its normal counterpart.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptors.

The melanocortins are peptide products of proopiomelanocortin post-translational processing that, among other functions, are thought to influence cognition. Recently, we isolated genes encoding two human melanocortin receptors, the melanocortin-3 receptor (hMC3R) and the melanocortin-4 receptor (hMC4R), which are expressed primarily in brain. We undertook the present studies to examine the structural features of melanocortins that determine activation of these two receptors. For our studies we expressed the coding regions of the hMC3R and hMC4R genes in Hepa cells using the eukaryotic expression vector CMVneo and examined the generation of intracellular cyclic 3',5'-adenosine monophosphate in response to stimulation with various melanocortins. Our findings indicate that the core heptapeptide sequence common to most of the melanocortins (amino acids 4-10 of adrenocorticotropic hormone [ACTH]) is the primary determinant for activation of hMC3R but, in addition, tyrosine2 is necessary for maximal response. Activity of hMC4R is heavily dependent on proline12, but full activity also requires a contribution by tyrosine2. These findings may provide insight into the development of targeted ligands for the brain melanocortin receptors.

Adrenocorticotropic Hormone↗

Frequent expression of CD3 epsilon in CD3 (Leu 4)-negative nasal T-cell lymphomas.

Adult natural killer (NK) cells had not generally been thought to express CD3 proteins other than zeta; however they were recently demonstrated to express CD3 epsilon in an activated condition. This prompted us to investigate the tumor tissues from 17 patients with Leu4-negative peripheral T-cell lymphoma, including eight with nasal T-cell lymphoma (NTCL), for the expression of CD3 epsilon. The tissues were immunohistologically stained with rabbit anti-human CD3 epsilon antibody. The expression of CD3 epsilon was more frequent in the tissues of nasal lymphoma than in the non-nasal lymphoma tissues: specimens from six of eight of the NTCL patients expressed CD3 epsilon, while only one of nine of the non-NTCL patients did so. The NTCL patients presented clinically with lethal midline granuloma, had histologic findings of tumor necrosis and angioinvasion, and had a peculiar CD2+, Leu4-, CD3 epsilon+, CD5-, CD7+, CD45RO+, CD4-, CD8-, beta F1-, T-cell receptor (TRC) delta 1-, CD56+ phenotype. This peculiar phenotype seems to be closely associated with NTCL. No clonal rearrangement of the TCR genes was detected in three NTCL patients examined. The NK cell origin of NTCL has been suggested by previous investigators. The phenotypic correspondence of our nasal tumors to adult activated NK cells supports this possibility, together with their lack of clonal rearrangement of the TCR genes.

Adult↗

Binding and cAMP studies of melanotropin peptides with the cloned human peripheral melanocortin receptor, hMC1R.

Binding and stimulation of cAMP by the melanotropin peptides alpha-MSH (alpha-melanocyte-stimulating hormone) and its superpotent analogues [Nle4, DPhe7]alpha-MSH (MT-I) and Ac-[Nle4,[formula: see text]alpha-MSH4-10-NH2 (MT-II) were undertaken to examine their respective properties on the human peripheral melanocyte melanocortin receptor, hMC1R. alpha-MSH was found to possess a binding IC50 value of 6.5 +/- 0.9 x 10(-9) M and cAMP EC50 value of 2.0 +/- 0.6 x 10(-9) M. MT-I possesses a binding IC50 value of 1.2 +/- 0.3 x 10(-9) M and a cAMP EC50 of 0.5 +/- 0.03 x 10(-9) M. MT-II possesses a binding IC50 of 0.57 +/- 0.08 x 10(-9) M and cAMP EC50 value of 0.20 +/- 0.05 x 10(-9) M.

Affinity Labels↗

WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia.

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.

Acute Disease↗

Expression of the interleukin-6 (IL-6), IL-6 receptor, and gp130 genes in acute leukemia.

Expression patterns of interleukin-6 (IL-6), IL-6 receptor (IL-6R), and gp130 genes in 39 patients with acute myeloid leukemia (AML), in 23 patients with acute lymphoblastic leukemia (ALL), and in 7 patients with acute mixed lineage leukemia (AMLL) were studied by quantitative reverse transcriptase-polymerase chain reaction. Significant levels of IL-6 were expressed in 8 (21%) of 39 AML patients and in 2 (29%) of 7 AMLL patients, whereas in ALL, the expression of IL-6 was almost negligible. IL-6R was expressed in all patients with AML and AMLL, whereas only half of ALL patients expressed low levels of IL-6R as compared with those with AML and AMLL. However, gp130 was ubiquitously expressed in all the leukemia patients, and there was no significant difference in gp130 expression among AML, ALL, and AMLL. Significant correlation was observed between the expression of IL-6R and gp130 in AML. When tested for in vitro response to IL-6, the leukemic cells from 3 of 7 AML, none of 3 ALL, and both of 2 AMLL patients significantly responded to IL-6, showing the correlation between the expression levels of IL-6R and gp130 and the responsiveness of leukemic cells to IL-6. These results showed that quantitation of IL-6R and gp130 expression by reverse transcriptase-polymerase chain reaction is useful for the rapid prediction of the responsiveness of leukemic cells to IL-6, especially in cases of administration of IL-6.

Adolescent↗

Molecular cloning, expression, and characterization of a fifth melanocortin receptor.

We report the isolation of a gene encoding a novel member of the family of melanocortin receptors. The mouse melanocortin-5 receptor (mMC5R) responds to melanocortins with an increase in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) concentrations. Stimulation of the mMC5R by the melanocortins revealed a hierarchy of potency in which alpha-melanocyte stimulating hormone (alpha-MSH) > beta-melanocyte stimulating hormone (beta-MSH) > adrenocorticotropic hormone (ACTH) > gamma- melanocyte stimulating hormone (gamma-MSH). Further structure-activity studies indicated that amino- and carboxyl-terminal portions of alpha-MSH appear to be key determinants in the activation of mMC5R whereas the melanocortin core heptapeptide sequence is devoid of pharmacological activity. Northern blot analysis demonstrated the expression of mMC5R mRNA in mouse skeletal muscle, lung, spleen, and brain.

Adrenocorticotropic Hormone↗

Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor.

We undertook these studies to explore the intracellular signaling mechanisms activated by a newly described human brain melanocortin receptor (hMC3R). Hepa cells transfected with the hMC3R gene responded to stimulation with alpha-melanocyte stimulation hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) with dose-dependent increases in cellular content of cyclic 3',5'-adenosine monophosphate (cAMP) reaching a maximum of over 1500% of control cells at the 10(-8) M dose (EC50 = 10(-11) M). In contrast, the production of [3H]inositol phosphates in cells prelabeled with myo-[2-3H]inositol exhibited a biphasic dose-response curve with increases as high as 155% of basal at 10(-11) M alpha-MSH or ACTH, but beyond that a dose-dependent decrease was observed. The inhibitory component of the dose-response curve could be abolished by pretreatment of transfected cells with the cAMP antagonist (Rp)-adenosine 3',5'-monophosphorothioate (Rp-cAMP) or the protein kinase A inhibitor H-89. Increases in intracellular calcium induced in transfected cells by alpha-MSH in doses ranging from 10(-11) to 10(-7) M could not be observed unless the cells were pretreated with H-89. By replacing the third intracytoplasmic loop of the canine H2-histamine receptor with that of hMC3R the biphasic characteristic of agonist-induced production of [3H]inositol phosphates was conferred to the chimeric receptor. These data indicate that the hMC3R is coupled to both cAMP and inositol phospholipid/Ca(2+)-mediated post-receptor signaling systems and that the latter response is regulated by protein kinase A activity.

Adrenocorticotropic Hormone↗

Serial neuroradiological studies in focal cerebritis.

We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed.

Aged↗