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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 253 records · Page 14Linked to original sources

Serum levels of parathyroid hormone-related protein are not elevated in patients with T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm which shares most clinical features with adult T-cell leukemia (ATL). We measured serum level of C-terminal parathyroid hormone-related protein (C-PTHrP) in patients with T-PLL and ATL. Serum C-PTHrP levels of eight patients with T-PLL (median 36.8 pmol/l; range 27.0-50.2 pmol/l) did not differ from those of 30 human T-lymphotropic virus type I (HTLV-I)-seronegative blood donors (median 37.0 pmol/l; range 22.6-54.0 pmol/l). The C-PTHrP levels in ten ATL patients (median 69.6 pmol/l; range 42.5-899.4 pmol/l) were significantly higher than those in healthy controls (p<0.0001) or T-PLL patients (p=0.001). We suggest that the serum level of PTHrP can provide useful information for differentiating between T-PLL and ATL.

Adult↗

Gastric enterochromaffin-like-cell tumor with liver and splenic metastases.

We report a patient with gastric enterochromaffin-like-cell tumor with liver and splenic metastases. He was 68 years old and presented with major complaints of epigastric pain and weight loss. Under the diagnosis of gastric carcinoma with liver metastasis, total gastrectomy with splenectomy and lateral segmentectomy of the liver was performed. Intraoperative findings resulted in a diagnosis of adenocarcinoma T3N2P0H1, in stage IVa. Histological examination of the resected specimens showed a well differentiated neuroendocrine carcinoma (enterochromaffin-like-cell tumor) with liver and splenic metastasis which demonstrated high-grade lymphatic and vascular invasion. There was no lymph node metastasis. The tumor cells in the stomach, liver and spleen were immunoreactive for chromogranin A and Grimelius--positive. We review the literature, as well as presenting this case report.

Aged↗

Treatment of traumatic atlanto-occipital dislocation in chronic phase.

We report the case of 27-year-old woman who presented with mild neurological deficits with significant anterior dislocation of the atlanto-occipital junction in a chronic phase after initial conservative treatment in another hospital. The importance of early diagnosis and treatment for atlanto-occipital dislocation is emphasized. The dislocation could not be reduced sufficiently either by halo ring cervical traction or surgical procedure 5 months after the accident. Therefore, transoral odontoidectomy for decompression of the medulla, together with the posterior occipitocervical fusion with a titanium loop brace was performed. The patient's symptoms disappeared completely within a few months after the operation. Magnetic resonance imaging findings suggesting soft tissue damage is the key to an early diagnosis and subsequent stabilization of traumatic atlanto-occipital dislocation in the early phase. Transoral decompressive odontoidectomy combined with posterior fusion may be considered for the treatment of irreducible atlanto-occipital dislocation in a chronic phase.

Adult↗

Expression of adenosine triphosphate-sensitive potassium channel subunits in female rat reproductive tissues: overlapping distribution of messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 and sulfonylurea-binding regulatory subunit 2.

OBJECTIVE: Potassium channel activation has been shown to decrease uterine tone and is a target for inhibition of uterine activity in the treatment of preterm labor. In addition, potassium channel activation also appears to be involved in oocyte maturation. The specific potassium channels responsible for these channel currents have not been identified but are known to be responsive to such agents as pinacidil and to be inhibited by glibenclamide. These findings suggest the presence of an adenosine triphosphate-sensitive potassium channel that is a complex of a weak inwardly rectifying potassium channel subunit 6.1 or 6.2 and sulfonylurea-binding regulatory subunit 1 or 2. STUDY DESIGN: The technique of reverse transcriptase-polymerase chain reaction was used to detect the presence of messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 1 and 2 and weak inwardly rectifying potassium channel subunit 6.1 and 6.2 in the ovary and myometrium of the pregnant rat. In situ hybridization histochemical analysis was used to identify the specific cell types expressing each messenger ribonucleic acid. RESULTS: Reverse transcriptase-polymerase chain reaction analysis found expression of messenger ribonucleic acid for sulfonylurea-binding regulatory subunits 1 and 2B and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 in rat myometrium and ovary during gestation. There was no evidence for expression of weak inwardly rectifying potassium channel subunit 6.2 messenger ribonucleic acid in the ovary or the myometrium of the pregnant rat. In situ hybridization histochemical examination localized expression of messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 2B and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 to uterine myocytes and granulosa cells of the corpus luteum. The cells expressing sulfonylurea-binding regulatory subunit 1 messenger ribonucleic acid could not be identified because of the scarcity of this messenger ribonucleic acid. Messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 1, messenger ribonucleic acid for sulfonylurea-binding regulatory subunit 2B, and messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 were also observed in the placenta by in situ hybridization histochemical examination. CONCLUSION: The results suggest that the major adenosine triphosphate-sensitive potassium channel expressed in the myometrium and the corpus luteum during pregnancy is a complex of sulfonylurea-binding regulatory subunit 2B and weak inwardly rectifying potassium channel subunit 6.1.

ATP-Binding Cassette Transporters↗

Transient dysfunction of the freestyle stentless xenograft.

After replacement of a bicuspid aortic valve with a Freestyle stentless xenograft, right coronary leaflet dysfunction and an elevated pressure gradient developed. Attempts to match the right and left ostia of the prosthesis, which were located at an angle of less than 120 degrees, to the native right and left ostia, which were located at 180 degrees, may have resulted in the leaflet distension. This is a suggestive finding about its implantation technique.

Aortic Valve↗

Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death.

OBJECTIVE: We tested the hypothesis that delayed afterdepolarization (DAD)-associated rhythms in German shepherd dogs with reduced anteroseptal left ventricular (LV) sympathetic innervation derive from abnormal beta-adrenergic receptor effector coupling. METHODS AND RESULTS: In anteroseptal LV midmyocardium of afflicted dogs, beta-receptor density was greater than that in normal dogs (P < .05), with affinity being equal in both groups. Basal and maximum isoproterenol (ISO) stimulated adenylyl cyclase activity of anteroseptal LV of afflicted dogs was greater than that in normal dogs (P < .05). Isolated anteroseptal M cell preparations of afflicted dogs studied with microelectrodes showed abnormal lengthening, rather than shortening of action potential duration in response to ISO, as well as a 61% incidence of 10(-7) mol/l ISO-induced triggered activity as compared to 12% in normals (P < .05). In contrast, there was no difference between afflicted and control dogs in triggered activity, beta-receptors or adenylyl cyclase activity in a normally innervated region of the ventricles. CONCLUSION: In this model there is an increase in beta-receptor density and beta-adrenergic stimulation of adenylyl cyclase and of triggered activity in anteroseptal myocardium but not in a normally innervated region of the heart. Hence, abnormal beta-adrenergic signal transduction appears associated with the neural abnormality identified in dogs with inherited VT.

Action Potentials↗

Steady-state and nonsteady-state action potentials in fibrillating canine atrium: abnormal rate adaptation and its possible mechanisms.

OBJECTIVE: Our goal was to study rate adaptation of atrial action potentials in non-steady and steady states to further our understanding of mechanisms determining inducibility and stability of atrial fibrillation. METHODS: We used standard microelectrode techniques to examine the characteristics of steady-state action potentials paced at regular cycle lengths (CL) and of nonsteady-state action potentials observed after an abrupt change of CL in atria from canine hearts that had been rapidly paced. RESULTS: We compared action potential characteristics among normal atria, atria in which chronic atrial fibrillation (cAF, lasting more than 3 days) had been induced and atria in which only nonsustained atrial fibrillation (nAF, lasting less than 12 h) had been induced. In steady-state, the rate adaptation of maximum diastolic potential (MDP) and action potential duration (APD) and markedly reduced in both cAF and nAF. Action potential characteristics did not differ between cAF and nAF atria, suggesting that factors other than electrophysiological properties determine the chronicity of AF. The time course of change in APD after an abrupt change of CL was altered in nAF/cAF atria; i.e., when CL was prolonged, APD also prolonged at the first beat, and then shortened during several subsequent beats (initial phase). Thereafter, APD slowly prolonged to a new steady-state (slow phase). In nAF/cAF atria, the initial phase was enhanced (greater shortening of APD) and the slow phase was reduced (less prolongation of APD). This latter phase was modified by ryanodine. CONCLUSIONS: Thus the reduced rate adaptation of steady-state APD is explained mainly by the loss of a slow phase of APD adaptation in nAF/cAF which is reversed in the presence of ryanodine. Therefore, in both nAF and cAF atria, rate adaptation of MDP as well as APD are reduced, nonsteady state as well as steady state, AP characteristics are markedly altered and these changes are partially explicable by Ca, -dependent processes.

Action Potentials↗

Noninvasive assessment of the cardiac baroreflex: response to downward tilting and comparison with the phenylephrine method.

OBJECTIVES: We studied the relation between changes in systolic blood pressure and RR interval during downward tilting in comparison with assessment of baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) and with measures of heart rate variability (HRV). BACKGROUND: The method most extensively used for assessing BRS involves bolus injections of phenylephrine. Several noninvasive methods proposed to assess BRS have not been widely applied in the clinical setting. METHODS: Sixteen healthy male volunteers were studied (mean age +/- SD 27.5+/-4.6 years). Arterial blood pressure using tonometry and electrocardiogram was simultaneously recorded. After 20 min of 70 degrees upright tilting, the table was returned to supine position at a speed of 3.2 degrees/s. Subsequently, BRS was assessed using an intravenous bolus injection of phenylephrine (2 to 3 microg/kg). Heart rate variability under resting conditions also was analyzed. RESULTS: In all subjects, a beat to beat systolic blood pressure increase associated with corresponding RR interval lengthening was observed during downward tilting as well as during phenylephrine administration. During both testing procedures, these two variables showed linear correlation, and the slope of regression line during downward tilting (DT-BRS) correlated significantly with Phe-BRS (r = 0.79, p = 0.0003). The DT- and Phe-BRS also correlated significantly with the high frequency component of resting HRV (r = 0.70, p = 0.0023 for DT-BRS; r = 0.58, p = 0.0185 for Phe-BRS). CONCLUSIONS: We conclude that in a small homogeneous group DT-BRS provided an assessment of reflex cardiac vagal function comparable to that obtained by the phenylephrine method.

Adult↗

Pathogenetic role of monoamine metabolism in complex febrile seizures.

To investigate the pathogenetic role of monoamine metabolism for febrile seizures, concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were evaluated in the lumbar cerebrospinal fluid of affected children. This series included children who underwent lumbar puncture within 4 hours after seizures, at which time the lumbar cerebrospinal fluid is presumed to represent a ventricular source of cerebrospinal fluid, without the consequence of a seizure. The subjects were 21 patients with simple febrile seizures, eight with complex febrile seizures, and eight control patients. The complex febrile seizure group had lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the control group, whereas the simple febrile seizure group and control group did not have a significant difference. Although statistically not significant, the complex febrile seizure group was inclined toward lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the simple febrile seizure group. These results implied that abnormal monoamine metabolism contributes to seizure susceptibility in the complex febrile seizure group. The simple febrile seizure group may be heterogeneous, and abnormal monoamine metabolism can play a role in seizure development for some children of this group.

Age Factors↗

Beneficial effects of long-term treatment with enalapril on cardiac function and heart rate variability in patients with old myocardial infarction.

BACKGROUND: The beneficial effects of the early use of angiotensin-converting enzyme inhibitors (ACEis) in patients with acute myocardial infarction (MI) are well documented. However, the effects of ACEis in patients with an old MI and preserved cardiac function have not yet been studied. We examined the effects of 12 months of enalapril treatment in patients with previous MI. METHODS AND RESULTS: Thirteen patients with an old MI and no overt congestive heart failure (CHF), aged 70 +/- 2 years, were treated with enalapril for 12 months. We also included 13 age- and sex-matched control patients who had a similar clinical background but were not treated with enalapril. Holter electrocardiography and echocardiography were performed at entry and after 12 months of treatment. Heart rate variability, low- and high-frequency powers (LF and HF), and the ratio between LF and HF (LF/HF) were analyzed. Changes from baseline to 12 months in HF, LF/HF, left ventricular end-diastolic dimension (LVEDD), and end-systolic dimension (LVESD) were significantly different in the enalapril group (HF, 8.1 +/- 0.9 to 9.3 +/- 0.9 milliseconds: LF/HF, 1.65 +/- 0.11 to 1.53 +/- 0.16; LVEDD, 57.2 +/- 1.6 to 54.7 +/- 1.6 mm; LVESD, 40.0 +/- 2.4 to 36.3 +/- 1.9 mm) compared with the control group (HF, 8.9 +/- 0.9 to 8.5 +/- 0.7 milliseconds; LF/HF, 1.78 +/- 0.18 to 1.88 +/- 0.15; LVEDD, 52.3 +/- 2.5 to 55.9 +/- 2.2 mm; LVESD, 32.5 +/- 2.6 to 36.1 +/- 2.6 mm; P < .05). The delta change (delta) in LVESD between the end and the start of study correlated inversely with deltaHF (r = -0.56; P < .05) and positively with deltaLF/HF (r = 0.65; P < .01). CONCLUSION: Our results suggest possible ongoing structural changes in patients with old MI even in the absence of overt CHF. Enalapril seemed to prevent such changes and to restore cardiac autonomic tone toward normal. Further prospective studies using a larger sample size are warranted to confirm potential beneficial effects of ACEis in patients with previous MI and preserved left ventricular function.

Aged↗

Enhanced hydrogen production by a mutant of Rhodobacter sphaeroides having an altered light-harvesting system.

A stable mutant of the photosynthetic bacterium Rhodobacter sphaeroides with an altered light-harvesting (LH) system (P3 mutant) was obtained by UV irradiation and characterized. The mutant exhibited a 2.7-fold decrease in the core antennal (LH1) content and 1.6-fold increase in peripheral antennal (LH2) content compared to the wild-type strain. The H2 evolution rates in the P3 mutant under 800- and 850-nm light, corresponding to the absorption maxima of LH2, were 1.5 times higher than in the wild-type strain. The wild-type absorption spectrum was restored in the P3 mutant when a 1.1-kb PCR-amplified fragment containing the puf promoter and pufQBA genes was ligated into a pRK-415 derivative and introduced into it. The transformant showed lower H2 production rates at 800 and 850 nm than the P3 strain carrying the control plasmid, indicating that the accelerated H2 production in the P3 mutant was a result of alterations in the LH system.

Journal Article↗

Immobilization of P450 monooxygenase and chloroplast for use in light-driven bioreactors.

P450 monooxygenases exhibit great potential for application to bioreactors for the decomposition of various hydrophobic chemicals including pollutant compounds. P450-containing microsomes were immobilized in spinach chloroplasts for use in light-driven bioreactors. We tested three methods (entrapment, adsorption and cross-linking) to immobilize chloroplasts and yeast microsomes containing a genetically engineered fusion enzyme between rat P450 1A1 and yeast P450 reductase. Entrapment in agarose gave the best activity for the conversion of 7-ethoxycoumarin to 7-hydroxycoumarin under illumination of 6200 lx. We then tested three light-driven bioreactors (two column-type and one batch-type reactors developed) using the immobilized gels. A two-phase column-type reactor with separately immobilized microsomes and chloroplasts showed a higher conversion rate than a reactor with co-immobilization of both components. The reactor showed a turnover rate of 6.32 mol product/mol P450/min after a 40-min run, and 2.49 after a 180-min run. These turnover rates are higher than the values reported by others using immobilized microsomal P450s.

Journal Article↗

Exogenous expression of p16INK4a is associated with decrease in telomerase activity.

In this study, gene transfection was used to determine whether the exogenous expression of p16INK4a modulated the biological characteristics of glioblastoma cells. The human glioblastoma cell line U87MG was doubly transfected with the plasmids pVgRXR and pIND harboring the wild-type p16 gene. The expression of p16INK4a in the resulting transfectants was regulated by the addition of the ecdysone homologue, muristerone A. When the cells expressed p16INK4a, their growth capacity was reduced and morphological changes such as an increase in cell size and cellular flattening were observed. The analysis of cell cycle regulation provided evidence that cells expressing p16INK4a were inhibited from entry into the cell cycle, as assessed by Ki-67 antigen expression. In addition, it was observed that the exogenous expression of p16INK4a was associated with decrease in telomerase activity.

Brain Neoplasms↗

Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis.

Many studies have previously confirmed high TNFalpha (tumor necrosis factor-alpha) production in sarcoidosis, and have shown that TNFalpha plays an important role in granuloma formation. We investigated TNFA and TNFB (lymphotoxin-alpha) gene polymorphisms in 26 cardiac sarcoidosis patients of Japanese origin. These studies revealed a significant increase in the more uncommon TNFA2 allele in the patient group, suggesting that the TNFA gene controls the genetic susceptibility to cardiac sarcoidosis.

Asian People↗

Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period.

Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38negative cells among CD34+ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3+/-10.4% vs 11.3+/-2.1%, respectively, n=5, P=0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34+CD38negative cells was significantly higher in day 1 PB than in the harvested BM (61.0+/-16.5% vs 9.3+/-3.5%, respectively, n=7, P=0.0002). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following allo-BMT.

ADP-ribosyl Cyclase↗

Additional translocation (8;21)(q22;q22) in a patient with Philadelphia-positive chronic myelogenous leukaemia in the blastic phase.

We report a case of Philadelphia-positive chronic myelogenous leukaemia in blastic phase with the additional translocation (8;21)(q22;q22), which is frequent in acute myeloid leukaemia but not in chronic myelogenous leukaemia. The t(8;21) was not detected in the chronic phase, and was the only additional chromosomal anomaly in the blastic clone. Reverse transcription-polymerase chain reaction revealed the AML1/ETO fusion transcript in the cells of blastic phase but not in those of chronic phase. Regarding t(9;22), the breakpoint on chromosome 22 occurred in the mu-BCR region of the BCR gene, resulting in hybrid BCR/ABL mRNA with an e19a2 junction. Our findings provided molecular evidence that t(8;21) can occur as an additional genetic change in Philadelphia-positive chronic myelogenous leukaemia.

Adult↗

Nasal chondromesenchymal hamartoma of infancy: the first Japanese case report.

The first Japanese case of nasal chondromesenchymal hamartoma, a rare infantile nasal neoplasm, is presented. A 4-month-old Japanese boy was referred to our Centre because of intranasal mass and oculomotor disturbance. Radiological images showed the intranasal tumor extending to the paranasal sinus, orbit, and anterior frontal fossa. Subtotal resection and radiation therapy to residual tumor were performed. There has been no recurrence of the tumor for 13 years. Histologically, the lesion demonstrated admixture of various mesenchymal elements, including cellular spindle cell stroma with occasional myxoid change, nodules of mature/immature cartilaginous tissue, focal osteoclast-like giant cells, and erythrocyte-filled spaces resembling aneurysmal bone cyst. The histology was consistent with the findings presented by McDermott et al. 1986. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin. Chondrocytes in the mature cartilaginous tissue were positive for S-100 and vimentin; chondrocytes in the immature cartilaginous tissue were positive for S-100, vimentin, and smooth muscle actin. Ultrastructurally, the spindle cells showed features of either fibroblast or myofibroblast.

Frontal Bone↗

Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands. METHODS: The localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls. RESULTS: In hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0. 22 +/- 0.09 (mean +/- sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001). CONCLUSION: The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid.

Adult↗