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H Nishimura

Publications and source records attributed to H Nishimura.

At least 451 records · Page 25Linked to original sources

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats.

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.

Adrenergic alpha-Antagonists↗

Intravenous methylprednisolone pulse therapy for Graves' ophthalmopathy.

To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.

Adult↗

Myelo-monocytoid immunophenotypes of B-cell chronic lymphocytic leukemia cells.

Leukemia cells from ten patients with B-cell chronic lymphocytic leukemia (B-CLL) and one with B-CLL of mixed cell type (B-CLL/PL) were analyzed to delineate the cellular characteristics, especially the myelomonocytic nature. Most of the surface phenotypes were consistent with the previous reports. However, the frequency of positivity for CD22 and CD25 was much higher in the examined cases of B-CLL than in Western reports. B-CLL cells frequently possessed antigens which are mainly expressed in myelomonocytic cells: 8/10 for CD11b and 4/10 for CD11c, although the presence of CD14 was not apparent (0/10). In addition, colony stimulating factor-1 receptors (CSF-1R) were expressed in 6 of the 10 B-CLL cases. The reactivity with antigens such as CD14, CD11c, and CSF-R was markedly enhanced by in vitro incubation. Alterations in antigen expression and in in vitro survival by growth factors for myelomonocytic lineage were observed in certain cases. These data imply that not only are B-CLL cells phenotypically closely related to myelomonocytic lineage but that they may also be influenced by growth factors for that lineage.

Aged↗

Disseminated pancreatic polypeptidioma.

Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-alpha or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.

Adult↗

Concentrations of lomefloxacin in radicular cyst and oral tissues following single or multiple oral administration.

Concentrations of lomefloxacin in serum, the wall and fluid of radicular cyst, gingiva, and jawbone following single or multiple oral administration were measured. The highest concentrations of lomefloxacin in serum, cyst wall, cyst fluid, gingiva, and jawbone occurred at 3 h after multiple administration, and were 2.31 micrograms/ml, 4.06 micrograms/g, 1.54 micrograms/ml, 4.72 micrograms/g and 2.79 micrograms/g, respectively. The mean concentration ratios of wall/serum, fluid/serum, fluid/wall, gingiva/serum, and jawbone/serum at the highest concentrations were 1.74, 0.73, 0.47, 2.52 and 1.20, respectively. Although most lomefloxacin concentrations in cyst and oral tissues following single oral administration did not exceed the MICs for 80% of clinically isolated strains of alpha-hemolytic streptococci, Staphylococcus aureus and Niesseria spp., most of those obtained after multiple oral administration exceeded the MICs except in the case of fluid.

Adult↗

Immature teratoma of the uterine fundus.

An exceedingly rare case of extragonadal immature teratoma, which occurred primarily in the uterus, is described. The tumor developed into the pelvic cavity from the uterine fundus and consisted of ectodermal, mesodermal and endodermal derivatives. There were also significant amounts of immature elements; immature neuroepithelium with brisk mitotic activity, immature mesenchymal tissue, immature cartilage, immature striated muscle and immature hepatic tissue. Histologically, it was classified as a grade 3 immature teratoma. Treatment consisted of total simple hysterectomy followed by 2 courses of combination chemotherapy with vincristine, actinomycin D and cyclophosphamide (VAC). The patient was well and without evidence of recurrence at 5 years post-operatively.

Adult↗

Induction of metallothionein and its localization in the nucleus of rat hepatocytes after partial hepatectomy.

Metallothioneins, a group of cysteine-rich heavy-metal binding proteins, are induced in the regenerating rat liver in response to the stimuli evoked by partial hepatectomy. We have investigated the expression of metallothionein genes and proto-oncogenes (c-fos, c-jun and c-myc), as well as specific localization of metallothionein in the liver cells after partial hepatectomy. Metallothionein mRNA was detected as early as 3 hr and reached a maximal level by 6 hr. Expression of the proto-oncogenes apparently preceded the elevation of metallothionein protein because the latter was maximal 18 hr after partial hepatectomy, followed by a decrease until 70 hr. Hepatocytes of the intact rat liver have metallothionein in the cytoplasm only. Interestingly, metallothionein was localized predominantly in the nucleus as early as 6 hr after partial hepatectomy, and the staining intensity of metallothionein became maximal at 15 hr, followed by detection in both the cytoplasm and nucleus at 24 hr or longer. The use of a confocal laser scanning microscope with both tissue sections and isolated nuclei has clearly shown that metallothionein immunofluorescence exists inside hepatocyte nuclei after partial hepatectomy. Expression of the proto-oncogenes c-fos and c-jun is elevated after partial hepatectomy, and the resultant heterodimer of gene products may contribute to the observed metallothionein gene induction. However, the observation that metallothionein protein levels were elevated until 18 hr after partial hepatectomy suggests that an alternative pathway for the induction of metallothionein gene expression may also be present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Rest and stress myocardial perfusion imaging on the same day with two injections of 99mTc-tetrofosmin].

99mTc-tetrofosmin myocardial perfusion imagings under different protocols were performed at rest and stress on the same day. In the stress/rest protocol, the exercise study was carried out first, and then the rest one followed. Eight patients were involved in the stress/rest protocol. Seven patients were examined in the reverse, rest/stress protocol. In any protocols, the injection interval was 3 hours, and injection doses in the first and second studies were 370 MBq and 740 MBq, respectively. Myocardial counts were obtained by placing region of interest over the myocardial walls in short axial SPECT images. Based on myocardial counts from the first injection and the wash-out rate of tetrofosmin, we calculated, at the second imaging, counts caused from the first injection. Approximately 20-25% of counts in the second study were found to be caused from the residual radiotracer. The residual radiotracers affected the interpretation of imagings of two patients we examined: one with marked reversible ischemia examined in the stress/rest protocol and the other with mild ischemic change examined in the rest/stress one. Our results suggested that some modifications of studies, such as the increase in the injection intervals or the reduce of the first-to-second dose ratio, might be necessary to conduct the same day protocols.

Exercise Test↗

[A case of bronchial artery aneurysm communicating with pulmonary artery].

A 48-year-old man was admitted to our hospital because of an abnormal shadow on the chest rentogenogram detected by the regular health screening. A tumorous shadow about 10 mm in diameter existed in the right lower lobe on chest X-ray film. It was suggested that the tumor was receiving blood flow from the aortic system by IVDSA and dynamic CT, right bronchial angiogram demonstrated a dilatation and aneurysm formation associated with anastomosis of the pulmonary artery. Aneurysmectomy and right bronchial arterial ligation were performed, and no other complication was observed. Bronchial artery aneurysm is a rare disease, and 25 cases have been previously reported in the literature in Japan.

Aneurysm↗

Induction chemoradiotherapy followed by surgery for stage III non-small cell lung cancer.

Twenty-five patients with stage III, non-small cell lung cancer were treated with cisplatin-based chemotherapy and thoracic radiation therapy followed by surgery. Thirteen patients had stage IIIA disease and 12, stage IIIB disease. The chemotherapy and radiotherapy were intensively combined with only a few days' interval between them. Radiation therapy delivering a total dose of 50-70 Gy was started 10 days after the beginning of chemotherapy. A few additional courses of chemotherapy were repeated until a thoracotomy was performed. All but two surgically-treated patients underwent tumor resection, with 19 lobectomies and four pneumonectomies. Eighteen patients underwent curative and five, non-curative resections. Pathological examination of the resected specimen provided accurate intrathoracic information. Six patients (24%) showed a pathologically complete response, with no cancer cells detected in the resected specimens. Severe postoperative complications occurred in five patients (20%), with one death. The disease recurred in five of the 18 patients who underwent a curative resection. A second primary tumor developed in two other patients. Seventeen patients (68%) are alive, with a median follow-up of 37 months after thoracotomy. The estimated three-year survival was 67% for all patients.

Adult↗

[Etoposide/cis-platinum (CDDP) combined chemotherapy for ovarian cancer: evaluation of optimum schedule for CDDP administration in chronic continuous exposure of ovarian cancer cells to low-dose etoposide in vitro].

Combined chemotherapy with etoposide and cis-platinum (CDDP) is considered a second line regimen for refractory cases of ovarian cancer. In addition to the time-dependent cytocidal kinetic of etoposide, much attention has been paid to low-dose continuous administration of etoposide. In this study, ovarian cancer cells (SHIN-3) were continuously exposed to low-dose etoposide in vitro to determine the optimum schedule for CDDP administration. Etoposide concentrations of 1-3 micrograms/ml were used; per os administration of etoposide at 25 mg x 2/day has been shown to produce a continuous plasma concentration of etoposide of around 1 microgram/ml. The results were as follows: 1) The IC50 of CDDP after 72 hours of exposure was 8.0 micrograms/ml and that of etoposide after 114 hours was 3.0 micrograms/ml. 2) After 100 hours of exposure to 1 microgram/ml of etoposide, cell cyclic phase analysis showed cells predominantly in G2/M phase arrest. 3) After 24-hour administration of CDDP, it was more than 24 hours before a cytocidal effect was observed. 4) During continuous exposure of SHIN-3 to etoposide (1 microgram/ml) for 6 days, CDDP was added on the 1st, 3rd, and 5th days. The largest ratio of growth inhibition with combined treatment to that with CDDP alone was attained on the 5th day. We conclude that, in combination regimens using low-dose continuous etoposide, CDDP should be added after etoposide administration is begun.

Administration, Oral↗

[A new operational method of functional neurosurgery combining micro-recording and MRI stereotaxy for the treatment of Parkinson's disease].

We have developed a new operational method for stereotactic functional neurosurgery using MRI stereotaxy combined with microelectrode recording. MRI stereotaxy shows us the individual variations of thalamic configurations. The tentative target points were determined using the MRI stereotaxy assisted software system which revised the distortion of MRI images. Consequently, the accuracy and safety of the microelectrode recording were increased. This, in turn, increased the accuracy of stereotactic thalamotomy while producing encouraging operational outcomes. The effectiveness of stereotactic thalamotomy for Parkinson's disease was confirmed by these excellent operative results. The symptoms improved and the dosage of medications, including L-DOPA, decreased. Furthermore, our results indicate that the distributing area of deep sensory neurons in the thalamus extended more posteriorly and upward than previously expected. Therefore, the functional and anatomical similarity between the human and monkey thalamus was reaffirmed. In this report, based on the above data, we reevaluated the neural mechanism of tremor and the role of stereotactic functional neurosurgery for Parkinson's disease.

Aged↗

[Twenty one multicentral studies on prognosis of advanced ovarian cancer; focused on correlation between primary surgical procedure following adjuvant chemotherapies and 4 year survival rates].

The treatment outcome of 778 patients with stage III ovarian cancer treated by surgery and chemotherapy between 1976 and 1990 in 21 institutions was analyzed retrospectively. Survival of patients treated between 1985 and 1990 was significantly superior to that before 1985 (Kaplan-Meier, p < 0.01). Four year survival rates were found to be distributed from 5 to 52% among institutions (p < 0.001, log-rank test). When survival rates were compared according to the relative dose intensity (RDI) of CDDP administered, patients who were given CDDP RDI > or = 0.9 had a favorable prognosis. The twenty-one institutions were divided into two groups: Standard (total abdominal hysterectomy and bilateral salpingo-oophorectomy) vs. standard+debulking (of as much gross tumor as can safely be performed) according to the operative procedure which was performed in each hospital. It was found that the four-year survival rate for patients treated in hospitals where standard surgery was done was 22.9 +/- 12.2%, whereas that in hospitals adopting standard+debulking surgery was 34.4 +/- 10.1% (p = 0.03, t-test). When the hospitals were divided into 4 groups according to combination of the operative procedure and CDDP RDI, the four year survival rates were 17.5 +/- 8.3% for standard+debulking+CDDP RDI < 0.9, 39.0 +/- 1.4% for standard+CDDP RDI > or = 0.9, 28.8 +/- 11.5% for standard+debulking+CDDP RDI < 0.9 and 37.8 +/- 8.0% for standard+debulking+CDDP RDI > or = 0.9.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Prediction of ovulation by urinary LH surge].

To investigate the usefulness of a semi-quantitative assay of urinary luteinizing hormone (LH) for predicting ovulation, the relationship among urinary LH, serum LH, serum estradiol (E2) and ultrasonographic observations of follicles were examined in 32 infertile women (35 cycles) at spontaneous (7), clomiphene (13) or cyclofenil (3) induced or hMG (12) induced cycles. Their urine samples were collected 3 times a day for LH assay, starting from about the 10th cycle day or when follicles having a diameter of 10mm or more were detected to the day of ultrasonographical confirmation of follicle ruptures. In the morning on these days, blood was taken twice daily for LH and E2 determination at intervals of 30 min. In spontaneous cycles, urinary LH was (P < 0.001) correlated to a significant extent with the serum LH and E2 levels, and follicle rupture was observed 1.9 days after the urine LH surge. In contrast, there was no significant correlation between the urine LH and serum LH or E2 levels in the ovulation induced cycles. In addition, the period from urine LH positive to follicle rupture was significantly (P < 0.05) prolonged in those cycles compared with that in spontaneous cycles. These results suggested that the urine LH determination was good for predicting ovulation in spontaneous cycles, but it was also necessary to monitor the follicle sizes by ultrasonography in ovulation induced cycles.

Adult↗

Cell surface accessibility of GLUT4 glucose transporters in insulin-stimulated rat adipose cells. Modulation by isoprenaline and adenosine.

Insulin-stimulated glucose transport activity in rat adipocytes is inhibited by isoprenaline and enhanced by adenosine. Both of these effects occur without corresponding changes in the subcellular distribution of the GLUT4 glucose transporter isoform. In this paper, we have utilized the impermeant, exofacial bis-mannose glucose transporter-specific photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propylamine (ATB-BMPA) [Clark & Holman (1990) Biochem. J. 269, 615-622], to examine the cell surface accessibility of GLUT4 glucose transporters under these conditions. Compared with cells treated with insulin alone, adenosine in the presence of insulin increased the accessibility of GLUT4 to the extracellular photolabel by approximately 25%, consistent with its enhancement of insulin-stimulated glucose transport activity; the plasma membrane concentration of GLUT4 as assessed by Western blotting was unchanged. Conversely, isoprenaline, in the absence of adenosine, promoted a time-dependent (t1/2 approximately 2 min) decrease in the accessibility of insulin-stimulated cell surface GLUT4 of > 50%, which directly correlated with the observed inhibition of transport activity; the plasma membrane concentration of GLUT4 decreased by 0-15%. Photolabelling the corresponding plasma membranes revealed that these alterations in the ability of the photolabel to bind to GLUT4 are transient, as the levels of both photolabel incorporation and plasma membrane glucose transport activity were consistent with the observed GLUT4 concentration. These data suggest that insulin-stimulated GLUT4 glucose transporters can exist in two distinct states within the adipocyte plasma membrane, one which is functional and accessible to extracellular substrate, and one which is non-functional and unable to bind extracellular substrate. These effects are only observed in the intact adipocyte and are not retained in plasma membranes isolated from these cells when analysed for their ability to transport glucose or bind photolabel.

Adenosine↗

(R)-(-)- and (S)-(+)-adenallene: synthesis, absolute configuration, enantioselectivity of antiretroviral effect, and enzymic deamination.

Synthesis of optically pure (-)- and (+)-adenallene 2 and 3 is described. Racemic adenallene (1a) was subjected to deamination with adenosine deaminase monitored by HPLC using a Chiralcel CA-1 column to give (-)-adenallene (2) and (+)-hypoxallene (4). The latter compound was converted to acetate 5. The reaction of 5 with trifluoromethanesulfonic anhydride and pyridine followed by ammonolysis furnished acetate 6 or (+)-adenallene (3) depending on the solvent used in the last step. Acetate 5 was smoothly transformed to the 6-chloro derivative 7, but an attempted ammonolysis led only to racemization and decomposition. Single crystal X-ray diffraction established the R-configuration of (-)-enantiomer 2. The latter forms a pseudosymmetric dimer in the lattice with the adenine moiety in an anti-like conformation. The torsional angles of the allenic bonds show departures from 90 degrees (91 and 97 degrees, respectively) and rotameric preference of the hydroxymethyl groups is different in both molecules of the dimer. The R-enantiomer 2 inhibited the replication and cytopathic effect of human immunodeficiency virus (HIV-1) in ATH8 cell culture with an IC50 of 5.8 microM, whereas the S-enantiomer 3 was less active (IC50 > 200 microM). The enantioselectivity of the anti-HIV effect is significantly lower than that of 2',3'-dideoxyadenosine. Kinetics of deamination of R- and S-enantiomers 2 and 3 catalyzed by adenosine deaminase gave the following parameters: Km values of S-form 3 and R-form 2 were 0.41 and 0.52 mM with Vmax being 530 and 18.5 mumol/min, respectively [corrected]. Again,, a much lower level of enantioselectivity of deamination was observed than that of D- and L-adenosine. These results indicate (i) different enantioselectivity of enantiomers 2 and 3 as HIV inhibitors and adenosine deaminase substrates and (ii) both R- and S-enantiomers 2 and 3 can function as nucleoside analogues with varied enantioselectivity for different enzymes or receptors.

Adenine↗

Effect of thiamin on cordycepin sensitivity in Saccharomyces cerevisiae.

The sensitivity of Saccharomyces cerevisiae to the antibiotic cordycepin (3'-deoxyadenosine) was found to be decreased by the addition of thiamin to the growth medium. A thiamin transport mutant of S. cerevisiae was also found to be resistant to the growth inhibitory effect of cordycepin. Not only the thiamin uptake but also adenosine uptake by this mutant cell was markedly reduced compared to those by the parent yeast cells. This strongly suggested that cordycepin, an analog of adenosine, is virtually taken up by the thiamin transport system of growing yeast cells; thus the drug sensitivity is decreased by the presence of thiamin in the growth medium.

Adenosine↗