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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 253 records · Page 14Linked to original sources
PubMed1997

Temporal variation in the effects of ophthalmic timolol on cardiovascular and respiratory functions in healthy men.

This study examined the effects of ophthalmic timolol and time of administration on cardiovascular and respiratory functions in healthy young male volunteers. Eight participants (mean age +/- standard deviation, 22 +/- 0.9 years) received either 50 microL of 0.5% timolol or placebo in the lower conjunctival sacs of both eyes in the morning or evening. Intraocular pressure, blood pressure, heart rate, and respiratory functions, including percent forced expiratory volume in 1 second and peak expiratory flow rate, were then measured for 3 hours after drug administration. Timolol reduced intraocular pressure and cardiovascular function at both administration times. However, a timolol-induced reduction in respiratory function was observed only in the evening: percent forced expiratory volume in 1 second, peak expiratory flow rate, and expiratory flow rate at 75% vital capacity were reduced by 3%, 7%, and 12%, respectively, 3 hours after administration. These results indicate that ophthalmic timolol reduces cardiovascular and respiratory functions in healthy young male subjects and that bronchial sensitivity to timolol differs between morning and evening.

Adrenergic beta-Antagonists↗
PubMed1997

Cyclin-dependent kinase 5 in Lewy body-like inclusions in anterior horn cells of a patient with sporadic amyotrophic lateral sclerosis.

Lewy body-like inclusion (LI) is a cytoplasmic inclusion body deposited in anterior horn cells of patients with amyotrophic lateral sclerosis (ALS), in which there are phosphorylated neurofilament proteins (NFP). Since phosphorylation of NFP occurs normally in the axon, aberrant phosphorylation of NFP should take place in these cell bodies. To clarify the mechanism of LI formation it is crucial to identify the kinase responsible for the phosphorylation. We found cyclin-dependent kinase 5 (cdk5) immunoreactivity in most of LI in an ALS patient. Since cdk5 phosphorylates NFP, cdk5 is a candidate kinase for NFP in LI and might be involved in the cytoskeletal disorganization in LI-containing neurons.

Adult↗
PubMed1997

Potentiation of pirarubicin activity in multidrug resistant cells by rifampicin.

The effect of the anti-tuberculosis drug rifampicin on pirarubicin activity was investigated in multidrug-resistant cells overexpressing P-glycoprotein. Rifampicin increased the sensitivity of pirarubicin to anthracycline-resistant mouse leukemic P388 cells and significantly enhanced the cytotoxicity and intracellular accumulation of pirarubicin in resistant cells, but had no effect in parent cells. By contrast, two other rifamycins, rifamycin B and SV, had no effect on pirarubicin accumulation in resistant cells. Rifampicin also enhanced pirarubicin-induced apoptosis and G2/M blockade on the cell cycle in resistant cells. These results show that rifampicin enhances the cytotoxic action of pirarubicin in resistant cells, at least partly via the inhibition of cellular pirarubicin efflux.

Animals↗
PubMed1997

A case of arrhythmogenic right ventricular dysplasia with left and right ventricular hypofunction in an elderly subject--long-term follow-up.

A 72-year-old man was admitted with palpitations caused by sustained ventricular tachycardia. He had been followed for 27 years, with admissions on 7 occasions, on account of ventricular tachycardias, atrial fibrillation, and congestive heart failure. Electrophysiologic examination detected 2 points of origin of ventricular tachycardia in the right and left ventricles. During the examination a myocardial infarction led to death. At autopsy, most areas of the right ventricle and the left ventricular apex were found to have been replaced by fatty tissue, pointing to severe fatty infiltration into the myocardium. Thus, this patient represented a unique cause of arrhythmogenic right ventricular dysplasia (ARVD) with severe fatty degeneration causing progression of ARVD. It is important that a diagnosis of ARVD is made carefully and rigorously in elderly subjects.

Aged↗
PubMed1997

Chronotoxicity of methotrexate in mice and its relation to circadian rhythm of DNA synthesis and pharmacokinetics.

The mechanisms underlying the circadian rhythm of methotrexate (MTX)-induced toxicity (body weight loss and leukopenia) were investigated from the viewpoints of the sensitivity of living organisms to the drug and the pharmacokinetics of the drug. ICR male mice were housed in a standardized light-dark cycle (lights on at 0700, off at 1900) with food and water ad libitum. The body weight loss after an intraperitoneal injection of MTX (400 mg/kg) was more serious in the late dark period and the early light period and milder in the late light period and the early dark period. The MTX-induced leukopenia was more serious in the late dark period and the light period and milder in the early dark period. Lower toxicity was observed when DNA synthesis, dihydrofolate reductase (DHFR) activity in bone marrow cells and folate level in plasma decreased, and higher toxicity was observed when they increased. There was a significant circadian rhythm in plasma MTX concentration, with a higher level in the light period and a lower level in the dark period. The circadian rhythm of plasma MTX concentration was associated with that of MTX-induced toxicity. The present study suggests that the circadian rhythm of MTX-induced toxicity is caused by that of the sensitivity of living organisms to the drug and the pharmacokinetics of the drug.

Animals↗
PubMed1997

Potentiating effects of calcium chelators on basal and stimulated aldosterone production by bovine adrenal glomerulosa cells in vitro.

We previously reported the potentiation of basal aldosterone production by the addition of the calcium chelator ethyleneglycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to an extracellular solution of bovine adrenal glomerulosa cells in vitro. To assess whether the addition of the calcium chelators ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and EGTA can potentiate basal and stimulated aldosterone production, we compared the effect of EDTA with that of EGTA on basal and the agonist (potassium; 8 mM, angiotensin II; 10 nM, ACTH; 10 nM)-stimulated aldosterone production by the cells in vitro. These two chelators lowered the extracellular ionized calcium ([Ca2+]o) concentration in a similar manner. The levels of basal and the agonist-stimulated aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) were significantly (P < 0.01 or less) increased when compared with those in the absence of EDTA and EGTA, respectively. These results show that the addition of EDTA and EGTA to an extracellular solution potentiates basal and the agonist-stimulated aldosterone production in vitro. Although an increase in basal aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) was completely inhibited by the voltage-dependent calcium channel antagonist nifedipine (1 microM) or the calmodulin antagonist pimozide (1 microM), the potentiation of the agonist-stimulated aldosterone production does not seem to be induced by CA2+/calmodulin-dependent nor cAMP-dependent systems. These findings suggest that calcium chelators such as EDTA and EGTA may possess activating effect on basal and stimulated aldosterone production in bovine adrenal glomerulosa cells.

Aldosterone↗
PubMed1997

Detection of subependymal veins using high-resolution magnetic resonance venography.

High-resolution magnetic resonance venography (HR-MRV) of intracranial subependymal veins using a two-dimensional Fourier-transform time-of-flight technique was performed on normal volunteers and clinical cases of cerebral disease. For the pulse sequence, fast-field-echo sequence was used with the following parameters: TR/TE/flip angle = 34 ms/12 ms/50 deg., 256 x 256 matrix, 1 mm effective slice thickness, 150 mm field of view, and one signal acquisition. Sequential vertical coronal sections were taken against the skull base. The anterior septal vein, the medial atrial vein, the anterior caudate vein and thalamostriate vein were detected in all subjects. In all clinical cases, HR-MRV was equal in diagnostic capability to conventional cerebral angiography.

Adult↗
PubMed1997

Use of fluid-attenuated inversion recovery (FLAIR) pulse sequences for differential diagnosis of hepatic hemangiomas and hepatic cysts.

Fluid-attenuated inversion recovery (FLAIR) imaging of hepatic hemangiomas (10 patients, 16 lesions) and hepatic cysts (8 patients, 10 lesions) was performed. All hemangiomas were hypointense on T1-weighted images and hyperintense on T2-weighted images. With Gd-DTPA (0.1 mmol/kg), all hemangiomas were enhanced but not all cysts. It was necessary to perform contrast enhanced imaging to differentiate hepatic hemangiomas from hepatic cysts. However, on FLAIR imaging, hepatic hemangiomas were strongly hyperintense and 9 of the 10 hepatic cysts were isointense. One of the hepatic cysts was slightly hyperintense. FLAIR images were useful in differential diagnosis of hepatic hemangiomas and hepatic cysts without using Gd-DTPA.

Cysts↗
PubMed1997

Evoked potentials in patients with chronic respiratory insufficiency.

P300, somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) are widely used neurophysiological methods for objectively evaluating cognitive, somatosensory and brainstem auditory functions. We studied the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency (PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2: 84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13 and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP were compared between the patients and controls. The P300 latency, N9-N13 and N13-N20 IPLs in SEP in the patients were significantly prolonged compared to the controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency and I-V IPL in BAEP were not significantly different between the patients and controls. These results suggest that chronic respiratory insufficiency influences the cognitive and somatosensory functions, and indicate that there is a selective vulnerability of evoked potentials to this condition.

Aged↗
PubMed1997

Rapidly progressive glomerulonephritis concomitant with diabetic nephropathy.

We describe a rare case of a rapidly progressive glomerulonephritis (RPGN) superimposed on diabetic nephropathy. A 68-year-old woman with non-insulin-dependent diabetes mellitus (NIDDM) complicated with diabetic triopathy demonstrated a rapid deterioration of renal function. Her urinary sediment contained many red blood cell (RBC) cells and casts, suggesting an additional renal disease accompanying diabetic nephropathy. Renal biopsy revealed crescent formation in many glomeruli characteristic of the pauci-immune type of RPGN. Steroid pulse therapy transiently halted the deterioration in renal function, but the patient died of pneumonia complicated with methicillin-resistant staphylococcus aureus (MRSA) infection. The unusual findings in diabetic nephropathy indicated the coexistence of primary glomerulonephritis and diabetic glomerulosclerosis in this case.

Aged↗
PubMed1997

Magnetic resonance imaging and angiographic appearance of meningioma of the fourth ventricle--two case reports.

A 47-year-old female presented with a transitional type meningioma entirely confined to the fourth ventricle. The tumor was totally resected. A 67-year-old female had undergone resection of an intraventricular transitional type meningioma of the fourth ventricle 9 years previously. She presented with a new meningioma of an obviously different origin at the posterior rim of the foramen magnum. The new meningioma was totally resected and the histological diagnosis was atypical meningioma. The magnetic resonance (MR) imaging characteristics of these two intraventricular meningiomas of the fourth ventricle were isointense and slightly hypointense to gray matter on the T1-weighted images, and hyperintense to gray matter on the T2-weighted images, with intense and homogeneous enhancement with gadolinium. Angiography showed the two intraventricular meningiomas fed by branches of the posterior inferior cerebellar arteries or superior cerebellar arteries. The second meningioma with dural attachment was fed by the right occipital artery. Intraventricular meningiomas of the fourth ventricle are not supplied by meningeal branches from vertebral and external cerebral arteries. MR imaging is the most useful tool in preoperative diagnosis, but cerebral angiography should also be performed to confirm the feeding vessels and the correct diagnosis.

Aged↗
PubMed1997

Effects of isolation housing and timing of drug administration on amikacin kinetics in mice.

AIM: To study the influences of social condition and drug administration time on amikacin metabolism in mice. METHODS: Forty Male ICR mice were randomly assigned into 4 groups according to 1) housing condition: individual housing (I, one mouse in a cage) or aggregated housing (A, 10 mice in a cage) and 2) drug administration time: at midday (D) or at midnight (N), i.e. I-D, I-N, A-D, and A-N groups. Amikacin was injected s.c. 15 mg.kg-1 after 4 wk of raising at D or N. Blood samples were taken at 5, 10, 15, 20, 30, and 60 min after medication in each mouse. Plasma amikacin was measured by enzyme immunoassay. The concentration-time data were fitted with one-compartment open model in each mouse and data were analyzed with group t test. RESULTS: The clearance (Cl) of amikacin was larger and the half-life (T1/2) was shorter in A-N group than in A-D or I-N groups respectively. AUC(0-1) in A-N group was less than in I-N group. No differences of kinetic parameters between 2 isolated housing (I-D and I-N) groups were found. CONCLUSION: Aggregated housing and midnight drug administration increased the disposition of amikacin.

Amikacin↗
PubMed1997

[A case of colon cancer with local recurrence successfully treated by systemic and local intra-arterial chemotherapy using a combination of 5-fluorouracil, interferon-alpha 2A, leucovorin and carboplatin].

A 59-year-old man with colon cancer was diagnosed as having a local recurrence of the disease, forming a huge intra pelvic tumor, accompanied by pulmonary metastasis 16 months after hemicolectomy. He received alternate systemic and local chemotherapy consisting respectively of a 5-day course of continuous infusion of 5-FU 600 mg/m2/day, bolus injection of leucovorin (LV) 20 mg/m2/day, intramuscular injection of interferon (IFN)-alpha 2a 6 x 10(6) IU/day, and intra-arterial administration of 5-FU, LV and carboplatin using reservoir catheter through pudendal artery, each repeated every 3 weeks. After 6 systemic and 8 local treatments, metastatic lesions disappeared and the intra-pelvic tumor shrunk by 62%, indicating a partial response. The patient then underwent dissection of the intra-pelvic tumor. Pathological examination indicated a curative resection. Alternate systemic and local intra arterial chemotherapy using a combination of 5-FU, LV, IFN and and carboplatin is highly promising for metastatic colorectal cancer with local recurrence.

Adenocarcinoma↗
PubMed1997

[Cell signaling and CDDP resistance].

Although evidence exists that intracellular signaling through oncogene products may play a role in the resistance of anticancer drugs, the underlying mechanism remains to be clarified. Using a HAG-1 cell line as a human epithelial model, we have studied the alteration of drug sensitivity and determined the mechanism of resistance induced in HAG-1 cells transfected with various oncogenes, which are highly expressed and activated in human cancers. Non-tumorigenic HAG-1 cells acquired fully neoplastic phenotype and resistance to Cisplatin (CDDP) by transfection with v-src but not by activated ras oncogene. The src-transfected cells showed a significant decrease in the formation of CDDP-induced DNA interstrand cross-links with rapid removal of these lesions. Upon treatment with src kinase inhibitors, the level of CDDP resistance and the rate of removal were both reduced in src-transformed cells. These results suggest the ability of v-src oncogene product but not ras to induce CDDP resistance by modulating the certain DNA repair pathway. Thus, intracellular signaling may be the appropriate target for strategies to reverse the drug resistance. In this review, we discuss the role of oncogenes important for signal transduction such as ras and those with protein tyrosine kinase activity in the drug resistance.

3T3 Cells↗
PubMed1997

Molecular and genetic analysis of two patients with Bernard-Soulier syndrome--identification of new mutations in glycoprotein Ib alpha gene.

We investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by performing molecular and genetic analysis. A flow cytometric and immunoblotting analysis showed GP Ib alpha to be absent from the platelet membrane of both patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the platelets, but in decreased amounts. Therefore, GP Ib alpha gene from both cases was sequenced after PCR amplification and subcloning. We identified a homozygous mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to 975 in GP Ib alpha gene from Case 1. In Case 2, compound heterozygosity was demonstrated in GP Ib alpha gene; an insertion of a single base (T) at cDNA number 1,418 in one allele, and a deletion of a single base (A) within the 7-adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new mutations in both patients appeared to cause a frameshift, which created a new termination codon shortly thereafter, and thus lead to a GP Ib alpha deficiency on the platelet membrane. Truncated mutant proteins could be detected in the plasma and platelets of Case 2, but not of Case 1. According to these findings, it is thus supposed that the properties and conformation of additional COOH-terminal peptides, which were supposedly synthesized as results of the mutations, may have an important role on the processing of mutant GP Ib alpha in megakaryocytes and platelets.

Adult↗
PubMed1997

Inhibition by 5-fluorouracil of ERCC1 and gamma-glutamylcysteine synthetase messenger RNA expression in a cisplatin-resistant HST-1 human squamous carcinoma cell line.

Pretreatment of 5-fluorouracil (5-FU), but not posttreatment, has been shown to augment the cytotoxicity of cisplatin (CDDP) or even circumvent CDDP resistance by inhibiting repair of platinum-DNA interstrand crosslinks as well as by reducing the cellular glutathione (GSH) contents in CDDP-resistant HST-1/CP0.2 human squamous carcinoma cells. Because exogenous thymidine, which compensates for 5-FU-mediated inhibition of de novo DNA synthesis via salvage pathway, did not affect this schedule-dependent synergism, the modulatory effect of 5-FU on CDDP resistance would be attributed to the 5-FU-induced RNA damage. We therefore examined the effect of 5-FU on the steady-state levels of messenger RNA (mRNA) of a human excision repair gene ERCC1 and gamma-glutamylcysteine synthetase (gamma-GCS) gene coding for a rate-limiting enzyme for GSH synthesis. The HST-1/ CP0.2 cells were found to have significantly more mRNA expression of these respective genes than do parental HST-1 cells. In these cells, 5-FU pretreatment progressively inhibited mRNA expression of both ERCC1 and gamma-GCS after removal of 5-FU, without affecting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. A maximal mRNA suppression was observed at 48 h posttreatment. Such 5-FU-induced suppression of mRNA transcripts of these genes seems to be consistent with its inhibitory activity on DNA repair capacity and cellular GSH contents. In contrast, 5-FU did not reduce the level of glutathione-S-transferase-pi (GST-pi) or DNA topoisomerase 1 mRNA. Although not convinced, our data suggest that 5-FU, when incorporated into RNA, may inhibit both GSH synthesis and repair of platinum-DNA adducts by downregulating the ERCC1 and gamma-GCS genes, thereby enhancing antitumor activity of CDDP and reversing resistance to CDDP in HST-1/CP0.2 cells.

Antimetabolites, Antineoplastic↗
PubMed1997

Acetazolamide challenge and technetium-99m-ECD versus iodine-123-IMP SPECT in chronic occlusive cerebrovascular disease.

UNLABELLED: We compared the acetazolamide challenge test using 99mTc-ECD SPECT and 123I-IMP SPECT images in patients with chronic occlusive cerebrovascular disease. We also evaluated the usefulness of linearization correction for acetazolamide challenge test of 99mTc-ECD SPECT. METHODS: Twenty patients with unilateral chronic occlusive cerebrovascular disease (10 patients had middle cerebral arterial lesion and 10 had internal carotid lesion) were included in the study. Split-dose (a dose fractioning was 1:2), and sequential SPECT technique was used for 99mTc-ECD SPECT studies while only acetazolamide challenge test studies for 123I-IMP SPECT were performed. Permeability surface area product model (PS model) and back-diffusion model (Lassen's correction) were used for linearization correction of acetazolamide challenge with 99mTc-ECD SPECT. RESULTS: Six of 16 patients with reduced vasodilatory capacity in 123I-IMP SPECT were underestimated by 99mTc-ECD SPECT acetazolamide challenge test. Relative ECD uptake normalized by cerebellar uptake compared with IMP uptake showed a nonlinear relationship, indicating relatively less uptake in high flow range. The underestimations of limited vasodilatory capacity observed in 99mTc-ECD SPECT without linearization correction was modified by linearization algorithm. However, the effect of correction based on PS model was superior than that of Lassen's correction. The corrected 99mTc-ECD uptake ratio, based on PS model, and IMP uptake ratio demonstrated a better linear relationship than that of Lassen's correction. CONCLUSION: Technetium-99m ECD SPECT corrected based on the PS model is a better method of linearization for evaluating cerebrovascular reserve using acetazolamide challenge.

Acetazolamide↗