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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 19 recordsLinked to original sources
PubMed1992

Determination of gliclazide in serum by high-performance liquid chromatography using solid-phase extraction.

A simple and sensitive high-performance liquid chromatographic method for a routine assay of gliclazide in serum is described. Serum samples spiked with glibenclamide (internal standard) were applied to Bond Elut C18 cartridges. After washing with phosphate buffer (pH 7.5) and water, the cartridge was eluted with 60% methanol. The eluate was evaporated to dryness. The residue was dissolved in methanol and injected onto an octadecyl silica column (5 microns, 150 mm x 4.6 mm I.D.). The mobile phase was 0.04 M potassium dihydrogenphosphate (pH 4.6)-acetonitrile-isopropyl alcohol (5:4:1, v/v). Ultraviolet detection at 227 nm was used. The minimum detectable level of gliclazide was 20 ng/ml.

Chromatography, High Pressure Liquid↗
PubMed1992

Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross-link removal in a HST-1 human squamous carcinoma cell line.

To elucidate the mechanism of the synergistic cytotoxicity of 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum(II) (CDDP), we studied the interaction of these agents using a human squamous carcinoma cell line (HST-1). Exposure to 5-FU for 24 h and to CDDP for 1 h produced a 50% inhibitory concentration of 1.0 micrograms/ml (7.7 microM) and 2.5 micrograms/ml (8.3 microM), respectively. The cytotoxic action of CDDP was augmented, and a greater than additive effect was observed when the cells were exposed to 5-FU (1.0 micrograms/ml; 7.7 microM) for 24 h before the CDDP treatment. This synergistic activity was maximal when the interval between 5-FU and CDDP exceeded 24 h. In contrast, the cytotoxicity of CDDP was attenuated when it preceded the exposure to 5-FU. Thymidine did not alter the 5-FU-CDDP interaction. Evaluation of the kinetics of the removal of DNA interstrand cross-links, measured by alkaline elution, showed a significant reduction of this removal in the cells exposed to 5-FU followed by CDDP with a drug-free interval of 48 h, as compared with cells exposed to CDDP alone, or to 5-FU immediately followed by CDDP, although no differences were found in the formation of DNA interstrand cross-links by CDDP among these cells. No significant differences in the accumulation of intracellular platinum were detected by atomic absorption spectrophotometry. These findings suggest that 5-FU modulates the repair of platinum-DNA adducts, thereby potentiating the antitumor activity of CDDP.

Carcinoma, Squamous Cell↗
PubMed1992

Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for human T cell leukemia virus type 1.

We have generated a number of EBV-transformed B cell lines producing human mAb against human T cell leukemia virus type 1 (HTLV-1) from the peripheral blood B lymphocytes obtained from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. Various synthetic peptides corresponding to antigenic regions of HTLV-1 gag and env proteins were used for the screening of antibodies in ELISA. In our study, four IgG mAb to the gag p19 amino acids 100 to 130, and 5 IgG mAb to the env p46 amino acids 175 to 199 were characterized. An immunofluorescence assay showed that all of these mAb specifically bound to the surface of HTLV-1-bearing cell lines. Among these mAb, one anti-gp46 mAb, designated KE36-11, neutralized the infectivity of HTLV-1 as determined by both the inhibition of HTLV-1-induced syncytium formation and transformation assays in vitro. An antibody-binding assay using overlapping oligopeptides revealed that KE36-11 recognized a new epitope locating between the gp46 amino acid sequence 187-193 (Ala-Pro-Pro-Leu-Leu-Pro-His). Another anti-gp46 mAb, designated KE36-7, showed antibody-dependent cellular cytotoxicity against HTLV-1-bearing cell line. KE36-7 bound strongly to the 10-mer peptide-gp46 187-196, and weakly to peptides containing the gp46 amino acid sequence 191-196 (Leu-Pro-His-Ser-Asn-Leu). These two epitopes, which are associated with HTLV-1 neutralization and antibody-dependent cellular cytotoxicity, are thus the first epitopes identified in human HTLV-1 infection. It is possible that passive immunization of humans with these two human mAb are effective on the protection of HTLV-1 infection in vivo.

Amino Acid Sequence↗
PubMed1992

Influence of food on the absorption of beta-methyldigoxin.

Nine healthy subjects received 0.2 mg of beta-methyldigoxin (beta-MD) orally in the fasting state, 30 minutes after and before a standard breakfast. The time-to-peak serum glycoside concentration was delayed and the peak concentration was lower in the postprandial state compared with the other regimens (P less than .01). The absorption rate constant was significantly reduced when beta-MD was given after a meal (1.55 +/- 1.75 hr-1) than before a meal (5.54 +/- 2.16 hr-1) and in the fasting state (5.22 +/- 3.06 hr-1)(P less than .01). Although the area under the serum glycoside concentration-time curve and the cumulative urinary excretion (CUE) of beta-MD, digoxin, and total drug (beta-MD plus digoxin) was not significantly different between three regimens, the CUE infinity tended to be smaller in the postprandial state compared with before a meal. The results indicate that the timing of drug administration in relation to a meal is an important factor leading to the fluctuations of serum glycoside concentration after oral beta-MD, which might be of some clinical importance.

Adult↗
PubMed1992

Circadian changes of valproate kinetics depending on meal condition in humans.

The objective of this study was to examine the effect of meal condition on circadian changes in valproic acid (VPA) kinetics. Two experiments were performed in 16 healthy men that were synchronized with diurnal activity and nocturnal rest as their routine life. In both experiments, four 200-mg tablets of VPA were given orally on two occasions in the morning (8:30 AM) or in the evening (8:30 PM). In each study, a randomized, single-dose, two-way crossover design was used, and 2 weeks elapsed between morning and evening trials. In experiment 1, eight subjects took a light meal as breakfast between 8:00 and 8:15 AM and a heavy meal as dinner between 6:00 and 6:30 PM to fit the subject's usual food amount. The mean peak plasma concentration (Cmax) was significantly higher (P less than .01), the time to peak concentration (tmax) was shorter (P less than .05), and the absorption rate (Ka) was larger (P less than .05) after the morning dose than after the evening dose. In experiment 2, the size and contents of meal in breakfast and dinner were prepared in the same manner as the standard breakfast for the subjects. Namely, eight subjects took the same light meal between 8:00 and 8:15 AM in the morning and between 8:00 and 8:15 PM in the evening. There was no significant circadian change in VPA kinetics under this same meal condition. These results suggest that the differences of meal condition between morning and evening in our daily life play a major role in the mechanism underlying the circadian changes of VPA absorption in man.

Absorption↗
PubMed1992

Localization of protein kinase C in human skeletal muscle.

The immunolocalization of protein kinase C (PKC) isozymes alpha, beta I and beta II, was investigated in human skeletal muscle. All three isozymes were present on the muscle fiber surface membrane and within the muscle fibers. The alpha-isozyme was most clearly delineated on the surface membrane of the muscle fiber and on small blood vessels in the connective tissue. The axons of myelinated intramuscular nerves stained intensely for the beta I isozyme, whereas the endoneurial connective tissue reacted more strongly for the alpha- and beta II-isozymes. PKC isozymes may regulate intracellular signal transduction in human skeletal muscle, as in the other tissues, but their exact role in muscle remains unknown.

Adult↗
PubMed1992

In vivo comparative therapeutic study of optimal administration of 5-fluorouracil and cisplatin using a newly established HST-1 human squamous-carcinoma cell line.

The efficacy and toxicity of 5-fluorouracil (5-FU) and cisplatin (CDDP) given in a sequential combination were evaluated in nude mice transplanted with HST-1, a newly established human squamous-carcinoma cell line. 5-FU and CDDP were given i.p. for 5 days and 1 day, respectively, either as single agents or in a sequential manner separated by a 24-h interval. The treatment was repeated every 30 days. Although inhibition of tumor growth was seen in all of the treated groups after two cycles, the sequence of 5-FU followed by CDDP significantly reduced the tumor burdens throughout all three courses and was more effective than the reverse sequence or either drug alone. Neither treatment-related death nor significant hematologic or nephrologic toxicities were seen, even following three cycles of therapy. Significant weight loss was observed only in mice treated with CDDP followed by 5-FU. This sequence dependence of the activity and toxicity of the 5-FU and CDDP combination should thus be incorporated into the design of a clinical trial.

Animals↗
PubMed1992

Treatment of small hepatocellular carcinoma.

Of the 692 patients with hepatocellular carcinoma (HCC) who were admitted to our hospital between 1976 and 1990, 60 (8.8%) had small HCC with a maximal diameter of below 2 cm. The outcome of these 60 cases was analyzed after they had been divided into 4 groups based on the therapeutic method used: operation group (17 cases), percutaneous ethanol injection therapy (PEIT) group (20 cases), transcatheter arterial embolization (TAE) group (13 cases), and oral anticancer drug therapy (per os) group (10 cases). The 1-, 2-, 3-, 4-, and 5-year survival values obtained for the operation group (100%, 87.5%, 87.5%, 87.5%, and 87.5%, respectively) were significantly higher than those found for the per os group (P < 0.01). The best therapeutic results were achieved in the operation group. Although the follow-up period for the PEIT group was short, the 2-year survival of this group was nearly equal to that of the operation group. Whereas the duration of survival tended to increase in inverse proportion to the severity of the underlying liver cirrhosis, the survival values did not differ between solitary and multiple tumors or among the different histological grades of HCC. In this series, 20 patients died; 9 deaths (45.0%) were due to progressive disease and 3 deaths (15.0%) were attributed to hepatic failure. Because the operation group included many patients who displayed relatively good liver function, we cannot rule out the possibility that their excellent outcome may have been associated with this background factor. Therefore, further prospective investigation is necessary to compare the efficacy of various therapies in patient groups with a homogeneous background.

Aged↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded sections.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index.

Antigens, Neoplasm↗
PubMed1992

Cardiac function and myocardial performance of 24-hour-preserved asphyxiated canine hearts.

A method of 24-hour storage of asphyxiated canine hearts for orthotopic cardiac transplantation was studied to expand the geographical size of the donor pool. Left ventricular function of asphyxiated hearts preserved for 24 hours (group 1, n = 8) was compared with that of hearts donated on-site (group 2, n = 5). Group 1 donors were pretreated with verapamil hydrochloride, propranolol hydrochloride, and prostacyclin. The donor hearts were perfused with warm blood cardioplegia in situ after 10 minutes of asphyxiation and then perfused with cold crystalloid cardioplegia for 2 hours. The hearts were excised and stored in ice-cold University of Wisconsin solution for 22 hours. At orthotopic transplantation, coronary perfusion with warm blood cardioplegia was performed before the graft aorta was unclamped. Conventional cardiac variables (eg, cardiac output and maximum rate of rise of left ventricular pressure), myocardial performance, and diastolic compliance of grafted hearts were assessed 1 hour after weaning from bypass. All recipients in both groups were easily weaned from cardiopulmonary bypass without inotropic agents, and there were no significant differences in cardiac variables between the two groups. These results strongly suggest that cadaver hearts can be preserved for 24 hours with satisfactory cardiac function.

Animals↗
PubMed1992

Coronary bypass using arterial grafts in homozygous familial hypercholesterolemia.

A 25-year-old man with homozygous familial hypercholesterolemia who had severe coronary artery disease underwent coronary revascularization by combined arterial grafts using bilateral internal mammary arteries and gastroepiploic artery. Early postoperative coronary angiography showed all the grafts patent without any stenosis. Because no atherosclerotic changes were seen in the specimens of each graft used, combined arterial grafting may have a role in the treatment of coronary artery disease in homozygous familial hypercholesterolemia.

Adult↗
PubMed1992

Transaortic patch angioplasty for left coronary ostial stenosis in a patient with Takayasu's aortitis.

A 35-year-old woman who had left coronary ostial stenosis and aortic valve regurgitation due to Takayasu's aortitis underwent transaortic patch enlargement of the stenosed left coronary ostium in combination with aortic valve replacement. This technique may be suitable and recommendable as an alternative to aortocoronary bypass grafting or endarterectomy for coronary ostial stenosis in Takayasu's aortitis.

Adult↗
PubMed1992

New side-holed sheath for intraaortic balloon pumping to maintain limb perfusion.

We developed a new side-holed shunt sheath for inserting intraaortic balloon pumps to maintain lower limb perfusion in patients with stenotic and tortuous aortoiliac arteries. This sheath has a large internal diameter and several side holes, which act as an internal shunt. It was useful and effective in 11 patients with severe aortoiliac occlusive lesions who required assistance by intraaortic balloon pumping.

Aortic Diseases↗
PubMed1992

Magnetic resonance imaging of a malignant transformation of an intracranial cellular blue nevus. A case report.

As a follow-up to a case previously reported, a rare case of malignant transformation of cellular blue nevus (CBN) in the central nervous system preoperatively diagnosed by magnetic resonance imaging (MRI) is reported. On MRI, the malignant portion of the nevus was slightly hyperintense on both T1- and T2-weighted images. In contrast, the benign portion with a great deal of melanin was hyperintense on T1-weighted image and hypointense on T2-weighted image. MRI was useful and indispensable for detecting the malignant transformation of CBN.

Brain Neoplasms↗
PubMed1992

Increase of peripheral B lymphocytes committed to the production of monoreactive and high affinity antibodies to HTLV-1 in patients with HAM/TSP.

We quantitated the frequency of B lymphocytes capable of producing antibodies to HTLV-1 in the peripheral blood from patients with HAM/TSP, non-HAM/TSP HTLV-1 carriers and seronegative healthy subjects. Epstein-Barr virus (EBV) was used as a polyclonal activator of B lymphocytes in a limiting dilution condition. We found that B lymphocytes committed to the production of monoreactive-IgG and -IgA antibodies to recombinant HTLV-1 (gag + env) hybrid protein were significantly increased in a number in patients with HAM/TSP as compared to non-HAM/TSP HTLV-1 carriers and seronegative healthy subjects. By transforming these B lymphocytes with EBV and fusing them with human-mouse heteromyeloma (F3B6), a stable hybridoma producing IgG monoclonal antibody (mAb) to HTLV-1 (gag + env) protein was generated from a patient with HAM/TSP. This mAb (IgG1, kappa), designated F31.1, specifically bound to the amino acid residues from 235 to 254 of HTLV-1 envelope glycoproteins (gp46) with high affinity (Kd = 4.0 x 10(-9) mol/l). These data indicate that the antigen-driven process of B lymphocytes maturation by HTLV-1 antigens is markedly increased in patients with HAM/TSP.

Antibody Affinity↗
PubMed1992

An appraisal of patch enlargement of the small aortic annulus in 33 patients undergoing aortic valve replacement.

To avoid the problem of valve prosthesis/patient mismatch in the late postoperative period, we have adopted patch enlargement of the small aortic annulus in 33 patients having undergone aortic valve replacement since 1975, when the aortic annulus could not accept a large enough prosthesis. The mean age was 40 years, including 2 children aged 4. The technique of patch enlargement utilized was Nicks' method wherein the incision does not extend onto the mitral leaflet. In 31 adult patients, the aortic annulus before enlargement ranged in diameter from 18 to 24 mm with an average of 20.8 mm. After enlargement, the diameter of the annulus was 25.0 mm on average. In 2 children, the mean diameter of the annulus was enlarged from 16.5 mm to 20.5 mm. There were 2 early deaths in the initial series and 2 late deaths. Patch enlargement of the small aortic annulus is a simple, safe, and effective adjunct permitting the insertion of a valve one or two sizes larger than that which could be accommodated by the native annulus.

Adolescent↗