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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 163 records · Page 9Linked to original sources
PubMed1999

Pharmacokinetic changes of theophylline and amikacin through the menstrual cycle in healthy women.

The objective of this open-label, single-dose study was to clarify the influence of the menstrual cycle on the pharmacokinetics of theophylline (n = 10) and amikacin (n = 8) in young healthy Japanese women with regular menstrual cycles. Each subject received an intravenous infusion of theophylline or amikacin sulfate at four different phases--mid-follicular (phase I), peri-ovulatory (phase II), mid-luteal (phase III), and premenstrual days (phase IV). In the theophylline study, there were no significant differences in the pharmacokinetic parameters among the four phases studied. In the amikacin study, CLtot was 15% higher in phase III than in phase I (p < 0.01). Vd beta was 35% higher in phase III than in phase I (p < 0.05). The other pharmacokinetic parameters of amikacin were not significantly altered during the menstrual cycle. Evidence suggests that the phase of the menstrual cycle may be a factor in determining the pharmacokinetics of amikacin.

Adult↗
PubMed1999

Electrical stimulation prolongs the survival days of leukemic mice treated with methotrexate.

To investigate effects of electrical stimulation on survival days of leukemic mice treated with methotrexate (MTX), L1210-bearing mice were treated by MTX and calcium folinate (leucovorin) rescue therapy (MTX: 400 mg/kg, followed by leucovorin at the dose of 7.5 mg/kg at 8, 15 and 24 hr after MTX) under electrical stimulation (foot shock: shock amplitude, 0.4 mA; voltage, 60-100 V/cm; shock duration, 5 sec; frequency, 0.5 Hz) of various lengths. The survival days were significantly prolonged by 6-hr electrical stimulation in combination with MTX, while plasma MTX concentrations and pharmacokinetic parameters such as the area under the curve (AUC-12 hr) and clearance (CL) were not significantly altered. Psychological stress did not alter the efficacy of MTX in the communication box paradigm. Amplified efficacy of MTX was shown in a length-dependent manner when electrical stimulation of various lengths were applied to L1210-bearing mice.

Animals↗
PubMed1999

Prognostic significance of polo-like kinase expression in esophageal carcinoma.

PLK (polo-like kinase), which belongs to a family of serine/threonine kinases and represents the human counterpart of structurally related protein kinases, polo of Drosophila melanogaster and CDC5 of Saccharomyces cerevisiae, may be implicated in spindle formation and chromosome segregation during mitosis. There are, however, few reports on the significance of PLK gene expression in human carcinomas. In order to evaluate its clinical significance, we examined the expression of the PLK mRNA in 49 esophageal and 75 gastric carcinomas, using reverse transcription-polymerase chain reaction analysis. In esophageal carcinomas, PLK overexpression was detected in 47 carcinomas (97%) when compared to the corresponding normal tissues. It is noteworthy that the patients with high-grade PLK overexpression represented a significantly poorer prognosis group than those with low-grade PLK overexpression (3-year survival rate: 54.9% vs 24.8%, p<0.05). A multivariate analysis demonstrated that the PLK mRNA expression status was an independent prognostic factor for patients with esophageal carcinoma. On the other hand, 55 gastric carcinomas (73%) were revealed to overexpress PLK mRNA, but the expression status showed no correlation with prognosis. This study demonstrated that the PLK overexpression was frequently observed in esophageal and gastric carcinomas, and appeared to be an independent prognostic factor for patients with esophageal carcinoma.

Adenocarcinoma↗
PubMed1999

Presence of RON receptor tyrosine kinase and its splicing variant in malignant and non-malignant human colonic mucosa.

The presence of RON and its variant isoform in malignant and non-malignant human colonic tissues was examined by immunohistochemistry using paraffin-embedded sections and RT-PCR analysis followed by direct sequencing of PCR product using RNAs isolated from frozen tissues. In normal colonic mucosa, RON was uniformly expressed in crypt cells, especially in the bottom of crypta. On the other hand, the expression was distributed heterogeneously in adenomas and in colon cancer. The expression of RON was significantly related to the degree of differentiation of colon cancer and the deletion of the expression was observed in colon cancer specimens with high incidence. The RT-PCR analysis of RNA isolated from non-malignant and malignant colonic tissue revealed the presence of two RON mRNA isoforms with 432-bp and 286-bp. Direct sequencing of major product of 432-bp was revealed to be identical to that of human wild-type RON. On the other hand, major product of 286-bp was revealed to be almost identical to that of a splicing variant of RON transcript which has been found in human gastric cancer cell line, KATO-III. The results obtained in this study may indicate that both wild-type RON and its variant isoform play an important role in regulating the normal function of colonic mucosa such as differentiation and motile activity and the expression of both wild-type RON and its variant isoform could be considered to be reduced during malignancy of human colonic mucosa.

Adenocarcinoma↗
PubMed1999

Differential tissular expression and localization of type IV collagen alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains and their mRNA in normal breast and in benign and malignant breast tumors.

Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. We investigated the cellular regulation and origin of these alpha(IV) chains in normal and neoplastic breast tissues by immunohistochemistry by using alpha(IV) chain-specific antibodies and by in situ hybridization. In normal breast, alpha1(IV) and alpha2(IV) chains were stained in all BM, whereas alpha5(IV) and alpha6(IV) chains were restrictively localized in a linear pattern in the BM of the mammary gland. Similar immunostaining profiles were observed in benign breast tumors and in the intraductal components of invasive ductal carcinoma. However, in invasive ductal carcinoma, alpha1(IV) and alpha2(1V) chains were discontinuously or negatively stained in the cancer cell nests, and the assembly of alpha5(IV) and alpha6(IV) chains into the BM was completely inhibited. Coexpression of alpha5(IV) and alpha6(IV) chains was related to the localization of alpha-smooth muscle actin (alpha-SMA)-positive myoepithelial cells. By in situ hybridization, in fibroadenoma and invasive ductal carcinoma, the signals for alpha1(IV) and alpha2(IV) mRNA were abundant in stromal cells. However, the signals for alpha5(IV) and alpha6(IV) mRNA were not seen in any of these cells. In contrast, in intraductal papilloma, coexpression of alpha1 (IV)/alpha2(IV) mRNA and alpha5(IV)/alpha6(IV) mRNA was identified in epithelial cells. The results indicate that the mammary gland forms a second network of BM composed of alpha5(IV)/alpha6(IV) chains, in addition to the classic network of alpha1(IV)/alpha2(IV) chains. The expression of type IV collagen alpha chains seems to be differentially regulated by the epithelial-myoepithelial interaction and to be associated with the invasive potential of breast cancer.

Breast↗
PubMed1999

[Neuronal kinases in glial cytoplasmic inclusions in patients with multiple system atrophy].

Glial cytoplasmic inclusions (GCI) occur characteristically in the cytoplasms of oligodendrocytes of brains with multiple system atrophy. We examined whether proline-directed protein kinases, which have been found in several neuronal inclusion bodies such as neurofibrillary tangles and Lewy bodies, are associated with GCI. We unexpectedly have observed cdk 5 and MAPK in GCI. These kinases were not immunolabeled in coiled bodies which are oligodendroglial inclusion bodies in brains with progressive supsranuclear palsy and Alzheimer's disease. We also found microtubule-associated protein 2 in oligodendrocytes in brains with MSA, which have not been observed in normal controls or neurological disease controls. Cdk 5 and MAP 2 are principally neuronal proteins. MAPK have been found in neuronal somata and some astrocytes, but not in oligodendrocytes. Thus, the present results suggest that oligodendrocytes in MSA harbor an abnormal phenotypic nature in terms of the aberrant expressions of the principally neuronal proteins.

Brain↗
PubMed1999

[TT virus(TTV) infection in patients with acute hepatitis].

A novel DNA virus, TT virus(TTV), has been reported in patients with posttransfusion hepatitis of unknown etiology. However association between TTV and acute hepatitis has not been shown. We investigated the prevalence of TTV in acute hepatitis. TTV-positive rates in acute hepatitis A, B, C, cytomegalovirus infection, Epstein-Barr virus infection, and acute hepatitis of unknown etiology were 15.3%, 21.8%, 60.0%, 0%, 10.0%, 22.6%, respectively. There were no significant differences in TTV prevalence between each etiology and healthy blood donors(20.8%). Clinical data were similar between patients with or without TTV. In this study we could not find any difference in the prevalence of TTV between acute hepatitis with known etiologies and that with unknown etiology. TTV did not affect the clinical features of acute hepatitis with known etiologies.

Acute Disease↗
PubMed1999

[Problems and prospects for combined chemotherapy with 5-fluorouracil and low-dose cisplatin].

Recently, the efficacy of combined chemotherapy with 5-fluorouracil and low-dose cisplatin for advanced gastrointestinal cancer has been reported in Japan. However, this method has not become established, because the underlying logic is unclear and the quality of its clinical trials has been unsatisfactory. We suggest the mechanism for this depends not only on the action of CDDP as a modulator of 5-FU, but also on a mutual biochemical modulation in which 5-FU acts as a modulator of CDDP and enhances the effect of CDDP. We expect that numerous phase II studies and the accumulation of reliable data will lead to improvements.

Animals↗
PubMed1999

[Clinical effectiveness of degradable starch microspheres (DSM) in patients with liver cancer].

Recently, degradable starch microspheres (DSM) have become available for use in patients with liver cancer in Japan. When DSM combined with a cytotoxic drug are infused through the hepatic artery, the steep drug concentration gradient to the tumor tissue results in a higher tissue drug concentration, which may elicit an increased antitumor response by blocking regional blood flow. Furthermore, the reduced systemic exposure of a coinjected drug can be translated into an increased regional extraction ratio due to blood flow reduction. DSM is infused via a catheter connecting to a subcutaneously implanted reservoir in outpatients. Pain is experienced by all patients. Other frequently observed adverse reactions are nausea and vomiting. However, these symptoms improve within a few hours. These observations indicate that intra-arterial chemotherapy combined with DSM may provide a more potent anticancer effect than a cytotoxic drug alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Improving the infrastructure for clinical trials in Japan].

It is necessary for us to reform the infrastructure for clinical trials in Japan in this new GCP era. Medical institutions for clinical trials should prepare to implement monitoring and auditing procedures for quality control and quality assurance of clinical trials. It is also necessary to ease the burden and improve the benefits of participating in clinical trials by subjects. Although there has been no effort to educate and train CRC/SC staff at all in Japan, future improvement in this area is needed to bring the quality of Japan's clinical trials up to international standards.

Antineoplastic Agents↗
PubMed1998

High levels of hepatocyte growth factor/scatter factor in diffuse-type bronchioloalveolar cell carcinoma.

BACKGROUND: Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen for various neoplastic cells, including neoplastic bronchial epithelia. METHODS: Immunoreactive hepatocyte growth factor/scatter factor (HGF/SF) was measured in extracts prepared from 129 nonsmall cell lung carcinoma (NSCLC) specimens, using an enzyme-linked immunosorbent assay. These specimens represented 5 cases of solitary/localized bronchioloalveolar cell carcinoma (BAC), 4 cases of diffuse/infiltrative BAC, 90 cases of non-BAC adenocarcinoma, 25 cases of squamous cell carcinoma, and 5 cases of large cell carcinoma. RESULTS: The mean concentration of immunoreactive HGF/SF was more than 19-fold higher in tissue extracts from diffuse-type BAG (265.0 +/- 110.2 ng/100 mg protein) than in those from solitary-type BAC (13.9 +/- 15.9, P < 0.005), non-BAC adenocarcinoma (13.8 +/- 14.9, P < 0.001), squamous cell carcinoma (13.2 +/- 14.4, P < 0.001), or large cell carcinoma (11.2 +/- 6.5, P < 0.005). When immunohistochemical staining for HGF/SF was performed, intense HGF/SF staining was uniformly observed in diffuse-type BAC tumor cells, but not in solitary-type BAC. CONCLUSIONS: Although BAC is included as a subtype of adenocarcinoma in the World Health Organization classification, diffuse-type BAC should be considered a distinct biologic entity, at least in terms of HGF/SF expression, from solitary-type BAC or non-BAC adenocarcinoma. In addition, the solitary and diffuse forms of BAC are known to be associated with different prognoses; for the latter, the prognosis is much poorer than for the former. The results of this study may at least partly explain this difference in prognosis.

Adenocarcinoma↗
PubMed1998

Interferon-alpha and -gamma inhibit the growth and neoplastic potential of v-src-transformed human epithelial cells by reducing Src tyrosine kinase activity.

To investigate whether interferons (IFNs) selectively suppress the growth of solid tumor cells with elevated protein tyrosine kinase (PTK) activity, we evaluated the effect of recombinant IFN-alpha2a and IFN-gamma on the proliferative and neoplastic potentials triggered by p60v-src using v-src-transformed HAG-1 human epithelial cells. When compared with control cells harboring the pSV2neo gene, the monolayer growth of v-src-transformed cell lines was inhibited by both recombinant IFNs, in a dose-dependent manner, whereas growth of ras-transfected cell lines was not affected. Moreover, IFNs markedly reduced the clonogenic growth of v-src-transformed cells in soft-agar rather than monolayer growth, suggesting the preferential activity of IFNs on anchorage-independent growth. Pretreatment of cells with Src or the Src-like PTK inhibitor herbimycin A or radicicol, alleviated dose-dependently the growth-inhibitory activity of IFN-alpha2a against v-src-transformed cells, suggesting that IFNs may share a common inhibitory pathway with Src PTK inhibitors. Accordingly, like herbimycin A, IFNs were found to reduce tyrosine phosphorylation of p60v-src and suppressed in vitro p60v-src kinase activity in v-src-transformed cells. Our data, together with the fact that IFNs inhibit the growth potential driven by Src but not by activated Ras, suggest that inhibition of signal transduction pathway through Src to downstream transduction events may be a primary mechanism of IFN-induced anti-prolifeative and anti-tumoral activity.

Adenocarcinoma↗