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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 271 records · Page 15Linked to original sources
PubMed1997

[Rational lymphadenectomy in patients with cervical nodes metastasis for carcinoma of the lower third esophagus].

Prognostic value of removing cervical nodes in patients with carcinoma of the lower third esophagus is extremely controversial. Of 93 patients with curative esophagectomy via trans-thoracic approach, cervical nodes were involved in five patients (13%), upper mediastinal nodes in 12 patients (30%), and para-aortic nodes in only one patients (3%) for 40 patients whose proximal part of the tumor invading the mid-esophagus from below. Of the remaining 53 patients with tumor extent confined to the lower third esophagus, cervical nodes were involved in only one patients (2%), upper mediastinal nodes in five patients (9%), and paraaortic nodes in six patients (11%). Three of the five patients with cervical metastasis whose proximal part of the tumor invading the mid-esophagus survived for at least 22 months or more following three-field lymphadenectomy. Removing the cervical nodes in patients with carcinoma of the lower third esophagus may have some role to improve the survival if the tumor invades the mid-esophagus from below.

Carcinoma, Squamous Cell↗
PubMed1997

Serum amyloid P component enhances induction of murine amyloidosis.

Serum amyloid P component (SAP), a common component of all known types of amyloid fibrils, protects amyloid fibrils from proteolysis in vitro. It is therefore speculated to contribute to the deposition of amyloid fibrils in various types of amyloidoses. However, a role for SAP in amyloid deposition is not yet known. To investigate the relationship between SAP and amyloid deposition, we used gene targeting techniques to generate a unique strain of mice carrying a null mutation at the sap locus. The resultant SAP-deficient mice displayed no obvious phenotypic abnormalities. We asked whether experimental amyloid A (AA) amyloidosis could be induced in the SAP-deficient mice. The wild-type and SAP-deficient mice did not differ in their synthesis of serum amyloid A, the precursor protein of AA amyloid fibril, in response to acute inflammation. The induction of AA amyloidosis, however, was significantly retarded in the SAP-deficient mice relative to wild-type mice. Our experiments present, for the first time, compelling evidence that, although not essential in the deposition of AA amyloid, SAP significantly accelerates this reaction. Thus, SAP enhances the induction of murine amyloidosis and may play an important role in the pathogenesis of human amyloidoses, including Alzheimer's disease.

Acute-Phase Reaction↗
PubMed1997

Cell cycle-dependent chronotoxicity of irinotecan hydrochloride in mice.

The mechanisms underlying the circadian rhythm of the toxicity induced by irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) were investigated from the viewpoint of the sensitivity of living organisms and the pharmacokinetics of the drug. ICR male mice were housed under standardized light-dark cycle conditions (lights on at 0700, off at 1900) with food and water ad libitum. The loss of body weight after an intraperitoneal injection of CPT-11 (100 mg/kg) was more serious in the late dark and the early light and milder in the late light and the early dark. The CPT-11-induced leukopenia was more serious in the late dark and milder in the late light. The lower toxicity of CPT-11 was observed when DNA synthesis and type I DNA topoisomerase activity in bone marrow cells decreased and the higher toxicity was observed when these activities began to increase. There were circadian stage-dependent changes in the concentrations of CPT-11 and its major metabolite (SN-38; 7-ethyl-10-hydroxycamptothecin) in plasma. The higher concentrations of CPT-11 and SN-38 in plasma were observed when the level of CPT-11-induced toxicity increased. The present study suggests that the toxicity of CPT-11 is influenced by circadian rhythm-dependent processes.

Animals↗
PubMed1997

Experimental quantitation of cation effect on nucleic acid stability.

Cation effect on DNA/DNA, RNA/RNA, and RNA/DNA stabilities was investigated quantitatively. Plots of predicted delta G degree 37 values vs. measured delta G degree 37 ones showed the same relationship for DNA/DNA, RNA/RNA, and RNA/DNA. The number of sodium ion concerned in a double helix formation was estimated, and the result indicated that the number of bound sodium ion may determine the duplex stability regardless of DNA/DNA, RNA/RNA, and RNA/DNA. Since these duplex stability can be predicted with the nearest-neighbor model, it is considered that the number of bound sodium ions is affected by the nearest-neighbor bases. The importance of the screening effect of the electrostatic repulsion by bound cations was also indicated for determining the duplex stability as well as the hydrogen bonding and stacking interactions.

Base Sequence↗
PubMed1996

Improved thermodynamic parameters and helix initiation factor to predict stability of DNA duplexes.

To improve the previous DNA/DNA nearest-neighbor parameters, thermodynamic parameters (deltaH degrees, deltaS degrees and deltaG degrees) of 50 DNA/DNA duplexes were measured. Enthalpy change of a helix initiation factor is also considered though the parameters reported recently did not contain the factor. A helix initiation factor for DNA/DNA duplex determined here was the same as that of RNA/RNA duplex (deltaG degrees(37) = 3.4 kcal/mol). The improved nearest-neighbor parameters reproduced not only these 50 experimental values used here but also 15 other experimental values obtained in different studies. Comparing deltaG degrees(37) values of DNA/DNA nearest-neighbor parameters obtained here with those of RNA/RNA and RNA/DNA, RNA/RNA duplex was generally the most stable of the three kinds of duplexes with the same nearest-neighbor sequences. Which is more stable between DNA/DNA and RNA/DNA duplexes is sequence dependent.

Chromatography, High Pressure Liquid↗
PubMed1996

Inhibitors of anchorage-independent growth affect the growth of transformed cells on poly(2-hydroxyethyl methacrylate)-coated surfaces.

We have described a microplate colorimetric assay to quantitate anchorage-independent cell growth, using plates coated with an anti-adhesive polymer poly (2-hydroxyethyl methacrylate) (polyHEMA).We investigated whether this method could be applied to human cancer cells of epithelial origin. HAG-1, a non-tumorigenic human gall-bladder carcinoma cell line, and its pSVneo and c-H-ras transfectants, which are also non-tumorigenic, did not grow on a polyHEMA-surface. In contrast, the v-src transformant which produced tumors in nude mice and formed colonies in soft agar, was able to proliferate on the coated surface, suggesting that tumorigenicity of human cancer cells correlates with the ability to grow on a polyHEMA-coated surface. We report on the feasibility of this method as a screening system for inhibitors of oncogenic transformation. Herbimycin A and radicicol, which have been reported to block Src function, suppressed the growth of v-src-transformed NRK and HAG-1 cells on the non-adhesive polyHEMA-surface at concentrations significantly lower than on plastic. Differences in the inhibitory concentrations were not observed with KB cells, and cytotoxic agents such as adriamycin did not show any selectivity between the 2 surfaces. Growth of ras-transformed cells on the coated surface was selectively blocked by L-739,749, a farnesyltransferase inhibitor. The results demonstrate that compounds causing reversion of transformed cells to normal, hence, selectively inhibiting cell growth in anchorage-independent conditions, can be screened using this microtiter plate assay.

Adenocarcinoma↗
PubMed1996

A carbonic anhydrase from the nacreous layer in oyster pearls.

It is believed that the polymorphism observed in calcium carbonate crystals, such as aragonite and calcite in mollusk shells, is controlled by organic matrix proteins secreted from the mantle epithelia. However, the fine structures of these proteins are still unknown, and to understand the molecular mechanisms of mineralization process, detailed structural analyses of the organic matrix proteins are essential. For this, we have carried out purification, characterization, and cDNA cloning of nacrein, which is a soluble organic matrix protein in the nacreous layer of oyster pearls. Northern blot analysis showed that the nacrein transcript was specifically expressed in mantle pallial. Analysis of the deduced amino acid sequence revealed that the protein contained two functional domains: one was a carbonic anhydrase and another was a Gly-Xaa-Asn (Xaa = Asp, Asn, or Glu) repeat domain; however, the carbonic anhydrase domain was split into two subdomains with insertion of the Gly-Xaa-Asn repeat domain between them. Our findings suggest that nacrein actually functions as a matrix protein whose repeated Gly-Xaa-Asn domain possibly binds calcium and as a carbonic anhydrase that catalyzes the HCO3- formation, thus participating in calcium carbonate crystal formation of the nacreous layer.

Amino Acid Sequence↗
PubMed1996

Increased brain tumor microvessel permeability after intracarotid bradykinin infusion is mediated by nitric oxide.

Nitric oxide (NO), a free radical gas implicated in a wide variety of biological reactions, is a novel signaling molecule that may regulate vasodilation, cerebral blood flow, and vascular permeability. This study was performed to determine whether NO mediates the selective increase in brain tumor microvessel permeability after intracarotid infusion of bradykinin in the RG2 rat glioma model. Intracarotid infusion of bradykinin selectively increased the transport of radiolabeled alpha-aminoisobutyric acid and dextran into brain tumors. Transport into normal brain was not increased. The administration of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester, significantly inhibited the increased transport into tumors for both tracers. The inhibitory effect of NG-nitro-L-arginine methyl ester on the response to bradykinin was reversed by L-arginine. The expression of two NO synthase (NOS) isoforms in cultured RG2 glioma cell lines and intracerebral RG2 glioma was examined by immunohistochemistry and Western blot analysis. High levels of expression of neuronal NOS were detected in cultured and intracerebral RG2 cells but not in normal brain tissue, except in rare neuronal cells. The endothelial form of NOS was also expressed in cultured RG2 cells, but not as strongly as neuronal NOS expression. In intracerebral RG2 gliomas, expression of endothelial NOS in the tumor was detected at higher levels than in normal brain. These findings indicate that RG2 rat gliomas express high levels of NOS, which regulate the production of NO, compared with normal brain. We suggest that the selective permeability increase in brain tumor microvessels after bradykinin infusion is mediated by NO. Furthermore, the absence of high levels of NOS in normal brain may account for the attenuated permeability response to bradykinin in normal brain microvessels.

Aminoisobutyric Acids↗
PubMed1996

Schedule-dependent reversion of acquired cisplatin resistance by 5-fluorouracil in a newly established cisplatin-resistant HST-1 human squamous carcinoma cell line.

In vitro continuous stepwise exposure of HST-1 human squamous carcinoma cell line to cisplatin (CDDP) for 12 months resulted in a 3.5-fold stably resistant subline designated HST-1/CP0.2. Compared with parental cells, this cell line showed a 1.8-fold increase in cellular glutathione (GSH) and a 50% reduction in initial numbers of DNA interstrand cross-links (ICLs), despite similar levels of intracellular platinum accumulation. Evaluation of the kinetics of DNA ICL removal at nearly equivalent levels of DNA ICL formation indicated that HST-1/CP0.2 cells appeared to remove DNA ICLs more rapidly than do HST-1 parental cells. Thus, both elevated cellular GSH and increased DNA repair capacity would be the major factors contributing to CDDP resistance. Pretreatment of HST-1/CP0.2 cells with 5-FU, with drug-free intervals of 24 to 48 hr before exposure to CDDP, completely reversed CDDP resistance, or even increased the sensitivity to a level greater than that of parental cells, whereas the opposite sequence had no effect on resistance. In parallel with augmentation of the cytotoxicity, the levels of cellular GSH were significantly reduced over 48 hr by 5-FU pretreatment. However, depletion of cellular GSH using buthionine sulfoximine resulted in partial reversal of CDDP resistance, indicating that reduction of cellular GSH alone is not sufficient for complete reversal of CDDP resistance. Our data, together with evidence that 5-FU modulates the repair of platinum-DNA cross-links, suggest that schedule-dependent, complete reversal of CDDP resistance by 5-FU might be attributed to its inhibitory effects on both GSH levels and the repair of platinum-DNA adducts. Thus, optimization for the drug administration schedule is important when aiming at therapeutic synergy and circumvention of acquired CDDP resistance.

Antineoplastic Agents↗
PubMed1996

Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers.

The serum levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were determined by radioimmunoassay in 38 patients with adult T-cell leukemia (ATL). Levels of serum DHEA and DHEA-S were also measured in 60 human T-lymphotropic virus type I (HTLV-I) carriers, and did not differ from those in 60 healthy control subjects. Serum levels in patients with ATL were lower than those in the age- and sex-matched healthy controls and in HTLV-I carriers with statistical significance. Serum DHEA and DHEA-S in male patients with acute and lymphoma-type ATL were 1.06 +/- 0.77 ng/ml and 245.8 +/- 192.9 ng/ml, respectively. Levels in male patients with chronic and smoldering-type ATL were 1.69 +/- 0.68 ng/ml and 477.6 +/- 251.5 ng/ml, respectively. Serum levels of DHEA and DHEA-S in patients with acute and lymphoma-type ATL were significantly lower than those in patients with chronic and smoldering-type ATL (P < 0.05). These data suggest that a decrease in serum levels of DHEA and DHEA-S may be associated with patients who have some clinical subtypes of ATL. Moreover, androgens may have a therapeutic role in patients with ATL, as administered in patients with hairy-cell leukemia. Because there is at present no curative chemotherapy for ATL, a trial combination of androgens and standard chemotherapy may be a reasonable therapeutic option in such patients.

Adrenal Cortex↗
PubMed1996

Comparison of serum hepatitis C virus RNA concentration by branched DNA probe assay with competitive reverse transcription polymerase chain reaction as a predictor of response to interferon-alpha therapy in chronic hepatitis C patients.

A study was carried out to assess the correlation between the serum concentration of hepatitis C virus RNA (HCV-RNA) in patients with chronic hepatitis, as measured by competitive reverse transcription polymerase chain reaction (cRT-PCR) and branched DNA probe assay (bDNA), and response to interferon-alpha (IFN alpha) therapy. The serum HCV-RNA concentration was evaluated by both cRT-PCR and bDNA in 54 patients who had received a total dose of 480 MU of IFN alpha. HCV subtypes were also identified in all patients. The measurement of serum HCV-RNA concentration by bDNA correlated significantly with that of cRT-PCR. The concentration of HCV-RNA in subtype 1 patients was significantly higher than that in subtype 2 patients when measured by bDNA, but not when measured by cRT-PCR. The correlation of HCV-RNA concentration between bDNA and cRT-PCR was associated with both subtypes 1 and 2. The difference in serum HCV-RNA concentration between complete and incomplete responders was more significant when measured by bDNA probe assay than by cRT-PCR. Moreover, only 1 of 26 patients with a HCV-RNA concentration of more than 1 x 10(6) eq/ml as measured by bDNA probe assay attained a complete response, while 19 of 28 patients with that of less than 1 x 10(6) eq/ml achieved it. Measurement of serum HCV-RNA concentration by bDNA probe assay was a better predictor of clinical response of IFN alpha therapy than measurement by cRT-PCR.

Adult↗
PubMed1996

Pancreatic cancer and hypercalcemia associated with von Recklinghausen's disease.

A 44-year-old man with von Recklinghausen's disease was admitted to our hospital presenting with left hypochondralgia. Computed tomography showed a large mass at the body and tail of the pancreas, with metastatic liver tumors. Endoscopic retrograde pancreatography revealed an obstruction of the main pancreatic duct at the body. In the course of the illness, the patient's serum calcium concentration increased gradually to 13.6 mg/dl, although bone scan with 99mtechnetium demonstrated no accumulation in the bones. Serum levels of parathyroid hormone related-protein and tumor necrosis factor were also elevated. Based on these findings, he was diagnosed as having pancreatic cancer with liver metastases and humoral hypercalcemia of malignancy associated with von Recklinghausen's disease. Postmortem examination revealed a solid tumor, measuring 6.0 x 6.0 x 8.0 cm, in the body and tail of the pancreas. Histologically, the tumor was moderately differentiated adenocarcinoma. The association of von Recklinghausen's disease with malignant neurogenic neoplasms is well established, whereas the association with non-neurogenic malignant neoplasm is considered to coincidental. Our current case suggests a possible relationship between von Recklinghausen's disease and pancreatic cancer.

Adenocarcinoma↗
PubMed1996

Acute pancreatitis with diabetic ketoacidosis associated with hypermyoglobinemia, acute renal failure, and DIC.

We report a case of acute pancreatitis with diabetic ketoacidosis associated with increased serum myoglobin concentration, acute renal failure, and disseminated intravascular coagulation. A 49-year-old man suffering from diarrhea, vomiting, and somnolence was admitted to the hospital. He had had flu-like symptoms for 4 days prior to the onset of these symptoms. He was a habitual drinker and had been consuming 360 ml-900 ml of the drink "shochu" (distilled spirits containing 28% alcohol) daily for 30 years. Laboratory data on admission revealed elevated serum levels of pancreatic enzymes, including amylase, trypsin, lipase, pancreatic secretory trypsin inhibitor (PSTI), phospholipase A2 (PLA2), and elastase-1, as well as elevated levels of glucose (373 mg/dl), ketone bodies (3675 mumol/l), and myoglobin (229.8 ng/ml). Treatment with subcutaneous insulin and intravenous administration of electrolyte fluid and the systemic protease inhibitor, gabexate mesilate, was begun immediately. Early after the initiation of treatment, there was an increase in serum creatinine (4.9 mg/dl), and thromobocytopenia (15000/microliters) was observed. The patient completely recovered from renal failure and acute pancreatitis, but required insulin therapy. Alcohol ingestion and dehydration are thought to have played a major role in the triggering of the acute pancreatitis. We examined the relationship among acute pancreatitis, diabetic ketoacidosis, and hypermyoglobinemia in the literature.

Acute Disease↗
PubMed1996

Immunohistochemical localization of brain-derived neurotrophic factor in adult rat brain.

To investigate the role of brain-derived neurotrophic factor in the central nervous system, we produced an anti-peptide antibody that specifically recognized brain-derived neurotrophic factor and performed immunohistochemistry for brain-derived neurotrophic factor-like immunoreactivity in normal adult rat brain. A synthetic peptide (EKVPVSKGQL), derived from mature brain-derived neurotrophic factor, was conjugated to bovine thyroglobulin at a ratio of 1:3 and used as an immunogen to produce a high-titre anti-brain-derived neurotrophic factor polyclonal antibody in Japanese white rabbits. Dot blotting demonstrated that the antiserum could detect 3.91 pmol of synthetic peptide, and Western blotting showed that the antiserum recognized one band with a molecular weight consistent with that of brain-derived neurotrophic factor. In immunohistochemistry, brain-derived neurotrophic factor-like immunoreactivity was widespread in adult rat brain, including cerebral cortex, hippocampus, basal forebrain, striatum, hypothalamus, brainstem and cerebellum. Not only neuronal somata but also nerve fibres showed positive staining. Our data suggest that brain-derived neurotrophic factor is transported through axons in a subpopulation of neurons in adult rat brain, and that brain-derived neurotrophic factor influences a great variety of neurons and acts as a neurotrophic factor in the central nervous system.

Animals↗
PubMed1996

Pericardial mesothelioma presenting as left atrial thrombus in a patient with mitral stenosis.

Primary pericardial mesothelioma is rare and remains a diagnostic and therapeutic challenge. Pericardial mesothelioma usually occurs independently of intracardiac lesions and infiltrates adjacent tissues superficially. An extremely rare case of malignant pericardial mesothelioma complicated by prior mitral valve surgery is reported. The tumour invaded the left atrium and mimicked a thrombus.

Diagnosis, Differential↗
PubMed1996

Pharmacokinetics of omeprazole (a substrate of CYP2C19) and comparison with two mutant alleles, C gamma P2C19m1 in exon 5 and C gamma P2C19m2 in exon 4, in Japanese subjects.

The pharmacokinetic profile of omeprazole was examined in 27 healthy Japanese volunteers, and the results were analyzed in relation to genotype for the two mutations, CgammaP2C19m1 in exon 5 and CgammaP2C19m2 in exon 4, associated with the poor metabolizer phenotype. Of the 27 individuals analyzed, 10 were homozygous for the wild-type (wt) allele in both exon 5 and exon 4 (wt/wt; 37.0%, pattern GI), five were heterozygous for the CgammaP2C19m1 (wt/m1; 18.5%, G2), five were heterozygous for the CgammaP2C19m2 (wt/m2; 18.5%, G3), two were heterozygous for the two defects (m1/m2; 7.4%, G4), and five were homozygous for the CgammaP2C19m1 (m1/m1; 18.5%, G5). The allele frequencies of the m1 and m2 mutation were 0.31 and 0.13, respectively. A correlation between the rate of metabolism of omeprazole and genotype was observed. The mean clearance values of omeprazole in patterns G1, G2, G3, G4, and G5 were 1369.0, 332.7, 359.0, 70.8, and 89.5 ml/hr/kg, respectively. The relative area under the serum concentration-time curve (AUC) ratio of omeprazole to 5-hydroxyomeprazole in patterns G1, G2, G3, G4, and G5 was 1:2.8:3.4:16:17.2. A similar relation was observed in the omeprazole/5-hydroxyomeprazole serum concentration ratio, determined 3 hours after drug intake (1:3:4:18.8:20.3). There were significant (p < 0.05 to 0.01) differences in the disposition kinetics of omeprazole between the subjects with patterns G1, G2, and G3 and the subjects with patterns G4 and G5. The results indicate that the 5-hydroxylation pathway of omeprazole is clearly impaired in subjects with m1/m2 and m1/m1.

2-Pyridinylmethylsulfinylbenzimidazoles↗