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Biomedical subjects

S Nojiri

Publications and source records attributed to S Nojiri.

At least 19 recordsLinked to original sources
PubMed2001

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear. Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin's lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR, P < .05; second or subsequent CR, P < .05; first PR, P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients' quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

Adult↗
PubMed2001

Association of serum antioxidant capacity with coronary artery disease in middle-aged men.

The possible involvement of oxidative damage in the progression of atherosclerosis has been suggested. There is some evidence that antioxidant therapy may be beneficial for the prevention of coronary heart disease. In this study, we investigated the relationship between coronary artery disease (CAD) and serum antioxidative status by measuring the total antioxidant status (TAS). Other relevant antioxidants, such as retinol, alpha, gamma-tocopherol, ascorbic acid, alpha, beta-carotenoids, erythrocyte glutathione peroxidase (GSH-Px) and oxidative products, were also determined in 31 male CAD patients with angiographically defined CAD and 66 male controls, aged 40-70 years, in a case-control study. The TAS levels, ratio and the concentrations of retinol, albumin, total protein and HDL cholesterol were significantly lower in the CAD patients than in the controls (p<0.01), and alpha-tocopherol and alpha/gamma-tocopherol were significantly higher in the CAD patients than in the controls. The TAS level correlated positively with gamma-GTP, GPT, GOT and uric acid (p<0.01). A multiple regression analysis in the CAD patients revealed that the TAS levels correlated most negatively with the number of diseased vessels. The concentrations of carotenoids and GSH-Px, as well as the alpha/gamma-tocopherol ratio were also significantly associated. Although conditional logistic regression analysis suggested low levels of HDL-cholesterol to be a significant coronary risk factor (OR=5.1, 95% CI=1.09-24.3), the TAS level showed no significant independent contribution to CAD. This study demonstrated an association of antioxidant parameters with the atherosclerosis progression, however, it did not confirm antioxidants as an independent risk factor for CAD event.

Adult↗
PubMed2000

Determination of sugar alcohols in confectioneries by high-performance liquid chromatography after nitrobenzoylation.

A method was developed for the determination of sugar alcohols, meso-erythritol, xylitol, D-glucitol, D-mannitol, maltitol and parachinit by high-performance liquid chromatography (HPLC). The sugar alcohols were converted into strong ultraviolet (UV)-absorbing derivatives with p-nitrobenzoyl chloride. HPLC was performed on a phenyl column, using acetonitrile-water (67:33) as mobile phase and UV detection (260 nm). The calibration curves for all sugar alcohols tested were linear in the 10-250 microg/ml range. The average recoveries of the sugar alcohols from four sugarless confectioneries spiked at 5 and 10% levels of six sugar alcohol standards ranged from 73.2 to 109.0% with relative standard deviations ranging from 0.7 to 9.0%. The detection limit of the developed method was 0.1% for the above sugar alcohols contained in the samples.

Calibration↗
PubMed2000

Roles of tissue transglutaminase in ethanol-induced inhibition of hepatocyte proliferation and alpha 1-adrenergic signal transduction.

The mechanisms by which ethanol inhibits hepatocyte proliferation have been a source of some considerable investigation. Our studies have suggested a possible role for tissue transglutaminase (tTG) in this process. Others have shown that tTG has two distinctly different functions: it catalyzes protein cross-linking, which can lead to apoptosis and enhancement of extracellular matrix stability, and it can function as a G protein (Galpha(h)). Under that circumstance, we speculated that the cross-linking activity would be decreased and that it would function to enhance hepatocyte proliferation in response to adrenergic stimulation. Ethanol treatment inhibited hepatocyte proliferation and led to enhanced tTG cross-linking activity, whereas treatment of hepatocytes with an alpha1 adrenergic agonist, phenylephrine, enhanced hepatocyte proliferation while decreasing tTG cross-linking. However, phenylephrine treatment of several hepatoma cell lines had no effect on cellular proliferation or tTG cross-linking activity, and of note, Northern blot analysis demonstrated that whereas primary hepatocytes had high levels of the alpha1beta adrenergic receptor (alpha1BAR) mRNA, the hepatoma cell lines did not have this mRNA. When the Hep G(2) cell line was stably transduced with an expression vector containing the alpha1BR cDNA, the cell line responded to phenylephrine treatment with enhanced proliferation and with decreased tTG cross-linking activity. Ethanol treatment of the alpha1BAR-transfected cells suppressed the phospholipase C-mediated signaling pathways, as detected in the phenylephrine-induced Ca(2+) response. These results suggest that phenylephrine stimulation of hepatocyte proliferation appears to be occurring through the alpha1BAR, which is known to be coupled with the tTG G protein moiety, Galpha(h), and that tTG appears to play a significant role in either enhancing or inhibiting hepatocyte proliferation, depending on its cellular location and on whether it functions as a cross-linking enzyme or a G protein.

Animals↗
PubMed2000

Suppression of epidermal growth factor-induced phospholipase C activation associated with actin rearrangement in rat hepatocytes in primary culture.

Hepatocytes maintained in primary culture for periods of 1 to 24 hours exhibited a rapid decline in epidermal growth factor (EGF)-induced activation of phospholipase C (PLC), as was evident in a loss of EGF-induced inositol 1,4,5-trisphosphate (IP(3)) formation and mobilization of Ca(2+) from intracellular Ca(2+) stores. The loss of PLC activation was not the result of a decrease in EGF receptor or phospholipase C-gamma1 (PLCgamma1) protein levels, nor the result of a loss of tyrosine phosphorylation of these proteins, but was associated with a decrease in EGF-induced translocation of PLCgamma1 to the Triton-insoluble fraction, presumably reflecting binding to the actin cytoskeleton. Disruption of F-actin by treatment of cultured hepatocytes with cytochalasin D recovered the EGF-induced IP(3) formation and Ca(2+) mobilization to the same level and with the same dose-response relationship as was obtained in freshly isolated cells. Analysis of PLCgamma1 colocalization with F-actin by confocal microscopy showed that PLCgamma1 was mostly distributed diffusely in the cytosol, both in freshly plated cells and in cells in culture for 24 hours, despite marked differences in actin structures. EGF stimulation caused a modest redistribution of PLCgamma1 and a detectable increase in colocalization with cortical actin structures in freshly plated cells or in cytochalasin D-treated cells, but in cells that had been maintained and spread in culture only a limited PLCgamma1 relocation was detected to specific actin-structure associated with lamellipodia and membrane ruffles. We conclude that actin cytoskeletal structures can exert negative control over PLCgamma1 activity in hepatocytes and the interaction of the enzyme with specific actin structures dissociates PLCgamma1 tyrosine phosphorylation from activation of its enzymatic activity.

Actins↗
PubMed1999

Rheologic analysis of gastric mucosal hemodynamics in patients with cirrhosis.

BACKGROUND: Portal hypertensive gastropathy causes some gastric mucosal microcirculatory disorders in cirrhotic patients, but the nature of the rheologic dysfunction in the gastric microcirculation remains to be clarified. METHODS: To examine the rheologic properties of the gastric microcirculation, we subjected 112 cirrhotic patients and 51 control subjects to endoscopic laser Doppler flowmetry and measured multiple variables of flow, red blood cell volume, and velocity. Furthermore, based on these results, we analyzed the shear rate which reflects the status of the microcirculatory system. To validate the laser Doppler flowmetry, we derived the relationship between red blood cell volume and cross-sectional areas of submucosal collecting venules; near-infrared endoscopy was used to evaluate this relationship. RESULTS: Analysis of shear rate according to the severity of portal hypertensive gastropathy showed that the mucosa was exposed to strong hemokinetic stress in severe cases, characterized by a higher shear rate than in control subjects or in mild cases. Nitroglycerin, administered by intravenous infusion (1.0 microg/kg/min), reduced blood flow and restored shear rate to control levels in patients with severe portal hypertensive gastropathy. CONCLUSION: This rheologic study of the gastric mucosa suggests that a disorder of the shear rate control mechanism in the microcirculation is associated with severe portal hypertensive gastropathy.

Endoscopy, Digestive System↗
PubMed1998

Aberrant crypt foci of the colon as precursors of adenoma and cancer.

BACKGROUND: Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer. METHODS: Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line. RESULTS: We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between the number of aberrant crypt foci, the presence of dysplastic foci, the size of the foci, and the number of adenomas. After sulindac therapy, the number of foci decreased, disappearing in 7 of 11 subjects. In the untreated control group, the number of foci was unchanged in eight subjects and slightly increased in one (P<0.001 for the difference between the groups). CONCLUSIONS: Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.

Adenoma↗
PubMed1998

Fluorescence detection of biotin using post-column derivatization with OPA in high performance liquid chromatography.

A sensitive and selective high-performance liquid chromatographic method with post-column derivatization, using o-phthalaldehyde (OPA) and 3-mercaptopropionic acid (3-MPA), is described for the determination of biotin in pharmaceutical preparations. The use of 3-MPA gives intense fluorescent derivative and improves the stability of biotin fluorophore towards oxidation to the picomole level. The fluorophore was detected at 453 nm (excitation at 342 nm). The calibration graph was linear for 20-200 ng per injection. The detection limit of biotin under these conditions was about 10 ng per injection. The RSDs were 1.9-3.4%. This method could be applied to pharmaceutical preparations without interference of other compounds.

3-Mercaptopropionic Acid↗
PubMed1994

[Determination of taurine, L-glutamine, vitamin U and L-aspartic acid in pharmaceuticals by high-performance liquid chromatography with pre-column derivatization].

A pre-column derivatization method for the high-performance liquid chromatographic determination of taurine (1), L-glutamine (2), vitamin U (3) and L-aspartic acid (4) in pharmaceuticals has been developed. The optimum requirements for the derivatization conditions and the stability of resulting derivatives were discussed. The compounds were converted into DNT derivatives through the amino group by reaction with sodium 2,6-dinitro-4-trifluoromethylbenzenesulfonate (DNTS) in 50% sodium borate at 60 degrees C for 30 min (1), at 60 degrees C for 90 min (2), at 60 degrees C for 80 min (3) and at 80 degrees C for 90 min (4). After the reaction mixtures were acidified with dil. HCl, the derivatives were separated on a Cosmosil 3C18 (4.6 mm i.d. x 50 mm) column using 1% acetic acid-methanol (13:7) containing 2 mM sodium 1-heptanesulfonate as mobile phase with a ultra violet detector at 280 nm. The precisions of the analytical values expressed as the coefficient of variation were below 2.0%. The recoveries of 1-4 added to various commercial samples were in the range of 97.8-100.6%.

Aspartic Acid↗
PubMed1992

Effect of Krestin (PSK) on the induction of IL-2 activated killer cells.

The effects of Krestin (PSK) on the generation of lymphokine-activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor-bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy.

Adjuvants, Immunologic↗
PubMed1988

[Induction of LAK cells by high density dialyzing culture device and its cytotoxicity].

Lymphokine activated killer (LAK) cells are generated by culture of lymphocytes with interleukin 2 (IL-2) in short term culture (3 to 5 days) and are used for adoptive immunotherapy for advanced cancer patients. The culture condition hitherto reported are essentially based on the rotating culture system, in which the maximum cell density was at 2 X 10(6) cell/ml and the cell recovery was usually less than 100%. The inability to induce LAK cells efficiently in vitro made the culturing of cells for therapy rather difficult and costly work because the mean infusion dose of LAK cells of one patient requires more than 1 X 10(10)/ml. We have therefore attempted to culture lymphocytes in 10 times higher concentration comparing with conventional methods. By using a new dialyzing culture system under continuous regulation of the amount of infused IL-2, nutrition medium, and pO2 and pCO2, we could culture cells at 2 X 10(7)/ml for more than 21 days and the resulted LAK cells showed a 100 times increase of activity on a per cell basis. By limiting dilution procedure, these killer cells mostly express T cell markers such as CD3 and CD8 but dose not express CD16.

Cell Division↗
PubMed1987

[A case of pericarditis carcinomatosa showing good response following local transfer of lymphokine-activated killer (LAK) cells].

A good therapeutic response following local transfer of lymphokine-activated killer (LAK) cells was obtained in a patient with cardiac tamponade due to breast carcinoma. A 41-year-old female was admitted with complaints of dyspnea and tachycardia. She had undergone left mastectomy at the age of 37 years and had received continuous oral administration of tamoxifen. Chest roentgenogram revealed cardiomegaly (CTR = 65%) and cardiac echogram showed marked retention of pericardial effusion. The cytology of the effusion was class V (adenocarcinoma). Cardiac tamponade proved refractory to combination chemotherapy using adriamycin, cyclophosphamide and 5-fluorouracil, and the effect of paracentesis was only temporary. Autologous peripheral blood lymphocytes were obtained through the cubital vein and cultured in vitro with 2 units/ml of human recombinant IL-2, (TGP-3, Takeda Pharm. Co.). After 4 days of cultivation, LAK cells were transferred intrapericardially 3 times. The cumulative infusion dose was 1.2 X 10(8) cells and the amount of combined IL-2 administration was 100 units/each transfer. Twenty-four days after initial infusion of LAK cells, the effusion disappeared. After then, recurrence has not been observed for 287 days. This case is the first trial of LAK therapy against pericarditis carcinomatosa and seems to be a useful way of treating this uncontrollable state without any serious side effects.

Adenocarcinoma↗
PubMedDate not supplied

Liquid chromatographic determination of sugar alcohols in beverages and foods after nitrobenzoylation.

Use of p-nitrobenzoyl chloride (PNBC) to form an ultraviolet-absorbing derivative was attempted to determine the sugar alcohols meso-erythritol, xylitol, D-sorbitol, and D-mannitol by liquid chromatography (LC). LC determination of derivatives was performed on an ODS column with acetonitrile-water (65 + 35) as mobile phase. Calibration curves were linear in the concentration range 0.01-100 micrograms/mL. Method sensitivity is 10 to 1000 times higher than that of LC with refractive index detection and gas chromatography with flame ionization detection. Recoveries of sugars added to various foods at 0.1 and 1% ranged from 91 to 102% for meso-erythritol, 75 to 115% for xylitol, 81 to 105% for D-sorbitol, and 81 to 108% for D-mannitol.

Beverages↗