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Biomedical subjects

M Saito

Publications and source records attributed to M Saito.

At least 145 records · Page 8Linked to original sources
PubMed2001

Abundant expression of uncoupling protein-2 in the small intestine: up-regulation by dietary fish oil and fibrates.

Mitochondrial uncoupling protein-2 (UCP-2) is widely expressed in various mammalian tissues, although its physiological functions are not well understood. We examined the effects of dietary fish oil on UCP-2 expression in the rat small intestine, in which UCP-2 mRNA levels are higher than in other organs. Feeding with fish oil (20%) up-regulated UCP-2 mRNA within 6 days in the small intestine as well as the liver, compared to feeding with soybean oil. This was mimicked by feeding with agonists for peroxisome proliferator-activated receptor alpha (PPARalpha) such as fenofibrate and bezafibrate, but not the PPARgamma agonist troglitazone. The bezafibrate-induced increase in UCP-2 expression was found within 2 days in the small intestine, but only after 6 days in the liver. The up-regulation of UCP-2 was also found in cultured intestinal epithelial cells (IEC-6) treated for 24 h with various long-chain fatty acids and PPARalpha agonists. These results indicated that intestinal UCP-2 is up-regulated through direct activation of PPARalpha by dietary fatty acids.

Animals↗
PubMed2001

Increased secretion of tumour necrosis factor and interleukin 6 from isolated, perfused liver of rats after partial hepatectomy.

The present study explored the changes in hepatic secretion of tumour necrosis factor (TNF) and interleukin 6 (IL-6) during the regenerative process of the liver, focusing on the role of Kupffer cells. The secretions of TNF and IL-6 from the perfused rat liver were increased after 67% partial hepatectomy, reaching a maximum at 48 h. The response of cytokine secretion induced by lipopolysaccharide (LPS: 1 microgram/ml) was also potentiated in regenerating liver. The secretion of TNF, but not that of IL-6, induced by LPS was almost totally suppressed by pretreatment of rats with gadolinium chloride, which depletes Kupffer cells. These results indicate that hepatic secretions of TNF and IL-6 are increased during the regenerative process of the liver. Kupffer cells play an important role in hepatic secretion of TNF, whereas the production of IL-6 can be achieved by other cells of the liver.

Animals↗
PubMed2001

Folding-unfolding of goat alpha-lactalbumin studied by stopped-flow circular dichroism and molecular dynamics simulations.

Folding reaction of goat alpha-lactalbumin has been studied by stopped-flow circular dichroism and molecular dynamics simulations. The effects of four single mutations and a double mutation on the stability of the protein under a native condition were studied. The mutations were introduced into residues located at a hydrophobic core in the alpha-domain of the molecule. Here we show that an amino acid substitution (T29I) increases the native-state stability of goat alpha-lactalbumin against the guanidine hydrochloride-induced unfolding by 3.5 kcal/mol. Kinetic refolding and unfolding of wild-type and mutant goat alpha-lactalbumin measured by stopped-flow circular dichroism showed that the local structure around the Thr29 side chain was not constructed in the transition state of the folding reaction. To characterize the local structural change around the Thr29 side chain to an atomic level of resolution, we performed high-temperature (at 400 K and 600 K) molecular dynamics simulations and studied the structural change at an initial stage of unfolding observed in the simulation trajectories. The Thr29 portion of the molecule experienced structural disruption accompanied with the loss of inter-residue contacts and with the water molecule penetration in the 400-K simulation as well as in four of the six 600-K simulations. Disruption of the N-terminal portion was also observed and was consistent with the results of kinetic refolding/unfolding experiments shown in our previous report.

Animals↗
PubMed2001

Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt's lymphoma cells.

Shiga toxin 1 (Stx1) produced by Escherichia coli has been reported to induce apoptosis in many different cell types, including Burkitt's lymphoma (BL) cells. Since it has been established that the caspases play essential roles as the effector molecules in the apoptotic process in most cases, we examined the kinetics of caspase activation during the process of Stx1-mediated apoptosis of BL cells. Using Ramos BL cells that are highly sensitive to Stx1-mediated cytotoxicity, we observed that multiple caspases, including caspase-3, -7, and -8 were promptly activated following Stx1 treatment, as indicated by both the procaspase cleavages and enhancement of cleavage of the tetrapeptide substrates of the caspases. In addition, the inhibition assay revealed that caspase-8 is located upstream of both caspase-3 and -7, suggesting that Stx1-mediated apoptosis utilizes a similar caspase cascade to that involved in Fas-mediated apoptosis. Neither anti-Fas mAb nor TNF-alpha, however, affected the Stx1-mediated apoptosis of Ramos cells. Although the precise mechanism of Stx1-mediated activation of caspase-8 is still unclear, we have demonstrated that crosslinkage of CD77, a functional receptor for Stx1, with specific antibody is sufficient to induce activation of caspase-8. Our findings should provide new insight into the understanding of the molecular basis of Stx1-mediated cell injury.

Antibodies, Monoclonal↗
PubMed2001

Single-step method for purification of Shiga toxin-1 B subunit using receptor-mediated affinity chromatography by globotriaosylceramide-conjugated octyl sepharose CL-4B.

A new single-step purification method for Shiga toxin (Stx) was developed using receptor-mediated affinity chromatography, in which Gb3Cer (globotriaosylceramide) was conjugated to octyl Sepharose CL-4B as a carrier. This method achieves high yield and high purity in a small column on which Gb3Cer has been immobilized at high density. Using this affinity column, the Stx1 B subunit was purified with homogeneity by a one-step procedure from a crude extract of recombinant Stx1 B subunit-producing Escherichia coli. The purified Stx1 B subunit conserved a natural pentamer structure confirmed by gel filtration and sedimentation equilibrium analysis. Furthermore, the purified Stx1 B subunit was able to bind specifically to Gb3Cer expressed on Burkitt's lymphoma cells. This versatile purification method can be used to isolate various types of natural as well as recombinant Stx, facilitating fundamental studies of human diseases caused by this toxin.

Blotting, Western↗
PubMed2001

Recurrent thymic carcinoid tumor in the pleural cavity. 2 cases of long-term survivors.

Thymic carcinoid is a rare malignant tumor having a high incidence of local recurrence and distant metastasis. To date, few reports have described the reoperative management of recurrent thymic carcinoid appearing as a pleural tumor. Here we report 2 such cases in long-term survivors. Long-term follow-up is recommended for patients with thymic carcinoid even after curative surgery. Aggressive treatment including surgical resection may prolong survival in these patients.

Carcinoid Tumor↗
PubMed2001

One missense mutation in the factor X gene causing factor X deficiency--factor X Kanazawa.

We investigated the molecular basis of factor X deficiency in a Japanese patient whose factor X activity and antigen level were 45% and 50% of normal control values, respectively. All exons and intron/exon junctions of the factor X gene were studied using a strategy combining polymerase chain reaction (PCR) amplification and nonradioactive single-strand conformational polymorphism (SSCP) analysis. Exon 5, containing the DNA fragment of the proband, showed aberrant migration by SSCP analysis. All exon-containing DNA fragments amplified by PCR were sequenced, and it was revealed that the proband was a heterozygote for a G --> A substitution in exon 5 of the factor X gene of the proband. This mutation predicts an amino acid replacement of arginine (Arg) for glycine (Gly) at codon 114 in the second EGF-like domain.

Aged↗
PubMed2001

Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency.

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.

Aged↗
PubMed2001

Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus.

We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.

Adjuvants, Immunologic↗
PubMed2001

Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients.

The objective of this study was to evaluate the relation between the clinical and plasma parameters and the changes in plasma endotoxin activity with 2 hours of endotoxin-adsorbing therapy using polymyxin B (PMX). A total of 88 consecutive patients were admitted for PMX treatment of severe sepsis or septic organ failure. Standard supportive care was continued without alteration during PMX treatment. Endotoxin, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) activities and clinical parameters were measured before, immediately after, and the day after PMX treatment. The mean APACHE II and III scores were 24.2 +/- 1.0 and 85.8 +/- 3.0, respectively. The 2-week survival rate was 51.1%. In survivors, TNFalpha, IL-6, IL-10, and PAI-1 activities were significantly decreased during the 2-hour PMX treatment, the following day, or both times. There was no significant change in the parameters, except for TNFalpha, after PMX in nonsurvivors. In the subgroup whose plasma endotoxin decreased more than 30%, IL-6, TNFalpha, and PAI-1 significantly decreased after 2 hours of PMX or the following day (or both), but all four parameters in nonsurvivors showed no significant change. Hence PMX adsorbed plasma endotoxins and contributed to reductions in plasma proinflammatory cytokine levels and to improved clinical parameters during the 2-hour treatment. Changes in these parameters correlated with changes in plasma endotoxin activity in survivors whose plasma endotoxin levels were adequately reduced.

APACHE↗
PubMed2001

Combined hepatocellular carcinoma and cholangiocarcinoma growing into the common bile duct.

We report a patient with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) growing into the common bile duct (CBD) and showing obstructive jaundice within 2 years of the onset of the disease. The patient was a 59-year-old Japanese man in whom, at the age of 57 years. a hepatic tumor was discovered by diagnostic imaging during follow-up of hepatitis B surface antigen (HBsAg)-positive liver cirrhosis. The tumor was diagnosed as HCC. Epirubicin was injected twice, intraarterially. The patient then received oral etoposide therapy for the next 14 months. The treatment was initially effective, but approximately 2 years after the hepatic tumor was discovered, local recurrence of the tumor and a tumor thrombus in the CBD were discovered. Although he was treated with percutaneous transhepatic biliary drainage (PTBD), to reduce obstructive jaundice, the jaundice was irreversible and he died of severe hepatic failure. The autopsy findings confirmed that the hepatic tumor was HCC-CC, in which the HCC and CC components expressed alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), respectively, which accurately reflected the disease process. The underlying mechanism of the growth of HCC-CC into the CBD may differ from the underlying mechanism of the development of icteric-type HCC.

Bile Ducts, Intrahepatic↗
PubMed2001

Effects of latanoprost and unoprostone when used alone or in combination for open-angle glaucoma.

PURPOSE: To evaluate the effects of latanoprost and unoprostone on the intraocular pressure (IOP) and on the tonographic outflow facility in glaucoma patients when used alone or in combination. DESIGN: Open label randomized clinical study. METHODS: Fifty-two patients (52 eyes) with primary open-angle glaucoma were randomly divided into two groups. One group initially received only latanoprost 0.005% once daily and the other group, only unoprostone 0.12% twice daily. The study period was 12 weeks: in the first 6 weeks, latanoprost or unoprostone was given as monotherapy, and in the last 6 weeks, patients received both drugs. IOP was measured every 2 weeks by one investigator masked to the medication received by patients during the study period in the same hour as on the baseline day. At Weeks 0, 6, and 12, the coefficient of aqueous outflow was measured by tonography. RESULTS: With latanoprost monotherapy, the baseline IOP of 22.9 +/- 2.4 mm Hg (mean +/- SD) decreased to 16.9 +/- 2.1 mm Hg (P<.01). When unoprostone was added to latanoprost, the IOP remained at 16.7 +/- 2.5 mm Hg. With unoprostone monotherapy, the baseline IOP of 22.7 +/- 2.1 mm Hg decreased to 19.4 +/- 2.4 mm Hg (P<.01). When latanoprost was added to unoprostone, the IOP decreased to 16.8 +/- 1.7 mm Hg (P<.01). There was no significant change in the coefficient of aqueous outflow with monotherapy or the combined use of the drugs. CONCLUSIONS: The combination of latanoprost and unoprostone does not result in a more potent hypotensive effect than latanoprost alone.

Adult↗
PubMed2001

Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemic patients.

Several studies have previously reported high levels of total tissue factor pathway inhibitor (TFPI) antigen in patients with hypercholesterolemia. The relationship between serum lipid concentrations and total and free-form TFPI antigen in 32 patients with primary type II hypercholesterolemia and 38 age- and gender-matched normolipemic control subjects was studied (Study Group I). Plasma concentrations of total TFPI (tTFPI) antigen, free-form TFPI (fTFPI) antigen, tissue factor antigen, factor VII activity (FVIIc), and prothrombin fragment 1+2 (F1+2) were measured. The median levels of tTFPI, fTFPI, FVIIc, and F1+2 were higher in hyperlipidemic patients compared with those in healthy subjects. The effect of lowering total cholesterol on hypercoagulability in 25 patients with type II hyperlipoproteinemia (Study Group II) were also studied. The median levels of tTFPI, FVIIc, and F1+2 decreased significantly after 6 months of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor therapy in the hypercholesterolemic patients. On the other hand, fTFPI did not change after therapy. Plasma tTFPI was strongly correlated with total cholesterol and low density lipoprotein (LDL)-cholesterol in hyperlipidemic patients. In contrast to the strong correlation between tTFPI and total cholesterol, the correlation between plasma fTFPI and total cholesterol was relatively poor. These results suggest that the activation of the anticoagulant system as well as the activation of the coagulation system may occur in association with hypercholesterolemia. Furthermore, the results of this study may suggest that lowering of total cholesterol in hyperlipidemic patients reduces the thrombin generation in plasma and that down-regulation of LDL does not affect the anticoagulant potency of TFPI in plasma.

Adult↗
PubMed2001

Early hilar lung cancer--risk for multiple lung cancers and clinical outcome.

In early hilar lung cancer patients, multiple lung cancers frequently develop. The clinical outcome of such patients were studied. A total of 91 patients, 88 men and three women, who were endoscopically diagnosed with early hilar lung cancer were studied retrospectively. Surgery was performed in 46 patients, while organ-sparing treatment, including photodynamic therapy (PDT), Nd-YAG (neodymium-yttrium, argon, garnet) laser vaporization, and radiotherapy, were done for 45 patients. During follow-up, newly developed lung cancers and/or malignancies in other organs were recorded. The average smoking index (cigarettes per day x years) was 1040. Synchronous and/or metachronous multiple lung cancers developed in 26/91 patients (28.6%). Malignancies in other organs were found in 12/91 (13.2%). The smoking index of patients with multiple lung cancers was significantly higher than for other patients. The overall 5 year survival rate was 70.7% in all patients, 76.0% in the surgery group, and 64.4% in the nonsurgery group. The lung cancer-specific 5 year survival rate was 89.8% in all patients, 89.3% in the surgery group, and 90.5% in the nonsurgery group. Early hilar lung cancer frequently accompanies other lung cancers or malignancies in other organs. A favorable prognosis can be obtained with organ-sparing treatment.

Adult↗