Formation of free-radical products by the reaction of dehydroascorbic acid with amino acids.
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Amino Acids↗
Biomedical subjects
M Yano
Publications and source records attributed to M Yano.
Actomyosin structure in contracting muscle detected by rapid freezing.
It is now widely accepted that the ATP-induced active sliding of adjacent thin and thick filaments mediated by myosin heads (cross-bridges) is responsible for muscle contraction. Despite intensive studies, the behaviour of the myosin heads during muscle contraction is still unclear. Recent progress in the rapid freezing electron microscope technique has greatly improved the temporal resolution of the images that can be obtained. Here, we report a new type of actomyosin structure captured by rapid freezing. We have analysed images from thin sections of freeze-substituted rabbit skeletal muscle rapidly frozen during isometric contraction. For comparison, we also studied relaxed and rigor muscles. Our results show that, during isometric contraction, most myosin heads are regularly arrayed along the helix of the actin filaments and that this actomyosin structure appears to be distinct from that observed in rigor muscle.
Actins↗
In vivo formation of codeinone-glutathione adduct: isolation and identification of a new metabolite in the bile of codeine-treated guinea pig.
Codeinone-glutathione adduct (CO-GSH) in the bile of guinea pigs given a subcutaneous injection of codeine was isolated and identified. Synthesized authentic CO-GSH was characterized by the mass and nuclear magnetic resonance spectra and used as the standard sample. The metabolite was isolated by preparative high-performance liquid chromatography on a C18 column. The fractions containing the conjugated metabolite were purified using Sep-Pak C18 cartridges. For further purification of the metabolite CO-GSH, a Radial Pak CN column was used. Structure assignment of the metabolite was then performed by fast-atom-bombardment mass spectrometry and 500 MHz Fourier-transform-NMR spectrometric analysis and identified as S-[4,5-epoxy-3-methoxy-17-methyl-6-oxomorphinan-(8S)-yl] glutathione.
Animals↗
Hepatitis C as the cause of chronic non-A, non-B hepatitis: high sensitivity of simultaneous measurement of core and non-structural antibodies.
First generation serologic tests (ELISA-1) for hepatitis C virus infection measure antibodies directed against a short non-structural segment of the virus (anti-c100-3). A major disadvantage of this test is that it lacks sensitivity in the identification of hepatitis C virus among patients at risk of infection. Thus, only 70-90% of chronic non-A, non-B cases are ELISA-1 positive. The present study set out to determine whether antibodies directed against the core region would be a more sensitive indicator of hepatitis C virus infection in patients with chronic non-A, non-B hepatitis. Sera were studied from 97 patients with raised serum alanine aminotransferase levels for more than 6 months in whom other causes of abnormal alanine aminotransferase were excluded. Using ELISA-1, 85 sera (87%) were anti-c100-3 positive. Sera were then tested for presence of antibody directed against Po, a core peptide of a Japanese strain of hepatitis C virus, using an ELISA method. Eighty-eight sera (91%) were anti-Po positive. Among the 12 anti-c100-3 negative patients, six were anti-Po positive. A second generation ELISA for anti-HCV (ELISA-2) incorporates a different antibody to the core region (c22-3) in addition to an expanded non-structural region, c200, which consists of c100-3 plus c33c. With these tests, all sera but one were positive, including 11 of 12 ELISA-1 negative and eight of nine anti-Po negative sera.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic Disease↗
Advances in hepatitis C: sero-epidemiology and natural history.
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Hepatitis C↗
Local spread of HDV infection transiently occurring in Japan.
Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were compared with the inhabitants of Oita City (an area with an average HBV carriage rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507) in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive serum samples in Kamigoto were collected before 1986, and the mean age of the positive individuals was significantly younger than that of the negative individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had definite liver disease. The route of infection was uncertain in most cases (i.e. sporadic), but two pairs of mothers and children were detected. Although the prevalence of anti-HDV positivity in Japan has been reported to be very low (about 1% or less), the present investigation showed that the local spread of HDV infection in Kamigoto occurred on a minor scale up to 1986. The infections presumably resulted from the closed environment and the high incidence of HBV carriage in these islands. Accordingly, there could be a considerable risk of the outbreak of HDV infection in the future under similar conditions, even in countries where the disease has never been detected previously.
Adolescent↗
Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: a multi-institution analysis.
Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69-76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.
Adolescent↗
Effect of whole body hyperthermia on ischemia and reperfusion injury of rat intestine: real-time ATP change studied using (31)P-MRS.
We studied the effect of hyperthermia pretreatment on subsequent small intestinal ischemia and reperfusion (I/R) injury in the rat. Systemic hyperthermia has been reported to induce heat shock proteins (HSPs) in several organs [1-6]. We examined the expression of HSP72 in the small intestinal mucosa using Western blotting and immunohistochemistry. We monitored energy metabolism using magnetic resonance spectroscopy continuously during a 60-min ischemia and the following 120 min of reperfusion. Expression of HSP72 in the small intestine was significantly increased at 6-8 h after hyperthermia. Intestinal ischemia was induced by clamping the superior mesenteric artery. Heating of the rat conferred substantial resistance to the I/R injury. In the untreated rats, beta-ATP decreased during ischemia (37.1 +/- 15.5% of the pre-ischemic value) and recovered on reperfusion, but reached only approximately 50% of the pre-ischemic value after 120 min of reperfusion. However, beta-ATP in the pretreated rats was maintained during ischemia at significantly higher levels and on reperfusion reached approximately 80% of the pre-ischemic value. These results indicate that hyperthermia protects the rat intestine from the I/R injury by unknown mechanisms which may include the induction of HSPs.
Adenosine Triphosphate↗
Studies of the expression of epidermal growth factor receptor in human renal cell carcinoma: a comparison of immunohistochemical method versus ligand binding assay.
We evaluated the expression of epidermal growth factor receptor (EGFR) in 21 patients with renal cell carcinoma (RCC) by immunohistochemical staining of frozen tumor sections using a monoclonal antibody for EGFR and by a ligand binding method using radiolabeled epidermal growth factor. EGFR was detected in 16 of the 21 cases by ligand binding, while 11 of the 21 cases were detected by immunohistochemical staining. A significant correlation was observed between the two methods in detecting EGFR (p < 0.0001). EGFR was detected by the ligand binding method in all patients who died of RCC. Four cases that were graded as EGFR-negative on immunohistochemistry died of RCC. Observations suggest the ligand binding method was more sensitive than the immunohistochemical method in detecting EGFR and forecasting patient survival.
Adult↗
Interrelation of intracellular proteases with total parenteral nutrition-induced gut mucosal atrophy and increase of mucosal macromolecular transmission in rats.
Total parenteral nutrition (TPN) is known to induce mucosal atrophy and to increase macromolecular transmission of the small intestine. The potential participation of various proteases in that process was investigated. Male Wistar rats were randomly divided into two groups: the TPN group (n = 11) received a standard TPN (250 kcal/kg per day, 1.78 g nitrogen/kg per day) and the FED group (n = 10) received a standard rat food for 1 week. This was followed by an examination of gut macromolecular transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) after intragastric injection and of the activities of gut mucosal cathepsins B, H, and L and of proteasome. Mucosal wet weight and protein content decreased significantly by TPN for 1 week. In both groups, the activities of all proteases in the ileum were significantly greater than in the jejunum. In the TPN group, cathepsin L and H activities in the ileum, and cathepsin B activity in both the jejunum and the ileum, were greater than those in the FED group. The portal concentration of FITC-dextran was higher than arterial and venous concentrations in the both groups. In the TPN group, the portal FITC-dextran concentration increased significantly compared with the FED group. In conclusion, active proteolysis is not associated with TPN-induced mucosal atrophy. Cathepsins activities in the ileum increase as a result of TPN. Interrelationship is implicated between increase of lysosomal protease activity and the deterioration of the intestinal barrier function, which permits macromolecular transmission.
Animals↗
Effects of nucleosides and a nucleotide mixture on gut mucosal barrier function on parenteral nutrition in rats.
BACKGROUND: We have previously reported that the addition of nucleosides and a nucleotide mixture (OG-VI) to total parenteral nutrition (TPN) prevents TPN-induced intestinal mucosal atrophy and results in increased intestinal cathepsin activities under TPN. The aims of the present study are to examine the effects of OG-VI on mucosal barrier functions and to clarify whether the intestinal cathepsins can be used as a new marker of mucosal barrier function. METHODS: Male Wistar rats were divided into three groups: FED (food ad libitum), TPN (a standard TPN solution), and OG (OG-VI in addition to the TPN solution). Mucosal barrier functions were analyzed by the lactulose/mannitol (L/M) test, mucosal ZO-1 messenger RNA level, and electron micrographs in the gut. Intestinal cathepsin B, H, and L activities were also measured. RESULTS: The L/M ratio for TPN was much higher than that for FED. Only lactulose excretion was significantly reduced by OG-VI. The intercellular spaces of the mucosal cells for TPN were significantly wider than those for FED, but were reduced in size by the addition of OG-VI. All cathepsin activities of the ileum were higher for TPN than for FED, whereas OG showed no increase. CONCLUSION: OG-VI contributes to the improvement of gut mucosal barrier function. Intestinal cathepsin activities can be used as a new marker of mucosal barrier function.
Animals↗
Nucleotides and intestine.
BACKGROUND: Dietary nucleotides play an important role in the growth and development of the intestine. Parenteral supplementation of nucleic acids may be necessary to maintain the mucosal proliferation and barrier functions during parenteral nutrition (PN). METHODS: Male Wistar rats were divided into 3 groups: FED (food ad libitum with saline infusion); PN (a standard PN solution); and OG (OG-6, a mixture of nucleotide and nucleosides, in addition to the PN solution). The mucosal wet weight, protein, and DNA contents, villous height and crypt depth, electronmicroscopic examination of the intercellular junctions, proliferating activity of the mucosal cells, mucosal permeability, bacterial translocation, and mucosal cathepsin activities were examined. RESULTS: The wet weight, protein, and DNA contents of the jejunal mucosa were significantly increased in the OG group, compared with those in the PN group. The morphometric examination revealed a significant increase in the villous height but not in the crypt depth in the OG group. The widths of both the tight and intermediate junctions were narrower in the OG group than those in the PN group. The activity of diamine oxidase was increased in the OG group, compared with that in the PN group. The ratio of proliferating cell nuclear antigen positive cells and the index of bromodeoxy uridine labeling index in the OG group were as high as in the FED group, and significantly higher than those in the PN group. The portal concentration of fluorescein isothiocyanate-dextran 70,000 after intragastric loading was significantly higher in the PN group than that in OG group. Likewise, the rate of urinary lactulose excretion after intragastric loading was higher in the PN group. The positive rate of bacteria cultured in mesenteric lymph nodes was higher in the PN group than in the OG group although the difference was not significant. The activities of mucosal cathepsins (B, H, and L), markers for phagocytic degradation of extrinsic substances and organisms, were higher in the PN group than those in the OG and FED groups. CONCLUSIONS: Parenteral supplementation of nucleic acids supports the mucosal cell proliferation and functions.
Administration, Oral↗
Interferon-induced sudden hearing loss.
With the increasing long-term use of interferon (IFN), several new adverse effects have been recognized. Very little attention, however, has been paid to auditory acuity. We encountered 3 cases of sudden hearing loss associated with IFN. We then conducted a prospective study to assess the auditory function of 73 patients receiving IFN. Auditory disability (tinnitus and/or hearing loss) occurred in 32 patients (43.8%) during IFN therapy, among which audiometry documented sensorineural hearing loss in 27 cases (36.9%); 17 (48.6%) of the 35 patients receiving IFN-beta had auditory disability, including hearing loss in 13 cases (37.1%), and 15 (39.5%) of 38 patients receiving IFN-alpha suffered from auditory disability. There was not much difference between the influences of IFN-alpha and -beta. Auditory disability frequently developed in the later stages of treatment, and most patients recovered 7-14 days after the discontinuation of IFN. The results demonstrate that sudden hearing loss can occur as a side effect of treatment with IFN. This may reveal the association between autoimmunity and sudden hearing loss.
Adult↗
Prognostic factors for recurrence in stage II and III gastric cancer patients receiving a curative resection and postoperative adjuvant chemotherapy.
Prognostic value of clinicopathologic factors and biologic markers was analyzed in 185 patients who received a curative resection and adjuvant chemotherapy of pathologically confirmed stage II or III gastric cancer. No difference was found between the chemotherapeutic regimens according to the frequency of recurrence, but tumor type, histology, depth of invasion, nodal metastasis, and lymphatic and venous invasion were significantly different between recurrent (n=62) and non-recurrent (n=123) patients. However, the degree of lymphatic dissection and the patterns of biological markers (DNA ploidy, p53 staining and PCNA labeling) were not different. Hepatic metastasis and venous invasion were more frequent on patients recurring within one year, compared to those who recurred later. Multivariate analyses showed that depth of invasion, level 2 lymph node metastasis and tumor histology were risk factors for recurrence. Pathologic factors were more important for predicting recurrence than biological markers.
Adenocarcinoma↗
Effect of citrus flavonoids on HL-60 cell differentiation.
Twenty-seven Citrus flavonoids were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase, and phagocytic activities. 10 flavonoids were judged to be active (percentage of NBT reducing cells was more than 40% at a concentration of 40 microM), and the rank order of potency was natsudaidain, luteolin, tangeretin, quercetin, apigenin, 3, 3, '4, '5, 6, 7, 8-heptamethoxyflavone, nobiletin, acacetin, eriodictyol, and taxifolin. These flavonoids exerted their activity in a dose-dependent manner. HL-60 cells treated with these flavonoids differentiated into mature monocyte/macrophage. The structure-activity relationship established from comparison between flavones and flavanones revealed that ortho-catechol moiety in ring B and C2-C3 double bond had an important role for induction of differentiation of HL-60. In polymethoxylated flavones, hydroxyl group at C3 and methoxyl group at C8 enhanced the differentiation-inducing activity.
Antineoplastic Agents↗
Hepatic resection with tumor thrombectomy for hepatocellular carcinoma with tumor thrombi in the major vasculatures.
BACKGROUND/AIMS: It is still controversial whether surgical or non-surgical treatments should be adopted for hepatocellular carcinomas (HCC) with tumor thrombi (TT) in the major vasculatures. We evaluate the effectiveness of and the indications for hepatic resection with tumor thrombectomy for such patients. METHODOLOGY: Seventeen patients with TT in the major vasculatures caused by HCC were enrolled. Eleven patients had Vp3 TT, 5 patients had Vv3 TT, and 1 patient had Vp3 and Vv3 TT, concurrently. Out of the 17 patients, 13 underwent hepatic resections with tumor thrombectomies and the remaining 4 received only hepatic resections without tumor thrombectomies. RESULTS: In patients with Vp3 TT, median and mean survival times were 7.8 and 18.5 months, respectively, and 1- and 5-year survival rates were 36.4% and 18.2%, respectively. In patients with Vv3 TT, median and mean survival times were 9.9 and 8.4 months, respectively. Patients who underwent hepatic resections with tumor thrombectomies had significantly better prognoses than those who did not receive tumor thrombectomies (p=0.0039). CONCLUSIONS: The prognosis of HCC patients with TT in the major vasculatures, who have relatively small primary tumors, good hepatic functional reserves and no distant metastases should be good, if hepatic resections with tumor thrombectomies are performed.
Adult↗
Clinical effects of actarit in rheumatoid arthritis: improvement of early disease activity mediated by reduction of serum concentrations of nitric oxide.
OBJECTIVE: We previously reported the presence of high serum concentrations of nitric oxide (NO) in patients with rheumatoid arthritis (RA). In this study we evaluated the effect of actarit on patients with early and advanced stages of RA and the relationship between RA activity and serum NO levels. METHODS: Thirty-seven RA patients who were undergoing care at Sasebo Chuo Hospital were entered into the study. Patients were divided into two groups based on the severity of their disease: group I (stages I and II) and group II (stages III and IV). NO concentrations in serum samples were measured by the chemiluminescence method. RESULTS: Morning stiffness, the number of tender and swollen joints, grip strength, pain score, modified Health Assessment Questionnaire score (mHAQ), ESR, CRP and the Lansbury index significantly improved during 24 weeks of treatment in group I. Patients in group II did not show improvement in morning stiffness, pain score, ESR or CRP during treatment. The concentrations of NO in group I were significantly reduced at 8 weeks after administration of actarit. Those in group II showed a delayed response; a significant decrease in NO occurred at 20 weeks. The improvement in the number of tender and swollen joints, grip strength, pain score, mHAQ and Lansbury index noted in group I preceded the fall in NO concentrations. CONCLUSION: Our results demonstrate that actarit improves disease activity in early phase RA by suppressing serum NO levels. The results suggest that NO is a useful marker for monitoring improvement in the early stages of RA.
Adult↗
Effect of coumarins on HL-60 cell differentiation.
Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.
Cell Differentiation↗