Measurement of hydroxyl radical by salicylate in striatum of intact brain.
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Animals↗
Biomedical subjects
M Komatsu
Publications and source records attributed to M Komatsu.
Different changes in concentrations of monoamines and their metabolites and amino acids in various brain regions by the herbal medicine/Toki-Shakuyaku-San between female and male senescence-accelerated mice (SAMP8).
Due to it's estrogen-secreting qualities, a Japanese herbal medicine, Toki-Shakuyaku-San may have a potential role for Alzheimer's disease in women. The effect of treatment with Toki-Shakuyaku-San testing on concentrations of monoamines, their metabolites and amino acids in the cortex, hippocampus and striatum of senescence accelerated mice (SAMP8) was examined and sex differences of SAMP8 and ddY mice was studied. In the female SAMP8, concentrations of gamma-aminobutyric acid, alanine, and glycine were elevated in three regions after treatment. The concentration of glutamate was decreased in the cortex, hippocampus, and striatum of female and male SAMP8 and not in female and male ddY mice. These results suggest that different effects of Toki-Shakuyaku-San treatment on concentrations of monoamines, their metabolites and amino acids in the brain tissue may be due to its stimulation of secreted estrogen on neurons.
Aging↗
Cloning and characterization of two neural-salient serine/arginine-rich (NSSR) proteins involved in the regulation of alternative splicing in neurones.
BACKGROUND: In neurones, alternative splicing regulates the functions of many gene products. However, the molecular basis of neural-specific splicing, and how splicing regulation is modulated in different neurones remains to be determined. RESULTS: We cloned two new SR proteins, Neural-salient SR proteins (NSSR) 1 and 2, which are present at higher levels in brain and testis. During the differentiation, NSSR 1 is detected only in the neuronal stage. Both the purified recombinant NSSR 1 and 2 proteins enhance the in vitro splicing activity of nuclear extract. Moreover, recombinant NSSR 1 protein enhances the assembly of ribonucleoprotein complexes with S100 fraction. Over-expression of NSSR 2 prevents the inclusion of either the Flip or Flop exons in the splicing of the GluR-B gene, resulting in an increase in the abnormal exon-skipping product. In contrast, transient transfection with NSSR 1 promotes the inclusion of the Flip exon so that the abnormal product is spliced to the mature spliced form. This suppression of exon skipping by NSSR 1 is observed even with co-transfection of NSSR 2. CONCLUSIONS: NSSR 1 and 2 were cloned from mouse cDNA libraries. Results indicate that NSSR 1 may play a crucial role in the regulation of alternative splicing in neurones.
Alternative Splicing↗
Genetic relationship and distribution of the Japanese wild boar (Sus scrofa leucomystax) and Ryukyu wild boar (Sus scrofa riukiuanus) analysed by mitochondrial DNA.
Mitochondrial genetic variations were used to investigate the relationships between two Japanese wild boars, Japanese wild boar (Sus scrofa leucomystax) and Ryukyu wild boar (S.s. riukiuanus). Nucleotide sequences of the control (27 haplotypes) and cytochrome b (cyt-b) regions (19 haplotypes) were determined from 59 Japanese wild boars, 13 Ryukyu wild boars and 22 other boars and pigs. From phylogenetic analyses, the mtDNA of Ryukyu wild boar has a distinct lineage from that of Japanese wild boar, which was classified into the Asian pig lineage. This result suggests that the Ryukyu wild boar has a separate origin from the Japanese wild boar.
Animals↗
Ac as a tool for the functional genomics of rice.
To examine whether the maize autonomous transposable element Ac can be used for the functional analysis of the rice genome, we used Southern blot analysis to analyze the behaviour of Ac in 559 rice plants of four transgenic families through three successive generations. All families showed highly active transposition of Ac, and 103 plants (18.4%) contained newly transposed Ac insertions. In nine of the 12 independent transpositions analyzed, their germinal transmission was detected. Partial sequencing of 99 Ac-flanking sequences revealed that 21 clones exhibited significant similarities with protein-coding genes in databases and four of them matched rice cDNA sequences. These results indicate preferential Ac transposition into protein-coding rice genes. To examine the feasibility of PCR-based screening of gene knockouts in rice Ac plants, we prepared bulked genomic DNA from the leaves of approximately 6000 rice Ac plants and pooled the DNA according to a three-dimensional matrix. Of 14 randomly selected genes, two gene knockouts were identified, and one encoding a rice cytochrome P450 (CYP86) gene was shown to be stably inherited to the progeny. Together, these results suggest that Ac can be efficiently used for the functional analysis of the rice genome.
Amino Acid Sequence↗
Tauroursodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell.
BACKGROUND: Ursodeoxycholic acid is used in the treatment of acute and chronic intrahepatic cholestasis because it ameliorates cholestasis and protects hepatocytes. However, few studies have examined the effect of bile acids on the function of Kupffer cells. METHODS: The effect of various bile acids on cultured rat Kupffer cells was studied in terms of phagocytic activity in response to latex particles and morphological alterations. Video-enhanced differential interference contrast microscopy was used. RESULTS: Taurochenodeoxycholic acid and taurodeoxycholic acid reduced the number of latex particles incorporated into Kupffer cells, but taurocholic and tauroursodeoxycholic acids enhanced phagocytosis of latex particles. Inhibition of phagocytosis by taurochenodeoxycholic acid or taurodeoxycholic acid was essentially dose dependent. Tauroursodeoxycholic acid also enhanced phagocytosis by Kupffer cells in which phagocytosis had been reduced by pretreatment with taurochenodeoxycholic acid or taurodeoxycholic acid. Incorporated latex particles had a distinct translocation speed of 0.084+/-0.024 microm/s (mean maximum speed+/-SD); the speed was in the same range with tauroursodeoxycholic acid treatment. Tauroursodeoxycholic acid induced a 56% expansion of cytoplasm, associated with increased ruffling and movement of intracellular organelles. CONCLUSIONS: These observations suggest that tauroursodeoxycholic acid enhances membrane trafficking without changing translocation speed.
Animals↗
High-dose natural interferon-alpha therapy for chronic hepatitis C with a high viral load: predictors of efficacy. The Aomori, Akita and Iwate Areas Viral Hepatitis Research Group.
BACKGROUND: The effectiveness of interferon against hepatitis C has been found to be greatly affected by viral factors. However, few controlled interferon trials have involved seemingly intractable cases of chronic hepatitis C. METHODS: In 44 patients with high hepatitis C virus RNA levels (> or = 10(5) copies/mL), we carried out a prospective, controlled study of two natural interferon-alpha regimens, seeking predictors of therapeutic efficacy. Total natural interferon-alpha doses over 6 months in two groups were 780 and 840 million units, respectively. RESULTS: High therapeutic efficacy was achieved with no significant outcome difference between the regimens. The virus eradication rate was 35% and the rate of sustained biochemical response was 45% for both regimens. Multivariate logistic regression analysis identified viral genotype as the only significant predictor of success in viral eradication. CONCLUSIONS: Hepatitis C virus genotype 2 showed high sensitivity to interferon-alpha and this therapy can be recommended even for patients with a high viral load of this genotype. In contrast, with genotype 1b, cure was extremely difficult in cases with 10(7) or more copies/mL with a single 6-month course of interferon-alpha.
Adult↗
Decreased tear lactoferrin concentration in patients with chronic hepatitis C.
BACKGROUND/AIMS: Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C. METHODS: Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed. RESULTS: Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p <0.00048). The cotton thread test results in the chronic hepatitis C group (12.9 (5. 5) mm) were significantly lower than in the control group (17.9 (5. 3) mm; p<0.00048). Also, in the chronic hepatitis C group, tear lactoferrin concentration correlated with the results of the cotton thread test (r = 0.35, p<0.05). CONCLUSION: Chronic hepatitis C patients showed both decreased tear volume, and decreased tear lactoferrin concentration. These findings suggest that there may be dysfunction of the lacrimal glands in patients with chronic hepatitis C, which may account for the mild dry eye.
Adult↗
GB virus C infection: clinical significance.
GB virus C (GBV-C) RNA positivity rates were examined in serum specimens from 231 patients with liver disease (23 patients with hepatitis B, 175 patients with hepatitis C, five patients with hepatitis B virus plus hepatitis C virus coinfection, and 28 patients with non-A, non-B, non-C hepatitis) to clarify the clinical significance of this virus. GBV-C RNA was detected in none of 12 patients with fulminant hepatitis, one of two patients with acute hepatitis positive for hepatitis B surface antigen and one of four patients with acute non-A, non-B, non-C hepatitis. Pathogenetic involvement of GBV-C was suspected in some patients in the latter group. Among patients with the non-B, non-C type of chronic disease, one of seven with cirrhosis (14%) and none with chronic hepatitis or hepatocellular carcinoma were GBV-C-positive. In chronic hepatitis C patients who had received interferon treatment, no difference was found in clinical findings, alanine aminotransferase (ALT) concentrations, histology or response to interferon between 11 patients who were GBV-C RNA-positive and 101 patients who were GBV-C RNA-negative. Moreover, changes in ALT after interferon therapy showed no relation to positivity for GBV-C RNA. On the basis of these findings, GBV-C appears to be an unlikely cause of initiation or progression of chronic hepatic diseases.
Adult↗
Membrane Mucins and Breast Cancer.
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Journal Article↗
Primary biliary cirrhosis associated with membranous glomerulonephritis.
A 33-year-old woman was admitted to our department for evaluation of liver dysfunction and proteinuria. A liver biopsy specimen showed ductular proliferation and moderate portal fibrosis indicating stage II primary biliary cirrhosis. A renal biopsy specimen showed mild to moderate mesangial cell proliferation without crescent formation or interstitial nephritis. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG), third component of complement (C3), and Clq on glomerular basement membranes. The findings indicated stage I membranous glomerulonephritis. Administration of ursodesoxycholic acid together with prednisolone, azathioprine, and dipyridamole decreased proteinuria and improved cholestatic liver dysfunction.
Adult↗
cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets.
Cyclic AMP potentiates glucose-stimulated insulin release by actions predominantly at a site, or sites, distal to the elevation of the cytosolic free Ca2+ concentration ([Ca2+]i). Glucose also acts at a site, or sites, distal to the elevation of [Ca2+]i via the ATP-sensitive K+ channel (K+ATP channel)-independent signaling pathway. Accordingly, using rat pancreatic islets, we studied the location of the action of cAMP and its interaction with the glucose pathway. Forskolin, an activator of adenylyl cyclase, raised intracellular cAMP levels and enhanced KCl-induced (Ca2+ -stimulated) insulin release in the presence, but not in the absence, of glucose. Thus, cAMP has no direct effect on Ca2+ -stimulated insulin release. The interaction between cAMP and glucose occurs at a step distal to the elevation of [Ca2+]i because forskolin enhancement of KCl-induced insulin release, in the presence of glucose, was demonstrated in the islets treated with diazoxide, a K+ATP channel opener. The enhancement of insulin release was not associated with any increase in [Ca2+]i. Furthermore, the interaction between cAMP and glucose was unequivocally observed even under stringent Ca2+ -free conditions, indicating the Ca2+ -independent action of cAMP. This action of cAMP is physiologically relevant, because not only forskolin but also glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pituitary adenylyl cyclase activating polypeptide exerted similar actions. In conclusion, the cAMP/protein kinase A pathway has no direct effect on Ca2+ -stimulated insulin exocytosis. Rather, it strongly potentiates insulin release by increasing the effectiveness of the K+ATP channel-independent action of glucose.
Adenosine Triphosphate↗
Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.
Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive K+ channel (K(ATP) channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 micromol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 micromol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K(ATP) channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.
Adenosine Triphosphate↗
Long-term prognosis of islet cell antibody-negative ketosis-onset diabetes with subsequent non-insulin dependency.
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Adolescent↗
[Multiple myeloma in siblings].
We encountered 2 patients with multiple myeloma in a family with 11 siblings, suggesting that the occurrence of the disease may be associated with genetic factors. Patient 1: The second daughter (age 79) was given a diagnosis of multiple myeloma and admitted to our hospital in December 1997 for treatment. IgG-lambda type M protein was detected by serum immunoelectrophoresis, punched out lesions (+) by X ray examination, and atypical plasma cells (14% of total) by bone marrow examination. Patient 2: The fifth daughter (age 68) received a diagnosis of multiple myeloma and was admitted to our hospital in May 1997 for treatment. Bence Jones-kappa type and IgA-kappa type M protein were detected by serum immunoelectrophoresis, punched out lesions (+) by X ray examination, and atypical plasma cells (90% of total) by bone marrow examination. It was noted that the sixth daughter had leukemia; hence, 3 of the 11 siblings had blood disorders. For this reason, HLA studies were performed and detected A31, B39, B51, and Cw7 in patient 1 and A31, B51, B62, and Cw4 in patient 2. Further case studies will hopefully reveal more details concerning the relationship between myeloma and HLA.
Aged↗
Comparison of differential diagnostic capabilities of 201Tl scintigraphy and fine-needle aspiration of thyroid nodules.
UNLABELLED: We assessed the ability of 201TI planar scintigraphy and fine-needle aspiration (FNA) biopsy to differentiate malignant from benign lesions by comparing the findings of these techniques with those of surgical histopathology for 107 patients with 109 thyroid nodules. METHODS: 201TI (74 MBq) was injected intravenously, and an early image and a delayed image were acquired after 10 and 120 min, respectively, for 10 min each. For 201TI planar scintigraphy, accumulation of the tracer in the nodules was visually scored and the nodules were grouped. Group A showed high activity in both early and delayed images. Group B revealed high activity in only the early image. Group C showed activity in the early image equal to that in normal tissues. Quantitative calculation of the washout rate was less than 0 in group CI and 0 or higher in group CII. Group D revealed low activity in the early image and variable activity in the delayed image. Three differential diagnosis methods were used for 201TI planar scintigraphy: method 1, in which only group A was considered malignant; method 2, in which both group A and group B were considered malignant; and method 3, in which groups A, B and CI were considered malignant. FNA results were assessed and classified by experienced pathologists. Two differential diagnosis methods were used for FNA: method a, in which malignancy was assigned to class IV (probably malignant or higher), and method b, in which malignancy was assigned to class III (possibly malignant or higher). RESULTS: Concerning 201TI methods 1, 2 and 3, sensitivity was 74.0%, 84.0% and 92.0%, respectively; specificity was 83.1%, 64.4% and 54.2%, respectively; and accuracy was 78.9%, 73.4% and 71.6%, respectively. For FNA, method a and method b had a sensitivity of 36.0% and 50.0%, respectively, and a specificity of 96.6% and 84.7%, respectively. The accuracy of both methods was 68.8%. For follicular lesions, sensitivity ranged from 80.0% to 90.0% for 201TI scintigraphy and from 10.0% to 30.0% for FNA. CONCLUSION: 201TI planar scintigraphy was found to be easier to use and more accurate than FNA in the differentiation of diagnosis of benign and malignant thyroid nodules based on visual scoring combined with quantitative evaluation.
Adolescent↗
Effect of folic acid on thymidylate synthase and thymidine kinase in regenerating rat liver after partial hepatectomy.
The effects of folic acid on liver regeneration after partial hepatectomy were investigated. The injection of folic acid inhibited the increases in the activities of thymidylate synthase and thymidine kinase in regenerating rat liver at 24 h after partial hepatectomy, with a concomitant reduction in DNA content. Northern blot analysis showed that this inhibition was due to the delay of the elevation of the mRNA levels of thymidylate synthase and thymidine kinase after partial hepatectomy. At 48 and 72 h, after partial hepatectomy, the thymidylate synthase activities in the folic acid injected rats increased to about 1.9- and 1.7-fold the corresponding control level, respectively, while thymidine kinase activities were similar to the control. Immunoblotting assay indicated that the increases in the thymidylate synthase activity at 48 and 72 h after partial hepatectomy were caused by a three fold increase in its protein level. Folic acid suppressed chymotryptic hydrolysis of thymidylate synthase. These suggest that folic acid increases the protein level of thymidylate synthase, at least in part, through protection against proteolysis.
Animals↗
Glucose action 'beyond ionic events' in the pancreatic beta cell.
For normal glucose homeostasis, insulin release by the pancreatic beta cell is vital. Until recently, it was thought that glucose-induced ionic events, such as closure of the ATP-sensitive K+ (KATP) channels, membrane depolarization, activation of the L-type voltage-dependent Ca2+ channels, Ca2+ influx and elevation of cytosolic free Ca2+, constitute the main signalling pathway in beta-cell stimulus-secretion coupling. However, since the discovery of 'non-ionic' glucose actions in the beta cell by the Aizawa and Henquin laboratories in 1991, data have accumulated that strongly indicate the physiological relevance of this signalling pathway. In this review, Toru Aizawa and colleagues discuss how the KATP channel-Ca2+ hypothesis was formulated, what was overlooked in the hypothesis, and then provide a comprehensive view of stimulus-secretion coupling in the beta cell, with an emphasis on non-ionic glucose actions.
Adenosine Triphosphate↗