[A case of non-Hodgkin's lymphoma with portal hypertension and nodular regenerative hyperplasia].
Explore the source record for details and available documents.
Female↗
Biomedical subjects
E Hashimoto
Publications and source records attributed to E Hashimoto.
[Function and amount of GTP binding proteins in postmortem human brain in dementia of the Alzheimer's type].
Qualitative or quantitative alterations of GTP binding (G) proteins in membrane preparations from parietal cortex and temporal cortex in postmortem human brain obtained from patients with dementia of the Alzheimer's type (DAT) and aged and postmortem delay matched controls were investigated by immunoblotting with polyclonal antibodies (RM/1, AS/7, GC/2, QL, SW/1) against specific G protein (Gs alpha, Gi alpha, Go alpha, Gq alpha, G beta, respectively) and the functional photoaffinity GTP analog [azidoanilido GTP (AAGTP)] labeling. Although the quantitative immunoreactivity showed no significant differences between the two groups, a marked reduction in AAGTP binding to Gs alpha was seen in the DAT group compared with controls in both parietal and temporal cortex. Moreover, the ratio of Gs alpha to Gi/o alpha AAGTP binding decreased significantly in the same regions of the DAT group. These results suggest that the disturbances of G protein mediated signal transduction may be involved in the pathophysiology of DAT.
Alzheimer Disease↗
[Age-related alterations on GTP binding proteins in postmortem human brain].
It is important that natural aging-related alterations are characterized to understand disabilities associated with aging. In this study, age-related alterations of GTP binding (G) proteins were examined in membrane preparations from several regions (frontal cortex, temporal cortex, parietal cortex, occipital cortex, caudate nucleus, amygdaloid body) in postmortem human brain. Subjects were free from neurologic or psychiatric disease. The quantity of G proteins (Gs alpha, Gi alpha, Go alpha, Gq alpha, G beta subunit) was determined by immunoblotting with polyclonal antibody (RM/1, AS/7, GC/2, QL, SW/1, respectively). The function of G proteins was examined by photoaffinity GTP analog [azidoanilido GTP (AAGTP)] binding. The immunoreactivities of Gi alpha and Gq alpha subunits were correlated inversely with age in many areas. In caudate nucleus, the GsL alpha (45 kDa) and Go alpha subunit immunoreactivities were decreased with age. And the G beta subunit immunoreactivities showed a negative correlation with age in temporal and occipital cortex areas. However, AAGTP labeling to Gs alpha and Gi/o alpha and the ratio of Gs alpha to Gi/o alpha AAGTP binding showed no age-dependent changes. Our findings suggest that the functional modulation may compensate for quantitative alterations of G proteins with human senescence.
Aging↗
[Development of IDDM during interferon-alpha therapy in chronic hepatitis C].
Explore the source record for details and available documents.
Adult↗
The risk factor for development of thyroid disease during interferon-alpha therapy for chronic hepatitis C.
OBJECTIVES: To determine the risk factors for the development of thyroid diseases during interferon-alpha therapy, we analyzed the patients with chronic hepatitis C who were treated with interferon-alpha. METHODS: One hundred nine patients with chronic hepatitis C (77 men and 32 women, ages 20-72 yr) were treated with interferon-alpha (alpha, 48; alpha 2a, 38; alpha 2b, 23) for 14-40 wk. Thyroid function tests and seven autoantibodies were assessed at the beginning and end of interferon-alpha therapy, and every other month. A logistic multiple regression model was used in the statistical analysis of risk factors for development of thyroid diseases. RESULTS: Among the 106 patients with normal pretreatment thyroid function tests, nine patients (three men and six women, ages 33-62 yr) developed thyroid diseases. However, among three patients with abnormal thyroid function tests, exacerbation of thyroid disease was not observed during interferon-alpha therapy. Logistic multiple regression model revealed that positivity for microsome antibody was a significant risk factor for the development of thyroid disease (p < 0.0001, chi 2 = 20.18). Actually, compared to patients without microsome antibody at the beginning of therapy, the incidence of thyroid diseases in the patients with pretreatment microsome antibody was very high: 3.3% (3/99) versus 60% (6/10), respectively. Six patients developed hyperthyroidism and three patients developed hypothyroidism. The patients with hyperthyroidism had atypical clinical features. CONCLUSION: Our study revealed that positivity for microsome antibody at the beginning of interferon-alpha therapy is a risk factor for thyroid dysfunction.
Adult↗
Reduced sensitivity to ethanol of Gs alpha and Gi/o alpha in the cerebral cortex of alcoholic patients.
In this study, we examined the quantity and quality of G proteins in membrane preparations from cortical regions (frontal, parietal, temporal and occipital cortex) in post-mortem brains obtained from subjects with chronic alcoholism and controls matched with respect to age and post-mortem delay (PMDT). Immunoblot analysis showed that the level of GsH alpha (52 kDa) was significantly decreased in temporal cortical membranes from alcoholics compared with controls, while no differences were observed in the amount of any G protein in frontal, parietal and occipital regions. Additionally, ethanol enhanced photoaffinity guanine nucleotide binding to both G alpha and Gi/o alpha in human cortical membranes. The percentage of increase in ethanol-stimulated photoaffinity GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholic patients in all cortical regions. These observations indicated that subsensitivities to ethanol-induced stimulation in G protein may contribute to impaired trans-signaling in cortical membranes of chronic alcoholics.
Alcoholism↗
Activation of protein-tyrosine kinase p72syk with concanavalin A in polymorphonuclear neutrophils.
We studied the abundance, subcellular distribution of a non-receptor protein-tyrosine kinase p72syk (Taniguchi, T., Kobayashi, T., Kondo, J., Takahashi, K., Nakamura, H., Suzuki, J., Nagai, K., Yamada, T., Nakamura, S., and Yamamura, H. (1991) J. Biol. Chem. 266, 15790-15796) in porcine polymorphonuclear neutrophils and the activation upon the stimulation with concanavalin A. The abundance was about 0.1% of total proteins and mainly distributed in the particulate fraction. Upon concanavalin A stimulation, the activity of p72syk increased within 30 s, attained to the maximum level at 1 min, and then returned to the basal level within 6 min. This activation was observed in a dose-dependent manner and abrogated by simultaneous addition of methyl alpha-mannopyranoside. When both extra- and intracellular Ca2+ were depleted, the activation of p72syk was still persistent; in contrast, the deactivation process was completely abrogated even at 6 min after stimulation. The replenishment of Ca2+ in the presence of A23187 resulted in a similar deactivation pattern as seen in the Ca(2+)-rich condition. In addition, genistein and herbimycin A, potent protein-tyrosine-kinase inhibitors, were capable of reducing concanavalin A-evoked p72syk activation and Ca2+ mobilization as well as the aggregation and lysozyme release. Furthermore, A23187-induced Ca2+ accumulation in inhibitor-treated cells resulted in the restoration of those cellular responses. These lines of evidence suggest that p72syk is activated with concanavalin A in a Ca(2+)-independent manner, participating in a mechanism of Ca2+ recruitment, and negatively regulated by a feedback mechanism through Ca2+ in neutrophils.
Animals↗
Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells.
Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down-regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C.
Amiloride↗
Phosphorylation sites of myelin basic protein by a catalytic fragment of non-receptor type protein-tyrosine kinase p72syk and comparison with those by insulin receptor kinase.
Myelin basic protein has been used as a model substrate for determination of substrate recognition motif of various protein kinases. In this report phosphorylated sites of bovine brain myelin basic protein were studied with a catalytic fragment of protein-tyrosine kinase p72syk. Three of four tyrosine residues in myelin basic protein were phosphorylated by this kinase. Major phosphorylated site was 134Y and minor phosphorylated sites were 68Y and 127Y. As the phosphorylation site by p56lck was only 68Y, the recognition motif of p72syk was quite different from that of p56lck. Furthermore, the fact that elution pattern on HPLC of the phosphopeptides obtained by insulin receptor kinase was different from that by p72syk suggested that the recognition motif of p72syk was also different from that of insulin receptor kinase. These results may suggest that each protein-tyrosine kinase has a specific substrate recognition motif.
Amino Acid Sequence↗
Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis.
We analyzed the immunophenotypes of hepatic cellular infiltrates by quantitative immunohistochemical methods in biopsy specimens from 20 patients with primary biliary cirrhosis (PBC), 19 with primary sclerosing cholangitis, and 11 with autoimmune chronic active hepatitis. Specifically, we sought to identify activated T cells, interferon-gamma-producing cells, and natural killer cells. The portal cellular infiltrate in PBC contained a preponderance of CD4 cells in comparison with CD8 cells, with a CD4/CD8 ratio of 2.45:1. The cellular infiltrate in areas of piecemeal necrosis contained mostly CD8 cells. Infiltrating CD8 cells in PBC had the surface phenotype of cytotoxic (CD8-positive, CD11b-negative) cells. Approximately 4% of T cells expressed interleukin 2 receptors. Interferon-gamma-staining cells were rarely identified (in less than 2%). Cells that expressed the natural killer cell markers CD16, CD56, or CD57 were infrequent, constituting approximately 5% of the cellular infiltrate. The composition of the infiltrates was similar in patients with PBC and chronic active hepatitis. Natural killer cells were twice as common in patients with primary sclerosing cholangitis (P < 0.05) as in those with PBC. The inflammatory infiltrates in areas of piecemeal necrosis were similar in the three diseases and differed from those found within the portal area, in that CD8 cells were preponderant. In all three liver diseases, almost 90% of bile ducts expressed class II HLA antigens. These findings support the hypothesis that cytotoxic T cells of either the CD4 or CD8 immunophenotype but not natural killer cells may be involved in the pathogenesis of PBC and chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Idiopathic portal hypertension; a histopathological study of 26 Japanese cases.
Analysis of 25 liver biopsy specimens and one autopsy specimen from 26 Japanese patients (23 women and three men) with idiopathic portal hypertension revealed findings that collectively appeared diagnostic for the condition. Changes in the portal tract included capillary dilatation, phlebosclerosis, and fibro-elastosis of the stroma. Many portal veins were dilated and had herniated into the surrounding hepatic parenchyma. Portal vein obliteration and loss of bile ducts were a rare complication. The acinar architecture was disturbed by: 1) capillary and necro-inflammatory bridging, mostly between portal tracts and terminal hepatic veins; 2) the formation of isolated megasinusoids in a random distribution; 3) displaced and abnormally large hepatic vein branches with or without phlebosclerosis and 4) slender, curved fibrous septa (hairline septa). Early nodular regeneration was found in 25% of the cases. Our review supports the contention that incomplete septal cirrhosis may be a late manifestation of idiopathic portal hypertension. It is not clear whether the biopsy findings in Japanese patients differ only in severity from those in western patients, or whether the conditions differ pathogenetically. Some histopathological findings in the Japanese cases, in particular the necro-inflammatory changes, are difficult to reconcile with portal hypertension as a primary haemodynamic abnormality.
Adult↗
GTP binding proteins in postmortem human brain.
Explore the source record for details and available documents.
Adult↗
Liver biopsy features of acute hepatitis C compared with hepatitis A, B, and non-A, non-B, non-C.
The diagnosis of acute hepatitis C (AHC) often can only be suspected because current serologic tests remain negative for over 3 months. Because histologic features might provide useful clues, we reviewed 85 liver biopsy specimens from 85 patients with acute viral hepatitis, comparing 22 cases of AHC with 23 cases of acute hepatitis A (AHA), 30 cases of acute hepatitis B (AHB), and 10 cases of acute hepatitis non-A, non-B, non-C (AHNC). AHC was characterized by dense portal lymphoid aggregates (7 cases) and Poulsen-Christoffersen-type cholangitis (8 cases); these lesions were not found in any other type of acute viral hepatitis, and thus appeared to be diagnostic. Sinusoidal inflammatory infiltrates also were common in AHC, particularly in biopsy specimens obtained during the early phase of the disease. These inflammatory infiltrates did not appear to affect adjacent hepatocytes. Necrosis in AHC usually was spotty and accompanied by mixed inflammatory cells. In AHNC, necrosis was also spotty but, as an added feature, pigmented macrophages predominated in them. In AHA, necrosis was predominantly periportal, whereas in AHB, severe zone-3 necrosis predominated. Fatty changes were predominantly microvesicular; they were common in AHC but were also found in other groups. Collectively, the described histologic features allowed diagnosis of AHC in biopsy specimens with reasonable confidence. However, histologic findings failed to predict the prognosis in individual cases.
Acute Disease↗
High incidence of mitral and tricuspid regurgitation in patients with Graves' disease detected by two-dimensional color Doppler echocardiography.
With two-dimensional (2D) color Doppler echocardiography, the cardiac and valvular function of 24 consecutive patients with a history of Graves' disease (17 were hyperthyroid and 7 were euthyroid at the time of the examination) were evaluated. The incidences of mitral regurgitation (MR), tricuspid regurgitation (TR) and MR plus TR were significantly higher in the patients with Graves' disease than in the age-matched control group of patients without this disease. In the patients who had signs of congestive heart failure (CHF) while they were hyperthyroid, a significantly higher incidence of severe TR was observed. This is the first report of a 2D color Doppler echocardiography study on the incidences of TR and/or MR in patients with Graves' disease. Our data indicate that in Graves' disease valvular dysfunction can be caused by systemic disorders and that severe TR is a possible risk factor for CHF.
Adult↗
[Effects of ethanol on GTP-binding protein function in human brain cortex].
The effect of ethanol "in vitro" on GTP-binding protein in postmortem human brain cortex membranes was analyzed using by photoaffinity hydrolysis resistant GTP analog (azidoanilido GTP, AAGTP). AAGTP identified stimulatory GTP binding protein [Gs alpha (42 KDa)] and inhibitory GTP binding protein [Gi alpha (40 KDa)] in human brain cortex membranes. Ethanol augmented the amount of AAGTP binding to both Gs alpha and Gi alpha in human temporal and parietal cortex membranes. These results show that ethanol "in vitro" elevates not only Gs functions but also Gi functions in postmortem human brain cortex.
Aged↗
[Final goal and problems in clinical chemistry examination measured by advanced analytical instruments].
In the field of clinical chemistry of Japan, the automation of analytical instruments first appeared in the 1960's with the rapid developments in electronics industry. After a series of improvements and modifications in the past thirty years, these analytical instruments became excellent with multifunctions. From the results of these developments, it is now well recognized that automated analytical instruments are indispensable to manage the modern clinical Laboratory. On the other hand, these automated analytical instruments uncovered the various problems which had been hitherto undetected when the manually-operated instruments were used. For instances, the variation of commercially available standard solutions due to the lack of government control causes the different values obtained in institutions. In addition, there are many problems such as a shortage of medical technologists, a complication to handle the sampling and an increased labor costs. Furthermore, the inadequacies in maintenance activities cause the frequent erroneous reports of laboratory findings in spite of the latest and efficient analytical instruments equipped. Thus, the working process in clinical laboratory must be systematized to create the rapidity and the effectiveness. In the present report, we review the developmental history of automation system for analytical instruments, discuss the problems to create the effective clinical laboratory and explore the ways to deal with these emerging issues for the automation technology in clinical laboratory.
Autoanalysis↗
[Study on the relation of human red cell membrane protein band 4.2 to red cell aging--in cases of obstructive jaundice].
The relation of human red cell membrane protein band 4.2 to red cell aging both in normal controls and in cases of obstructive jaundice was studied. The studied subjects were 9 people aged 20 to 73 years, the serum bilirubin levels of whom ranged from 4.8 to 26.7mg/dl. And normal controls were 9 people aged 20 to 30 years. First, we separated red cells into several fractions depending on red cell aging by the method of Vettore et al. The analyses of polyacrylamide gel electrophoresis (PAGE) of each RBC membrane sample by Fairbanks' system revealed the results as follows. Primarily, it was observed that in comparison with band 4.1, band 4.2 both in normal controls and in cases of obstructive jaundice increased depending on red cell aging. Secondly, it was suggested that the decrease of band 4.2 protein in cases of obstructive jaundice should not be due to the higher level of serum bilirubin but to the lower level of red cell aging. Because the obstructive jaundice could shorten the life span of red cells and make the average aging level of red cells younger.
Adult↗
[Alcohol consumption and brain adenylate cyclase system in rats: brain adenylate cyclase activity in alcohol-preferring AA and alcohol-avoiding ANA rats].
Brain adenylate cyclase (AC) activity in the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats was examined. Both basal and Gpp(NH) p-stimulated AC activities were higher in the cerebral cortex of the ANA rats than in the AA rats. Isoproterenol-stimulated AC activity tended to increase in the cerebral cortex of the ANA rats compared to the AA rats. Basal AC activity in the striatum of the AA rats was higher than that in the ANA rats, however, striatal Gpp(NH)p-stimulated AC activity was not different between the two rats lines. In the mesolimbic and cerebellum, there was no difference in AC activity between the rat lines. These results suggest that the noradrenergic function in the cerebral cortex has an important role in the regulation of alcohol intake.
Adenylyl Cyclases↗