[Ischemic stress and molecular chaperon].
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Animals↗
Biomedical subjects
T Kamada
Publications and source records attributed to T Kamada.
Reactivity of cerebral blood flow to carbon dioxide in hypertensive patients: evaluation by the transcranial Doppler method.
OBJECTIVE: To evaluate hypertensive cerebral involvement before cerebrovascular accidents. DESIGN: Cerebral microvascular responses to changes in the arterial partial pressure of CO2 (pCO2; the CO2 reactivity) were compared among patients with different stages and severity of hypertensive disease. PATIENTS: Fifty-eight patients with hypertension, 11 with borderline hypertension, 15 hypertensives with cerebral infarction and 58 normotensive controls were studied. METHODS: The cerebrovascular CO2 reactivity was determined by measuring simultaneously the end-tidal pCO2 and the blood flow velocity in the middle cerebral artery using transcranial Doppler sonography under hypocapnic, normocapnic and hypercapnic conditions. RESULTS: CO2 reactivity was impaired in the hypertensive patients compared with in the normotensive controls, but less so than in the symptomatic hemisphere of the hypertensive patients with cerebral infarction. The CO2 reactivity in the borderline hypertensive patients was greater than that in both the symptomatic and asymptomatic hemispheres of the hypertensive patients with cerebral infarction. In the subjects without cerebral infarction, two risk factors for cerebral atherosclerosis (age and hypertension) were negatively correlated with cerebrovascular CO2 reactivity. In the hypertensive patients age and the estimated duration of hypertension were negatively correlated with cerebrovascular CO2 reactivity. CO2 reactivity in the patients with hypertensive or arteriosclerotic retinopathy or ST-T changes on their electrocardiogram was impaired compared with that in the patients without such changes. CONCLUSIONS: Hypertension affected the microvascular reactivity of the brain before the development of cerebrovascular accidents, and its effect varied dependently on the extent of involvement of other target organs.
Adult↗
[The diagnosis of a mutation of the insulin receptor by non-radioisotropical RT-PCR-SSCP analysis].
We evaluated a 24 years old diabetes woman with type A insulin resistant (patient "Yakushima") who had some typical symptoms as acanthosis nigricans, hirsutism and virilization. Insulin binding to the patient's erythrocytes was significantly decreased to about 30% of the normal control. In order to determine the mutation of the insulin receptor, we used for reverse transcript-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis without using radiolabeled materials. We also analysed the nucleotide sequence with non-isotropical probe. Our results suggested that the mutation was heterozygous, and the patient had a new missense mutation substituted Asn461 for Thr461 in the alpha-subunit.
Adult↗
Protective effect of ebselen on constrictive hepatic vasculature: prevention of alcohol-induced effects on portal pressure in perfused livers.
The effect of an organoselenium compound, ebselen [2-phenyl-1,2-benzisoselenazol-3-(2H)-one], on ethanol-induced liver damage through perturbation of microcirculation was investigated in perfused livers from fed rats. Infusion of ethanol at concentrations > or = 25 mM into the portal vein increased portal pressure in a concentration-dependent manner. Release of lactate dehydrogenase (LDH) into the effluent perfusate was minimal at 30 min; thereafter LDH release began to increase gradually until the end of the experiment (60 min after the onset of ethanol infusion) and was dependent on ethanol concentration. Simultaneous infusion of ebselen at a concentration of 10 or 30 microM with ethanol reduced significantly this ethanol-induced increase in portal pressure by 50 to 75% (P < .05) and LDH release by 70% (P < .05). When endothelin-1 or phenylephrine was infused into the liver, portal pressure was increased, reaching maximal levels (50 +/- 17 and 46 +/- 7 mm of H2O, respectively) and then decreasing gradually. Ebselen reduced the maximal increase in portal pressure induced by endothelin-1 (18 +/- 2 mm of H2O) by 64% (P < .05). In addition, ebselen decreased the maximal levels of portal pressure induced by phenylephrine (8 +/- 1 mm of H2O) by 83% (P < .05). These data indicate that ebselen has a vasodilative effect on constriction of hepatic vasculature and diminishes ethanol-induced hepatic damage by offsetting ethanol-induced increase in portal pressure. Thus, ebselen may prove useful for treatment of alcoholic liver injury via improvement of microcirculatory disturbances.
Animals↗
[Transcription factors for the insulin gene].
Production of insulin is stringently restricted to the beta cells of the endocrine pancreas. The major mechanism directing this specificity operates at the level of transcription. Previous studies have demonstrated that the tissue specificity in the insulin gene expression results from the cell-specific activity of its 5'-flanking enhancer/promoter, which limits the expression of a linked gene to the beta cell in tissue culture and transgenic mouse. Deletion, mutation, DNase I foot-printing, and gel-shift analyses revealed the presence of multiple cis-acting motifs. A set of positive and, possibly, negative trans-acting factors that are found in insulin-producing and noninsulin producing cells bind to these cis-acting elements and thus regulate transcription. Included among those are IEB (E-box)-binding IEF-1, a nuclear protein complex which consists of two basic helix-loop-helix proteins, and CT-box (TAAT box)-binding IPF1/STF-1, a homeodomain-containing transcription factor.
Animals↗
Selective alpha 1-adrenergic inhibition improves decrease glucose disposal in patients with essential hypertension.
This study evaluated insulin secretion and insulin sensitivity before and after short-term oral administration of doxazosin in patients with essential hypertension. The hypertensive group consisted of 11 nonobese subjects (aged 41.0 +/- 2.5 years (mean +/- SEM), body mass index 24.0 +/- 0.53 kg/m2). The normotensive group consisted of 12 subjects matched to the hypertensive group for age and body mass index. The hypertensive group showed significantly higher concentrations of prestimulated and stimulated plasma insulin and plasma C peptide than normal groups. The insulin-mediated glucose disposal rate during euglycaemic clamp (M-value) was significantly lower in the hypertensive group than in normal controls (7.32 +/- 0.56 vs 8.88 +/- 0.34 mg/kg/min, P < 0.05). After one month of doxazosin treatment blood pressure was significantly reduced (P < 0.05). The short-term administration of doxazosin improved the M-value significantly to 8.60 +/- 0.62 mg/kg/min without a significant change in stimulated plasma C-peptide level. These data show that hypertension is associated with increased insulin secretion and impaired insulin sensitivity. Selective alpha 1-adrenergic inhibition with doxazosin improves the decreased glucose disposal rate associated with hypertension.
Administration, Oral↗
Split dose iodine-123-IMP SPECT: sequential quantitative regional cerebral blood flow change with pharmacological intervention.
UNLABELLED: At least two quantitative rCBF measurements are needed to evaluate rCBF changes with pharmacological intervention. We have developed the split dose 123I-IMP SPECT method, which enables measurement of rCBF to be repeated in a short time. METHODS: Thirty-one cerebrovascular disease patients were investigated to assess reproducibility and vasoreactivity to acetazolamide. During 44-min dynamic SPECT imaging, 123I-IMP injection and respective arterial sampling were performed twice at an interval of about 25 min. The rCBF values were calculated using a microsphere model in which the washout of 123I-IMP from the brain can be negligible in the first several minutes after injection. For the second rCBF measurement, the remaining activity due to the first 123I-IMP injection was estimated and subtracted from the total brain activity. RESULTS: In ten patients, two consecutive resting mean rCBF values in the MCA territory (CBF1 and CBF2) had good correlation (CBF1 = 47.4 +/- 4.0 (ml/min/100 ml: mean +/- s.d.), CBF2 = 45.2 +/- 8.2, CBF2 = 0.900*CBF1 + 2.9, r = 0.915). In 11 patients with occlusive lesions in the unilateral ICA system, mean rCBF in the MCA territory was increased by only 27.7% +/- 14.0% in the affected side by a 1-g intravenous acetazolamide injection, while 44.5% +/- 12.3% increase was found in the nonaffected side. In 10 patients without a major arterial lesion, a 49.7% +/- 17.0% increase of rCBF was demonstrated. CONCLUSIONS: This split dose method 123I-IMP SPECT can be useful to estimate vascular reserve.
Acetazolamide↗
Serum hepatitis C virus RNA quantity and histological features of hepatitis C virus carriers with persistently normal ALT levels.
We studied hepatitis C virus carriers with normal liver function to evaluate the histological features of their livers and the replicative levels of hepatitis C virus. Liver biopsies were performed in 22 hepatitis C virus carriers with persistently normal ALT levels. Hepatitis C virus RNA in serum was quantified with a competitive assay that combined reverse transcription and the polymerase chain reaction, which is based on co-amplification of the target RNA with known amounts of synthetic mutated RNA. Three patients had normal livers on histological study, whereas the other 19 had chronic persistent hepatitis, with lymphoid infiltrates or aggregates in portal tracts commonly observed but intralobular inflammatory changes absent or minimal. The titer of hepatitis C virus RNA (logarithmic transformed copy number per milliliter of serum) varied from 4.0 to 8.0 (mean +/- S.D.: 6.3 +/- 1.1); it was significantly lower in the three patients with normal livers (4.3 +/- 0.2) than in those with chronic persistent hepatitis with mild (6.4 +/- 0.8, n = 11) or moderate (7.1 +/- 0.5, n = 8) portal inflammation. The titer of hepatitis C virus RNA was correlated with the total score (r = 0.68) and the score for portal inflammation (r = 0.68) in the histological activity index. These results indicated that there seem to be "healthy carriers" of hepatitis C virus with extremely low levels of viral replication. However, in most hepatitis C virus carriers with persistently normal ALT levels, there are inflammatory changes in the portal tracts, with severity depending on the replicative levels of hepatitis C virus.
Adolescent↗
Carbon dioxide reactivity by consecutive technetium-99m-HMPAO SPECT in patients with a chronically obstructed major cerebral artery.
UNLABELLED: In the management of major cerebral artery obstruction, cerebral perfusion reserve is key to introducing cerebral revascularization surgery. The purpose of this study was to evaluate the feasibility of assessing cerebral perfusion reserve by consecutive 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) SPECT with 5% carbon dioxide (CO2) inhalation. METHODS: The CO2 inhalation and consecutive 99mTc-HMPAO SPECT study was performed on 30 chronic ischemic cerebrovascular disease patients with unilateral major cerebral artery obstruction and on 27 patients without. CO2 reactivity was expressed as the percent increase of 99mTc-HMPAO accumulation from the baseline (%Change) and as a constant k' that was the ratio of 99mTc-HMPAO accumulation per 1 mmHg change of end-tidal CO2 tension by exponential curve fitting. RESULTS: The mean %Change and k' in the middle cerebral artery (MCA) territory on the side without an obstructive lesion or in the cerebellum ranged from 10.0% to 11.1% and from 0.98% to 1.13% per mmHg, respectively. In the MCA territory, an obstructive lesion was noted in 5.9% versus 0.54% per mmHg in the contralateral MCA territory (p < 0.01). Eleven of 30 patients with major cerebral artery obstruction revealed significant asymmetry in the k' value between bilateral MCA territories. CONCLUSION: The results showed compromised cerebral perfusion reserve in the obstructed major cerebral artery territory. The present method was proven clinically useful for evaluating cerebral perfusion reserve in patients with unilateral major cerebral artery obstruction.
Adult↗
Buoyant density of hepatitis C virus recovered from infected hosts: two different features in sucrose equilibrium density-gradient centrifugation related to degree of liver inflammation.
Hepatitis C virus is reported to have a low buoyant density in sucrose. To determine the density of hepatitis C virus in the circulation of infected hosts and its association with the degree of liver inflammation, we examined serum samples from 10 patients who were positive for both hepatitis C virus antibody (C100 antigen) antibody and serum hepatitis C virus RNA. After the serum was ultracentrifuged in sucrose density gradient (10% to 60%), the hepatitis C virus RNA titer in each collected fraction was quantified by means of competitive reverse transcription-polymerase chain reaction. In samples from five blood donors, the hepatitis C virus RNA titer had a single peak at fractions with densities of 1.08 to 1.11 gm/ml. In samples from five patients with ALT abnormalities, the titer had two peaks at fractions with 1.09 to 1.10 gm/ml and 1.22 to 1.25 gm/ml. After the selected samples were treated with detergents and ultracentrifuged, the titer in the 1.08 to 1.11 gm/ml fractions decreased and that in the 1.22 to 1.25 gm fractions increased. This result implied that the hepatitis C virus density changed with removal of the viral envelope by lipid solvents. Thus the buoyant density of hepatitis C virus in sucrose was 1.08 to 1.11 gm/ml for an intact virion and 1.22 to 1.25 gm/ml for what was presumed to be a nucleocapsid. These results demonstrated that HCV virion is a dominant form in the circulation of blood donors without ALT abnormalities. In patients with liver inflammation HCV particles with higher densities of 1.22 to 1.25 gm/ml coexist with virion in the circulation, which might be presumed nucleocapsids.
Adolescent↗
Three-dimensional display of liver, spleen, hepatoma, and blood vessels by MR imaging and computer graphics.
The technique of generating 3-D images from CT and MR data has made progress. Manipulation of the images has become simpler, the processing time shorter, and the quality better. Clinical application of this technique has been performed for images of brain (5, 7, 8) and bone (1, 2, 6), but only a few studies have been done of abdominal organs (3, 4).
Adolescent↗
Role of nitric oxide in ethanol-induced perturbation of hepatic microcirculation in rat liver.
Microcirculatory disturbance is one of the main pathogenetic features of alcoholic liver damage. We have demonstrated that ethanol increased portal pressure, leading to hepatic hypoxia and hepatocellular necrosis. In this ethanol-induced hepatic vasoconstriction, nitric oxide, an endothelial derived relaxing factor, dilated constrictive hepatic vasculature and reduced liver injury by improving the microcirculatory disturbance.
Animals↗
Alcohol and endogenous nitric oxide in hepatic microcirculation.
This study investigated the role of endogenous nitric oxide in the regulation of hepatic vascular tone in the presence of ethanol. In the perfused rat liver, upon the initiation of ethanol infusion into the liver, portal pressure was increased in a dose-dependent manner, reaching maximal levels in 2-5 min, then decreasing gradually. Simultaneous infusion of N(G)-monomethy 1-L-arginine, a nitric oxide synthesis inhibitor, enhanced this ethanol-induced increase in portal pressure. This enhancement was reversed by simultaneous infusion of a precursor of nitric oxide, L-arginine. These results suggest that endogenous nitric oxide acts as a vasodilator which reduces ethanol-induced vasoconstriction, thus improving the perturbation of hepatic microcirculation by ethanol.
Animals↗
Influence of ethanol on insulin receptor substrate-1-mediated signal transduction during rat liver regeneration.
Chronic ethanol exposure inhibits the capacity of the liver to regenerate. Insulin is a potent hepatotrophic factor, and tyrosyl phosphorylation (TP) of the intracellular insulin receptor substrate-1 (IRS-1) protein plays a crucial role in hepatocyte growth. The present investigation determined whether ethanol interferes with IRS-1-mediated signal transduction during liver regeneration induced by partial hepatectomy (PH) using the chronic ethanol-fed rat model. Tyrosyl phosphorylation of IRS-1 was strikingly increased and two peaks of TP were observed at 2 and 12 hr prior to the major wave of DNA synthesis in isocaloric pair-fed control animals; a blunted and delayed response was found in the ethanol-fed group. Furthermore, association of IRS-1 with phosphatidylinositol 3-kinase (PtdIns 3-kinase), a Src homology 2 (SH(2)) domain containing signal transduction molecule, was enhanced at 2 and 12 hr after PH in controls. In ethanol-fed rats, a single peak of association at 4 hr was observed. More important, PtdIns 3-kinase enzymatic activity was strikingly enhanced by the association with tyrosyl phosphorylated IRS-1 at 2 and 12 hr after PH, whereas in ethanol-fed animals this activity was greatly diminished and delayed to 6 and 36 hr, respectively. The biological consequence of this ethanol effect on TP of IRS-1 was a reduction and delay of the hepatic regenerative response after PH. These results indicate that one potential molecular mechanism whereby ethanol inhibits hepatocyte DNA synthesis is through its action on the IRS-1-mediated signal transduction pathway.
Animals↗
Determination of blood and urine manganese (Mn) concentrations and the application of static sensography as the indices of Mn-exposure among Mn-refinery workers.
Early detection of neurophysiological abnormalities is believed to be most effective for the early diagnosis of chronic manganism. The static sensography was applied during the periodical health examination and the significance of total distance of the postural sway (i. e. postural sway index) as a neurophysiological index was studied in relation to the blood and urine manganese concentrations. Sixty-six workers in a manganese (Mn)-refining factory, aged 29-59 (mean 47) years, were examined from 1984 to 1989. Mn-exposed workers had been engaged in alternating shifts and the mean duration of Mn exposure was 22.6 years before the health examination in 1984. Air-borne dust and Mn levels in the working environment were 0.07-2.74 mg/m3 and 0.02-0.46 mg/m3. The mean values of the parameters in Mn-exposed workers fluctuated as follows: blood Mn concentrations 19.1-26.9 micrograms/l [control; Mean 17.8 (Standard deviation 5.2) micrograms/l], urine Mn concentration 2.60-4.22 micrograms/g Creatinine [control; Geometric mean 1.16 (Geometric standard deviation 1.93) micrograms/g Creat.] and postural sway index 51.4-94.6 cm/30 sec [control; Geometric mean 59.7 (Geometric standard deviation 1.4) cm/30 sec.]. Although there were no significant correlations between the postural sway index and blood and urine manganese concentrations, the usefulness of this kind of simple neurophysiological test should be further investigated in combination with other established examinations.
Adult↗
Internucleosomal DNA cleavage involved in ischemia-induced neuronal death.
Pyramidal neurons of the hippocampal CA1 are known to be particularly vulnerable to transient ischemia resulting in "delayed neuronal death". Recent studies using aurintricarboxylic acid suggested that ischemia- or excitotoxin-induced neuronal death should share intracellular mechanisms in common with apoptosis. It is, however, unclear about involvement of endonucleases. Here using a transient (5 min) forebrain ischemia model in gerbils, we found that internucleosomal DNA fragmentation developed between 48 and 54 hr recirculations, accompanied with simultaneous or slightly preceding destruction of microtubule-associated protein 2. These results suggest that endonucleases, maybe activated by elevated intracellular Ca2+, play an important role in delayed neuronal death as well as in apoptosis.
Animals↗
[Proliferation mechanism of hepatitis C virus and effectiveness of interferon therapy].
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Adult↗
N-acetylglucosaminyltransferase III and V messenger RNA levels in LEC rats during hepatocarcinogenesis.
The LEC (Long-Evans with a cinnamon-like color) rat is a mutant of the Long-Evans strain which develops hereditary hepatitis and hepatoma with age. Activities and mRNA levels of N-acetylglucosaminyltransferase III and V (GnT-III and GnT-V, respectively) were determined during hepatocarcinogenesis in this rat using a LEA (Long-Evans with an agouti color) rat as a control. GnT-III activity in LEC rat liver increased after 30 weeks of age, at the stage of chronic hepatitis, to about 2.5-11.5 times the level in LEC rats aged 1-9 weeks. GnT-V activity in the LEC rat liver increased after 20 weeks of age, at the stage of acute hepatitis, to about 1.5-2.5 times the level in LEC rats of 1-9 weeks of age and then remained elevated. Both enzymes showed more dramatic increases in males than in females. The mRNA levels of the enzymes increased in proportion with the enzyme activities. Furthermore, GnT-III and GnT-V mRNAs were highly expressed in both cancer lesion and adjacent tissues. In one case of hepatoma with lymph node metastasis, GnT-III and GnT-V mRNA expression was much higher in the metastatic lesion than in the original cancer. GnT-III and GnT-V levels in the original cancer lesions were similar to those in the cancer lesions of the other LEC rats. These results indicated that expression of GnT-III and GnT-V was induced by chronic liver damage and hepatocarcinogenic changes in the LEC rats.
Age Factors↗