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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 397 records · Page 22Linked to original sources
PubMed1993

Changes in antibodies to specific hepatitis C virus antigens with interferon-alpha therapy: analysis by recombinant immunoblot assay.

Antibodies to hepatitis C virus NS3 (C33C), NS4 (5-1-1 and C100-3), and core (C22-3) proteins were tested for by a second-generation recombinant immunoblot assay of serum samples from 42 chronic hepatitis C patients treated with interferon-alpha. Antibodies to 5-1-1 and C100-3 were found in 83% (35/42) before therapy, and those to C22-3 and C33C in all patients. At 6 months after therapy withdrawal in patients with sustained virus clearance, only antibodies to 5-1-1 and C100-3 showed significant decreases (p < 0.05) (5/5 and 7/7, respectively). Antibodies to C22-3 and C33C decreased less frequently in only 11% (1/9) (p < 0.01) and 44% (4/9) (p < 0.05), respectively. Thus, antibodies to 5-1-1 and C100-3 are prone to decrease following a decline in viremia. The antibody to the C22-3 (core) protein was least likely to decrease and may serve as a reliable marker of exposure to the virus.

Adult↗
PubMed1993

Quantitative analysis of antibodies to hepatitis C virus during interferon-alpha therapy.

We quantified IgG antibodies to structural (core) and nonstructural (C100-3) hepatitis C virus proteins in 42 patients with chronic hepatitis C treated with a 6-mo course of interferon-alpha. Sera were drawn before and at the end of therapy and also 6 mo after therapy withdrawal; they were stored for later analysis of antibodies and serum hepatitis C virus RNA. Sustained virus clearance was observed at the end of therapy and 6 mo after therapy withdrawal in nine cases; it was accompanied with sustained reductions of antibody to hepatitis C virus core protein and antibody to C100-3 protein. A sustained reduction of antibody to hepatitis C virus core protein was specific to sustained virus clearance, although that of antibody to C100-3 protein was not. None of the patients who did not show reductions of levels of both antibodies at the end of therapy displayed sustained virus clearance. Five patients showed hepatitis C virus RNA negativity and normal aminotransferase levels at the end of therapy without reduction of antibody to hepatitis C virus core protein levels. Of these five patients, relapse of hepatitis occurred in four, and viremia was present 6 mo after therapy withdrawal in all cases. These results demonstrate that testing for antibody titers may add information for evaluating virus clearance after interferon therapy.

Adult↗
PubMed1993

[Relationship between reduced myocardial uptake of beta-methyl-p-(123I)- iodophenyl-pentadecanoic acid (123I-BMIPP) and regional diastolic ventricular dysfunction in patients with hypertrophic cardiomyopathy].

To assess whether regionally depressed myocardial uptake of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), is related to regional ventricular diastolic dysfunction in patients (pts) with hypertrophic cardiomyopathy (HCM), we carried out 123I-BMIPP myocardial SPECT and radionuclide ventriculography (RNV) at rest in 9 HCM pts (eight pts with asymmetric septal hypertrophy (ASH), and one patient with apical hypertrophy). The defects of 123I-BMIPP were semiquantitatively estimated by segmental analysis. Regional LV function was determined by sector analysis in RNV: regional peak filling rate (rPFR), regional time to peak filling rate (rTPFR), and early 1/3 filling rate (1/3 fil) were estimated in the LV septal and posterior sectors. Wall thickness was evaluated with M-mode echocardiography. As results, the defects of 123I-BMIPP myocardial SPECT, were found frequently in septal wall, but any defect was not recognized in all septum with significant hypertrophy. Also, the degree of septal hypertrophy was not significantly related to BMIPP defect score. However, the regional diastolic function (rPFR, rTPFR, 1/3 fil) in the septal lesions with 123I-BMIPP defects was decreased more than those without 123I-BMIPP defect in HCM. Furthermore, the relative regional diastolic dysfunction (the differences between rTPFR and 1/3 fil in the septum and in the posterior wall) was significantly related to BMIPP defect score. In conclusion, this results suggest that the decreased uptake of 123I-BMIPP is related to regional diastolic dysfunction more than wall hypertrophy.

Aged↗
PubMed1993

[Quantitative assessment of cerebral blood flow by 123I-IMP SPECT: venous sampling method with hand warming in the water bath].

In order to establish a noninvasive, quantitative method for measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, we attempted to employ continuous venous sampling instead of arterial sampling. Forty two patients with cerebrovascular diseases were classified into two groups, with (group II: n = 35) and without (group I: n = 7) hand warming. In group II, either hand was warmed, wrapping in a hot blanket (group IIA) or immersed in a 44 degrees C water bath (group IIB). In each patient, immediately after intravenous bolus injection of 222 MBq IMP, arterial and venous blood samples were collected continuously for 5 min from the radial artery and the cubital vein, respectively. By octanol extraction, IMP was divided into the unmetabolized and metabolized fraction. The ratio of 123I-IMP radioactivity of venous blood compared to arterial blood (pass ratio, referred as %PR) was calculated in three fractions, whole blood, unmetabolized, and metabolized fraction. By using these parameters, we assessed the possibility to estimate the amount of unmetabolized IMP fraction of arterial blood, usually used as an input function, from venous samples. In group I, %PR demonstrated a considerable variation between individuals (whole IMP, 47.5 +/- 24.6% (mean +/- SD): unmetabolized IMP, 46.0 +/- 24.5%: metabolized IMP, 51.8 +/- 27.4%). In group II, especially in group IIB, both increase of %PR value and the decrease in variation (whole, 77.9 +/- 5.6%: unmetabolized, 75.7 +/- 5.7%: metabolized, 86.7 +/- 8.7%) were observed, which permitted the further calculation based on the assumption that %PR value was constant in each IMP fraction (whole blood and unmetabolized fraction).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Expression of the protein kinase C genes during liver regeneration].

Protein kinase C (PKC) plays an important role in intracellular signaling. PKC consists of a family of at least eight distinct enzymes. How PKC can be responded to liver regeneration and growth is largely unknown. In an in vivo experiment, regenerating liver after partial hepatectomy (Hx) and carbon tetrachloride (CCl4) administration, expression of the PKC alpha-type was increased, with a single peak, after Hx and CCl4 administration. On the other hand, the PKC epsilon-type gene was activated with biphasic peaks following Hx but was elevated with a single peak after the CCl4 administration. In an in vitro experiment using primary cultured hepatocytes, both of the PKC alpha-type and epsilon-type genes could be induced only by combination of insulin and serum. These results demonstrate that both isoforms of PKC are identically regulated by extra- and intracellular stimuli, thereby influencing growth control of hepatocytes.

Animals↗
PubMed1993

Evaluation of structural change in diffuse liver disease with frequency domain analysis of ultrasound.

To evaluate structural changes in diffuse liver disease, frequency domain analysis was applied to ultrasonic signals from the liver. We assumed that liver tissue is a collection of semiregularly arrayed small scatterers of ultrasound. We applied cepstral analysis to the ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum caused by an interference effect among liver scatterers of a given spacing. Patients with liver conditions involving nonspecific change (n = 6), chronic hepatitis (n = 11), cirrhosis (n = 7) or fatty liver (n = 6) were examined. One hundred ultrasonic signals were obtained noninvasively with a 3.5-MHz transducer, and the space among scatterers was calculated for each signal using cepstrum analysis. Two statistical parameters, mode and kurtosis, were determined from the distribution of the space among scatterers for each patient; these parameters were compared with the histological findings in the liver. Space among scatterers kurtosis decreased with progress of liver fibrosis, and space among scatterers mode increased in cirrhosis. Neither space among scatterers kurtosis nor space among scatterers mode was affected by pathological fat in the liver. These results suggest that we can evaluate fibrotic changes in diffuse liver disease and that we can also noninvasively discriminate diffuse fibrotic liver disease from fatty liver.

Chronic Disease↗
PubMed1992

Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons.

We investigated whether reversible oxidative stress induced by the administration of the superoxide dismutase inhibitor, diethyldithiocarbamate, could induce tolerance to subsequent cerebral ischemia in gerbil hippocampal neurons. Mature male gerbils received intraperitoneal injections of diethyldithiocarbamate (1.0 g/kg), which led to reduced superoxide dismutase activity and increases in thiobarbituric acid-reactive substance in the brain. Cerebral ischemia was produced by occluding the bilateral common carotid arteries for 5 min, either 2 or 4 days after diethyldithiocarbamate injection. One week after ischemia, samples from each brain were stained with hematoxylin-eosin to evaluate ischemic neuronal damage in the hippocampal CA1 sector. Diethyldithiocarbamate treatment 4 days before ischemia had significant protective effects against cerebral ischemia, while diethyldithiocarbamate 2-day pretreatment and vehicle treatment failed to show neuroprotection. Biochemical examinations showed a clear induction of heat shock protein 72 and a significant increase in manganese-containing superoxide dismutase in the hippocampus in animals treated with diethyldithiocarbamate 4 days prior to ischemia. These results suggested that the oxidative stress caused by diethyldithiocarbamate could induced tolerance to ischemia in the gerbil brain, and that the increase in the biosynthesis of manganese-containing superoxide dismutase and heat shock protein 72 could provide a biochemical explanation of the tolerance induced under these conditions.

Animals↗
PubMed1992

cDNA cloning of rat LRP, a receptor like protein tyrosine phosphatase, and evidence for its gene regulation in cultured rat mesangial cells.

Protein tyrosine phosphatases (PTPases) are a family of enzymes that play a crucial role in the regulation of signal transduction mediated by reversible protein tyrosine phosphorylation. To understand the significance of PTPases in physiological and pathophysiological processes in the kidney, we isolated three cDNA segments encoding PTPases (LAR, LRP and a novel PTPase) from rat kidney by polymerase chain reaction (PCR). Using PCR product as a probe, we isolated a full-length cDNA of rat LRP. LRP cDNA encoded a single membrane spanning protein consisted of 796 amino acids, with two tandemly located intracellular PTPase domains. By Northern analysis, a ubiquitous pattern of LRP gene expression in rat tissues was demonstrated. In cultured rat mesangial cells, LRP mRNA was detected and the mRNA level was suppressed by either interleukin-1 or interleukin-6 treatment.

Amino Acid Sequence↗
PubMed1992

Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a hepatitis-B-virus-transfected cell line.

The human hepatoblastoma-derived cell line HB611 secretes hepatitis-B surface antigen (HBsAg) and hepatitis-B e antigen (HBeAg) into the medium. Hepatitis-B-virus (HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5-azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alpha-fetoprotein (AFP) decreased with the 5-azacytidine treatment. Southern blot analysis of DNA digested with HpaII or MspI showed that 5-azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5-azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA.

Azacitidine↗
PubMed1992

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.

Adenocarcinoma↗
PubMed1992

Expression of MBP-HCV NS1/E2 fusion protein in E. coli and detection of anti-NS1/E2 antibody in type C chronic liver disease.

To characterize the putative NS1/E2 (non-structural protein 1/envelope 2) domain of HCV (hepatitis C virus), we expressed the hydrophilic three-quarters of this domain in a form of MBP (maltose binding protein) fusions in Escherichia coli. When we checked the positive frequency of antibody to this fusion protein, 17% of patients with type C chronic liver disease had this antibody. However, they were all positive for HCV-RNA in sera. These results suggest that the appearance of anti-NS1/E2 antibody does not serve as evidence of viral clearance.

ATP-Binding Cassette Transporters↗
PubMed1992

Auditory response properties and spatial response areas of single neurons in the pontine nuclei of the big brown bat, Eptesicus fuscus.

Using free-field acoustic stimulation conditions, we studied the response properties and spatial sensitivity of 146 pontine neurons of the big brown bat, Eptesicus fuscus. The best frequency (BF) and minimum threshold (MT) of a pontine neuron were first determined with a sound broadcast from a loudspeaker placed ahead of the bat. A BF sound was delivered from the loudspeaker as it moved across the frontal auditory space in order to locate the response center at which the neuron had its lowest MT. Then the basic response properties of the neuron to a sound delivered from the response center were studied. As in inferior collicular and auditory cortical neurons, pontine neurons can be characterized as phasic responders, phasic bursters and tonic responders. They have both monotonic and non-monotonic intensity-rate functions. However, most of them are broadly tuned as are cerebellar neurons. Auditory spatial sensitivity was studied for 144 pontine neurons. In 9 neurons, variation of MT with a BF sound delivered from several azimuthal and elevational angles along the horizontal and vertical planes crossing the neuron's response center was measured. In addition, variation in the number of impulses with several stimulus intensities at 10 dB increments above a neuron's MT delivered from each angle was also studied. The auditory spatial sensitivity of other pontine neurons was studied by measuring the response area of each neuron with stimulus intensities at 3, 5, 10, 15 or 40 dB above its lowest MT. The response areas of pontine neurons expanded asymmetrically with stimulus intensity, but the size of the response area was not correlated with either MT or BF. In half of the pontine neurons studied, the response area expanded greatly and eventually covered almost the entire frontal auditory space. The response areas of the other half of the pontine neurons only expanded to a restricted area of frontal auditory space. Two possible neural mechanisms underlying these two types of response areas are hypothesized. The response centers of all 144 neurons were located within a small area of the frontal auditory space. The locations of response centers of these neurons are not correlated with their BFs. The distribution pattern of these response centers is comparable to that of superior collicular and cerebellar neurons but is different from that of inferior collicular and auditory cortical neurons. The results of our study suggest that auditory information is integrated in the pontine nuclei before being further sent into the cerebellum.

Acoustic Stimulation↗
PubMed1992

Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats.

Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the hemorrhagic shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-alpha.

We tested serial serum samples for hepatitis C virus RNA from patients undergoing treatment for chronic hepatitis C with interferon-alpha using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 20 patients with chronic hepatitis who had serum antibody to hepatitis C virus (anti-C100-3). Before therapy, hepatitis C virus RNA was detected in 18 (90%) and 20 (100%) patients using primer sets derived from the NS3 region or the 5'-noncoding region of hepatitis C virus, respectively. Hepatitis C virus RNA became undetectable in all patients whose ALT level fell into the normal range during therapy. However, hepatitis C virus RNA reappeared in all patients whose ALT levels rose again after therapy, usually before the relapse. In patients whose ALT levels did not become normal, hepatitis C virus RNA did not disappear during therapy. Thus therapy with interferon-alpha appears to be beneficial in chronic hepatitis C because of its suppressive effects on hepatitis C virus replication. Detection of hepatitis C virus RNA in serum is useful for evaluating the antiviral effect of interferon.

Adult↗