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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 163 records · Page 9Linked to original sources
PubMed1996

Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma--its relationship to alcohol drinking and the age of transfusion.

Alcohol drinking has been reported to be an important factor that modulates the development and prognosis of chronic hepatitis B; however, little is known about an interrelationship between alcohol intake and the progression of chronic hepatitis C to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We attempted to clarify this interrelationship in patients with hepatitis C and history of blood transfusion. Thirty LC and 85 HCC patients were enrolled. In patients with LC, no significant correlation was observed between the amount of alcohol intake and the period from transfusion to diagnosis. The period from transfusion to diagnosis in HCC patients with alcohol intake > or = 46 g/day and < 46 g/day were 26 +/- 6 and 31 +/- 9 years, respectively, resulting in a significant difference (p < 0.05). The period from transfusion to diagnosis of LC and/or HCC showed significant negative correlation with the age of transfusion (r = 0.82, Y = -0.67X + 48.0, p < 0.01; r = 0.76, Y = -0.70X + 54.1, p < 0.001, respectively). This correlation was also observed in patients with HCC, regardless of the amount of alcohol intake. In conclusion, these data suggest that alcohol drinking might be an important factor that promotes an occurrence of HCC in patients with hepatitis C, and that hepatitis C virus infection in the elderly promotes development of liver disease via LC to HCC.

Adult↗
PubMed1996

Delayed neuronal death in ischemic hippocampus involves stimulation of protein tyrosine phosphorylation.

Glutamate triggers neuronal degeneration after ischemia-reperfusion in the brain. However, the details of intracellular signal transduction that propagates cell death remain unknown. The present work investigated whether protein tyrosine phosphorylation mediates neuronal death in the ischemic brain. Transient forebrain ischemia for 5-10 min in Mongolian gerbils or intoxication with the glutamate analogue kainic acid (12 mg/kg) in Sprague-Dawley rats caused neuronal death selectively in the hippocampus 2-4 days or 1 day later, respectively. Under these conditions, 160-, 115-, 105-, 92-, and 85-kDa proteins showed a significant increase in tyrosyl residue phosphorylation selectively in the hippocampus 3-12 h after ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine kinases, including pp60c-src, were activated without a change of tyrosine phosphatases. Administration of radicicol, a selective inhibitor of tyrosine kinases, attenuated stimulation of tyrosine phosphorylation and hippocampal degeneration after ischemia or kainic acid injection. The results suggest that protein tyrosine phosphorylation might propagate delayed neuronal death in the mature hippocampus through glutamate overload after ischemia-reperfusion.

Animals↗
PubMed1996

Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity.

We investigated whether loss of myocardial protection after ischemic preconditioning (IP) is related to the extent of deactivation of activated ecto-5'-nucleotidase. The coronary arteries of mongrel dogs were occluded four times for 5 min separated by 5 min of reperfusion (IP). Five (IP1), 30 (IP2), 60 (IP3), and 120 min (IP4) after the fourth 5-min coronary occlusion or after a corresponding nonischemic period (control groups), the coronary arteries were occluded for 90 min followed by 6 h of reperfusion. The infarct size-limited effect of IP gradually disappeared in the IP2 (21.6 +/- 3.9%) and IP3 (33.8 +/- 3.6%) groups compared with the IP1 group (8.3 +/- 1.6%) and returned to the control level in the IP4 group (39.9 +/- 5.2%). The increased ecto-5' -nucleotidase activity due to the IP procedure decreased according to the order of IP1 to IP4 groups. Infarct size was inversely correlated with ecto-5'-nucleotidase activity (P < 0.001). An inhibitor of ecto-5'-nucleotidase blunted the infarct size-limiting effect of IP. The infarct size-limiting effect of IP decreased as the activation of ecto-5'-nucleotidase was blunted. These results suggest that ecto-5'-nucleotidase activity plays a key role in the cardioprotection of IP.

5'-Nucleotidase↗
PubMed1996

Role of activation of ectosolic 5'-nucleotidase in the cardioprotection mediated by opening of K+c channels.

We tested the hypothesis that the opening of ATP-sensitive K+ channels contributes to activation of ectosolic 5'-nucleotidase and the infarct size-limiting effect of ischemic preconditioning. In open-chest dogs, the left anterior descending coronary artery was occluded four times for 5 min each, separated by a 5-min period of reperfusion (ischemic preconditioning, n = 8). After this procedure, the coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Infarct size was smaller in this group than in the group (control, n = 8) with a 45 min interval instead of the ischemic preconditioning procedure (40.1 +/- 3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limiting effect of ischemic preconditioning (infarct size, 37.3 +/- 5.8%; n = 7), and transient exposures to cromakalim and nicorandil mimicked it [infarct size, 10.1 +/- 3.1 (n = 7) and 11.1 +/- 2.7% (n = 8), respectively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in the ischemic preconditioning group compared with that in the control group; this preconditioning-induced increase in 5'-nucleotidase activity was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n = 5) and nicorandil (n = 5). The infarct size-limiting effect due to cromakalim and nicorandil was blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct size, 37.7 +/- 5.6 (n = 9) and 36.8 +/- 4.8% (n = 7), respectively] and 8-sulfophenyltheophylline (infarct size with cromakalim, 44.7 +/- 4.6%; n = 7). We conclude that activation of ectosolic 5'-nucleotidase due to the openers of ATP-sensitive K+ channels contributes to the infarct size- limiting effect of ischemic preconditioning.

5'-Nucleotidase↗
PubMed1996

Diurnal heart rate variability in healthy subjects: effects of aging and sex difference.

To study the effects of aging and gender, circadian profiles of heart rate variability were evaluated for 105 healthy volunteers by frequency domain analysis of a Holter electrocardiogram record. The low-frequency (LF) component representing cardiac beta-adrenergic function showed high values for the 0800-1200 period in male subjects and the 1200-2400 period in female subjects. The high-frequency (HF) component representing parasympathetic function showed a peak for the 0000-0600 period in both male and female subjects independent of age. Male subjects showed significantly higher %LF [LF/(LF + HF) x 100] than female subjects. LF showed consistently highly significant correlation with age. These basic findings can help elucidate the diurnal profile of cardiac nerve function and how it is affected by aging and sex difference.

Adult↗
PubMed1996

Adenosine inhibits leukocyte-induced vasoconstriction.

Polymorphonuclear leukocytes (PMNs) can induce endothelium-dependent constriction of vascular rings. Because adenosine inhibits the function of PMNs, we examined the effects of adenosine on the PMN-induced coronary vasoconstriction. We measured changes in the isometric tension of isolated rings of canine coronary arteries suspended in an organ chamber filled with Krebs-Henseleit solution after the addition of autologous PMNs. N-formyl-L-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMNs increased the tension of the coronary artery with the endothelium in a concentration-dependent manner. Treatment of FMLP-stimulated PMNs with adenosine inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. Stimulation of PMNs with CGS-21680C, but not with cyclohexyladenosine, inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. However, treatment of coronary arteries with adenosine had no effect on the adherence of PMNs to the endothelium and the PMN-induced constriction. These results suggest that stimulation of adenosine A2a receptors on PMNs may inhibit the PMN-induced vasoconstriction by inhibiting the adhesion of PMNs to the endothelium.

Adenosine↗
PubMed1996

Inhomogeneous disappearance of myofilament-related cytoskeletal proteins in stunned myocardium of guinea pig.

The decrease in Ca2+ responsiveness of myofilaments in stunned myocardium implies that there may be structural changes in proteins composing the contractile machinery. To elucidate the lesion in stunned myocardium, isolated guinea pig hearts were subjected to global ischemia at 37 degrees C and reperfused. SDS-PAGE revealed that the contents of desmin, alpha-actinin, and spectrin decreased in the myofibrillar fraction isolated from hearts reperfused after 60-minute ischemia compared with nonischemic control hearts. To examine the change of cytoskeletal proteins in stunned myocardium, immunohistochemical studies with antibodies against these proteins were performed after 15 minutes of ischemia. In stunned myocardium, the staining was largely intact, but there were some lesions where desmin was not stained and alpha-actinin and spectrin were only weakly identified. The percentage of normally stained areas in the myocardium (percent stained area), quantified by image processing, was significantly lower in stunned myocardium (79.6 +/- 3.6%, mean +/- SEM) than in nonischemic control myocardium (96.5 +/- 0.7%). Percent recovery of developed pressure significantly correlated with percent stained area (r = .82, P < .001). In hearts subjected to 15-minute ischemia but not reperfused, or in hearts reperfused with Ca(2+)-free solution after 15-minute ischemia, staining by the antibodies remained intact, suggesting that the change of the cytoskeletal proteins is mediated by Ca2+ overload during reperfusion. In hearts treated with the protease inhibitor leupeptin (50 mumol/L) or calpain inhibitor I (100 mumol/L), both developed pressure and staining were well preserved. These results indicate that contractile dysfunction in stunned myocardium has a strong correlation with the disappearance of cytoskeletal proteins that may be mediated by a Ca(2+)-dependent intracellular protease activated during reperfusion. The disruption of cytoskeletal proteins is a possible mechanism for stunning, although it may be a secondary effect of protease activation.

Actin Cytoskeleton↗
PubMed1996

A low-affinity vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus.

In this study, a mutation in vasopressin Type 2 receptor (V2R) in a patient with hereditary nephrogenic diabetes insipidus (NDI) has been identified and characterized. The sequencing of the V2R gene from the patient revealed that there was a missense mutation (TAT to TGT) resulting in the substitution of 205Tyr for Cys in the putative third extracellular domain. The expression analysis in COS cells showed that the binding affinity of the mutant receptor (KD = 19.8 nM) for arginine vasopressin was much lower than that of the wild-type receptor (KD = 1.8 nM) so that intracellular cAMP production stimulated by arginine vasopressin was impaired in cells with the mutant V2R. From these results, it was concluded that the single amino-acid substitution of V2R is responsible for this familial disease.

Adult↗
PubMed1996

The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells.

The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. As a step toward understanding the molecular basis of glucokinase (GK) gene regulation, we assessed the structure and regulation of the human GK gene beta-cell-type promoter. The results of reporter gene analyses using HIT-T15 cells revealed that the gene promoter was comprised of multiple cis-acting elements, including two primarily important cis-motifs: a palindrome structure, hPal-1, and the insulin gene cis-motif A element-like hUPE3. While both elements were bound specifically by nuclear proteins, it was the homeodomain-containing transcription factor insulin promoter factor 1 (IPF1)/STF-1/PDX-1 that bound to the hUPE3 site: IPF1, when expressed in CHO-K1 cells, became bound to the hUPE3 site and activated transcription. An anti-IPF1 antiserum used in gel-mobility shift analysis supershifted the DNA protein complex formed with the hUPE3 probe and nuclear extracts from HIT-T15 cells, thus supporting the involvement of IPF1 in GK gene activation in HIT-T15 cells. In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. These results revealed some conservative but unique features for the transcriptional regulation of the beta-cell-specific genes in humans. Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions.

Amino Acid Sequence↗
PubMed1996

Cochlear histopathology of the mutant bustling mouse, BUS/Idr.

The inner ear of mutant bustling mice, BUS/Idr, was examined histopathologically. LM examinations revealed an age-dependent degeneration of the auditory organ of Corti in BUS homozygotes, but not heterozygotes. Cochlear base-to-apex gradient in severity of the degeneration was noted. First signs of degeneration were found in the outer hair cells of the cochlear basal turn at about 3 weeks of age, followed by degeneration of the spiral ganglion cells which occurred slowly. As examined by SEM, stereociliary derangements of both the inner and outer hair cells were apparent in homozygotes as early as after 10 days. No normal arrays of stereocilia were found in homozygotes examined at 10 days through 6 months. The results of immunohistochemical examinations suggest that the sensory cells of the Corti's organ of homozygotes are structurally once normally innervated. No significant difference was found in the expression of protooncogene c-mos in the CNS between BUS homozygotes and control mice. We propose that BUS mice be categorized as a member of the so-called "waltzer-shaker" mutants group.

Age Factors↗
PubMed1996

Treatment with recombinant interferon-alpha 2a for patients with chronic hepatitis C: predictive factors for biochemical and virologic response. Osaka Liver Disease Study Group.

BACKGROUND: The heterogeneity of the hepatitis C virus (HCV) genome has been reported to be associated with the effectiveness of interferon therapy. We investigated the correlation of the viral and host factors, including the degree of sequence complexity of the HCV genome for responses to interferon-alpha in patients with chronic hepatitis C. METHODS: Ninety-seven patients received a 26-week course of recombinant interferon-alpha 2a therapy. The sequence complexity of the envelope 1-2 region was evaluated by polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. RESULTS: Of the 85 patients who completed the treatment, 31 (36%) achieved a sustained response, and 28 (33%) showed a sustained loss of HCV RNA. A low HCV RNA level, determined by the branched DNA probe assay, and serotype group 2 HCV correlated with a sustained response. In patients with serotype group 1 HCV of more than the threshold of the branched DNA probe assay, a band number on PCR-SSCP analysis of more than 2 could be associated with inefficacy of interferon therapy. Multivariate analysis in the 50 patients whose sera were available for all the virologic tests showed that only the HCV RNA level is independently predictive of a sustained response. CONCLUSIONS: Determination of the HCV RNA level is most important for predicting the response before interferon therapy. PCR-SSCP analysis may be useful as an additional test for patients with a high HCV RNA level of serotype group 1 HCV.

Adult↗
PubMed1996

[Non-specific neurological complaints and silent cerebral infarction].

To clarify the relationship between non-specific neurological complaints and silent cerebral infarction (SCI), we studied 82 patients (56 +/- 8 years old; mean +/- SD) who presented with at least one complaint (headache, dizziness, forgetfulness) and 76 normal volunteers with no complaints (55 +/- 7 years old). All subjects were evaluated with a questionnaire for complaints and with 0.5 T magnetic resonance imaging of the brain for the presence of SCI. Several risk factors for stroke were also studied. SCI was significantly more common in the patients (18%) than in the normal subjects (7%, p < 0.05). SCI was more common in subjects with dizziness (40%) and in those with headache (18%) than in those with no complaints (p < 0.01, p < 0.05, respectively). Dizziness and forgetfulness were closely associated with SCI (p < 0.05). Two risk factors for stroke, age and hypertension, correlated with SCI. These results clearly show that non-specific neurological complaints are closely related to SCI.

Aged↗
PubMed1996

Increased Parasympathetic Nerve Tone in Tinnitus Patients Following Electrical Promontory Stimulation.

Cutaneous digital blood flow (CDBF) during electrical promontory stimulation was measured by laser Doppler flowmetry in 46 tinnitus patients. In patients with tinnitus suppression. CDBF was increased. In contrast, patients in whom treatment did not suppress tinnitus experienced no change in digital blood flow. The cutaneous digital blood flow of patients who experienced slight relief did not differ significantly from patients who experienced no relief. The ratio of CDBF before and after treatment did not correlate with patient age, audiogram pattern. Our results suggest that relief of tinnitus was closely related to increased parasympathetic nerve tone.

Journal Article↗
PubMed1996

Improved Selective Attention and Word Perception in Tinnitus Patients Treated with Electrical Stimulation.

Grammatically correct but nonsense twenty 4-segment sentences mixed with multiple talk recorded on CD were delivered to ears tested in 47 tinnitus patients at a comfortable level via a headphone. The signal-to-noise ratios were 0dB, 5dB and 10dBSPL. Patients were requested to repeat what they heard before and after electrical treatment. A sinusoidal wave of 10kHz at the intensity of about 200mA was delivered to ears for 30 minutes by using a plate electrode for ECG at the tragus or a stimulating Pt-Ir electrode on the middle ear. Alternatively, 0.5mA DC was delivered to patients using a iontophoretic instrument. Improved word perception under noises was observed in most patients with tinnitus relief following electrical stimulation of the ear, demonstrating that electrical stimulation improved auditory selective attention. There may be a relationship between tinnitus relief and improved selective attention. It may be electrical stimulation of the ears that produced improved selective attention, inducing tinnitus relief and improved word perception according to our previous reports.

Journal Article↗