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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 181 records · Page 10Linked to original sources

Hepatitis C virus replicative levels and efficiency of genotyping by specific PCR and antibody assay.

We studied factors which influence the detection of hepatitis C virus genotypes by the group-specific PCR of the sequence within the core region gene and by the newly developed genotype-specific NS4 antibody assay. Genotyping was performed on 75 hepatitis C virus carriers in Japan, where patients with hepatitis C viremia are exclusively infected with genotype 1b, 2a, and 2b. PCR failed to identify genotypes in 8 (11%) patients, whereas 12 (16%) patients, including the 8 patients mentioned above, could not be genotyped by the serological assay. Serological genotypes showed almost complete agreement with those found by the PCR except that double infection was revealed in only two of the eight patients serologically judged to be coinfected with genotypes 1 and 2. In each assay, disease activity and levels of viremia assessed by a competitive reverse transcription PCR assay were significantly lower in patients infected with untypeable isolates than in those infected with typeable ones (P < 0.01). The PCR could identify the genotypes of isolates from all 64 patients with levels of viremia of > or = 10(6) copies/ml, and the genotype-specific antibody responses were found in 60 (94%) patients. In contrast, isolates from only 3 (27%) of 11 patients with low levels of viremia (< 10(6) copies/ml) could be genotyped by the PCR (P < 0.00001), and these patients showed the genotype-specific antibody responses (P < 0.00001). These findings suggest that low levels of hepatitis C virus replication may reduce the efficiency of genotyping by serological assay as well as by PCR.

Adult↗

The sequence element of the internal ribosome entry site and a 25-kilodalton cellular protein contribute to efficient internal initiation of translation of hepatitis C virus RNA.

Translation of hepatitis C virus (HCV) RNA is initiated by internal entry of ribosomes into the 5' noncoding region (NCR). This process depends on genomic elements within the 5' NCR called the internal ribosome entry site (IRES) and may involve host factors. The alpha-branch structure (nucleotides 47 to 67) of the HCV IRES is considered a cis-acting element critical for translation initiation because it is indispensable for translation in vitro (S. Fukushi, K. Katayama, C. Kurihara, N. Ishiyama, F. B. Hoshino, T. Ando, and A. Oya, Biochem. Biophys. Res. Commun. 199:425-432, 1994). In order to further characterize the function of the alpha-branch, we determined whether sequence exchange within the alpha-branch had any effect on translation initiation. An in vitro translation study revealed that the stem sequences of this region played an important role in efficient IRES function. In addition to several HeLa cell proteins, which had a binding affinity for the 5' NCR, a novel 25-kDa protein that specifically interacted with the HCV IRES was discovered. The binding affinity of the 25-kDa protein for the 5' NCR was correlated with the efficiency of translation initiation of HCV RNA, indicating a critical role for the 25-kDa protein in HCV translation.

Animals↗

Prolongation of QTc interval in patients with Parkinson's disease.

QTc intervals were measured in 30 patients with Parkinson's disease and 30 healthy control subjects. The mean value of QTc intervals in patients with Parkinson's disease significantly exceeded that of healthy controls (418 +/- 14 ms vs. 403 +/- 18 ms). Prolongation of the QTc interval was unrelated to the administration of levodopa. The mean QTc interval in patients whose Hoehn and Yahr score was III or more was significantly greater than that of patients whose score was II or less (424 +/- 12 ms vs. 410 +/- 12 ms). A significant correlation between the QTc interval and the Valsalva ratio, as well as the overshoot, was identified. The QTc interval is closely related to autonomic nervous system dysfunction, including abnormal baroreceptor reflex function, in patients with Parkinson's disease.

Antiparkinson Agents↗

Study on baths with crude drug. III. The effect of ligustici chuanxiong rhizoma extract on the percutaneous absorption of some natural compounds.

To investigate the permeability of natural compounds through hairless mouse skin, compounds having a range of lipophilicity, i.e., ginsenoside-Re (1), baicalein (2), glycyrrhizin (3), baicalein (4), wogonin (5), honokiol (6), magnolol (7), bergapten (8), shikonin (9) and sinomenine (10) were used. These compounds permeated through the skin a little, however, they were generally accumulated into the skin. The uptake amount into the skin of each compound related to their lipophilicities in the in vitro experiment. Furthermore, Ligustici Chuanxiong Rhizoma (Senkyu) ether extract (SEE) enhanced their permeability into the skin; especially, it exhibited an effect on the skin permeability of moderately lipophilic compounds such as 4, 8. The effect of SEE in vivo was similar to that obtained in the in vitro experiment. From these results, it was clarified that natural compounds having high lipophilicity sufficiently permeated into the hairless mouse skin owing to their accumulative property, and SEE enhanced the permeability of the moderately lipophilic compounds into the skin.

Animals↗

Effect of coronary risk factors on coronary angiographic morphology in patients with ischemic heart disease.

We investigated the effects of hypercholesterolemia, hypertension, and diabetes mellitus, which are major coronary risk factors, on the angiographic morphology of coronary artery lesions in 204 patients with previous myocardial infarction or stable-effort angina: 39 patients with hypercholesterolemia (serum total cholesterol > 240 mg/dl) without hypertension and diabetes, 51 patients with hypertension without diabetes and hypercholesterolemia, 24 patients with diabetes without hypertension and hypercholesterolemia, and 90 patients without any of these 3 risk factors (control). Patients without coronary artery lesions were excluded. The severity of coronary artery lesions is expressed as the Gensini score and the morphology is classified according to Rosch's classification. The distribution of coronary artery lesions did not differ significantly between the 4 groups. The Gensini score was significantly higher in the hypercholesterolemia group than in the other groups (p < 0.05). Short concentric lesions were more frequent in the hypercholesterolemia group than in the control group (p < 0.01), and tubular regular lesions were more frequent in the hypertension and diabetes groups than in the control group (p < 0.01). These results suggest that hypercholesterolemia has a greater influence on the severity of coronary artery lesions than does hypertension or diabetes, and that the progression of coronary atherosclerosis may differ among patients with these risk factors.

Adult↗

High affinity binding of azasetron hydrochloride to 5-hydroxytryptamine3 receptors in the small intestine of rats.

The binding affinity of azasetron hydrochloride (azasetron) for the 5-hydroxytryptamine3 (5-HT3) receptor in a tissue preparation of rat small intestine was investigated by using [3H]granisetron as a radioligand. Scatchard analysis of specific [3H]granisetron binding revealed a single population of saturable binding sites in the tissue preparation. At this site, azasetron was concentration-dependently competitive with [3H]granisetron, and it inhibited the specific [3H]granisetron binding with a Ki value of 0.33 nM. Azasetron has a high affinity for 5-HT3 receptor in the gastrointestinal organ, the very site of its antiemetic action against chemotherapy-induced emesis.

Animals↗

High levels of serum interleukin-10 are associated with a poor response to interferon treatment in patients with chronic hepatitis C.

BACKGROUND: It still remains unclear whether some immunologic factors affect the response to interferon treatment. We therefore examined whether the pretreatment levels of serum interleukin-10 and soluble intercellular adhesion molecule-1 can be associated with the response to interferon treatment in patients with chronic hepatitis C. METHODS: One hundred and two patients with chronic hepatitis C treated with interferon alpha-2b were divided into three groups on the basis of patterns of biochemical interferon response. Pretreatment levels of serum interleukin-10 and soluble intercellular adhesion molecule-1 were determined using enzyme-linked immunosorbent assay. Hepatitis C virus (HCV) typing was performed with a serologic enzyme-linked immunosorbent assay. RESULTS: For patients with serotype I (n = 76) the numbers of sustained, transient, and non-responders were 12 (16%), 43 (56%), and 21 (28%), respectively. In serotype-I patients the pretreatment levels of serum interleukin-10 in non-responders were significantly higher than those in sustained or transient responders, although no significant differences were observed in HCV RNA quantity between them. There were no significant differences in the pretreatment levels of serum soluble intercellular adhesion molecule-1 among the three groups. CONCLUSION: These findings suggest that high serum interleukin-10 levels may be related to a poor response to interferon treatment in serotype-I patients with chronic hepatitis C.

Adult↗

[Relationship between cognitive deficits, behavioral disturbances and falls in patients with dementia].

Prospective study was conducted in order to investigate the relationship between cognitive and behavioral disturbances and falls in dementia. Falls and fall-related fractures were studied in 154 ambulatory patients who were admitted to a geriatric intermediate nursing facility with a diagnosis of Alzheimer's type dementia (DAT) or mixed Alzheimer and vascular dementia (MIX). The Mini-Mental State (MMS) was used for the evaluation of cognitive status, and the Dementia Behavior Disturbance Scale (DBD) was used as a behavioral parameter. In order to evaluate problematic behavior in walking, a derivative scale (DBD-W) was developed from the DBD by choosing three items relevant to wandering. During the 3 months of observation, 61 patients fell more than once; 15 of them experienced fractures. The mean MMS scores were higher in non fallers, fallers who did not sustain fractures and those complicated with fractures, in that order, and the difference between the non fallers and fallers with fractures was statistically significant. When the subjects were divided into three subgroups on the basis of the MMS scores, there was a trend toward a higher ratio of fallers or those complicated with fractures in the subgroup with the lower MMS score. The DBD and DBD-W scores were not associated with falls or fractures, although fallers had a slightly higher DBD or DBD-W score than non fallers. These findings suggest that the risk of falling or fracture becomes higher with the advance of cognitive impairment in institutionalized ambulatory patients with DAT or MIX. The findings also suggest that behavioral disturbances are not necessarily associated with falls or fractures.

Accidental Falls↗

[Clinicophysiological study of tremor in Parkinson's disease: quantitative tremor-based assessment of motor count using actigraphy].

In Parkinson's disease, resting tremor is often the initial symptom. This report focuses on the mechanism underlying tremor in Parkinson's disease and quantitative assessment of tremor. Central factors including Vim (nucleus ventralis intermedius) in the thalamus, and peripheral factors, such as acceleration of input pathways from muscle spindles via muscle tonus, are important aspects of the tremor mechanism in Parkinson's disease. It has also been suggested that tremor in Parkinson's disease is associated with parasympathetic and sympathetic dysfunctions. Objective assessments of tremor, such as the application of surface electromyography, are useful in the diagnosis and treatment of Parkinson's disease. Actigraph, as introduced herein, is a three dimensional motor sensing apparatus. Therefore, motor counts over 0.01 G can be detected by actigraphy. To date, this device has been used for evaluating akinesia in Parkinson's disease and insomnia. In this study, actigraphy was used in Parkinson patients with tremor, and it reflected motor activity in the wrist and was associated with the severity of hand tremor. Activities of daily living (ADL) are disturbed by hyperkinesia of the hand for Parkinson patients with hand tremor. We demonstrated that actigraphy is a simple and quantitative method of assessing motor activity in Parkinson patients with tremor.

Aged↗

[Central motor conduction time using magnetic and vibratory stimulation in Parkinson's disease, especially in patients with rigidity].

Rigidity, tremor, akinesia and disorder of postural reflex are the main clinical features of Parkinson's disease. We presented the mechanism underlying rigidity and assessed central motor conduction time (CMCT) using magnetic, with or without vibratory, stimulations. Basal ganglia, especially, the internal pallidum, and the thalamus play major roles in the mechanism of rigidity in Parkinson's disease. Hyperexcitability of the spinal motor nucleus due to low threshold has been recognized. Magnetic stimulation is painless and is simpler than electric stimulation. Therefore, this method is used clinically for evaluating conduction disturbance of the upper motor neurons in multiple sclerosis, cerebrovascular disease and so on. CMCT measured by magnetic and/or electric stimulation may be abbreviated or normal in Parkinson's disease, according to the literature, though controversy persists in this regard. In our study, CMCT was normal in Parkinson patients. However, CMCT was reduced in patients with rigidity and tremor. Furthermore, in a portion of the patients, CMCT was further abbreviated by also applying vibratory stimulation. These observations support the hypothesis that cells in the thalamus, cortex and spinal cord and/or pathways in these portions of the central nervous system are excitable or activated in Parkinson patients with rigidity and tremor. However, elucidation of the mechanisms underlying rigidity and tremor awaits further investigation.

Humans↗

[Detection of GBV-C RNA among non B non C hepatocellular carcinoma patients].

Recently, an RNA virus member of the flaviviridae, GBVirus C(GBV-C) was isolated from the serum of patient with cryptogenic hepatitis, but clinical significance for this virus has been not known now. To estimate the prevalence of GBV-C, we investigated the presence of GBV-C RNA by reverse transcription-nested polymerase chain reaction in the serum from various liver disease patients. The results were summarized as follows: [Table: see text] Among these, only 5 patients gave positive results, and these 5 cases had the history of blood transfusion before. Especially both non B non C HCC patient and non A non B non C fulminant hepatitis patient were negative for GBV-C on admission, while positive after blood transfusion as treatment. In the non B non C HCC patient, GBV-C RNA persisted over a period of several months after transfusion, while no remarkable elevation of ALT was observed. These results demonstrated that GBV-C/HGV may be transfusion-transmissible, and may not associated with severe chronic liver disease such as liver cirrhosis or HCC.

Biomarkers↗

Nucleotide sequence of the 5' noncoding region of hepatitis G virus isolated from Japanese patients: comparison with reported isolates.

The nucleotide sequences of the 5' noncoding region (NCR) of hepatitis G virus (HGV) from sera of Japanese patients were determined. Among these isolates, there was a high degree (> 96.9%) of sequence identity, whereas identity with previously reported GB virus-C or HGV strains was low (> 87.0%). Phylogenetic analyses showed that the HGV strains from Japanese patients clustered in groups distantly separated from previously reported strains. Among the Japanese HGV isolates, the genetic distances corresponded to subtype differences observed within hepatitis C virus (HCV) isolates, whereas the differences between the Japanese isolates and the prototypes corresponded to genetic distances observed between HCV genotypes. The Japanese HGV isolates found in this study should be placed in a new genotype distinct from previously described isolates.

Base Sequence↗

Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels.

The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8-153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29% vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10(6.4 +/- 1.1) vs. 10(6.5 +/- 0.7) copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers.

Adult↗

Low expression of erythrocyte complement receptor type 1 in chronic hepatitis C patients.

Primate erythrocyte complement receptor type 1 (CR1) plays an essential role in complement-associated immune complex clearance by transporting complexes to macrophages in the liver and/or spleen. Antibody-bound hepatitis C virus, which consists of immune complexes, is observed in patients with chronic hepatitis C. The aim of this study was to clarify the pathophysiological roles of erythrocyte CR1 in hepatitis C virus-infected individuals. We quantified the expression of erythrocyte CR1 with a fluorescence-activated cell sorter system in 57 chronic hepatitis C and 37 chronic hepatitis B cases and 20 normal volunteers. Complement-bound immune complexes were quantified by means of an enzyme-linked immunosorbent assay using anti-C1q and anti-C3d antibodies. Hepatitis C virus-infected patients showed lower erythrocyte CR1 and higher C3d immune complex levels than volunteers (P < 0.01 and P < 0.05, respectively). An inverse correlation was observed between the erythrocyte CR1 and C3d immune complex levels in hepatitis C virus infection (r = -0.300, P = 0.032). The erythrocyte CR1 levels in hepatitis C virus infection were lower in patients with severe liver inflammation, cirrhosis, or hepatocellular carcinoma than in those with mild inflammation, whereas the levels did not differ regardless of the disease stage in hepatitis B virus infection. These findings demonstrate that the expression of erythrocyte CR1 is related to immune complex quantity and the severity of liver disease in hepatitis C virus infection.

Adult↗

Electric field distribution of event-related potentials in stroke patients.

Electrical field distributions of event-related potentials (ERP's) were recorded during an auditory "oddball paradigm" and were analyzed in terms of time and space. Fourteen normal subjects and 14 chronic patients were cerebral thrombosis were studied. For the components N1 and P3 of the ERP's to target stimuli, reference-independent measures (latency, global field power, location of maximal or minimal potential, and location of centroids) were determined. Stroke patients displayed P3 abnormalities in latency, amplitude, and electrical field on the scalp. In addition, N1 electrical fields were also abnormal. These ERP abnormalities correlated significantly with the extent of mental function impairment in the stroke patients, and they improved after administration of a cerebral metabolic enhancer (Nefiracetam: DM-9384). The ERP's seemed to be sensitive in indicating the effects of the drug. These data suggest that time-course analysis of the spatial distribution of the ERP electrical field might be useful for evaluation of the extent of mental function impairment and the efficacy of drugs.

Aged↗

Analysis of the core region of HCV genome isolated from patients with chronic hepatitis C during intervals of normal ALT concentration.

We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.

Aged↗