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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 73 records · Page 4Linked to original sources

Influence of age and disease severity on high resolution CT lung densitometry in asthma.

BACKGROUND: Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. METHODS: Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than -950 HU (RA(950)) on high resolution CT (HRCT) scans. RESULTS: In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%TLCO, %TLCO/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. CONCLUSIONS: Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.

Adult↗

Epstein-Barr virus nuclear antigen-1-dependent and -independent oriP-binding cellular proteins.

OBJECTIVE: Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and the replication origin, oriP, are essential for the replication and maintenance of latent EBV DNA in cells, but no enzymatic activity has been associated with EBNA-1 protein alone. In this study, we have searched for host cellular proteins that interact with EBNA-1 protein in various B cell lines latently infected with EBV, including a recently EBV growth-transformed cell line. METHODS: By using gel shift analysis, we investigated the interactions of an oligonucleotide containing a single EBNA-1 recognition site, derived from the family of repeats (FR) element of oriP, with protein from cell extracts. RESULTS: The FR oligonucleotide bound a (72-kD) cellular protein in the absence of EBNA-1 and without induction of the previously reported 'anti-EBNA-1 proteins'. The FR oligonucleotide formed complexes with additional proteins from EBNA-1-synthesizing cell lines; these complexes were abolished or supershifted by anti-EBNA-1 monoclonal antibodies. SDS-PAGE analyses of 35S-Met-labeled proteins that bound to a biotin- conjugated FR oligonucleotide, fractionated by a glycerol gradient centrifugation and affinity-purified with streptavidin, showed three major bands, a 72-kD protein, the FR binding of which seemed to be independent of EBNA-1, a 64-kD protein in both EBNA-1-transfected and latently EBV-infected cell lines, and a 45-kD protein in EBV-infected cell lines, which was most prominent in a recently EBV growth-transformed cell line. CONCLUSIONS: The FR element forms complexes with cellular proteins in the absence and presence of EBNA-1. These 72-, 64- and 45-kD cellular proteins might be involved in the function of the oriP and EBNA-1 system.

Binding Sites↗

Polymorphism of the 5'-upstream region of the human SNAP-25 gene: an association analysis with schizophrenia.

Recent studies have suggested that synaptic abnormalities may be part of the pathophysiology of schizophrenia. SNAP-25 (synaptosomal-associated protein of 25 kD) is one of the synaptic proteins responsible for presynaptic neurotransmission, axonal elongation and synaptogenesis. Genetic variation in the 5'-upstream region of the SNAP-25 gene was analyzed in 87 unrelated schizophrenic patients and 100 healthy controls. A novel polymorphic (TAAA)(n) tandem repeat was identified in the 5'-upstream region. There were no significant differences between the patient and the control groups in the distribution of repeat numbers of alleles or genotypes. In addition, no associations were found between the polymorphism for subtypes, longitudinal courses or positive family history of the patients. Our results suggest that polymorphisms in the 5'-upstream region of the SNAP-25 gene have no association with schizophrenia.

Adult↗

Polymorphisms in the promoter and coding regions of the synapsin III gene. A lack of association with schizophrenia.

The human synapsin III gene, located on chromosome 22q12-13, has previously been reported to indicate a susceptibility for schizophrenia. Noval rare variants (Thr136Thr in exon 3, Pro468Ser, Glu525Gln and Pro534Leu in exon 12, and 1769 G/C in the untranslated region of exon 13) were found in addition to the polymorphic variant (-196 G/A in the promoter region). No significant differences in genotypic or allelic frequencies of the -196 G/A polymorphism were found between 87 unrelated schizophrenic patients and 100 healthy controls, even when the patients were diagnostically subdivided into subtypes and course specifiers. Furthermore, allelic frequencies of the GATG repeat in intron 1 were not significantly different between the patients and the controls. These results suggest that synapsin III gene polymorphisms are not associated with schizophrenia.

Adult↗

Antiviral activity of fattiviracin FV-8 against human immunodeficiency virus type 1 (HIV-1).

A novel antiviral agent, fattiviracin FV-8, purified from the culture broth of Streptomyces microflavus strain No. 2445, showed potent antiviral activities against human immunodeficiency virus type 1 (HIV-1), herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and influenza A and B viruses. The action mechanism of fattiviracin FV-8 against HIV-1 was examined. As a result, the agent was thought to act on HIV-1 particles directly without lysis of the particles, and it affords the inhibition of viral entry into the host cells.

Animals↗

Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.

We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model.

Animals↗

Polymorphisms of the CCK, CCKAR and CCKBR genes: an association with alcoholism study.

OBJECTIVE: Cholecystokinin (CCK) plays an important role in the functioning of the central nervous system via an interaction with dopamine and other neurotransmitters. The dopaminergic system has been implicated in the maladaptive behaviors associated with drugs of abuse (e.g., alcohol and cocaine). We analyzed genetic variations in the promoter and coding regions of the CCK, CCKA-receptor (CCKAR) and CCKB-receptor (CCKBR) genes, and performed association analyses with alcoholism. METHOD: A total of 214 Japanese male patients with alcoholism (93 with delirium tremens, 49 with hallucinations, 38 with seizures and 83 without any of these symptoms) and 98 age-matched Japanese male controls were examined using PCR-based Single Strand Conformational Polymorphism (SSCP) analysis. RESULTS: A total of 8 variants in the CCK gene, 11 variants in the CCKAR gene and 9 variants in the CCKBR gene were detected in the present study. Nominally significant differences between alcoholics and controls were found at the -85 locus of the CCKAR gene (p = .035). In addition, patients displaying hallucinations showed a higher frequency of the homozygous genotype of the allele (GT)8 at the -388 locus of the CCKAR gene (p = .042) and homo- and heterozygous genotypes of the T allele at the -333 locus (p = .025), relative to other patients. However, these differences were not significant after Bonferroni correction. CONCLUSIONS: Our data suggest that polymorphisms of the CCK, CCKAR and CCKBR genes do not play a major role in alcohol withdrawal symptoms (even though significant associations were found among polymorphisms at the -388 and -333 loci of the CCKAR gene and hallucinations, the rate was nonsignificant after Bonferroni correction).

Adult↗

A patient with severe palindromic rheumatism and frequent episodes of pain.

A 44-year-old man began to experience episodes of joint pain with erythema in his knees, elbows, shoulders, and hands in April 1996. He was diagnosed as having palindromic rheumatism. Due to the increasing frequency and severity of these episodes, he was admitted to our hospital in May 1999. Heat therapy to the affected area produced a rapid improvement in symptoms. In addition, the continued use of physical therapy during symptom-free periods tended to reduce the frequency and severity of pain attacks. We present this case and discuss treatment options in patients with palindromic rheumatism.

Adult↗

Cavernous angioma of the corpus callosum mimicking an astrocytic tumor--case report.

A 49-year-old female presented with a mass at the genu of corpus callosum manifesting as vertiginous sensation persisting for a couple of months. The preoperative diagnosis based on neuroimaging was astrocytic tumor, probably an oligodendroglioma. The mass was totally excised through a left interhemispheric approach without postoperative neurological deficits. Histological examination of the mass revealed only vascular components with tiny hemorrhage, compatible with cavernous angioma. Cavernous angioma at the genu of corpus callosum is very rare, and definitive diagnosis can be achieved only through surgery. Surgical intervention should be considered before starting radiotherapy without histological confirmation.

Corpus Callosum↗

Association of a novel point mutation (C159G) of the CTLA4 gene with type 1 diabetes in West Africans but not in Chinese.

Here, we report on the detection of a novel point mutation of the CTLA4 gene at nucleotide position 159 (C-->G) leading to amino acid substitution at position 53 (I-->M), as well as its association with type 1 diabetes in two ethnically distinct populations. Subjects included 182 unrelated type 1 diabetes children and 201 control subjects from Ghana, West Africa. The Chinese study population consisted of 350 type 1 diabetic children and 420 healthy control subjects from central China. Polymerase chain reaction-single-strand conformation polymorphism and sequence analysis were used to screen for polymorphisms in the CTLA4 gene. CTLA4 49 (A-->G) mutation conferred a risk of type 1 diabetes in the Chinese children (odds ratio 1.78, 95% CI 1.58-2.0), but not in the West African children (1.17, 0.84-1.64). On the other hand, the novel CTLA4 159 (C-->G) mutation conferred a risk of type 1 diabetes in the West African children (2.1, 1.54-2.86), but not in the Chinese type 1 diabetic children. The novel CTLA4 gene polymorphism at nucleotide position 159 significantly associated with type 1 diabetes in West Africans, but not in Chinese. On the other hand, the CTLA4 gene polymorphism at nucleotide position 49 significantly associated with type 1 diabetes in Chinese, but not in West Africans.

Abatacept↗

[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese].

Multiple forms and gene loci of human alcohol dehydrogenase (ADH EC: 1.2.1.3) and aldehyde dehydrogenase (ALDH, EC: 1.2.1.3) in the major pathway of alcohol metabolism have been found and characterized in the last two decades. With the coenzyme NAD, these enzymes catalyze the reversible conversion of organic alcohols to ketones or aldehydes, and aldehyde to acetic acid. The ADH genes are mapped to chromosome 4p21-25, but the ALDH genes are localized at different chromosomes. The cytochrome P450 2E1 (CYP2E1) gene, which is mapped to chromosome 10q24.3-qter contributes also the conversion of ethanol to acetaldehyde. Genetic polymorphisms have been reported in these alcohol metabolizing enzymes. The metabolisms of alcohol and acetaldehyde in liver and blood after drinking alcohol are thought to be influenced by the interactive action of these enzymes. Amongst the five major classes of the ADH subunits (alpha, beta, gamma, pi, chi, sigma), beta and gamma subunits show genetic polymorphisms. Recently a new nomenclature for ALDH genes has been recommend based on divergent evolution and chromosomal mapping. Two major isoforms designated as cytosolic ALDH1 and mitochondrial ALDH2 can be distinguished by their electrophoretic and kinetic properties as well as by their subcellular localization. Mitochondrial ALDH2 is a major enzyme in the oxidation of acetaldehyde derived from ethanol metabolism. The catalytic deficiency of ALDH2 isozyme is responsible for flushing and other vasomotor symptoms caused by higher acetaldehyde levels after alcohol intake. So far, frequencies of the two alleles of ALDH2 in Mongoloid have been reported in the different population groups. The catalytic deficiency of ALDH2 is caused by a structural point mutation at amino acid position 487, where a substitution of Glu to Lys resulting from a transition of G (C) to A (T) at 1510 nucleotide from the initiation codon has occurred. Individuals deficient in ALDH2 activity refrain from excessive drinking of alcohol due to the aversive reactions, leading to protection against alcoholism. Prevalence of the ALDH2*1 allele is associated with alcoholism, and subsequent studies have confirmed the allelic association with alcoholism in different ethnic groups. The effects of polymorphisms of ADH2 and CYP2E1 remained controversial, even in the same ethnic group. Investigation of mutations for the transacting cis-element in promoter region of the ALDH2 gene will provide important information with respect to regulation of this gene. Transfection assays using the first 600 bp of the upstream nucleotide sequences indicated that a region from -75 to -120 was necessary for the ALDH2 gene expression, and especially NF-Y/CP1 binding site from -92 to -96 (CCAAT box) is important in the expression of the gene. A novel polymorphism due to the nucleotide replacement at -357 G to A was found in all the population groups. Alcoholism is thought to be a multifactorial disease with complex mode of inheritance in addition to psychological and social factors, and many studies of family, adoption and twins concerning alcoholism have revealed that hereditary factor is an important determinant for developing alcoholism. Genetic association studies have contributed to the identification of a number of genetic risk factors for the chronic diseases influenced by genetic disorders and environmental factors.

Alcohol Dehydrogenase↗

[A clear cell type meningioma in the upper eyelid ascertained by immunohistochemical examination].

BACKGROUND: We encountered a rare case of clear cell meningioma in the upper eyelid. CASE: A 66-year-old man presented with a slow by progressive, well-defined, soft globelar tumor in the left upper eyelid. The tumor showed homogeneous isodensity and was contrasty in a computed tomograph. Histologically, oval-shaped cells with clear cytoplasm had both streamed and whorl configurations, but showed neither psammomas nor calcification. Immunohistochemically, vimentin, epithelial membrane antigen, and protein S-100 were expressed by the tumor cells. CONCLUSIONS: Eyelid meningioma may originate from embryonal remains of the arachnoid in the sheath around the trigeminal nerve, and may vary histologically. Immunohistochemical examination helps to define cases of uncommon subtypes of meningioma.

Aged↗

[Follicular bronchiolitis associated with pulmonary tuberculosis--report of a case].

The patient, a 39-year-old man, presented in May 1997 with an untreated persistent cough with excessive sputum of 5 years' duration. He was admitted to hospital because of the severity of the symptoms and the presence of acid-fast bacilli in his sputum. These bacilli were identified as Mycobacterium tuberculosis by the polymerase chain reaction method. After treatment with antituberculous drugs was initiated, his symptoms and the patchy infiltrative shadows on his chest radiographs gradually resolved. However, the patient continued to expectorate a purulent sputum, showed diffuse micronodular shadows on chest radiographs, and had hypoxemia as well as mixed ventilatory and small airway disturbances on pulmonary function tests. We performed a video-assisted thoracoscopic biopsy of the lung, which revealed follicular bronchiolitis.

Adult↗

[Clinical study on the cases in which INH or RFP was discontinued during treatment for pulmonary tuberculosis].

Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.

Adolescent↗

[Pulmonary Mycobacterium Kansasii infection in the southern area of Fukuoka prefecture].

Cases of pulmonary infection caused by Mycobacterium kansasii (Mk) in our hospital located at the mid-northern area of the Kyushu district, which is in the southern part of Fukuoka prefecture were evaluated. Mk infection is not so rare in other areas of Japan, such as Tokyo and Kinki district, however, there has been no published report on the disease from the Kyusyu district. Therefore, the frequency and the clinical features of our cases of Mk infection were analyzed. During 17 years from 1982 to 1998, there were 14 patients of Mk infection out of 241 nontuberculous mycobacteriosis (NTM). There were 595 patients of culture-positive pulmonary tuberculosis without prior treatment (Tbc). The proportion of Mk/Tbc was 2.4% and that of Mk/NTM was 5.8%. During the period A (from 1982 to 1994) the ratio of Mk/Tbc was 5/462 (1.1%), while on the other side that of Mk/Tbc during the period B (from 1995 to 1998), it was 9/133 (6.8%), which was significantly (P < 0.01) higher compared with that in the period A. Although the patients of Mk infection in our hospital had been rare until 1994, from the results mentioned above, it was considered that the frequency of Mk infection in our hospital has increased to some extent since 1995. One of the characteristics in our cases was that the ratio of female (42.9%) was relatively high. All the female patients were considered to be compromised hosts. The results of the drug resistance tests were consistent with the other reports in our country. By the combination treatment including rifampicin as the major drug, the negative conversion of culture were obtained within 2 months in all our cases.

Adult↗

[Tuberculosis of the elderly (above the age of 75) in national hospitals].

In Japan tuberculosis is becoming rapidly the disease of the elderly. We studied the background, the type and level of hospital cares needed, and the outcome of patients with pulmonary tuberculosis (sputum smear and/or culture positive) above the age of 75 who were admitted to 8 national hospitals during the period from January 1 to December 31, 1997. The study included 150 patients (male: 109, female: 41, mean age: 81.6), of whom 25% needed care in a single-bed room, 84.3% had underlying diseases (cardiovascular diseases: 43.3%, malignant diseases: 20.9%, neuro-psychiatric diseases: 13.4%), and 47.6% needed cares mainly in feeding and excretions. 92 patients (62.6%) improved and 45 patients (30.6%) died, of whom the cause of death was directly related to tuberculosis in 42. The mean hospital stay was 4.7 months. However, in 42 patients whose cause of death was related to tuberculosis, 66% died within 3 months, while in 102 patients who were discharged 71% stayed more than 3 months. The same comparison was done in 508 patients with bacteriologically proven tuberculosis above the age of 75 admitted to National Tokyo Hospital during the period from 1990 to 1999. The result was almost the same, among 133 patients died in the hospital 60% died within 3 months, while in 375 patients who were discharged hospital stay was more than 3 months in 70%. In the near future, the elderly will occupy more than 25% of the beds of the tuberculosis ward in Japan and most of them have underlying diseases other than tuberculosis. Because tuberculosis, once the disease of the young, is becoming rapidly the disease of the elderly, it is imperative for us to make necessary adjustments to meet this inevitable trend.

Aged↗