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Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 163 records · Page 9Linked to original sources

An immunohistochemical study of the localization of biglycan, decorin and large chondroitin-sulphate proteoglycan in adult rat temporomandibular joint disc.

To analyse regional variations in extracellular matrix components of adult rat temporomandibular joint discs, immunohistochemical techniques were used to examine the localization of two small dermatan-sulphate proteoglycans, biglycan and decorin, and a large chondroitin-sulphate proteoglycan. Staining for biglycan was intense in the posterior band, although it had a rather weak and even distribution throughout the disc. In contrast, staining for decorin was faint in the intermediate zone and the central part of the posterior band, moderate in the anterior and posterior attachments and most intense in the junction between the anterior band and attachment. The upper surface of the disc stained more intensely than the lower. Similarly, there was intense staining for large chondroitin-sulphate proteoglycan in the peripheral band, but both the anterior and the temporal parts of the posterior attachments were faintly stained. These results demonstrate marked regional differences in the expression of biglycan, decorin and large chondroitin-sulphate proteoglycan in the temporomandibular joint discs of adult rats. These variations probably reflect the different biomechanical environments caused by the complicated articulatory functions of the temporomandibular joint.

Animals↗

Morphological and functional changes in coronary vessel evoked by repeated endothelial injury in pigs.

OBJECTIVE: We examined the morphological changes induced by repeated endothelial denudation in coronary artery (CA), as well as functional changes in the endothelium-dependent and smooth muscle responses to various vasoactive agents during the process of intimal thickening. METHODS: We observed vascular responses in denuded and non-denuded portions of pig CA while being fed a normal diet (n = 11, N group) or 2% cholesterol diet (n = 25, C group) to intracoronary acetylcholine (ACh), 5-hydroxytryptamine (5-HT), substance P (SP), and isosorbide dinitrate (ISDN) with and without the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v.) over a period of 8 weeks. Balloon endothelial denudation of the left anterior descending CA was carried out every 2 weeks. RESULTS: In N group, maximum vasoconstriction was obtained with ACh 2 weeks after the first denudation [26 +/- 5% vs. 1 +/- 1% pre-denudation, p < 0.05]. L-NAME did not affect ACh-induced CA diameter changes. Thereafter, the response to ACh was attenuated by repeated denudation in N groups. However, the degree of 5-HT-induced CA narrowing at the denuded portion increased from 7 +/- 4% (0 week) to 88 +/- 8% (8 weeks) (p < 0.05). The changes resulted in severe myocardial ischaemia, and suggested that endothelium-dependent vasodilation was progressively attenuated while hyperreactivity of vascular smooth muscle simultaneously increased. Vasodilation induced by SP was attenuated somewhat, but ISDN-induced vasodilation was preserved. Although mild hypercholesterolaemia was induced in C group, the vascular responses to these vasoactive agents did not differ from those of N group. CONCLUSIONS: Repeated CA endothelial injury and regeneration induce the change of morphology and vascular reactivity in the denuded portion regardless of atherogenic diet. This study strongly suggests that intimal thickening caused by repeated endothelial injury and regeneration induces specific vascular responses to vasoactive agents. Moreover, it is also suggested that during the progression of intimal thickening, increased vascular smooth muscle contraction and decreased endothelium-dependent dilation appear in a stimulus-dependent manner, often leading to severe coronary vasoconstriction accompanied with definitive ECG ST change.

Acetylcholine↗

Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients.

BACKGROUND/AIMS/METHODS: The aim of this study was to elucidate the rate of development to cirrhosis and the rate of appearance of hepatocellular carcinoma in chronic viral hepatitis and to assess the risk factors for the development of disease in 2215 consecutive patients with viral hepatitis who were prospectively studied for a median observation period of 4.1 years. RESULTS: The rates of development to cirrhosis were 7.6%, 21.7%, and 32.2%, at the 5th, 10th, and 15th year, respectively. The carcinogenesis rates were 3.4%, 10.5%, and 22.4% at the 5th, 10th, and 15th year, respectively. The appearance rates of cancer in 645 patients with only hepatitis B surface antigen and in 1500 patients with only anti-hepatitis C virus antibodies were 2.1% and 4.8% at the 5th year, 4.9% and 13.6% at the 10th year, and 18.8% and 26.0% at the 15th year, respectively. The proportional hazard model identified that the amount of alcohol intake (p= 0.0002) and the indocyanine green retention rate (p= 0.022) were independently associated with carcinogenesis in hepatitis type B; and stage of hepatitis (p<0.0001), gamma-glutamyl transpeptidase (p= 0.0046), history of blood transfusion (p=0.0093), albumin (p=0.012), and amount of alcohol intake (p= 0.031) were independently associated with the carcinogenesis rate in hepatitis type C. Although the severity of portal fibrosis was closely correlated with the future disease development and carcinogenesis in chronic hepatitis C, it was not a good predictor in chronic hepatitis B. CONCLUSION: These epidemiological results suggest that there are some differences in the activity and modes of disease progression and cancer promotion between hepatitis B virus infection and hepatitis C virus infection.

Adolescent↗

Imprinting in Prader-Willi and Angelman syndromes.

Imprinted genes are marked in the germline and retain molecular memory of their parental origin, resulting in allelic expression differences during development. Abnormalities in imprinted inheritance occur in several genetic diseases and cancer, and are exemplified by the diverse genetic defects involving chromosome 15q11-q13 in Prader-Willi (PWS) and Angelman (AS) syndromes. PWS involves loss of function of multiple paternally expressed genes, while mutations in a single gene, UBE3A, which is subject to spatially restricted imprinting, occur in some AS patients. Identification of mutations in the imprinting process in PWS and AS has led to a definition of an imprinting center (IC), involving the promoter (in PWS) or an alternative transcript of the SNRPN gene (in AS). The IC regulates initiation of imprint switching for all genes in a 2 Mb imprinted domain during gametogenesis. Imprinting mutations define a novel mechanism of genetic disease because they have no direct effect in the affected patient but, rather, it is the parental germline effect of an IC mutation that leads to disease in the offspring.

Angelman Syndrome↗

Clinical and electroencephalographic findings in juvenile type DRPLA.

We present five different types of dentatorubral-pallidoluysian atrophy in one Japanese family. Two siblings and their paternal uncle manifested the juvenile type dentatorubral-pallidoluysian atrophy, the siblings' father had the late-adult type, and another paternal uncle had the early-adult type. Gene analysis confirmed the diagnosis for the proband and her sibling. By following the clinical courses and electroencephalographic changes, we found that the types of epileptic seizures and the electroencephalograms of the juvenile dentatorubral-pallidoluysian atrophy patients changed as the illness progressed. The siblings exhibited different levels of clinical severity despite the similar deoxyribonucleic acid expansion detected in their lymphocytes.

Adolescent↗

A DNA repair defect in a patient with ataxia, mental retardation, and short stature.

A 12-year-old girl developed ataxia that gradually progressed. At age 18 the patient presented with mental retardation, cachectic dwarfism, microcephalus, and a progeroid appearance but no photosensitive skin lesions or deafness. On analysis of fibroblasts, unscheduled DNA synthesis was reduced to 50% of normal, but colony-forming ability after ultraviolet irradiation was normal. The symptoms and phenotype of the patient were distinguished from those in Cockayne syndrome and xeroderma pigmentosum. This case is interesting because the defect in DNA repair after ultraviolet irradiation was detected in a patient with neurologic disturbances but without photosensitive skin lesions.

Abnormalities, Multiple↗

Phenotypic variability in a family with a mitochondrial DNA T8993C mutation.

Two patients are described in a family with a mitochondrial DNA T8993C point mutation. Patient 1, the proband, was a 4-year-old male, and his clinical features were consistent with those of Leigh syndrome, including lactic acidosis, motor development delay, and symmetric basal ganglia lesions on magnetic resonance imaging (MRI). His mental development was delayed mildly, but he has not demonstrated neurologic deterioration. Patient 2 was his maternal aunt. She developed her first neurologic sign at 18 months of age, thereafter her development ceased and regressed. She had lost her head control and become bedridden by 4 years of age and died at 20 years of age, demonstrating a more severe clinical course than that of Patient 1. Analysis of mitochondrial DNA from peripheral leukocytes of Patient 1 revealed a T8993C mutation of 99%. Patient 2 was demonstrated to have the same mutation at high abundance (99%) in the frozen myocardium and in the formaldehyde preserved spinal cord, with only 18% mutant mitochondrial DNA present in the formaldehyde preserved sciatic nerve. The mother of Patient 1, who was phenotypically normal (sister of Patient 2), had 35% mutant mitochondrial DNA in peripheral leukocytes. The authors' findings suggest that T8993C phenotypes are highly variable and that the proportion of the mutant mitochondrial DNA may vary among tissues and not correlate well with clinical severity.

Base Sequence↗

Characterization and primary structure of a base non-specific and acid ribonuclease from Dictyostelium discoideum.

A base non-specific and acid RNase was isolated from cellular slime mold (Dictyostelium discoideum) cells in a homogeneous state (about 2.4 kDa) by SDS-polyacrylamide gel electrophoresis. The RNase (RNase DdI) has a pH optimum of 5.0. The amino acid sequence of RNase DdI was determined by a combination of protein chemistry, a search of Data base, Dicty cDB and further sequence analysis of cDNA from the same bank. RNase DdI consists of 198 amino acid residues, and about 13.3, 0.9, 1.2, 3.3, and 1.0 residues of mannose, xylose, glucose, GlcNAc, and GalNAc, respectively. RNase DdI has two characteristic conserved segments of the RNase T2 family, and thus belongs to the RNase T2 family. Considering the fact that most of the RNase activity of D. discoideum is present in the lysosomal fraction [Wiener and Ashworth (1970) Biochem. J. 118, 505-512], it was concluded that the lysosomal RNase in D. discoideum is a member of the RNase T2 family. The amino acid sequence of RNase DdI is highly homologous with that of Physarum polycephalum RNase (RNase Phyb), and its amino acid sequence seems to be similar to those of plant/animal type RNases, rather than fungal RNases. The location of RNase DdI in the phylogenetic tree of the RNase T2 family was estimated.

Amino Acid Sequence↗

Proposal of Craurococcus roseus gen. nov., sp. nov. and Paracraurococcus ruber gen. nov., sp. nov., novel aerobic bacteriochlorophyll a-containing bacteria from soil.

Sequences of the 16S rRNA gene were determined for three strains of aerobic bacteriochlorophyll a-containing bacteria isolated from soil. The sequence of two strains (NS89(T) and NS102) were identical for approximately 1500 nucleotides. Phylogenetic analysis revealed that the three strains belonged to the alpha-1 subclass of the Proteobacteria, constituting one line of descent. The three strains are comparatively related to Roseoccus thiosulfatophilus, which is an aerobic bacteriochlorophyll a-containing bacterium. The 16S rRNA gene sequence similarity and the DNA-DNA relatedness allow the proposal of two new genera, Craurococcus gen. nov. and Paracraurococcus gen. nov. The type species are Craurococus roseus sp. nov. and Paracraurococcus ruber sp. nov., and their type strains are NS130(T) (=JCM 9933(T)) and NS89(T) (=JCM 9931(T)), respectively.

Bacteriochlorophylls↗

Correlation of a polymorphism in the interleukin-1 receptor antagonist gene with hepatic fibrosis in Japanese alcoholics.

The aim of this study was to determine whether there is any association between interleukin-1 receptor antagonist (IL1-Ra) genotype and alcoholic liver disease. The IL1-Ra genotype was assessed in 102 Japanese male alcoholic liver disease patients and 46 healthy subjects by polymerase chain reaction with leukocyte DNA. The distribution of IL1-Ra genotype and the allelic frequencies in Japanese healthy subjects are both significantly different from that previously reported in Caucasians (A1/A1 genotype: 95.7% in Japanese vs. 54.0% in Caucasians, p < 0.001; A1 allele: 97.8% vs. 73.4%, p < 0.001). The frequency of A1 heterozygotes tended to be higher in Japanese alcoholics with fibrosis, compared with those without fibrosis (14.9% vs. 2.9%). Furthermore, within the fibrotic groups, cumulative alcohol intake was significantly lower in A1 heterozygotes than in the A1 homozygotes (877 +/- 118 kg vs. 1369 +/- 90 kg,p < 0.05). In conclusion, a genetic polymorphism in the IL1-Ra gene may influence the risk of developing hepatic fibrosis in Japanese alcoholics. The same study should be conducted in Caucasian patients having more frequency of IL1-Ra A1 heterozygotes.

Adult↗

Predictive factors in eradicating hepatitis C virus using a relatively small dose of interferon.

Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus in 30-40% of patients. Several predictive factors for eradication of the virus have been reported and a higher dose of IFN tends to result in elimination of the virus. However, a small dose of IFN sometimes is as effective as a large dose in eradicating the virus. The predictive factors for such a response are not well established. We retrospectively analysed 50 patients with chronic hepatitis C who were treated with relatively small amounts of IFN (equal or less than 252 million units). Eleven patients were responders (elimination of hepatitis C virus (HCV) and normalization of alanine amino transferase (ALT) for at least 6 months), but the remaining 39 were non-responders. Multivariate analysis showed that the pretreatment viral load and total dose of IFN per kilogram of bodyweight were significant predictive factors of response to therapy. We also assessed the amino acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon 2209-2248, of HCV in serum samples obtained from 31 patients with HCV genotype 1b. The presence of more than one amino acid substitution in the ISDR tended to correlate with HCV genotype 1b elimination. As IFN is expensive and has a number of serious side effects, our study suggests that the optimal dose of IFN may vary from one patient to another and that more stringent criteria should be used to select the optimal dose for therapy.

Adult↗

Biochemical and histological features of hepatitis G virus infection.

To assess the biochemical and histological characteristics of hepatitis G virus (HGV) infection, we examined four patients who were infected with HGV only (HGV group), and compared them with 16 patients infected with both HGV and hepatitis C virus (HCV; HGV + HCV group) and 18 patients infected with HCV only (HCV group). Biochemical examination showed a significantly low level of serum alanine aminotransferase (ALT) in the HGV group, and that the gamma-glutamyl transpeptidase (gamma-GTP)/ALT ratio in the same group was significantly higher than in the other two groups. Although all three patient groups had a similar degree of liver fibrosis, both the degree of periportal inflammation and total histological activity index were significantly lower in the HGV group than in the other two groups. Fibrous enlargement of the portal tract without lymphoid infiltration and thin fibrous septa was characteristically observed in the HGV group. No significant difference was found between the HGV + HCV group and HCV group. Our results suggest that biochemical and histological changes in HGV infection are very mild and quite different from those of HCV infection.

Adult↗

Effects of dichloroacetate in three patients with MELAS.

We present the clinical and laboratory effects of dichloroacetate (DCA) in three children with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) who had not responded to other medications. Administration of DCA lowered the elevated levels of lactate and pyruvate in the serum and CSF. DCA ameliorated abdominal pain, headache, and strokelike episodes, and improved cognitive function and fatigability in the three patients during the study period. Some transient liver dysfunction, hypocalcemia, and peripheral neuropathy were observed. The use of DCA in MELAS merits further study.

Adolescent↗

Glomerulonephritis in autopsy cases with hepatitis C virus infection.

The glomerular changes of 188 consecutive autopsy cases with hepatitis C virus (HCV) infection were studied. The glomerular changes were classified as follows: Category I: membranoproliferative glomerulonephritis (MPGN; 21 cases, 11.2%), 2) Category II: membranous nephropathy (MN; 5 cases, 2.7%), 3) Category III: mesangial proliferative glomerulonephritis (MesGN; 33 cases, 17.6%), 4) Category IV: mesangial thickening type without proliferative mesangial cell (MT; 44 cases, 23.4%), and 5) Category V: almost normal glomeruli (85 cases, 45.2%). Glomerulonephritis was defined as glomeruli with an increase in mesangial matrix or a thickening of the capillary walls in the glomeruli; categories I-IV corresponded to glomerulonephritis in this study. Multivariate analysis, using a multiple logistic model, indicated that glomerulonephritis with HCV infection was the most strongly correlated to the existence of esophagogastric varices. Abnormal urinalysis, that is transient or continuous microhematuria or proteinuria, was observed in only 23 (12.2%) cases. These results showed that in HCV-RNA positive patients with esophagogastric varices the possibility of glomerulonephritis should be considered.

Adult↗

[Significance of accumulation of arteriosclerotic risk factors in elderly people: from a study conducted in Tanno-Sobetsz].

Data from an 18-year prospective study were used to investigate the effect of accumulation of arteriosclerotic risk factors in elderly people on cerebrovascular and cardiovascular disease mortality rates. Risk factors include smoking, hypertension, diabetes mellitus, hyperlipidemia, and obesity. We compared survival rates between a group with few risk factors (< two risk factors) and a group with many risk factors (> or = two risk factors) in four groups of subjects: middle-aged men (< 61-years-old) and middle-aged women and elderly men (> or = 61-years-old) and elderly women. In the elderly male group, the survival rate was lower in subjects with many risk factors than in those with few risk factors. In the middle-aged male group, however, there was no difference between the two risk groups. On the other hand, in the middle-aged female group, the survival rate was lower in subjects with many risk factors than in those with few risk factors, while no difference was found between the two risk groups in the elderly female group. The results indicated that the effects of an accumulation of risk factors are different in men and women and greater in elderly men than in elderly women.

Adult↗

[Role of impaired glucose tolerance in the progression of hypertension].

The present report describes the relationship between the glucose tolerance and hypertension surveyed in a ten-year longitudinal epidemiological study in two rural communities in Hokkaido, Japan. The 1972 subjects (928 men and 1044 women, aged 40-64, mean 51.1 +/- 7.0 years) were randomly selected in 1977 and 1978, underwent a 50-g oral glucose tolerance test (GTT) at the first year. The prevalences of borderline hypertension (BHT) and of hypertension (HT) were highest in those with diabetes mellitus (DM), followed by those with borderline diabetes (BDM) and those normal glucose tolerance (NGT). Systolic and diastolic blood pressure were significantly and positively correlated with plasma glucose levels during fasting (FPG), 60 min. after GTT (60G), and 120 min. after GTT (120G), and were ordered as follows: NGT < BDM < DM. The FPG, 60G and 120G plasma glucose levels were all significantly higher in BHT and HT than in NT. The prevalences of the progression to hypertension from non-hypertension over the ten-year follow-up period were ordered as follows: NGT < BDM < DM. Glucose levels in progression group were higher than those in non-progression group. Multiple logistic regression analysis indicated that age, glucose intolerance, systolic blood pressure, and obesity index were significant predictors of the progression to hypertension. These results indicate that impaired glucose tolerance may be associated with hypertension, and might play a role in the development of hypertension.

Adult↗