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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 361 records · Page 20Linked to original sources

Genetic organization and diversity of the 3' noncoding region of the hepatitis C virus genome.

The 3' noncoding region (3' NCR) of the hepatitis C virus (HCV) genome contained in viral particles was analyzed by an RNA linker ligation followed by reverse transcription-polymerase chain reaction. Sequence analysis of the amplified fragment from four strains, including different genotypes 1b, 2b, 3a, and 3b indicated that the 3' NCR is composed of between 200 and 235 nts. The sequence of the 3' NCR consists of a type-specific region (immediately following the termination codon), a poly(U) stretch, a C(U)n-repeat, and highly conserved region termed the core element. The poly(U) stretch and C(U)n-repeat regions varied in length and in sequence among different genotypes. Core elements having putative secondary structure consisted of 98 or 100 nts and were highly conserved in all genotypes. Most of the nt changes found in different genotypes did not affect the secondary structure of the core elements, suggesting that this region may play an important role in replication, stabilization of the HCV RNA, and/or packaging of the genome. Most of the HCV-1b strains carried two U residues at the 3' end of the core element, while the minor HCV-1b strains had no U residues, demonstrating that there are two variants in type 1b strains. Amplification of the core element using linker-primed cDNA was comparable with that using the 3' proximal core element-primed cDNA, indicating that the 3' end of HCV genome was terminated by an OH group.

Base Sequence↗

Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/ LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis.

Animals↗

Rapid growth of hepatocellular carcinoma after or during interferon treatment of chronic hepatitis C: report of three cases.

We report herein the cases of three patients in whom marked rapid growth of hepatocellular carcinoma (HCC) became evident after or during interferon (IFN) treatment for chronic hepatitis C. The HCC tumors were 10, 4.7, and 3.1 cm in size, and were found 7 months, 10 weeks, and 10 weeks after the initiation of IFN, respectively, in cases 1, 2, and 3. The clinical courses of these three patients suggest that the progression of HCC was more rapid during the IFN treatment period. Thus, we propose that abdominal ultrasonic (US) examination should be performed monthly in patients with chronic hepatitis who undergo IFN treatment.

Adult↗

Combined treatment of a dural arteriovenous malformation of the lateral sinus using transarterial and direct lateral sinus embolisation.

An 80-year-old man presented with a dural arteriovenous malformation (DAVM) involving the left lateral sinus. A carotid angiogram showed the lateral sinus to be occluded proximally and distally, with unusual retrograde venous outflow from the residual sinus to the cortical veins, including a dilated vein of Labbé. Single photon emission computed tomography showed reduced left frontal and temporal cerebral blood flow. We concluded that the risk of bleeding from the DAVM was high and that the patient needed to be treated immediately. However, his age made surgical removal of the DAVM hazardous and we therefore chose to treat him by transarterial and direct lateral sinus embolisation via a burr hole.

Aged↗

Mucopolysaccharidosis IVA: a comparative study of polymorphic DNA haplotypes in the Caucasian and Japanese populations.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulphate sulphatase (GALNS). The genetic heterogeneity at the GALNS locus was studied in 62 mutant alleles and 376 normal alleles in the Caucasian population and also in 40 mutant and 100 normal alleles in the Japanese population. For this study, six different restriction fragment length polymorphisms (RFLPs) at the GALNS locus were analysed to search for the frequency of each RFLP produced by StyI, SphI, RsaI, HaeIII, StuI and HapII restriction endonucleases. We detected a total of 27 haplotypes in the Caucasian and Japanese population. Of these 27 haplotypes, 18 haplotypes were present in the Caucasian population and the most common of these was haplotype 1 (ABHcde) in both mutant and normal alleles. In contrast, in the Japanese population we found 20 of the 27 haplotypes and the most common in mutant and normal alleles was haplotype 2 (abhcDE). Within these two populations a parent in the MPS IVA family has an average probability of greater than 77% (in the Caucasian population 77.27% and in the Japanese population 78.26%) of being heterozygous, and hence informative for linkage, at one or more GALNS RFLP sites. Our results delineate the molecular heterogeneity of MPS IVA haplotypes, as well as their significant interpopulation variation, and make prenatal diagnosis and carrier detection possible in the majority of families with one affected child.

Acetylgalactosamine↗

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis.

CONCLUSION: Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). BACKGROUND: We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. METHODS: Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. RESULTS: The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Adult↗

Hyperinsulinaemia accelerates accumulation of cholesterol ester in aorta of rats with transplanted pancreas.

Hyperinsulinaemia may play a role in the development of atherosclerosis; however, the direct effect of endogenous insulin on the atherosclerotic process is not well understood. To clarify this situation we performed pancreas transplantation with systemic venous drainage in Wistar Shionogi (WS) and Spontaneous Hypertensive (SHR) rats. Both rats received syngeneic pancreaticoduodenal transplants from donor rats. SHR rats were used to observe the additive effects of both hypertension and hyperinsulinaemia on the atherosclerotic process. Peak blood insulin levels after a glucose load were approximately two times higher in transplanted rats than in non-transplanted WS and SHR rats. By contrast, there was no difference in plasma glucose responses between transplanted and non-transplanted rats. Hyperinsulinaemia was not related to dyslipidaemia and hypertension in transplanted rats. Nine months after transplantation, the cholesterol ester contents of the aortas of both WS and SHR transplanted rats were significantly higher than in the control rats (WS: 1.9 +/- 1.0 vs 3.8 +/- 2.1 mg/g dry tissue, p < 0.01; SHR: 1.7 +/- 1.3 vs 3.7 +/- 1.4 mg/g dry tissue, p < 0.05). No differences were demonstrated in the thickness of the intima or in the histology of the aortas of transplanted and control rats. To study the mechanism for cholesterol ester accumulation in the arterial wall, we measured neutral cholesterol ester hydrolase activities in vascular medial smooth muscle cells. Insulin significantly suppressed neutral cholesterol ester hydrolase activities in medial smooth muscle cells. Our results indicate that endogenous hyperinsulinaemia contributes to the development of atherosclerosis by accelerating cholesterol ester accumulation in the arterial wall.

Animals↗

Partial-thickness tears of the rotator cuff. A clinicopathological review based on 66 surgically verified cases.

This review is based on 66 patients with partial-thickness tears of the rotator cuff, verified at operation. Their average age was 54 years, and all had symptoms of subacromial impingement. The duration of shoulder pain was for between 2 and 108 months (mean 11.4 months). Ultrasonography, arthrography and bursography were helpful in establishing the diagnosis. On exploration, tears were found in the supraspinatus tendon, with 9 extending into the infraspinatus. After anterior acromioplasty, excision of the diseased portion and tenorrhaphy were undertaken. Satisfactory results were obtained in 62 patients (94%) with an average follow-up of 32 months. Spontaneous repair at the torn site was never seen. In addition to Neer's staging of impingement, we propose a new classification based on the integrity of the cuff tendon. We conclude that a partial-thickness cuff tear is an important cause of shoulder disability, which deserves much more clinical attention; misdiagnosis is common and leads to mismanagement. When conservative treatment fails, accurate diagnosis and proper surgical repair are essential.

Adult↗

Echogenic fetal bowel in the third trimester associated with trisomy 18.

We present the first case of trisomy 18 in which echogenic fetal bowel was detected in the third trimester after normal echogenicity was documented during the second trimester. Fetal karyotyping should be considered in cases of increased echogenicity of the fetal lower abdomen in the second as well as the third trimester.

Abnormalities, Multiple↗

Effects of beraprost sodium and prostaglandin E1 on skin blood flow in diabetic rats and normal dogs.

1. The present study was undertaken to compare the effects of beraprost sodium (BPS), a stable prostaglandin I2 analog, with prostaglandin E1 (PGE1) on the skin blood flow in anesthesized diabetic rats and anesthetized dogs. 2. In anesthetized diabetic rats, BPS, but not PGE1, caused a dose-dependent and significant increase in femoral skin blood flow. 3. In anesthetized dogs, PGE1 significantly increased femoral arterial blood flow than BPS. However, BPS significantly increased in-step skin blood flow than PGE1. 4. The above data suggest that BPS may be clinically useful for the treatment of circulatory insufficiency of lower extremities in diabetic patients.

Alprostadil↗

Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain.

The kinetics of platelet-derived growth factor messenger RNA synthesis in the substantia nigra and in the striatum, before and after unilateral intranigral 6-hydroxydopamine injection, was studied and compared with that after sham operation by a quantitative reverse transcription-polymerase chain reaction. The kinetics of brain-derived neurotrophic factor messenger RNA was studied as a comparison. Furthermore, the expression of platelet-derived growth factor A- and B-chain proteins was analysed by enzyme-linked immunosorbent assay and immunohistochemistry. In the ipsilateral striatum of 6-hydroxydopamine-lesioned rats, the signal density of messenger RNA for both A- and B-chains had already increased at one day and remained at an elevated level during the observation period of four weeks. In the substantia nigra ipsilateral to the lesion, a strongly increased level of B-chain and, to a lesser extent, of A-chain messenger RNA was already detected at 4h, reaching a maximal level at one day. No significant increase was seen either in sham-operated rats or in the contralateral striatum and substantia nigra. Amounts of platelet-derived growth factor proteins were examined separately by enzyme-linked immunosorbent assay in both sides of the substantia nigra, striatum and cortex. Three days after 6-hydroxydopamine lesions the levels of both platelet-derived growth factor A- and B-chains increased in the ipsilateral striatum, substantia nigra, and cortex. An increase in the A-chain was also observed in the contralateral side of the brain. The signal for brain-derived neurotrophic factor messenger RNA increased in the striatum in the lesioned side and, to a lesser extent, in the contralateral side, as well as in the substantia nigra, where a significant difference was observed when compared with the contralateral side. Semiquantitative immunohistochemical analysis on the substantia nigra confirmed the enhanced platelet-derived growth factor expression, revealing that the majority of the platelet-derived growth factor-producing cells were neurons. In summary, we have shown that platelet-derived growth factor messenger RNA as well as its protein are induced after injury to dopaminergic cells. These data indicate an important role of platelet-derived growth factor in the dopaminergic system.

Animals↗

Changes in eosinophil and leukocyte infiltration and expression of IL-6 and IL-7 messenger RNA in mite allergen patch test reactions in atopic dermatitis.

Patch testing with crude dust mite extracts after removal of homy layers was performed on normal-appearing skin of 11 adult patients with atopic dermatitis and high mite-specific IgE antibody scores. Positive skin reactions were observed in 9 subjects. Skin biopsy specimens were obtained from positive reaction sites at 2, 6, 12, 24, and 48 hours after allergen challenge and subjected to histologic studies and extraction of messenger RNA (mRNA). Perivascular infiltration of small mononuclear cells began at 2 hours and was followed by eosinophilic infiltration at 6 hours, and the number of eosinophils continued to increase at 24 and 48 hours. In addition to the increased expression of IL-4, IL-5, and tumor necrosis factor-alpha mRNA during the time course detected by reverse-transcription polymerase chain reaction, mRNA of IL-6 and IL-7 was also up-regulated. After the removal of test patches with mite allergen, the number of eosinophils started to decrease in a time-dependent manner. Histopathologic findings at 48 hours after removal showed lymphocyte-dominant infiltration intermingled with occasional eosinophils. These mite allergen patch test reactions may provide a useful model for studying the pathogenesis of atopic eczema, especially with regard to the initiation of eosinophil infiltration and the alternative increase in lymphocytes.

Adult↗

Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumours.

The distribution of bone morphogenetic protein (BMP) type I receptors and the activin type I receptor (ActR-I) was investigated in 16 cases of human glioma and five cases of non-tumourous gliosis tissue by immunohistochemical technique. Both BMP type IA (BMPR-IA) and the type IB (BMPR-IB) receptors were detected in human glioma cells. A significant increase in BMPR-IB in tumour cells was observed in malignant glioma compared with both low-grade astrocytomas (n=16, P<0.005) and gliosis (n=13, P<0.001). However, enhancement of BMPR-IA staining was moderate and ActR-I staining was only weakly expressed in the malignant glioma tumours. Osteogenic protein (OP)-1/BMP-7, which is known to bind BMPR-IA, BMPR-IB and ActR-I, was expressed in nervous tissue and was also detected in anaplastic areas of malignant glioma. In contrast to the tissue materials, BMPR-IA was expressed to a stronger degree than BMPR-IB in human glioma cell lines; the growth of these cells was suppressed by OP-1. These results suggest the presence of BMP receptors and a functional role for BMPs in malignant glioma.

Activin Receptors↗

Modification of macrophage function and effects on atherosclerosis.

Various factors are involved in the maturation and differentiation process of monocytes to macrophages and subsequent foam cell formation in atherosclerotic lesions. Macrophage colonystimulating factor, in particular, specifically promotes growth and differentiation of the monocyte-macrophage lineage, by activating various functions in mature macrophages and by influencing the atherosclerotic process. Vascular smooth muscle cells migrate from the media to the intima of the arterial wall, where they are transformed into macrophage-like foam cells that express two characteristic macrophage genes, scavenger receptor and macrophage colony-stimulating factor receptor genes.

Angiotensin II↗

Transcription factor PU.1 mediates induction of c-fms in vascular smooth muscle cells: a mechanism for phenotypic change to phagocytic cells.

The macrophage colony-stimulating factor receptor encoded by the c-fms gene is expressed in vascular intimal smooth muscle cells isolated from atherosclerotic lesions. A combination of platelet-derived growth factor-BB and epidermal growth factor induces stable expression of c-fms in normal vascular medial smooth muscle cells. The mechanism by which these growth factors induce c-fms expression has now been investigated in an attempt to gain insight into the events that underlie the phenotypic conversion of vascular smooth muscle cells in atherosclerosis. Deletion analysis of the c-fms promoter revealed that the region including a binding site for transcription factor PU.1 was required for transcriptional activity in human aortic medial smooth muscle cells. Mutation in the PU.1 binding site markedly reduced promoter activity. Northern (RNA) blot analysis demonstrated that growth factors induced the expression of PU.1 mRNA in vascular medial smooth muscle cells and that PU.1 mRNA was expressed in vascular intimal smooth muscle cells. PU.1 antisense oligonucleotides inhibited growth factor-induced c-fms expression and foam cell formation. These results suggest that transcription factor PU.1 plays an essential role in the phenotypic conversion of vascular smooth muscle cells to macrophagelike cells by mediating the induction of c-fms.

Aorta↗