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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 487 records · Page 27Linked to original sources

Full-length sequence of the genome of hepatitis C virus type 3a: comparative study with different genotypes.

Hepatitis C virus (HCV) type K3a (type 3a), which represents a minor genotype in Europe, the U.S.A. and Asia, appears to be significantly distributed throughout Australia and Brazil. We amplified the HCV-K3a/650 genome by reverse transcription polymerase chain reaction in ten overlapping fragments and determined the nucleotide sequences. The total sequence was 9454 bases in length and contained an open reading frame of 3021 amino acids, which is 10 or 11 amino acids longer than in HCV type 1 and 12 amino acids shorter than the sequence of type 2. These differences were due to the different lengths of both the putative envelope protein E2 and the NS5A regions, whose nucleotide lengths differ between types 1 and 2 also. Phylogenetic analysis of the putative core region and a portion of NS5B encoding the Gly-Asp-Asp motif indicated that HCV-K3a closely matched the corresponding type 3a group. The deletion and addition of amino acids in both E2 and NS5A may be associated with their pathobiological features.

Amino Acid Sequence↗

Genomic heterogeneity of rice dwarf phytoreovirus field isolates and nucleotide sequences of variants of genome segment 12.

Electrophoretic profiles of the dsRNAs of field isolates of rice dwarf virus (RDV) were compared with those of an isolate maintained at Hokkaido University (RDV-H). Unexpectedly, the genomic dsRNAs of most of the field isolates showed distinct electrophoretic mobility profiles. This was the case even among isolates from the same region. Genome segment 12 (S12) from some variants migrated faster than S12 from RDV-H. These RNAs were converted to full-length cDNAs and sequenced. S12 from all the variants had the same length of 1066 nucleotides with nucleotide sequence identities of 96 to 99%. Three open reading frames previously reported were present in all the variants, and the sequence identities were 95 to 99% for P12, 98 to 100% for P12OPa, and nearly 100% for P12OPb. A comparison of the nucleotide and amino acid sequences of the variants with sequences of the RDV-H and Akita isolate showed that there are two genomic types, one represented by RDV-H and the other by the Akita isolate.

Base Sequence↗

Temporomandibular joint osteoarthritis: a comparative clinical and tomographic study pre- and post-treatment.

Nineteen patients with definite and suspected temporomandibular joint (TMJ) osteoarthritis participated in this study. All patients were treated by dental care including bite plane therapy. By comparing the pre-treatment clinical symptoms and TMJ tomograms with those post-treatment, efficacy of the dental treatment applied for these patients has been assessed. Since TMJ pain and limitation of mouth opening were considerably improved in almost all patients post-treatment, this suggests that the clinical prognosis of TMJ osteoarthritis can be favourable. On the other hand, radiographic changes post-treatment were variable. The longitudinal changes found in the TMJ tomograms were classified into four types. The frequency of Type 2 and Type 3, which indicate the occurrence of TMJ remodelling during the observation period, was fairy high (20 TMJs and 14 patients).

Adult↗

Nucleotide sequence of rice dwarf phytoreovirus genome segment 2: completion of sequence analyses of rice dwarf virus.

The complete nucleotide sequence of rice dwarf phytoreovirus genome segment 2 (S2) was determined to be 3,512 nucleotides long with one open reading frame initiating at nucleotide 15 and terminating at nucleotide 3363. The encoded polypeptide was predicted to have 1,116 residues with a relative molecular weight of 123 kD. Comparison of S2 of two isolates showed they had identical lengths and 97 and 98.3% nucleotide and amino acid sequence identities, respectively. A search of the Swiss-Prot data base (R 22.0) failed to find any proteins with significant homology to the S2-encoded protein. Determination of the nucleotide sequence of the S2 has completed the sequence determination of the genome of rice dwarf virus. Homology searches made for proteins encoded by each of the genomic segments showed that the polypeptide encoded by S11 has similarity to histone H1 protein and VP6 of blue tongue virus, indicating it might possess nucleic acid binding properties.

Amino Acid Sequence↗

Antigen-induced airway hyperresponsiveness is associated with infiltration of eosinophils in lung tissue, but not with bronchoalveolar lavage eosinophilia or neutrophilia.

To examine the role of airway inflammation in airway hyperresponsiveness (AHR), we developed an animal model of AHR in guinea pigs and examined the histopathologic changes of these airways. Guinea pigs were actively sensitized with dinitrophenylated Ascaris suum extract and challenged with inhalation of the same extract. Six and 24 h after antigen challenge, airway responsiveness to inhaled acetylcholine (ACh), bronchoalveolar lavage fluid (BALF) and lung histology were studied. Airway responsiveness to inhaled ACh increased 6 h after antigen challenge (p < 0.05), but an increase in airway responsiveness was not observed 24 h after antigen challenge as determined by PC300 (the minimum concentration of ACh at which the respiratory resistance exceeded 300% of baseline value). The number of eosinophils and neutrophils in BALF increased 6 and 24 h after antigen challenge compared to sensitized, nonchallenged guinea pigs, peaking at 24 h after antigen challenge. On the other hand, the numbers of infiltrating eosinophils in bronchial and bronchiolar tissues increased 6 and 24 h after antigen challenge compared to sensitized, nonchallenged guinea pigs, peaking at 6 h after antigen challenge. We therefore conclude that AHR after allergen exposure in sensitized guinea pigs is associated with an increase in infiltrating eosinophils in lung tissue but not with BAL eosinophilia or BAL neutrophilia.

Aerosols↗

Induction of LDL receptor-related protein during the differentiation of monocyte-macrophages. Possible involvement in the atherosclerotic process.

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional receptor that binds to apolipoprotein E-rich lipoproteins, lipoprotein lipase, alpha 2-macroglobulin, lactoferrin, and tissue plasminogen activator. We studied the mRNA expression of LRP in human monocyte-derived macrophages and THP-1 cells. mRNA expression of LRP was induced during cell differentiation from human monocytes to macrophages or after incubation with phorbol ester (tetradecanoylphorbol acetate 100 ng/mL) in THP-1 cells, and the addition of 30 ng/mL macrophage colony-stimulating factor further enhanced LRP expression. These results indicated that the expression of LRP depended on the stage of differentiation and maturation of monocytic cells. mRNA expression of LRP was also enhanced in human monocyte-derived macrophages in the presence of acetylated low-density lipoprotein and in aorta of rabbits fed a high-cholesterol diet. We hypothesize that the LRP induced in monocyte-derived macrophages is involved in the initial process of atherosclerosis by interacting with its multiple ligands.

Animals↗

Idiopathic pulmonary fibrosis. Epidemiologic approaches to occupational exposure.

Idiopathic pulmonary fibrosis (IPF) risk-related factors were epidemiologically investigated on the basis of 1,311 Japanese IPF autopsy cases selected from the annual complications of autopsy data records in Japan during a 12-yr period. Age and sex distribution of the subjects revealed a high peak in their seventh decade with males predominating. The IPF rate was more than two times higher (p < 0.01) among subjects engaged in occupations that exposed them to dust or organic solvents compared with those in other jobs. To ascertain job characteristics, an autopsy-case control study was conducted using other annual volumes of the autopsy data records and a similar tendency was observed. Then, a live-case control study was undertaken of 86 subjects with IPF. A significantly higher odds ratio was noted among metal production workers and miners compared with healthy and hospital control subjects (1.37 and 1.34, respectively, p < 0.01), and also a significantly lower odds ratio among subjects who frequently eat fish. Taken together with results of recent in vitro studies, the intrapulmonary deposition of hazardous dusts, especially metallic dusts, appears to play at least a partial role in initiating IPF.

Adolescent↗

Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1.

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), a complication of long-term hemodialysis. However, the pathological role of beta 2M in HAA remains to be determined. Recently, we demonstrated that beta 2M in the amyloid deposits of HAA is modified with advanced glycation end products (AGEs) of the Maillard reaction. Since AGEs have been implicated in tissue damage associated with diabetic complications and aging, we investigated the possible involvement of AGE-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA. AGE- and normal-beta 2M were purified from urine of long-term hemodialysis patients. AGE-beta 2M enhanced directed migration (chemotaxis) and random cell migration (chemokinesis) of human monocytes in a dose-dependent manner. However, normal-beta 2M did not enhance any migratory activity. AGE-beta 2M, but not normal-beta 2M, increased the secretion of TNF-alpha and IL-1 beta from macrophages. Similar effects were also induced by in vitro prepared AGE-beta 2M (normal-beta 2M incubated with glucose in vitro for 30 d). When TNF-alpha or IL-1 beta was added to cultured human synovial cells in an amount equivalent to that secreted from macrophages in the presence of AGE-beta 2M, a significant increase in the synthesis of collagenase and morphological changes in cell shape were observed. These findings suggested that AGE-beta 2M, a major component in amyloid deposits, participates in the pathogenesis of HAA as foci where monocyte/macrophage accumulate and initiate an inflammatory response that leads to bone/joint destruction.

Adult↗

Secretion-recapture process of apolipoprotein E in hepatic uptake of chylomicron remnants in transgenic mice.

To investigate the role of apoE in hepatic uptake of chylomicron remnants, we studied chylomicron metabolism in transgenic mice overexpressing apoE in the liver. Plasma clearance of injected 125I-labeled human chylomicrons was fivefold faster in transgenic mice than in controls. Immunohistochemistry demonstrated that apoE was specifically localized at the basolateral surface of hepatocytes from fasted transgenic mice. After injection of a large amount of chylomicrons, the density of the cell surface apoE was markedly reduced and vesicular staining was observed in the cytoplasm, suggesting that the cell surface apoE was used for hepatic endocytosis of chylomicrons and remnants. Polyacrylamide gel analysis of chylomicrons and remnants that had been reisolated from plasma and from liver membrane after the injection of chylomicrons showed the particles to be enriched with apoE mainly after their influx into the liver rather than during their residence in plasma. These results provide strong evidence for the secretion-recapture process of apoE, whereby chylomicron remnants enter the sinusoidal space, acquire apoE molecules, and subsequently are endocytosed. Data from experiments with very low density lipoprotein and LDL showed that this system is specific for chylomicron remnants.

Animals↗

Proteoglycan form of macrophage colony-stimulating factor binds low density lipoprotein.

We recently isolated a proteoglycan form of macrophage colony-stimulating factor (PG-M-CSF) that carries a chondroitin sulfate glycosaminoglycan chain. Here, we examined the interaction of PG-M-CSF with low density lipoprotein (LDL). When LDL preincubated with PG-M-CSF was fractionated by molecular size sieving chromatography, it was eluted earlier than untreated LDL. When LDL was preincubated with chondroitin sulfate-free 85-kD M-CSF instead of PG-M-CSF, the elution profile of LDL remained unchanged, indicating specific interaction between PG-M-CSF and LDL. The level of PG-M-CSF binding in the wells of a plastic microtitration plate precoated with LDL was significant, this binding being completely abolished by pretreatment of PG-M-CSF with chondroitinase AC, which degrades chondroitin sulfate. The addition of exogenous chondroitin sulfate or apolipoprotein B inhibited the binding of PG-M-CSF to LDL in a dose-dependent manner, indicating that the interaction between PG-M-CSF and LDL was mediated by the binding of the chondroitin sulfate chain of PG-M-CSF to LDL apolipoprotein B. PG-M-CSF was also demonstrated in the arterial wall, and there were increased amounts of PG-M-CSF in atherosclerotic lesions. The in vitro interaction between PG-M-CSF and LDL thus appears to have physiological significance.

Aorta↗

Evaluation of pulmonary arterial pressure in acute pulmonary embolism.

Twenty-six patients with acute pulmonary embolism underwent hemodynamic examination. Twenty-three of the patients were free of prior cardiopulmonary diseases. The other 3 patients had prior history of cardiac disease. In the 23 patients, the mean pulmonary arterial pressure (PAm) ranged from normal range to 35 mmHg at the time of the embolic event and generally declined within ten days after the embolic event. However, in the 3 patients with a history of disease, reelevation of PAm was observed during the pressure monitoring. PAm was positively correlated with the extent of pulmonary vascular obstruction (r = 0.863, p < 0.01) and also with mean right atrial pressure (RAm, r = 0.830, p < 0.01). In the presence of prior cardiac disease, PAm in patients with normal preembolic PAm increased proportionally to the extent of obstruction. Continuous hemodynamic monitoring is valuable for estimating the degree of embolic obstruction and the speed of embolus resolution and for detecting new embolic episodes in some cases.

Acute Disease↗

Mechanism of an early lysis by fatty acids from axenic Phormidium tenue (musty odor-producing cyanobacterium) and its growth prolongation by bacteria.

We have previously demonstrated that bacteria-containing Phormidium tenue, a cyanobacterium which produces musty odor 2-methylisoborneol, grew beyond 8 weeks, whereas axenic alga perished suddenly between the 3rd week and the 4th week while being cultured in the laboratory. This mechanism was investigated. It is assumed that when algal cells grow beyond a certain level, the supply of CO2 becomes inadequate and results in the rapid lysis of axenic alga. At that time, inhibitory substances liberated from algal cells kill the surviving alga. Since the process occurs continuously, this alga is finally annihilated. On the other hand, since inhibitory substances are metabolized or degraded by bacteria coexistent with alga, bacteria-containing P. tenue maintains growth for a long time. The growth-inhibitory substance was found to be unsaturated free fatty acids.

Bacteria↗

Synthesis and antitumor activities of prodrugs of benzoylphenylureas.

Various benzoylphenylurea derivatives were synthesized as candidate prodrugs and their antitumor activities were examined in vivo against P388 leukemia. All of the prodrugs were soluble in most organic solvents and showed good antitumor activities against P388 leukemia cells in mice when dosed intraperitoneally or orally.

Animals↗

Increased plasma gluconeogenic and system A amino acids in patients with pancreatic diabetes due to chronic pancreatitis in comparison with primary diabetes.

We examined the plasma amino acid profiles of 17 patients with pancreatic diabetes in comparison with those of 14 healthy subjects and 16 patients with primary diabetes of similarly poor glycemic control. We also measured fasting plasma glucagon and free insulin levels in patients with pancreatic diabetes and in those with primary diabetes. The fasting plasma amino acid level was highest in patients with pancreatic diabetes. Furthermore, the plasma glucagon level in patients with pancreatic diabetes was significantly low, and negative correlations were found between glucagon and glucagon-related System A and gluconeogenic amino acids. On the other hand, the levels of branched-chain amino acids (BCAA) and System L amino acids, which are subjected to change in the state of diabetes mellitus, increased in patients with pancreatic diabetes. From the above results, we determined that the amino acid profile in patients with pancreatic diabetes resembled that in patients with total pancreatectomy. It is our opinion that the increases of amino acid levels (gluconeogenic and System A amino acids) in patients with pancreatic diabetes is not dependent on maldigestion/malabsorption under treatment, but is mainly dependent on glucagon deficiency.

Amino Acids↗

Decreased counterregulatory hormone responses to insulin-induced hypoglycemia in patients with pancreatic diabetes having autonomic neuropathy.

Thirteen patients with pancreatic diabetes caused by calcifying pancreatitis were divided into 2 groups; 5 with diabetic autonomic neuropathy [AN(+) group] and 8 without [AN(-) group]. They were subjected to an insulin-induced hypoglycemic stress test to evaluate their blood pancreatic glucagon, adrenalin, and cortisol responses. When a blood glucose level below 45 mg/100 ml was defined to be hypoglycemia, all the patients in the AN(-) group exhibited peripheral adrenalin responses, with a significant increase (mean, 19.0 times the basal level) in the blood adrenalin level. Among the AN(+) group, on the other hand, central nervous symptoms became evident rather than the peripheral adrenalin response (the blood adrenalin level hardly exceeded the basal level). With the exception of a single patient, none exhibited responses in the blood pancreatic glucagon levels. Only one patient showed a minimal cortisol response but the remaining 12 reacted normally in the cortisol release. The findings are summarized as follows: in pancreatic diabetes, insulin-induced hypoglycemia causes little change in pancreatic glucagon secretion; when the condition is complicated with autonomic neuropathy, central nervous symptoms develop while the blood adrenalin level hardly increases. These findings indicated that patients with pancreatic diabetes complicated with diabetic autonomic neuropathy have a risk of lapsing into an acute hypoglycemic coma and difficulty in recovering from the hypoglycemic state.

Alcoholism↗

Octreotide decreases biliary and pancreatic exocrine function, and induces steatorrhea in healthy subjects.

A somatostatin analogue (SMS-201-995, hereinafter "octreotide") was s.c. administered to 5 healthy subjects under consecutive dripping of CCK-PZ (cholecystokinin-pancreozymin) and secretin (0.01 CHR U/kg/minutes), after inserting a Dreiling double tube into Treitz's ligament. Bile acid concentration, and bicarbonate and lipase excretions in duodenal juice were determined every 10 minutes up to 120 minutes and compared with controls. Moreover, octreotide (100 micrograms) was s.c. administered to 5 healthy subjects 30 minutes before meals for 7 days. Fecal fat and bile acid excretions before and after administration were determined. Bile acid concentration, and bicarbonate and lipase excretions in the octreotide group decreased to 1/3-1/4 that of controls. Bile acid concentration became 0 mM for 60 minutes. Fecal fat excretion increased; obvious steatorrhea occurred in 2 cases. Fecal bile acid excretion decreased to about 1/4. These results suggest that decreases in bile acid secretion should be considered, as well as pancreatic lipase and bicarbonate secretions, when fatty stool occurs after octreotide administration.

Adult↗

Increased risk factors for coronary artery disease in Japanese subjects with hyperinsulinemia or glucose intolerance.

OBJECTIVE: To understand the interrelationship of coronary artery disease (CAD) risk factors including hyperlipidemia, hypertension, and glucose intolerance to prevent and better manage this disease. RESEARCH DESIGN AND METHODS: We performed a 100-g oral glucose tolerance test in 2,113 subjects, and we evaluated their plasma lipid levels, blood pressure (BP), and plasma glucose and plasma insulin responses. RESULTS: Multiple regression analysis demonstrated a significant relationship of either BP, plasma triglyceride (TG), or high-density lipoprotein (HDL) cholesterol levels to plasma insulin and glucose response after the glucose load. Plasma cholesterol levels were related only to the plasma glucose response. In subjects matched for age, sex, and body mass index (BMI) with hyperinsulinemia or normoinsulinemia, the hyperinsulinemic subjects had a significantly higher mean BP and plasma TG level than the normoinsulinemic subjects (128.8/82.3 vs. 122.9/79.3 mmHg and 172.1 vs. 119.4 mg/dl), and the HDL-cholesterol level was significantly lower (43.9 vs. 47.8 mg/dl). Furthermore, subjects matched for age, sex, and BMI with glucose intolerance had a higher mean BP (128.4/81.8 vs. 123.5/78.7 mmHg) and higher plasma TG level (154.2 vs. 123.0 mg/dl) than those without glucose intolerance. CONCLUSIONS: Based on these findings, subjects with hyperinsulinemia or glucose intolerance should be carefully managed to prevent CAD, because they have more numerous and more severe risk factors than subjects with normal plasma insulin levels or subjects without glucose intolerance.

Blood Glucose↗