[Malignant insulinoma which expressed a unique creatine kinase isoenzyme: clinical value of arterial embolization as a palliative therapy] [In Process Citation]
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Journal Article↗
Biomedical subjects
H Yasuda
Publications and source records attributed to H Yasuda.
Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway.
Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a family of serine/threonine kinases. Here we demonstrate that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells. Aurora2 protein has a rapid turnover rate with a half-life of approximately 2 h. In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of unstable proteins. The treatment of mammalian cells with proteasome inhibitors blocks Aurora2 degradation. Furthermore, Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein is turned over through the APC-ubiquitin-proteasome pathway. Oncogene (2000) 19, 2812 - 2819
Anaphase-Promoting Complex-Cyclosome↗
[Occupationally induced hydrofluoric acid burns: an analysis of 9 patients from the aspect of occupational health].
We report here 9 patients suffering from hydrofluoric acid burn who visited our clinic from July, 1979 to February, 2000. These 9 cases occupied 25% of all chemical burn cases experienced in our clinic. All the patients were men ranging in age from 20 to 53 (mean age 35 years; average 36.8 years). At the time of accidental exposures, 6 patients had been engaged in washing or cleaning work, and 2 had been changing the parts of instruments containing hydrofluoric acid. Eight patients received burns on the hands and/or fingers. During the work, 2 patients had used vinyl chloride or rubber gloves, but three patients employed no protection for the hands. After the symptoms began to develop, it was found that the glove of one patient had a pin hole. Coupled with the occasions described in previous reports, the causal factors of hydrofluoric acid burn could be divided as follows: 1) negligence or carelessness of workers, in particular skilled persons, in handling hydrofluoric acid, 2) ignorance of the dangerousness of hydrofluoric acid, 3) the presence of pin hole (s) in protection gloves, and 4) unexpected accident. Hydrofluoric acid is one of the most corrosive inorganic acids, and can produce progressive and serious tissue necrosis with severe pain. To prevent burns due to this chemical, enlightenment and reeducation of the workers regarding the hazard of hydrofluoric acid are necessary.
Accidents, Occupational↗
[A case of squamous cell carcinoma that developed on chronic tar dermatosis].
A 79-year-old Japanese man visited our clinic for evaluation of a large tumor on the left wrist and multiple keratotic tumors. He had handled creosote oil, which is a purified product of coal tar production, for 50 years. Physical examinations revealed poikiloderma with multiple hyperkeratotic tumors on the back of his hand and forearm bilaterally, and a cauliflower-like tumor, 80 x 60 x 15 mm in size, on the left wrist. Histopathologically, the large tumor showed a proliferation of atypical squamoid cells with many keratinization foci, indicating well-differentiated squamous cell carcinoma.
Aged↗
Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the activity of SCF(skp2) toward p27(kip1).
The periodic expression of cell cycle proteins is important for the regulation of cell cycle progression. The amount of CDK inhibitor, p27(kip1), one such protein, seems to be regulated by the ubiquitin-proteasome system. The ubiquitin ligase (E3) toward p27(kip1) is thought to be SCF(skp2). The activity of SCF(skp2) was increased by the addition of Roc1 protein to the complex. Furthermore, the ubiquitination of p27(kip1) seemed to be dependent on the phosphorylation of T187 of p27(kip1) because the mutant T187A was not ubiquitinated at all in an in vitro ubiquitination system. Cullin-1, a component of SCF, is modified by ubiquitin-like protein Nedd8. The modification site of cullin-1 was shown to be K696 because the K696R mutant was not modified. When the effect of the Nedd8 modification on the SCF(skp2) activity toward p27(kip1) was investigated, the activity was markedly decreased by using the Nedd8-unmodified mutant cullin-1 (K696R), indicating that the modification may play an important role on the SCF(skp2) activity toward p27(kip1).
Amino Acid Sequence↗
Apoptosis and impaired axonal regeneration of sensory neurons after nerve crush in diabetic rats.
We investigated the possible induction of apoptosis of dorsal root ganglion (DRG) neurons and the defect of nerve regeneration after crush injury with reference to the JNK/c-jun and cAMP pathway in streptozocin-induced diabetic rats. In addition, the effects of a PGE1 analogue were tested in diabetic rats. At day 0 (before axonal injury), no TUNEL-positive DRG neurons were observed in any group. From day 1 to 7 after axonal injury, TUNEL-positive DRG neurons were seen in diabetic rats, but not in non-diabetic or PGE1-treated diabetic rats. The regeneration distance at day 7 after crush injury was shorter in diabetic rats than in the other groups of rats. The time course of JNK/c-jun phosphorylation did not parallel apoptosis. At day 7, the cAMP content of DRG was higher than that at day 0 in non-diabetic and PGE1-treated rats, whereas it was not increased after 7 days in diabetic rats. These results indicate that in diabetic rats apoptosis of DRG neurons is induced by axonal injury independently of the JNK/c-jun and cAMP pathway and that PGE1 rescues DRG neurons from apoptosis and improves axonal regeneration in diabetic rats.
Afferent Pathways↗
Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase.
Partial amino acid sequence of 80 kDa oxidized protein hydrolase (OPH), a serine protease present in human erythrocyte cytosol (Fujino et al., J. Biochem. 124 (1998) 1077-1085) that is adherent to oxidized erythrocyte membranes and preferentially degrades oxidatively damaged proteins (Beppu et al., Biochim. Biophys. Acta 1196 (1994) 81-87; Fujino et al., Biochim. Biophys. Acta 1374 (1998) 47-55) was determined. The N-terminal amino acid of diisopropyl fluorophosphate (DFP)-labeled OPH was suggested to be masked. Six peptide fragments of OPH obtained by digestion of DFP-labeled OPH with lysyl endopeptidase were isolated by use of reverse-phase high-performance liquid chromatography, and the sequence of more than eight amino acids from the N-terminal position of each peptide was determined. Results of homology search of amino acid sequence of each peptide strongly suggested that the protein was identical with human liver acylpeptide hydrolase (ACPH). OPH showed ACPH activity when N-acetyl-L-alanine p-nitroanilide and N-acetylmethionyl L-alanine were used as substrates. Glutathione S-transferase (GST)-tagged recombinant ACPH (rACPH) was prepared by use of baculovirus expression system as a 107-kDa protein from cDNA of human erythroleukemic cell line K-562. rACPH reacted with anti-OPH antiserum from rabbit. rACPH showed OPH activity when hydrogen peroxide-oxidized or glycated bovine serum albumin was used as substrates. As well as the enzyme activities of OPH, those of rACPH were inhibited by DFP. The results clearly demonstrate that ACPH, whose physiological function has not yet been well characterized, can play an important role as OPH in destroying oxidatively damaged proteins in living cells.
Amino Acid Sequence↗
Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase.
We previously showed that oncoprotein MDM2 has ubiquitin ligase activity toward tumor suppressor p53. In that paper, we showed very weak homology in the carboxyl terminal portion between MDM2 and E6AP (HECT domain). We mutated the cysteine residue (C464) corresponding to the residue essential for the ubiquitin ligase activity of E6AP and this mutation diminished the ligase activity of MDM2. The cysteine residue described above is also one of the cysteine residues that form the RING finger domain of MDM2. We tried to find out whether the diminishing of the activity by the mutation is attributable to the disruption of the RING finger domain or not. When the ring finger domain of MDM2 was deleted, the truncation mutant did not have the ubiquitin ligase activity. When we mutated the seven cysteine residues of RING finger domain of MDM2 in the carboxyl terminus, the disruption of each residue in the RING finger completely diminished the ubiquitin ligase activity of MDM2 toward MDM2 itself and toward tumor suppressor p53. These data indicate that the RING finger domain in MDM2 is essential for its ubiquitin ligase activity toward p53 and itself.
Amino Acid Sequence↗
Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction.
Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF-dependent bone marrow macrophages (M-BMM phi) appeared within 3 d. Tartrate-resistant acid phosphatase-positive osteoclasts were also formed when M-BMM phi were further cultured for 3 d with mouse tumor necrosis factor alpha (TNF-alpha) in the presence of M-CSF. Osteoclast formation induced by TNF-alpha was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti-RANK (ODF/RANKL receptor) antibody. Experiments using M-BMM phi prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-alpha. Osteoclasts induced by TNF-alpha formed resorption pits on dentine slices only in the presence of IL-1alpha. These results demonstrate that TNF-alpha stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL-RANK system. TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases.
Acid Phosphatase↗
Evaluation of diabetic neuropathy through the quantitation of cutaneous nerves.
The significance and usefulness of immunohistochemically quantitated cutaneous nerves in the evaluation of diabetic neuropathy was examined in biopsied skins of the calf from healthy subjects (n=12) and non-insulin dependent diabetic patients (n=32) with diabetic sensory neuropathy. Skin samples were immunostained with antibodies against protein gene product (PGP) 9.5, a pan-axonal marker. A quantitative analysis to determine nerve fiber (NF) number and nerve lengths (NLs) was performed on nerve fibers of the epidermis and the dermis and on nerves surrounding sweat glands. Nerve function tests were performed on the biopsied sites and erythrocyte aldose reductase level was determined by enzyme-linked immunosorbent assay. Numbers of epidermal NFs, NLs of epidermis and dermis and NL around sweat glands were significantly decreased in diabetic patients compared with control subjects (P<0.001, P<0.001, P<0.01, P<0.01, respectively). NL of epidermis showed a significant correlation with NL of dermis (P<0.01). Sural nerve conduction velocity was significantly correlated with NL of dermis (P10.8 (average in 555 diabetic patients) ng/mgHb) possessed a shorter NL of dermis NFs than those with lower AR level (<10.8) (P<0.05). These findings suggest that the quantitation of cutaneous nerves in biopsied skin samples provides important information about diabetic neuropathy and may improve the understanding of the pathophysiology of sensory nerve terminals in diabetic neuropathy.
Aldehyde Reductase↗
Wider indications for the local resection of gastric cancer by adjacent lymphadenectomy.
BACKGROUND AND OBJECTIVES: A variety of minimal invasive treatment strategies for early gastric cancer without reducing the curability have been introduced, however, the indications for the local resection of early gastric cancer have not been precisely established. METHODS: Two approaches are adopted in this study to elucidate indications for local resection. One is a retrospective review of surgically resected, postoperatively histologically proven early gastric cancers between 1976 and 1996 (611 patients), and the other is the patient selection from those who underwent modified D(1) lymphadenectomy in a prospective manner between 1987 and 1996, based on the preoperative and intraoperative diagnoses of mucosal, node negative, nonpalpable gastric cancer (125 patients). In these approaches, patterns of nodal involvement in association with clinicopathological characteristics of gastric cancer were investigated. RESULTS: The depressed with ulceration type and histologically high grade type were predominant characteristics of mucosal, node positive gastric cancer patients. Of these patients, after the exclusion of those who were diagnosed to have submucosal or advanced cancer preoperatively or who had palpable cancer intraoperatively, the gastric cancer < or =4 cm in maximum diameter had positive nodes confined to only one station adjacent to the cancer without simultaneous nodal involvement in the other stations. CONCLUSIONS: Local resection can be performed for gastric cancers < or = 4 cm in maximum diameter that meet our criteria for modified D(1) lymphadenectomy, in association with the frozen section confirmation of cancer negative in the simultaneously dissected lymph nodes in the stations adjacent to the cancer. The adjacent lymphadenectomy and frozen section examination make the application of local resection possible for a wider segment of patients.
Adult↗
A deleted form of human hepatocyte growth factor stimulates hepatic lipogenesis and lipoprotein synthesis in rats.
Here we report the effect of the recombinant human deleted form of hepatocyte growth factor (dHGF) on lipid metabolism in rats. In primary cultured rat hepatocytes, dHGF accelerated incorporation of [(14)C]acetate into cellular lipids in a concentration-dependent manner. dHGF also increased the gene expression and enzyme activity of glucose-6-phosphate dehydrogenase, a rate-limiting enzyme of the pentose phosphate pathway, in hepatocytes. These results suggest that dHGF stimulates hepatocyte lipogenesis through upregulation of the pentose pathway and NADPH formation. Injection of dHGF into normal rats induced elevation of the serum triglyceride, phospholipid and cholesterol levels dose-dependently and in the same time course as the liver growth. dHGF injections stimulated the [(14)C]acetate incorporation into the liver lipids, but not into the adipose tissue nor the small intestine. Serum very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels were elevated by dHGF injections. [(14)C]Leucine incorporation into VLDL and LDL was also increased by dHGF injections. In rats with alcohol-induced fatty livers, dHGF treatment markedly diminished the accumulated liver triglyceride, while elevating serum lipid concentrations. The present results indicate that dHGF stimulates exclusively hepatic lipogenesis and increases serum lipoprotein levels in rats.
Animals↗
1H- and 31P-magnetic resonance spectroscopy and imaging as a new diagnostic tool to evaluate neuropathic foot ulcers in Type II diabetic patients.
AIMS/HYPOTHESIS: We studied 36 Type II (non-insulin-dependent) diabetic patients without occlusive arterial diseases in the lower extremities and 12 age-matched and sex-matched non-diabetic subjects to clarify the association between diabetic polyneuropathy and foot ulcers using 1H- and 31P-magnetic resonance spectroscopy and imaging. METHODS: The 36 diabetic patients consisted of 12 patients with superficial foot ulcers and 24 patients free from this disease. We measured fat to water and phosphocreatine to inorganic phosphate (PCr:Pi) ratios and calculated the intracellular pH of resting plantar muscles by depth-resolved surface-coil spectroscopy using an 1H-31P double tuned coil. Furthermore, foot vasculature, fat and PCr contents of plantar muscles were visualised by phase-contrast angiography, T1-weighted spin-echo imaging and 31P-chemical shift imaging. RESULTS: The 12 foot ulcer patients showed a reduced PCr to Pi ratio (p < 0.001) and peripheral nerve functions (p < 0.01-0.001) but an increased fat to water ratio (p < 0.001) and intracellular pH (p < 0.001) compared with the 24 patients without ulcers. From stepwise multiple regression analyses, motor nerve function as well as severity of nephropathy was associated with both fat to water and PCr to Pi ratios. When these patients were categorised into three groups based on their level of motor nerve function, the frequency of foot ulcers of the lowest group was higher than that of the highest group. CONCLUSION/INTERPRETATION: Our findings indicated that motor nerve dysfunction in diabetic patients was closely associated with impaired energy metabolism, fatty infiltration and increased intracellular pH of plantar muscles and high frequency of foot ulcers. These new techniques could contribute to help clarify the predisposing factors for foot ulcers.
Aged↗
Usefulness of waveform analysis of popliteal artery in type II diabetic patients using gated magnetic resonance 2D-cine-PC imaging and 31P spectroscopy.
AIMS/HYPOTHESIS: We studied 76 patients with Type II (non-insulin-dependent) diabetes mellitus and 16 age-matched non-diabetic subjects (control group) to clarify qualitative and quantitative abnormalities of waveform and flow volume of the popliteal artery. METHODS: The 76 diabetic patients comprised 16 patients with occlusive arterial disease in the lower extremities [arteriosclerosis obliterans (ASO) group] and 60 patients free from this disease (non-ASO group). We flow analysed the popliteal artery and measured the phosphocreatine to inorganic phosphate ratio of resting plantar muscles to identify risk factors for foot lesions using gated magnetic resonance two-dimensional cine-mode phase-contrast imaging and 31P spectroscopy. RESULTS: The control and non-ASO groups had a triphasic waveform with systolic, early and late diastolic components. All ASO patients had an abnormal monophasic waveform and a lower ankle brachial index than that of the control and non-ASO groups. To clarify the mechanism of reduced flow volume of lower extremities, we assigned the 60 patients of the non-ASO group to the three subgroups based on their levels of total flow volume of the popliteal artery. The lowest group showed an abnormal triphasic waveform with lower amplitudes of systolic and late diastolic components and flow velocities in foot arteries than those of the highest group although ABI was similar. From stepwise multiple regression analysis, late diastolic flow volume was identified as an independent determinant for the phosphocreatine to inorganic phosphate ratio (r2 = 0.484, p < 0.001). CONCLUSION/INTERPRETATION: Waveform analysis of popliteal artery provides a powerful tool for identifying impaired peripheral circulation caused by either occlusive arterial disease or increased arterial resistance in diabetic patients.
Adult↗
Limited pancreatectomy: significance of postoperative maintenance of pancreatic exocrine function.
This study attempted to clarify whether limited pancreatectomy (duodenum-preserving total pancreatic head resection [DPTPHR], or medial pancreatectomy [MP], maintain pancreatic exocrine function more than conventional pancreaticoduodenectomy (Whipple) or pylorus-preserving pancreaticoduodenectomy (PPPD). A total of 125 patients (18 with Whipple, 71 with PPPD, 13 with DPTPHR, and 23 with MP) were studied. Fecal chymotrypsin and p-type amylase, and pancreatic function diagnostant (PFD) tests were used for evaluation. There were no differences in preoperative background. Pancreatic function was seen to be significantly lower after surgery than before surgery in patients who underwent the Whipple procedure and PPPD (P < 0.05), but there was no difference between pre- and postoperative pancreatic function in patients who underwent DPTPHR and MP. Postoperative pancreatic function was shown to be significantly worse in Whipple procedure and PPPD patients than in those with DPTPHR and MP (P < 0.05). Patients who underwent the Whipple procedure and PPPD showed significantly lower pancreatic function than patients who underwent DPTPHR and MP (P < 0.05). There was no difference in pancreatic function between patients who underwent DPTPHR and those with MP. DPTPHR and MP, both of which preserve the entire duodenum, maintain pancreatic function more than the Whipple procedure and PPPD.
Aged↗
Caries inhibitory activity of cacao bean husk extract in in-vitro and animal experiments.
Cacao bean husk extract (CBH) was examined for inhibitory effects on the caries-inducing properties of mutans streptococci in vitro and on caries development in specific pathogen-free Sprague-Dawley rats infected with mutans streptococci. CBH reduced the growth rate of almost all oral streptococci examined, which resulted in the reduction of acid production. Furthermore, insoluble glucan synthesis by the glucosyltransferases from Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 was significantly inhibited by CBH. Hence, the sucrose-dependent cell adherence of mutans streptococci was also depressed by CBH. The administration of CBH in drinking water resulted in significant reductions of caries development and dental plaque accumulation in rats infected with either Strep. sobrinus 6715 or Strep. mutans MT8148R, and the minimum cariostatic concentration was 1.0 mg/ml. These results indicate that CBH possesses powerful anticariogenic potential.
Analysis of Variance↗
Cariostatic activity of cacao mass extract.
Chocolate is suspected to contain some caries-inhibitory substances. The cariostatic activity of cacao mass extract (CM), the main component of chocolate, was examined in vitro and in experimental animals. CM showed no detectable effects on the cellular growth and acid production of mutans streptococci. On the other hand, the cell-surface hydrophobicity of mutans streptococci was significantly reduced by the presence of CM. Furthermore, insoluble glucan synthesis by the glucosyltransferases from either Streptococcus mutans MT8148R or Strep. sobrinus 6715 was inhibited by CM, but not significantly. Hence, the sucrose-dependent cell adherence of mutans streptococci was also depressed by CM. Finally, CM in both a 40% sucrose diet and drinking water resulted in reductions of caries development and plaque accumulation in rats infected with Strep. sobrinus 6715, but not significantly. These results indicate that cacao mass extract possesses some anticariogenic potential, but its anticaries activity is not strong enough to suppress significantly the cariogenic activity of sucrose.
Animals↗
Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils.
Immunological effects of a variety of local anesthetics on adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils were compared. Neutrophils were isolated by peritoneal lavage from rats, 4 h after injection of 1% glycogen. Lidocaine, mepivacaine, procaine, prilocaine and tetracaine at 1 mg/ml inhibited adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide in neutrophils. Moreover, lidocaine, mepivacaine, procaine and prilocaine at 0.1 mg/ml inhibited the production of superoxide anion and hydrogen peroxide but not adhesion or phagocytosis. In contrast, tetracaine at 0.1 mg/ml inhibited phagocytosis, and the production of superoxide anion and hydrogen peroxide but not adhesion. At 0.01 mg/ml, however, tetracaine inhibited the production of superoxide anion and hydrogen peroxide; in contrast, other drugs failed to affect neutrophil function. These results suggest that the local anesthetics may affect adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils.
Anesthetics, Local↗