Bone and soft tissue sarcomas: summary of the Third United States/Japan Clinical Trials Summit (Seattle, Washington).
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Bone Neoplasms↗
Biomedical subjects
A Uchida
Publications and source records attributed to A Uchida.
Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR.
We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.
Animals↗
A posterior lumbar approach for retroperitoneoscopic adrenalectomy: assessment of surgical efficacy.
OBJECTIVES: To compare the efficacy of retroperitoneoscopic adrenalectomy by a posterior lumbar approach (RPA) with that obtained by a transperitoneal anterior approach (TAA) or retroperitoneal lateral flank approach (RLA). METHODS: Fifty-one patients underwent endoscopic adrenalectomy by three approaches, including laparoscopic adrenalectomy by TAA in 33, retroperitoneoscopic adrenalectomy by RLA in 5, and retroperitoneoscopic adrenalectomy by RPA in 13. RESULTS: The average adrenal tumor size was 27 mm (range 8 to 65). The average number of trocars required for RPA was 3.2 which was significantly less than that for TAA and for RLA (4.2 and 4.1, respectively). The conversion rate to open surgery was 9.1% by TAA, 0% by RLA, and 7.7% by RPA. The average operating time for TAA was 252 minutes, which was significantly shortened to 194 minutes by RLA and 142 minutes by RPA (P < 0.02). The average blood loss was 101 mL for TAA and was negligible by RLA and RPA (22 and 32 mL. respectively). CONCLUSIONS: RPA allowed direct access to the main adrenal vascular supply before the gland was greatly manipulated. Endoscopic adrenalectomy by TAA or even by RLA required extra ports for retraction of liver, spleen, vena cava, or adrenal gland, with higher chance of vein avulsion. RPA was technically feasible and most effective for retroperitoneoscopic adrenalectomy in regard to the simplicity of vascular control. The operating time, perioperative morbidity, and cost were reduced with this approach.
Adrenal Gland Neoplasms↗
Rotary dislocation of the capitate: a case report.
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Adult↗
Granulocyte colony-stimulating factor receptor expression on human transitional cell carcinoma of the bladder.
Receptors for granulocyte colony-stimulating factor (G-CSFRs) have been confirmed on the cell surfaces of several non-haematopoietic cell types, including bladder cancer cells. This observation has naturally led to the hypothesis that the expression of G-CSFR on these cells may enhance their growth by G-CSF. In this study, the expression of G-CSFR was determined in both established human bladder cancer cell lines and primary bladder cancers. We studied five different human bladder cancer cell lines (KU-1, KU-7, T-24, NBT-2 and KK) and 26 newly diagnosed bladder tumours. G-CSFR mRNA expressions on cultured cell lines were determined using the reverse transcriptase polymerase chain reaction (RT-PCR) method. Furthermore, the G-CSFR binding experiments on the cultured cell lines were conducted using the Na(125)I-labelled G-CSF ligand-binding assay method. Moreover, the G-CSFR mRNA expressions on primary bladder tumour specimens were assessed using the in situ RT-PCR method. Three out of the five cultured cell lines (KU-1, NBT-2 and KK) exhibited G-CSFR mRNA signals when the RT-PCR method was used. The G-CSFR binding experiments showed an equilibrium dissociation constant (K[d]) of 490 pM for KU-1, 340 pM for NBT-2 and 103 pM for KK cells. With in situ RT-PCR, the tumour cells of 6 out of 26 primary bladder tumour specimens (23.1%) presented positive G-CSFR mRNA signals. Thus, in this study, G-CSFR expression was frequently observed on bladder cancer cells. Therefore, the clinical use of G-CSF for patients with bladder cancer should be selected with great care.
Carcinoma, Transitional Cell↗
YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo.
BACKGROUND: We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1, 4benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo. METHODS: We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs. RESULTS: YF476 replaced the specific binding of [125I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with Ki values of 0.068, 0.62 and 0.19 nM, respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED50 value of 0.0086 micromol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 micromol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED50 values of 0.018 and 0.020 micromol/kg, respectively, but did not affect histamine-induced acid secretion. CONCLUSION: These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.
3T3 Cells↗
Extremely thermostable phosphoenolpyruvate carboxylase from an extreme thermophile, Rhodothermus obamensis.
Phosphoenolpyruvate carboxylase (PEPC) was purified from an extremely thermophilic bacterium, Rhodothermus obamensis, growing optimally at 80 degrees C, which had recently been isolated from a shallow marine hydrothermal vent in Japan. The native enzyme was a homotetramer of 400 kDa in molecular mass, as estimated by gel filtration chromatography, and the subunit exhibited an apparent molecular mass of 100 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The optimum temperature for enzyme activity was 75 degrees C. The enzyme exhibited an absolute requirement for divalent cations and a pH optimum of 8.0. The enzyme was extremely thermostable and there was no loss of enzyme activity on incubation for 2 h at 85 degrees C. The enzyme exhibited a positive allosteric property with acetyl-CoA and fructose 1,6-bisphosphate, and a negative one with L-aspartate and L-malate. These effectors affected not only the thermophilicity but also the thermostability of the enzyme, and the substrate, co-factors, and salts increased the thermostability as well. The extrinsic thermostabilization might be a possible mechanism for adaptation of the enzyme to high temperature.
Acetyl Coenzyme A↗
Expression of the Escherichia coli bo-type ubiquinol oxidase with a chimeric subunit II having the CuA-cytochrome c domain from the thermophilic Bacillus caa3-type cytochrome c oxidase.
The C-terminal periplasmic domain of subunit II of the Escherichia coli bo-type ubiquinol oxidase was replaced with the counterpart of the thermophilic Bacillus caa3-type cytochrome c oxidase containing the CuA-cytochrome c domain by means of gene engineering techniques. The chimeric terminal oxidase was expressed by a pBR322 derivative in a terminal oxidase deficient mutant of E. coli, although the amount of the chimeric enzyme was smaller than that of the Escherichia coli bo-type ubiquinol oxidase expressed by the original cytochrome bo-expressing plasmid. The chimeric enzyme showed much higher TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) oxidase activity than the wild-type cytochrome bo, but lower activity than the thermophilic Bacillus caa3-type cytochrome c oxidase. The chimeric subunit II was confirmed to bind to heme C. These results suggest that the CuA-cytochrome c domain grafted to this membrane anchor can facilitate electron transfer from reduced TMPD to low-spin protoheme b in subunit I.
Bacillus↗
Interleukin-6 is a useful marker for early prediction of the severity of acute pancreatitis.
Twelve patients with acute pancreatitis admitted to our department between January 1993 and December 1994 were studied prospectively and classified into two groups (severe group, five patients; mild group, seven patients), according to the criteria for grading severity of acute pancreatitis proposed by the Research Committee for Intractable Diseases of the Pancreas, Japanese Ministry of Health and Welfare (1990). To evaluate markers for early estimation of the severity of acute pancreatitis, we measured serum changes in various parameters. In the severe group interleukin-6 (IL-6) levels were increased significantly 5, 24, 72, and 120 h after the onset (p < 0.01), compared with the mild group. C-reactive protein (CRP), thrombin antithrombin III, and alpha 2-plasmin inhibitor plasmin complex levels were significantly increased only at the 72-h time point. Peak values of interleukin-8 (IL-8) and soluble human E selectin were observed at 5 and 72 h, respectively, after the onset. There was a significant correlation between IL-6 at 5 h and both pancreatic secretory trypsin inhibitor (r = 0.85) and CRP (r = 0.94) at 72 h. We therefore conclude that IL-6 is a useful marker for assessment of the severity of acute pancreatitis in its early stages.
Acute Disease↗
Identification and characterization of XPC-binding domain of hHR23B.
hHR23B was originally isolated as a component of a protein complex that specifically complements nucleotide excision repair (NER) defects of xeroderma pigmentosum group C cell extracts in vitro and was identified as one of two human homologs of the Saccharomyces cerevisiae NER gene product Rad23. Recombinant hHR23B has previously been shown to significantly stimulate the NER activity of recombinant human XPC protein (rhXPC). In this study we identify and functionally characterize the XPC-binding domain of hHR23B protein. We prepared various internal as well as terminal deletion products of hHR23B protein in a His-tagged form and examined their binding with rhXPC by using nickel-chelating Sepharose. We demonstrate that a domain covering 56 amino acids of hHR23B is required for binding to rhXPC as well as for stimulation of in vitro NER reactions. Interestingly, a small polypeptide corresponding to the XPC-binding domain is sufficient to exert stimulation of XPC NER activity. Comparison with known crystal structures and analysis with secondary structure programs provided strong indications that the binding domain has a predominantly amphipathic alpha-helical character, consistent with evidence that the affinity with XPC is based on hydrophobic interactions. Our work shows that binding to XPC alone is required and sufficient for the role of hHR23B in in vitro NER but does not rule out the possibility that the protein has additional functions in vivo.
Amino Acid Sequence↗
Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity.
XPC-hHR23B protein complex is specifically involved in nucleotide excision repair (NER) of DNA lesions on transcriptionally inactive sequences as well as the nontranscribed strand of active genes. Here we demonstrate that not only highly purified recombinant hHR23B (rhHR23B) but also a second human homolog of the Saccharomyces cerevisiae Rad23 repair protein, hHR23A, stimulates the in vitro repair activity of recombinant human XPC (rhXPC), revealing functional redundancy between these human Rad23 homologs. Coprecipitation experiments with His-tagged rhHR23 as well as sedimentation velocity analysis showed that both rhHR23 proteins in vitro reconstitute a physical complex with rhXPC. Both complexes were more active than free rhXPC, indicating that complex assembly is required for the stimulation. rhHR23B was shown to stimulate an early stage of NER at or prior to incision. Furthermore, both rhHR23 proteins function in a defined NER system reconstituted with purified proteins, indicating direct involvement of hHR23 proteins in the DNA repair reaction via interaction with XPC.
DNA Repair↗
Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small intestinal inflammation.
Intraluminal bacteria, food intake, and bile play important roles in indomethacin-induced small intestinal inflammation in rats. Tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) inhibit hydrophobic bile acid-induced damage in various types of cells. We investigated the effects of these bile acids along with the possible influence of other bile acids on this model of inflammation. Clinical and intestinal inflammatory parameters and bile secretion were assessed after 7-day dietary bile acid pretreatments and subsequent indomethacin injections. UDCA significantly enhanced indomethacin-associated reductions in food intake and body weight, increases in gross inflammatory scores and myeloperoxidase activity, and the shortening of small intestinal length. Taurochenodeoxycholic acid (TCDCA) significantly normalized the clinical inflammatory parameters, prevented indomethacin-induced increases in the biliary contents of secondary bile acids and hydrophobicity index, and tended to attenuate the intestinal inflammation. Although elevated biliary levels of muricholic acids and a decreased hydrophobicity index were evident before indomethacin injection in the TCDCA case, these alterations could not explain the TCDCA-mediated protection. Dietary TCDCA attenuates whereas UDCA exacerbates intestinal inflammation in this model. Alterations in the bile composition (increases in UDCA and chenodeoxycholic acid) may explain the observed modification effects.
Animals↗
Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats.
We investigated the effects of dietary diosgenin (Dio), a plant-derived sapogenin, on indomethacin (Indo)-induced intestinal inflammation and alterations in bile secretion in rats. In anesthetized rats, bile secretion, intestinal inflammation, and blood chemistry were assessed 3 days after two subcutaneous injections of Indo given 24 h apart. Dio (> 80 mg.kg-1.day-1) pretreatment significantly inhibited weight and food intake decreases and intestinal inflammation. This protective effect was confirmed by examination of gross and histological findings and intestinal myeloperoxidase activity. Dio significantly increased biliary cholesterol (Chol) output and prevented the decreases in bile flow, bile acid output, and biliary alpha-muricholic acid and the increases in biliary hyodeoxycholic acid, deoxycholic acid, and hydrophobicity index of bile. Significantly more biliary Chol and phospholipids were present in macromolecules separate from bile acids and Indo in Dio-treated rats. Dio significantly increased the elimination constant of Indo and reduced plasma Indo levels at 3 and 12 h but did not influence biliary secretion of Indo for 3.5 h after injection. Although Dio dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in this model, it may also compromise the anti-inflammatory action of indo.
Acute Disease↗
Purification, properties, and N-terminal amino acid sequences of guar gum-degrading enzyme from Bacillus circulans K-1.
A guar gum-degrading enzyme of the newly isolated Bacillus circulans K-1 was purified to an electrophoretically homogeneous state. The molecular weight of the purified enzyme was 62,000 by SDS-PAGE. The purified enzyme was separated into a least six isozymes by isoelectric focusing and the pI of these isozymes were 5.4, 5.5, 5.6, 5.8, 6.0, and 6.2, respectively. The N-terminal amino acid sequences of the typical three of these proteins were all the same, Ala-Ser-Gly-Phe-Tyr-Val-Ser-Gly-Thr-Lys-Leu-Asp-Ala-Thr-Gly-Gln-Pro-Phe- Val- Met-Arg. The enzyme was most active at pH 6.9 and at 64 degrees C. The enzyme was activated slightly by Al3+ and inhibited strongly by Sn2+ and Zn2+, N-bromosuccinimide, 2-mercaptoethanol, and ethylenediamine-tetraacetic acid.
Amino Acid Sequence↗
Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.
To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance.
Angiotensin Receptor Antagonists↗
Skeletal metastases from soft-tissue sarcomas. Incidence, patterns, and radiological features.
We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and 1995 to study the incidence, distribution, time of appearance, and radiological findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a mean period of 18.6 months after admission. The incidence of skeletal metastases differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma, dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show higher incidences. The regional bones close to the primary tumour were affected in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%). Radiologically, the metastatic bony lesions predominantly showed osteolytic changes, and there were pathological fractures in 21 of 44 lesions.
Adolescent↗
Influence of local recurrence on the prognosis of soft-tissue sarcomas.
We have investigated the significance of local recurrence on survival in 173 patients with localised soft-tissue sarcomas of the limbs and of the trunk. The overall survival rates at five and ten years were 75.2% and 68.0%, respectively. After definitive surgery at our hospitals, there was local recurrence in 25 patients (14.5%). After inadequate operations elsewhere, there was a higher incidence of late local recurrence (28.3%), in comparison with those with primary tumours treated by us (9.0%), or patients referred to us immediately after inadequate surgery elsewhere (10.2%). Because of small numbers these differences in the survival rates were not statistically significantly different. Univariate survival analysis showed that local recurrence after definitive surgery (p = 0.006) together with the histological grade (p = 0.0002), the size of the tumour (p = 0.002), its depth in relation to deep fascia (p = 0.003), and the surgical margin (p = 0.0001) were the significant prognostic factors. Local recurrence at the initial presentation did not affect survival. Multivariate analysis showed that local recurrence after definitive surgery also lost its apparent prognostic significance.
Adolescent↗
[Spontaneous pyeloduodenal fistula: a case report].
A 71-year-old female presented with recurrent episodes of right flank pain and fever for the past several years. No pathogens were detected in the urine culture. Abdominal X-ray revealed staghorn calculi of the right kidney. Computerized tomography revealed pneumopelvis and staghorn stones of the right kidney. A nephrectomy was indicated based on the results of intravenous pyelography (IVP) and renogram which revealed a right non-functioning kidney. The adhesion of the right kidney with the duodenum and a transverse colon was so strong that a nephrectomy, a wedge resection of the duodenum and a transverse colectomy were performed. There was a fistula between the renal pelvis and the second portion of the duodenum. The fistula was speculated to have occurred by the spontaneous rupture of the renal pelvis to the duodenum. To the best of our knowledge, this is the 15th case of spontaneous nephroduodenal fistula in Japan.
Aged↗