Germline and somatic mutations in von Hippel-Lindau disease gene and its significance in the development of kidney cancer.
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Carcinoma, Renal Cell↗
Biomedical subjects
H Okuda
Publications and source records attributed to H Okuda.
[Renal angiomyolipoma with a tumor thrombus extending into the right atrium--a case report].
We present a case of spontaneous rupture of renal angiomyolipoma with a tumor thrombus extending from the right renal vein and inferior vena cava to the right atrium. A 41-year-old woman, previously in good health, was referred to our hospital with right flank pain. Computed tomography showed fat densities in both tumor and thrombus. Other imaging examinations also demonstrated a large right renal mass (18 cm in diameter), a long tumor thrombus (13 cm in length) and a small left renal tumor (1.5 cm in diameter). Right nephrectomy and en-bloc removal of the intra caval and intracardiac tumor thrombus were performed on cardiopulmonary bypass. It was pathologically diagnosed as an angiomyolipoma without tuberous sclerosis. At present, three years after surgery the patient is doing well, showing neither metastasis nor increase of the left renal angiomyolipoma. To our knowledge, our case seems to be the 3rd case report of renal angiomyolipoma with a tumor thrombus extending to the right atrium. We conclude that renal angiomyolipoma even with an intra cardiac tumor thrombus can be resected safely and successfully.
Adult↗
[A case of sudden death by pulmonary embolism after angio-embolization of renal cell carcinoma extending into the inferior vena cava].
We report a 42-year-old renal-transplanted man with renal cell carcinoma (RCC) in the native kidney. He was admitted with gross hematuria and general fatigue as the chief complaint. Ultrasonography, computed tomography, magnetic resonance imaging and angiography, revealed a right RCC with intracaval tumor thrombus extending to the level of hepatic veins. Since selective renal angiography demonstrated a hypervascular tumor, angio-embolization was performed preoperatively. However, he died suddenly the next morning despite aggressive resuscitative measures. Autopsy revealed bilateral pulmonary arteries obstructed by the tumor thrombus. Renal arterial embolization is useful for advanced RCC, and side effects are mostly transient and well tolerated by the patients. However, indications for angio-embolization should be selected carefully with such a fatal case as this patient kept in mind.
Carcinoma, Renal Cell↗
[Use of the intubating laryngeal mask for tracheal intubation in three patients with difficult airways].
The intubating laryngeal mask has a potential role for tracheal intubation in patients with difficult airways, but there have been only reports of the techniques of blind tracheal intubation through the intubating laryngeal mask. The success rate of blind intubation at the first attempt may be merely 50-60% even in patients with normal airways. We report the use of the intubating laryngeal mask for tracheal intubation in three patients with difficult airways, in whom a tube was easily inserted through the laryngeal mask into the trachea either blindly, using a fiberoptic bronchoscope or using a lighted stylet.
Adult↗
[Clinical study of carcinoma of the penis].
We reviewed six cases of carcinoma of the penis seen at our department during the last 12 years. The mean age and mean followup period were 56 +/- 11 years and 53 +/- 42 months, respectively. Inguinal lymphadenopathy was evident in all patients, one of whom was diagnosed as having nodal metastasis because of the persistence of adenopathy after antimicrobial therapy. Four patients, had Jackson Stage 1, 1 Stage 2 and 1 Stage 3 cancer. The patient with Stage 3 cancer underwent total penectomy and bilateral inguinal lymphadenectomy. He died of cancer 2 years after the operation. The 5 patients with stage 1 or 2 underwent partial penectomy without lymphadenectomy. Pathological examination showed moderately differentiated squamous cell carcinoma (SCC) in 2 patients with stage 2 and 3 cancer, well differentiated SCC in 3 and verrucous carcinoma in the other patient with stage 1 cancer. Prophylactic external radiation therapy to the groin was performed in 3 of the 4 patients with invasion to corpus spongiosum (pT2). Two of the 3 patients developed mild radiation dermatitis, and no major complications were observed. The 5 patients with clinically negative nodes showed no evidence of recurrence after surgery. As reported by others, inguinal node metastasis appears to worsen the prognosis of patients with carcinoma of the penis.
Adult↗
Characteristics of cell-membrane and extracellular proteoglycans in monkey submandibular gland.
We investigated the characteristics of cell-membrane and extracellular proteoglycans in the monkey submandibular gland using enzymatic digestion and Western blot analysis. Extracellular proteoglycans and cell-membrane proteoglycans were extracted from the phosphate-buffered saline (PBS) soluble fraction and microsomal fraction of submandibular glands, respectively, and purified partially by ion exchange chromatography. Cellulose acetate membrane electrophoresis and immunoblotting with 3G10 monoclonal antibody or 6B6 monoclonal antibody showed that the extracellular proteoglycans contain several heparan sulfate proteoglycans (117, 67, 47 and 35 kDa core proteins) and a dermatan sulfate proteoglycan (45-50 kDa core protein), while the cell-membrane proteoglycans contain only a heparan sulfate proteoglycan with 69 kDa core protein. These results indicate that the several extracellular heparan sulfate proteoglycans may be released ectodomains of the cell-membrane proteoglycans from cell surface. It is suggested that the cell-membrane and extracellular proteoglycans may regulate the function of growth factors and the microenvironment in the normal submandibular gland.
Animals↗
[Experimental research of Ephedra sinica's influence on lipid metabolism of lipocyte].
OBJECTIVE: To study the influence of Ephedra sinica on the lipid metabolism of lipocyte. METHOD: The rat's epididymal lipocytes were used to observe the effect of Ephedra sinica in lipogenesis from 14C-glucose and lipolysis promoted by norepinephrine (NE). RESULT: Ephedra sinica can promote lipogenesis from glucose, which is related with the pH value of matrix solution; and it also can inhibit the lipolysis promoted by NE. CONCLUSION: Ephedra sinica can promote the lipogenesis of lipocyte that is not induced by ephedrine, the mechanism being similar to that of insulin.
Adipocytes↗
[Neoadjuvant chemotherapy for advanced cervical cancer].
Twenty-five patients with advanced cervical cancer (IIb-IVa) were treated with neoadjuvant chemotherapy followed by radical hysterectomy or radiotherapy. According to the evaluation by MRI, complete response was achieved in 2 cases and partial response in 17 cases. Eventually the response rate was 76%. The response rate was higher in squamous cell carcinomas (85%) than adenocarcinomas or adenosquamous carcinomas (67%). The histological effect is superior in squamous cell carcinomas than adenocarcinomas or adenosquamous carcinomas. Radical hysterectomy was performed in 5 cases of 11 (45%) stage III-IVa cervical cancers. There was no correlation between tumor size and response to NAC. NAC therapy may be useful therapy in advanced cervical cancers, especially squamous cell carcinomas.
Adenocarcinoma↗
Guinea pig liver Mu-class glutathione S-transferase M1-2 cross-reacts with antibodies to both rat Mu- and theta-class glutathione S-transferases.
Two novel major heterodimeric Mu-class glutathione (GSH) S-transferases (GSTs), designated M1-2 and M1-3*, were isolated from guinea pig (gp) liver cytosol and purified to homogeneity together with a known major homodimeric Mu-class gpGSTM1-1 (reported as GST b by R. Oshino, K. Kamei, M. Nishioka, and M. Shin, 1990, J. Biochem. 107, 105-110). These three gpGSTs were quantitatively retained on an S-hexyl-GSH affinity column and separated as homogeneous proteins by chromatofocusing. Subunits of the heterodimers were inseparable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but could be completely separated by reverse-phase partition high-performance liquid chromatography. A molecular cloning study demonstrated that the gpGST subunit M2 consisted of 217 amino acid residues with a calculated molecular mass of 25,562 and shared 84% identity in overall amino acid sequence with gpGSTM1-1. N-terminal amino acid sequences of peptides from the gpGST subunit M3* with a blocked N-terminus strongly suggested that it should belong to the Mu class. Western blot analysis using antisera raised against purified rat (r) GSTsA1-2 (Alpha), M1-1, P1-1 (Pi), and T2-2 (Theta) indicated that gpGSTsM1-1 and M1-3* cross-reacted only with anti-rGSTM1 antibody. However, gpGSTM1-2 cross-reacted intensely to almost the same extent with antibodies to both rGSTsM1-1 and T2-2. A homodimeric gpGSTM2-2, artificially constructed from native gpGSTM1-2 by treatment with guanidine hydrochloride followed by dialysis, intensely cross-reacted with antibodies to both the rat Mu- and Theta-class GSTs. Thus, the gpGST subunit M2 provided the first evidence for the double immuno-cross-reaction of a GST with polyclonal antibodies to two different classes of GSTs.
Amino Acid Sequence↗
Alkaline lipase from brain: is it the same enzyme as pancreatic lipase from pancreas?
A new alkaline lipase was detected in rat brain and its properties were compared with those of the well-characterized pancreatic lipase and pancreatic lipase-related protein 2. The activity of the alkaline lipase was determined using trioleoylglycerol emulsion at pH 8.0. Subcellular fractions were prepared from brain homogenates by differential centrifugation. Lipase activities of the cytosolic fraction (the supernatant obtained by differential centrifugation of 100,000g) were stimulated by addition of colipase and bile salts and inhibited by addition of an antibody against rat pancreatic lipase. The partially purified enzyme had an isoelectric point of pH 6.8, which was identical to that found for rat pancreatic lipase. The enzyme had interfacial activation and dependence on colipase in the presence of bile salts. The enzyme had no measurable phospholipase A activity. The band produced by the enzyme on SDS-polyacrylamide gel electrophoresis was identical to that of the rat pancreatic lipase when detected by immunoblotting analysis using an antibody against pancreatic lipase. These results show that pancreatic lipase such as alkaline lipase is in rat brain.
Animals↗
Identification of 5' flanking sequence of RH50 gene and the core region for erythroid-specific expression.
The Rh blood group antigens are carried by two distinct but homologous membrane proteins encoded by two closely related genes, RCHE and RHD. Rh50 glyco-protein is the membrane protein tightly associated with Rh polypeptides and is critical for expression of Rh antigens. The amino acid sequence and predicted membrane topology of Rh50 glycoprotein are significantly homologous with those of the Rh proteins. Northern blot analysis of leukemic cell lines showed that expression of RH50 gene is restricted to cells with erythroid features. HEL and K562 cells showed a transcription levels ratio of 1 to 9.9 for Rh50, and 12.3 to 1 for Rh. The nucleotide sequence of 5' flanking region of RH50 gene and functional promoter assays also supported the erythroid-specific regulation of the gene, whereas the sequence had lower homology with the promoter sequence of RH genes. Seven GATAs, nine E-boxes, two CACCCs, one YY1, and one October motif were identified in the 1868bp 5' flanking sequence. The core promoter of RH50 gene was located within 68bp length from the translation start position, which included an inverse GATA motif, although obvious motifs for Sp1 or erythroid Krüppel-like factor were lacking. The inverse GATA motif was the target sequence of GATA-1 protein, and disruption of the motif abolished the transactivating activity of erythroid cells. These studies confirm the erythroid-specific expression of Rh antigens, but suggest distinct regulatory mechanisms for RH vs RH50 genes.
Amino Acid Sequence↗
Effect of long-term treatment of 3T3-L1 adipocytes with chlorate on the synthesis, glycosylation, intracellular transport and secretion of lipoprotein lipase.
Lipoprotein lipase (LPL) is synthesized and glycosylated in the endoplasmic reticulum (ER), transported through the Golgi to the cell surface, and finally secreted. To examine the role of heparan sulphate proteoglycans (HSPG) in the synthesis, activity, intracellular transport and secretion of LPL, 3T3-L1 adipocytes were cultured for 7 days in the presence of 20 mM chlorate, an inhibitor of sulphation of HSPG. Treatment of cells with 20 mM chlorate for 7 days caused a 55% decrease in LPL activity in the intracellular compartment and a 79% decrease in the cell-surface compartment. The synthetic rate of LPL in chlorate-treated cells was identical with that in control cells as determined by biosynthetic labelling. The study with endoglycosidase H (endo H) showed that the treatment with chlorate increased the proportion of LPL subunits which were totally endo H-sensitive. The study with a heparin-Sepharose column showed that 3T3-L1 adipocytes contained three forms of LPL. The first form, accounting for 35% of the LPL, did not bind to the heparin-Sepharose column and had little or no activity; the second form, accounting for 32%, bound to the column and was eluted with 0.4-0.75 M NaCl but had no activity; the third form, accounting for 33%, bound to the column and was eluted with 0.8-1.2 M NaCl and had activity. In chlorate-treated cells, the first form accounted for 66% of the LPL, the second form 15% and the third form 19%. When cells were incubated for 1 h with brefeldin A, which translocates Golgi proteins to the ER [J. Lippincott-Schwartz, L.C. Yuan, J.S. Banifacino and R.D. Klausner (1989) Cell 56, 801-813; J. Lippincott-Schwartz, J. Glickman, J.E. Donaldson, J. Robbins, T.E. Kreis, K.B. Seamon, M.P. Sheetz and R.D. Klausner (1991) J. Cell Biol. 112, 567-577], the chlorate-induced decrease in cellular LPL activity was restored. These findings indicate that LPL synthesized in chlorate-treated cells can be processed to be fully active, but chlorate-treated cells are unable to transport LPL to the Golgi and accumulate inactive LPL with a lower affinity for heparin in the ER. The treatment with chlorate decreased the proportion of LPL subunits that were endo H-resistant, indicating that the processing of oligosaccharide chains of LPL in the trans-Golgi was impaired in chlorate-treated cells. The amount of 35S-labelled LPL secreted by chlorate-treated cells was identical with that secreted by control cells, whereas the level of LPL activity in the medium of chlorate-treated cells was 25% of that in the medium of control cells, indicating that most of the LPL secreted by chlorate-treated cells was inactive.
3T3 Cells↗
Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine.
An enzymatic study was performed to clarify the mechanism of 18 acute deaths in patients who had received the new oral antiviral drug, sorivudine (SRV), during anticancer chemotherapy with 5-fluorouracil (5-FU) prodrugs. Human dihydropyrimidine dehydrogenase (hDPD), playing a key role in the liver as the rate-limiting enzyme in catabolism of 5-FU, was expressed in E. coli, purified and incubated in the presence of NADPH with SRV or (E)-5-(2-bromovinyl)uracil (BVU), a metabolite of SRV produced by human gut flora. hDPD was rapidly and irreversibly inactivated by BVU, but not by SRV. Radioactivity of [14C]BVU was incorporated into hDPD in the presence of NADPH in a manner reciprocal to the enzyme inactivation. In the absence of NADPH, hDPD was not inactivated by BVU, nor radiolabeled with [14C]BVU. Thus, as we demonstrated previously with studies using the rat, the acute deaths were strongly suggested to be attributable to markedly elevated tissue 5-FU levels which were responsible for irreversible inhibition of hDPD by covalent binding of a reduced form of BVU as a suicide inactivator.
Antiviral Agents↗
Different angiogenic pathways in human cervical cancers.
OBJECTIVE: The objective of this study is to clarify the association between the expression of two types angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase(dThdPase) and clinicopathological features, including tumor angiogenesis, in cervical cancers. METHODS: The expression of VEGF and PD-ECGF was evaluated by immunohistochemical staining of tumor specimens from 73 patients with stage Ib-IIb cervical cancer (51, squamous cell carcinoma; 19, adenocarcinoma; 3, adenosquamous carcinoma) who underwent radical hysterectomy. The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. RESULTS: The microvessel density in adenocarcinomas was significantly higher than that in squamous cell carcinomas (P < 0.01). The intensity of VEGF expression in adenocarcinomas was significantly stronger than that in squamous cell carcinomas (P < 0.05). In contrast, the expression of PD-ECGF in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P < 0.0001) and adenosquamous carcinomas (P < 0.01). There was an inverse relationship between VEGF expression and PD-ECGF expression among all patients studied (P < 0.001). The microvessel density was significantly correlated with the intensity of VEGF expression (P < 0.05). In contrast, there was no correlation between the microvessel density and the expression of PD-ECGF. CONCLUSIONS: The expression of VEGF appears to be involved in the promotion of angiogenesis in cervical cancers. Furthermore, we propose that angiogenic pathways may be different in different types of cervical cancers.
Adenocarcinoma↗
Renal cell carcinoma of native kidneys in renal transplant recipients.
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Adult↗
Recurrence of membranoproliferative glomerulonephritis in renal allografts.
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Adolescent↗
Temporary scapho-trapezoidal joint fixation for Kienböck's disease in a 12-year-old girl: a case report.
Temporary scapho-trapezoidal joint fixation with Kirschner wires was performed for stage IIIB Kienböck's disease in a 12-year-old girl. Preoperative evaluation with radiographs and magnetic resonance imaging confirmed the diagnosis. After 4 months of fixation, wrist range of motion was improved and pain was decreased. Postoperative magnetic resonance imaging revealed revascularization and fracture healing. Temporary scapho-trapezoidal fixation may be useful in the treatment of selected cases of Kienböck's disease in children.
Bone Nails↗
Effects of extract of oyster on lipid metabolism in rats.
We examined the effects of oyster (Ostrea gingas Thunb.) water extracts on hyperlipemia and liver injury produced in rats by feeding on peroxidized oil. The extracts of oyster were found to reduce the levels of serum free fatty acid, triglyceride, lipid peroxide and liver cholesterol in the peroxidized oil-treated rats. In addition, we found that the water extracts of oyster inhibited adrenaline-induced lipolysis, and that these extracts stimulated lipogenesis from glucose in isolated fat cells of rats. The active substance was isolated and identified as adenosine by direct comparison with an authentic sample.
Animals↗