Biomedical subjects
Publications and source records attributed to Y C Ou.
Based on the standard transfer matrix, a formally exact quantization condition for arbitrary potentials, which outflanks and unifies the historical approaches, is derived. It can be used to find the exact bound-state energy eigenvalues of the quantum system without solving an equation of motion for the system wave functions.
Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communication, we provided evidence to demonstrate that tissue-specific expression of OC was also regulated at the RNA splicing level. We identified incompletely spliced variants of human OC mRNA, which retain one or more introns during RNA splicing, existing dominantly in non-osseous organs. Northern blot analysis identified two OC RNA transcripts expressed in normal human tissues, but the expression level of the transcripts varied between the tissues. Most non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marrow. Sequence analysis showed that four of five RNA variants contained intron 1 in common and the dominant one contained all three introns. MG63, an osteoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor cells. Combined study of in situ hybridization and immunohistochemistry revealed that OC RNA was highly expressed in prostate tumor epithelial cells while only very low levels of protein were detected, which confirms that there are OC RNA variants in non-osseous tissues. In conclusion, we demonstrated that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be further investigated.
BACKGROUND: Nephroid metaplasia is a benign and rare lesion that is confined to the lamina propria of the urinary tract. The leading cause of these lesions is previous trauma to the urothelium. METHOD: We report a case of nephroid metaplasia of a graft kidney from a living-unrelated donor. This patient presented to our clinics due to painless gross hematuria 1 month after renal transplantation. RESULT: Although malignancy was suspected in the beginning due to a filling defect demonstrated by urography, only percutaneous excision of the tumor was performed to preserve the renal function. However, the pathological result disclosed nephroid metaplasia. CONCLUSION: Hematuria warrant aggressive evaluation because underlying malignancy in a immunocompromised patient might be relatively progressive.
A combination of experimental and simulation approaches were used to analyze the clonal growth of preneoplastic, enzyme-altered foci during liver carcinogenesis in an initiation-promotion regimen. Male Fisher 344 rats, 8 weeks of age, were initiated with a single dose (200 mg/kg, i.p.) of diethylnitrosamine (DEN). Beginning 2 weeks later, animals were exposed to daily gavage consisting of 0.1 mmol/kg pentachlorobenzene (PECB) or hexachlorobenzene (HCB) in corn oil vehicle for 6 weeks. Partial hepatectomy was performed 3 weeks after initiation. Experimental data including liver weight, hepatocyte density (number of hepatocytes/unit volume), 5-bromo-2'-deoxyuridine-labeling index for analysis of cell division rate, and number and volume of glutathione-S-transferase pi-positive foci were collected 23, 26, 28, 47, or 56 days after initiation. Model parameters describing liver growth were obtained directly from the experimental data. The probability of mutation/division of normal cells and the growth rate of initiated cells were inferred by a comparison of model outcomes with the observed time courses of foci development. To describe the time-dependent increases in foci volume and the concomitant reduction of foci number observed in all treatment groups, the calibrated model for the DEN controls incorporated the hypothesis of two initiated cell populations (referred to as A and B cells) within the framework of the two-stage model. The B cells are initiated cells that have a selective growth advantage under conditions that inhibit the growth of A cells and normal hepatocytes. The parameter values defined in the DEN controls were used to evaluate experiments involving the administration of PECB or HCB. Both PECB and HCB caused a significant increase in foci volume compared with the DEN controls. HCB treatments resulted in increased proliferation of normal hepatocytes, which was not observed for PECB under the same treatment regimen. The best description of the data resulted from the model incorporating the hypothesis that PECB and HCB promoted the growth of foci via increased net growth rates of B cells. We present here a biologically based clonal growth simulation platform to describe the growth of preneoplastic foci under experimental manipulations of initiation-promotion studies. This simulation work is an example of quantitative approaches that could be useful for the analysis of other initiation-promotion studies.
A rare case of ureteral stump metastasis 3 months after nephrectomy for a renal cell carcinoma is presented. A 62-year-old female had undergone right radical nephrectomy 3 months earlier because of renal cell carcinoma in our hospital, and she came back due to gross hematuria. Cystoscopy revealed a papillary mass with a vascular pedicle protruding from the right ureteral orifice. Transurethral resection of the bladder tumor over right ureteral orifice was performed and the pathologic result showed clear cell adenocarcinoma, which argued in favor of a metastatic lesion from the previous renal cell carcinoma. Ureterectomy and a bladder cuff excision were then adopted for this patient, but no residual tumor was found over the remaining ureter. Nevertheless, the patient died of cancer 36 months after the event of ureteral stump metastasis.
Primary renal sarcoma represents approximately one per cent of all primary tumors of the kidney in adults. We report an unusual case of primary renal sarcoma with inferior vena cava (IVC) thrombus. This patient presented with hemorrhagic shock due to tumor rupture. Emergent radical nephrectomy and vena caval thrombectomy were performed. Histological examination proved a clear cell sarcoma.
BACKGROUND: The value of lymphadenectomy in the management of renal cell carcinoma (RCC) remains controversial. Most would agree that lymphadenectomy (LD) provides accurate pathologic staging for prognostic data. The question remains whether there is any significant therapeutic benefit from extensive lymph node dissection with radical nephrectomy. The aim of this study was to compare outcomes in sampled lymphadenectomy (SLD) and extensive lymphadenectomy (ELD) with radical nephrectomy for RCC. METHODS: One hundred and thirty-seven patients with RCC were enrolled in this study from Oct. 1982 to Dec. 1996. Eighty-one patients received radical nephrectomy with SLD (stage I: 43, II: 16, III: 22). Fifty-six patients received radical nephrectomy with ELD (stage I: 30, II: 11, III: 15). RESULTS: The mean number of lymph nodes removed by SLD was 4 (ranged from 1 to 8). The mean number of lymph nodes removed by ELD was 16.1 (ranged from 9 to 32). Overall 5-year survivals for SLD in stages I, II and III were 98%, 80% and 38%, respectively. Overall 5-year survivals for ELD in stages I, II and III were 92%, 84% and 40%, respectively. CONCLUSIONS: There is no significant therapeutic benefit from ELD in patients with RCC receiving radical nephrectomy.
Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. To study the molecular mechanisms underlying cell cycle inhibition by MeHg, we assessed the involvement of p21 (Waf1, Cip1), a cell cycle regulatory gene implicated in the G1 and G2 phases of cell cycle arrest, in primary embryonic cells and adult mice following MeHg exposure. Previous literature has supported the association of increased p21 expression with chondrocyte differentiation. In support of this finding, we observed an increasing p21 expression during limb bud (LB), but not midbrain central nervous system (CNS) cell differentiation. Both embryonic LB and CNS cells responded to MeHg exposure with a concentration-dependent increase in p21 mRNA. In the parallel adult study, C57BL/6 female mice were chronically exposed to 10 ppm MeHg via drinking water for 4 weeks. While there was limited or absent induction of Gadd45, Gadd153, and the gamma-glutamylcysteine synthetase catalytic subunit, p21 was markedly induced in the brain, kidney, and liver tissues in most of the animals that showed MeHg-induced behavioral toxicity such as hyperactivity and tremor. Furthermore, the induction of p21 mRNA was accompanied by an increase in p21 protein level. The results indicate that the activation of cell cycle regulatory genes may be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms. Continued examination of the molecular mechanisms underlying cell cycle inhibition may potentially lead to utilization of this mechanistic information to characterize the effects of MeHg exposure in vivo.
Previous studies indicate that the ability of cells to up-regulate levels of intracellular glutathione (GSH) synthesis may determine their sensitivity to MeHg exposure. The purpose of the current study is two-fold. First, we determined whether the vulnerability of the developing central nervous system (CNS) to MeHg lies in its intracellular GSH content. The intracellular GSH content and the activity of gamma-glutamyl cysteine synthetase (GCS) were determined with and without MeHg exposure in primary cultures of rat embryonic CNS cells. In addition, the effect of GSH modulation on MeHg-induced cytotoxicity was determined. Second, we characterized the mechanism of GCS regulation, initially by studying the GCS heavy chain subunit (GCS-HC). Primary embryonic limb bud cells were used as a reference cell type for comparing the response of CNS cells. The results indicate that constitutive intracellular GSH content, GCS activity, and GCS-HC mRNA and protein levels of CNS cells were approximately ten-, two-, five-, and ten-fold higher, respectively, than those in limb bud cells. A dose-dependent increase in GSH levels and GCS activity was observed in CNS and limb bud cells following 1 and 2 microM MeHg exposure for 20 hr. Further characterization of GCS up-regulation in CNS cells showed that the increase in GCS activity following MeHg exposure, unlike limb bud cells, was not accompanied by an elevation of GCS-HC mRNA and protein levels. Pretreatment with N-acetylcysteine led to a significant increase in intracellular GSH, while L-buthionine-(S,R)-sulfoximine (BSO) resulted in decreased GSH levels, however neither pretreatment had a significant impact on MeHg-induced cytotoxicity in either cell type. Our results suggest that although oxidative stress may mediate aspects of MeHg toxicity, disruption of GSH homeostasis alone is not responsible for the sensitivity of embryonic CNS cells to MeHg.
A new type of electropositive filter media particle was tested to adsorb bacteriophage f2 and enteric viruses from tap water. 3 x nutrient broth (pH 7.2) was used to elute the adsorbed viruses, and the eluate was reconcentrated by polyethylene glycol (Mw 6000) precipitation with a final concentration of 10% (wt./vol.). The adsorption of bacteriophage was reliable and efficient, and not affected by the pH value, temperature, turbidity and organic materials in water. This method gave a recovery of Polio 1 virus 96.0% for small-volume tap water; 88.7% for large-volume water; and gave a comparable recovery of HAV, Coxsackie B3 and Echo 7 from tap water. The concentration method need not acidify virus-containing water, add exogenous multivalent cation salts, or require expensive equipment.
BACKGROUND: We assessed the in vitro culture growth of erythroid progenitors [burst forming unit-erythroid (BFU-E)] and serum erythropoietin (EPO) levels in different groups of polycythaemia to determine the discriminative power in differential diagnosis of polycythaemia. METHODS: We used the methylcellulose culture technique to study the growth of endogenous erythroid colonies (EECs) and EPO-dependent BFU-E from bone marrow (BM) and/or peripheral blood (PB) cells from 40 patients with polycythaemia vera (PV), 13 with secondary polycythaemia (SP), 19 with pure erythrocytosis (PE), five with PE and PV evolution later (PE-PV), and 12 with relative polycythaemia (RP). The serum EPO levels were measured by radioimmunoassay before treatment in 47 patients, 23 SP patients, 19 PE patients, five PE-PV patients and 16 RP patients, as well as after treatment in 38 PV patients, five PE-PV patients and 12 PE patients. RESULTS: The results of the erythroid progenitor culture assay showed that the numbers of EPO-dependent BFU-E in BM did not differ significantly among groups. The PB BFU-E were significantly higher in PV than in SP or PE, and no statistical difference were found among patients with SP, PE and RP. There was a correlation between BM BFU-E and PB BFU-E in the individual PV and PE patients. EECs were present in all BM and PB cultures of untreated and phlebotomy-treated PV and PE-PV patients, but were absent in 6 of 17 PV patients who had received cytotoxic therapy. EECs were not found in SP, PE and RP. PB could substitute for BM in the EEC or the BFU-E assay. Both pretreatment and post-treatment serum EPO levels of PV and PE-PV were similar, which were significantly lower than SP, PE or RP. The serum EPO levels in treated PV or PE-PV patients who had normal haematocrit values were not significantly different from those in untreated patients. In contrast, the phlebotomy-treated PE patients had significantly higher serum EPO values than untreated PE patients. In the differentiation between PV and PE, the sensitivity, specificity, positive predictive value and negative predictive value of post-treatment serum EPO levels at a cut-off level of < or = 9 UL-1 were 74%, 92% and 52% respectively. The discriminative power of post-phlebotomy serum EPO levels was even higher with a positive predictive value of 80% and negative predictive value of 92% for the prediction of PV evolution in patients with pure erythrocytosis of unknown origin. CONCLUSION: The present study showed that apart from EEC assay, the post-phlebotomy serum EPO level was a sensitive and specific parameter in the differential diagnosis of polycythaemia, in particular for the identification of PV among patients with unclassifiable polycythaemia.
BACKGROUND: The aim of this study was to compare outcomes in patients with symptomatic and incidental renal cell carcinoma (RCC). METHODS: From October 1982 to December 1996, 200 patients with RCC were enrolled in this study. Their medical records were reviewed for symptoms, tumor stage, and lymph node and metastatic status. Symptomatic and incidental RCCs were compared by the overall survival rate of patients. The survival rate was determined by the Kaplan Meier method. Log rank testing was used to analyze the statistical difference in the survival period between both groups. RESULTS: The proportion of incidental RCC was 21% (42/200). The majority of cases (73.8%) were diagnosed primarily by abdominal ultrasonography. Incidental RCCs were smaller in size than symptomatic RCCs (5.1 +/- 2.0 cm vs. 7.5 +/- 1.8 cm, p = 0.001). Incidental RCCs were of a lower stage, and patients with incidental RCCs had significantly longer overall survival rates than those with symptomatic RCCs (p < 0.001). CONCLUSIONS: Ultrasonography is a useful tool for the detection of incidental RCC. Improvement in the overall survival rate of incidental RCC patients suggests that when these tumors are identified earlier, treatment results are better.
BACKGROUND: Experience suggests that tumor growth is dependent on angiogenesis. The intensity of angiogenesis in human cancer is reported to be predictive of the probability of metastasis in many types of cancer. The aims of this study were 1) to determine the relationship of microvessel density (MVD) in renal cell carcinoma to pathologic stage, and 2) to evaluate the role of MVD in metastasis. METHODS: Paraffin-embedded tumor specimens were reviewed from 34 unselected patients with RCC who had undergone surgery from 1986 to 1990 at Taichung Veterans General Hospital. The pathology findings and clinical records were reviewed to note relationships between pathologic stage and whether or not metastasis had occurred. Specimens were studied from 16 cases (eight Stage I cancers, five Stage II and three Stage III) without metastasis and from 18 cases (two Stage I, six Stage II, six Stage III and four Stage IV) in which metastasis later developed. Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Microvessels were counted in a x-400 field (0.1885 mm2/field) in the most active areas of neovascularization. RESULTS: The 16 patients without metastasis have survived for between 65 and 136 months (mean, 94.5 months), up to the present time. Of the 18 patients with metastasis, 15 died and three survived, with mean survivals of 42.8 months (range, 12-99 months). Mean overall MVD was 99.6 vessels; mean MVD was 98.5, 96.2, 109.3 and 90.0 in Stages I, II, III and IV tumors, respectively. Mean MVD was 99.3 in patients without metastasis and 99.9 in patients with metastasis. CONCLUSIONS: MVD does not correlate with pathologic stage and is of no prognostic significance in renal cell carcinoma.
We evaluated the possible correlation between intracellular glutathione (GSH) and drug sensitivity of urothelial cancer. Tissue GSH content of surgical specimens from 20 patients with urothelial cancer was assayed with high performance liquid chromatography (HPLC). GSH levels of cancer tissue (7.887 +/- 6.176 microM/mg protein) were significantly higher than GSH levels of normal mucosa (1.345 +/- 1.252 microM/mg). All patients having measurable lesions were then treated with methotrexate, epirubicin and cisplatin (MEC). These patients were classified into three groups according to clinical response criteria. GSH content in cancer tissue from four patients with complete response was 0.804 +/- 1.183 microM/mg protein. However, the cancer cells from patients with partial response and non-response contained a significantly higher level of GSH (6.295 +/- 2.459 (n = 8) and 12.955 +/- 6.141 microM/mg protein (n = 8), respectively). Intracellular glutathione content may play an important role in intrinsic resistance of urothelial cancer to MEC chemotherapy. It might be potentially used to predict drug sensitivity in urothelial cancer patients before starting chemotherapy.
The Sm core proteins of U1, U2, U4/U6 and U5 snRNPs include B(B1), B'(B2), N(B3), D1, D2, D3, E, F and G polypeptides. We have isolated genomic clones encoding the Sm-D1 protein using the Sm-D1 cDNA as probe. Southern blotting and DNA sequencing analysis of these clones revealed the presence of an Sm-D1 multigene family in the human genome. Three gene members have been identified. Two of the genes are without introns and contain mutations compared to the cDNA sequence. They appear to be processed pseudogenes. The third gene, termed SNRPD1, shares 100% identity to the cDNA sequence including both 5'- and 3'-untranslated regions (UTR); it contains three introns. Analysis of the 5'-flanking region of the SNRPD1 gene revealed promoter activity, suggesting this is the functional gene that encodes the Sm-D1 protein. The promoter activity was localized in a 0.38 kb PstI fragment using CAT reporter gene fusion assays. Addition of an SV40 enhancer element did not enhance the transcription directed by that fragment. Sequence comparison of the 0.38 kb promoter sequence with the promoters of the Sm-E gene and U1 snRNA genes revealed several homologous motifs, suggesting that genes encoding the snRNP components may be coordinately regulated.
Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. Studies on the mechanism of MeHg-induced toxicity reveal that inhibition of cell cycle progression may be one way by which MeHg interferes with normal development. In this study, we utilized primary rodent embryonic neuronal cell (CNS) and limb bud (LB) cultures to determine the mRNA expression level of two genes involved in cell cycle arrest, Gadd45 and Gadd153, both during cellular differentiation and in response to MeHg exposure. A differential expression pattern of Gadd45 and Gadd153 was observed during CNS and LB differentiation in culture. However, both CNS and LB cells responded to MeHg exposure with a concentration-dependent increase in Gadd45 and Gadd153 mRNA. Previous studies have shown that MeHg exposure (2 microm) of CNS cells for 24 hr causes a fourfold decrease in the number of cells passing through the cell cycle. The present study shows that at the same exposure concentration, a five- to eightfold increase in Gadd45 mRNA levels and a two- to fourfold increase of Gadd153 was observed. Induction of Gadd45 was also noted in adult female mice chronically exposed to 10 ppm MeHg, a dose that caused developmental toxicity in vivo. Based on the known involvement of the Gadd genes in cell cycle arrest, activation of these genes could be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms.
We studied the in vitro culture growth of bone marrow and blood erythroid progenitors and serum erythropoietin (EPO) levels by radioimmunoassay in 24 patients with idiopathic erythrocytosis (IE). All patients had an increased red blood cell (RBC) mass and lacked a cause of secondary polycythemia, but did not fulfill the diagnostic criteria of polycythemia vera (PV). Marrow and blood cultures were obtained simultaneously; the results of endogenous (EPO-independent) erythroid colony (EEC) growth were parallel in both cultures. EECs were present in five patients, all of them developed PV 3 to 48 months later. The EEC number did not correlate with the time to the progression of PV. In contrast, none of the 19 EEC-negative patients had PV evolution during a median follow-up period of 38 months. Three of the five IE patients in whom EECs formed displayed vascular complications during their clinical course compared with three of 19 patients who did not have EEC. The serum EPO levels were variable: low in five, normal in 14, and high in five patients. Serial measurements of serum EPO levels in three of five patients who had high initial levels showed persistently elevated values; the underlying cause of the increased EPO production could not be defined during a follow-up period of more than 36 months. Of the five patients who subsequently developed PV, two had low serum EPO levels and three had normal values at initial evaluation. Serum EPO levels did not correlate with the occurrence of thrombotic complications. Our results show that serum EPO levels have limited value in determining the underlying cause of IE and cannot predict the clinical course of patients with IE, whereas the assessment of EEC in bone marrow or blood can identify IE patients who will have PV evolution.
BACKGROUND: The aim of this study is to compare the application of gaseous retroperitoneoscopic (GR) and gasless retroperitoneoscopy-assisted (GLRA) unroofing of renal cysts. METHODS: Fourteen patients with symptomatic simple renal cysts had undergone unroofing of the cyst with GR in seven cases and GLRA in seven others. Three trocars (10 mm, 10 mm and 5 mm) were inserted in the GR procedure. A 3 cm flank muscle-split incision was made and retroperitoneoscopy was performed through the same incision in the GLRA procedure. Then, the cyst was unroofed. RESULTS: The mean operative time was 104.3 minutes in the GR group and 52.1 minutes in the GLRA group, respectively (p = 0.001). The mean requirement of postoperative meperidine hydrochloride injection was 21.4 mg in the GR group and 71.4 mg in the GLRA group, respectively (p = 0.017). In the GR group, the mean postoperative stay was 3.7 days, and the time needed for return to normal activity was 7 days. In the GLRA group, the mean postoperative stay was 4.6 days, and the time needed for return to normal activity was 8 days. CONCLUSIONS: GR and GLRA techniques for unroofing of renal cysts are safe, effective and minimally invasive. GLRA is easy to perform and a more time-saving procedure when compared to GR, however, the patients of GLRA suffered more postoperative pain than after GR. GLRA is recommended in patients who had received retroperitoneal surgery or who have multiple renal cysts.