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Biomedical subjects

J L Chin

Publications and source records attributed to J L Chin.

At least 19 recordsLinked to original sources

Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids) mRNA in prostate tissue.

While performing reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total mRNA from prostate cancer specimens, two forms of PSP94 cDNA were detected. RT-PCR products were analysed by Southern blotting and probing with exon-specific oligonucleotides. In the short form of PSP94 mRNA, designated as PSP57, exon III was found to be deleted. The two mRNA forms were confirmed by cloning and sequencing of the RT-PCR products and were found to result from alternative splicing. The alternatively spliced form, PSP57, was characterized by sequence analysis. PSP94 and PSP57 possess identical exons I and II, including identical secretion signal peptide and the 5' untranslated sequences. PSP57 has a frame-shifted exon IV and encodes a putative 57 amino acid protein with a novel, highly basic C-terminus of 41 amino acids. PSP57 mRNA was detected in other urogenital tissues (kidney, bladder) and in most tumor cell lines tested, but was not detectable in other tissues such as breast and lung. In prostate tumor cell lines, PSP57 mRNA was aberrantly spliced and localized in the nuclear fraction of the cell. Our results suggest the possible existence of a novel PSP protein that originates from alternative splicing of PSP94 mRNA in urogenital tissues.

Aged

Induction of hepatic metallothionein I in tumour-bearing mice.

Metallothionein (MT) is an intracellular metal-binding protein which has been implicated in various biological roles, including heavy-metal detoxification and zinc and copper homeostasis, and has putative antioxidant properties. High levels of MT have been detected in certain human tumours, but its functions are unclear. The presence of tumour may cause stress conditions along with alterations in host metabolism, such as the redistribution of metals and, subsequently, in changes in hepatic MT isoforms. The distribution of basal levels of MT-1 and MT-11 isoforms in livers of different strains of mice and their induction in mice inoculated with tumour cells are investigated. While Balb-c, C57/BL and CD1 mice strains had an equal distribution of both hepatic MT isoforms, MT-I and MT-II. In addition, MT-I was the predominant isoform synthesised (> 88%) in the livers of all strains of mice at 24 h after injection with either cadmium or zinc salts. After inoculation with human testicular T7800 or T7799 tumour cells, the major form of MT induced in the livers of nude (nu/nu) mice was Zn-MT-I, and its concentration was positively correlated with the size of the inoculated tumours (r2 = 0.85). A similar positive relation was found in the livers of Balb-c mice inoculated with MM45T mouse bladder tumour cells (r2 = 0.96). Following surgical removal of T7800 tumour, hepatic MT concentrations returned to basal values. There was an increase in plasma MT levels in tumour-bearing mice and it was positively correlated with the increase in hepatic MT levels. These results demonstrate a specific increase in hepatic MT-I isoform in tumour-bearing mice, and this may be due to a generalised stress during tumour growth.

Analysis of Variance

Metallothionein expression and resistance to cisplatin in a human germ cell tumor cell line.

Expression of intracellular metallothionein (MT) has been linked to cis-diamminedichloroplatinum (cDDP) resistance in human germ cell tumor cell lines. To determine whether exposure to cDDP would select for cells with increased MT expression, the MT content of the human teratocarcinoma cell line T7800 was measured after development of resistance to cDDP by exposure to progressively higher drug concentrations (6.25-25 microM). cDDP-resistant cells (T7800R) had significantly higher MT mRNA and MT protein, increased resistance to killing by cDDP and altered in vitro growth kinetics compared to parental T7800 cells. cDDP resistance in a variety of other human tumor cell lines correlated with MT content, with no significant difference in glutathione level. These data indicate that selection in vitro for cDDP resistance in human germ cell tumors coselects for cells with enhanced MT content. However, selected cells differed in characteristics other than MT content. They had a slower growth rate and, although the rank order of MT level in T7800, T7800R and other human tumor cell lines correlated very well with cDDP resistance, differences in the level of MT expression did not correspond with differences in the absolute level of cDDP resistance. These results suggest that increased MT expression is concomitant with increased cDDP resistance in a variety of human tumor cell lines. However, measured differences in MT levels may not accurately reflect the degree of cDDP resistance differences among those cells.

Cell Division

Fatal air embolism during radical retropubic prostatectomy.

Air embolism during urological surgery only rarely has been reported. We report a case of fatal air embolism occurring during radical retropubic prostatectomy. This entity is discussed in an attempt to raise the level of awareness of this rare but potentially lethal complication, especially in view of the ever increasing popularity of radical retropubic prostatectomy as the treatment for organ confined carcinoma of the prostate.

Aged

Self-contained, inflatable penile prosthesis: magnetic resonance appearance.

The appearance of an inflatable penile prosthesis, visualized on a short tau inversion recovery sequence, is reported, in a patient who had magnetic resonance imaging for pelvic pain subsequent to radical cystoprostatectomy for bladder carcinoma. With suppression of adjacent fat signal, the prosthesis is well delineated from adjacent structures. The fluid-containing cylinders of the prosthesis are of very bright signal intensity, with the relief valve assembly of low signal intensity.

Humans

Metallothionein in testicular germ cell tumors and drug resistance. Clinical correlation.

BACKGROUND: Metallothioneins (MT) are endogenous metalloproteins involved in the homeostasis of essential metals and detoxification of toxic metals. Some recent experimental studies suggested tumor resistance to cisdiamminedichloroplatin may be associated with overexpression of MT in the tumor. METHODS: The presence of MT in 33 primary testicular germ cell tumor specimens was assessed immunohistochemically using a rabbit polyclonal rat liver MT antibody that cross-reacted with human MT. The data were correlated with the patients' clinical course. RESULTS: Seminomas stained weakly or not at all for MT, regardless of the clinical stage. Most nonseminomas stained heavily for MT. The more advanced staged nonseminomas tended to stain more heavily for MT. CONCLUSIONS: In view of the considerable experimental evidence as well as some inferential clinical data involving MT in cis-diamminedichloroplatin resistance, there appears to be a role for MT in cis-diamminedichloroplatin resistance in germ cell tumors. Further studies to elucidate the role of MT in germ cell tumor chemoresistance are warranted.

Cisplatin

Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis.

The role of metallothionein (MT) in cisplatin (cis-DDP) resistance and renal toxicity was investigated in C3H mice inoculated with mouse bladder tumor (MBT-2). C3H mice were inoculated s.c. with 1 x 10(6) MBT-2 cells/mouse on day 0. Mice were given injections of proparglyglycine (PPG) (500 mumol/kg s.c.) once a day for 3 days from day 7 to day 9 and with ZnSO4 (200 mumol/kg s.c.) once a day for 2 days from day 8 to day 9. cis-DDP (50 mumol/kg i.p.) was administered 10 days after MBT-2 cell inoculation. Since MT contents in the tumor and kidneys were significantly increased by administration of ZnSO4, both the antitumor activity of cis-DDP and its renal toxicity were reduced. However, coadministration of PPG reduced MT induction in tumor without affecting the level of renal MT. As a result, PPG could clearly overcome the MT-mediated cis-DDP resistance of tumors without compromising the protective effect exerted by renal MT on nephrotoxicity of the drug. It was suggested, therefore, that PPG may be a promising adjunct in cancer chemotherapy to overcome the drug resistance of tumors caused by the elevated level of MT.

Alkynes

Intrarenal bacillus Calmette-Guerin therapy for upper urinary tract carcinoma in situ.

Of 17 renal units from 11 patients treated with intrarenal bacillus Calmette-Guerin (BCG) for positive selective upper tract urine cytology 16 had negative radiographic studies and 1 had a papillary renal pelvic lesion. The standard diagnostic maneuvers were used to rule out other sources of positive cytology from the lower tracts. Six patients had bilateral involvement, 3 had prior contralateral nephroureterectomy and 2 had unilateral positive cytology but were poor surgical risks. The BCG solution was administered weekly by retrograde ureteral catheterization and instillation during 1 hour. One patient had fever during the initial treatment and received antituberculous therapy. Other side effects included transient hematuria in 3 patients and irritative urinary symptoms in most patients. Of 11 patients (12 renal units) 8 had normalization of the urinary cytology with a median followup of 36 months. One patient had unilateral conversion of the cytology result but the contralateral papillary tumor persisted, requiring nephroureterectomy. The remaining 2 patients had persistently positive cytology results and the disease progressed. Longer followup and further experience with intrarenal BCG are required before the exact role of this treatment modality in upper tract urothelial malignancies, including carcinoma in situ, can be determined.

Aged

Loin pain-hematuria syndrome: role for renal autotransplantation.

The loin pain-hematuria syndrome is a poorly understood constellation of symptoms consisting of persistent hematuria and intractable loin pain with negative comprehensive urological evaluation. The patients are severely debilitated by the pain and are usually dependent on narcotics. Various medical and surgical treatments have been tried unsuccessfully, ultimately leading to nephrectomy in many instances. The symptoms may subsequently occur contralaterally. Renal autotransplantation as a form of nephron-sparing denervation therapy for relief of pain was performed on 12 kidneys in 10 patients (2 bilaterally). Excluding 3 patients with followup of less than 1 year (all 3 are pain-free), 8 of the 9 autotransplantations have resulted in dramatic relief of pain, curtailment of narcotic use and return of the patient to normal daily function. Median followup was 43 months (range 15 to 53 months). The remaining patient had pain in the graft area necessitating transplant nephrectomy 4 months later. For patients severely affected by pain and narcotic dependence with this syndrome, renal autotransplantation may provide a nephron-sparing surgical solution.

Adult

Concomitant treatment of MBT-2 bladder tumour by tumour necrosis factor alpha and interferon alpha in conjunction with delayed type hypersensitivity immunotherapy.

In our previous study [9], we reported the anti-tumour effect of TNF on mouse bladder tumour (MBT-2) both in vivo and in vitro. Inoculation of a single dose of TNF alone caused significant but transient tumour growth inhibition. Subsequent repeated doses of TNF did not sustain or augment the anti-tumour effect. The current experiments were undertaken to assess the anti-tumour activity of (i)-concomitant treatment of TNF-A and IFN-A against MBT-2 bladder tumour and (ii)-concomitant TNF + IFN-A treatment in conjunction with T-DTH (delayed-type hypersensitivity) immunotherapy. Systemic administration of multiple doses of TNF + IFN-A in vivo caused initial partial tumour regression followed by tumour growth inhibition up to 14 days following treatment. This combined treatment showed an enhanced anti-tumour effect compared to TNF-A treatment alone. Immunotherapy of MBT-2 tumour-bearing mice with T-DTH "immune" effector cells alone did not cause significant tumour growth inhibition. In contrast, concomitant administration of both T-DTH effector cells and TNF + IFN-A in MBT-2 tumour-bearing mice resulted in significant tumour growth inhibition for up to 16 days. The immune effector cells conferring immunotherapy were isolated from the spleens of tumour-immunized, "DTH-primed" animals and were characterized as Lyt 1+2- helper/DTH T cells (CD4+ phenotype). These cells mediate both DTH response to MBT-2 tumour antigens as well as anti-MBT-2 tumour protection. In vitro treatment of the "immune" cells with TNF-A resulted predominantly in the proliferation of Lyt 1+ T cells versus Lyt 2+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Characterization of MBT-2 tumour cell "variant" resistant to tumour necrosis factor.

Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 "variant" tumour cell population emerged in vitro. This concurred with the finding of transient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant "variant" MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of "variant" MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.

Animals

Immunohistochemical localization of metallothionein in transitional cell carcinoma of the bladder.

Metallothionein is a metal binding protein thiol found in high concentrations in the liver and kidney. Recent evidence has linked overexpression of cellular metallothionein with tumor cell resistance to chemotherapeutic drugs, such as alkylating agents and cis-diamminedichloroplatinum (II) (cisplatin). We studied the metallothionein content of 9 human transitional cell carcinomas of the bladder with immunohistochemical methods. All tumors stained positive for metallothionein and the staining was localized almost exclusively to the cytoplasm. Uroepithelium displaying dysplastic changes or carcinoma in situ demonstrated the greatest intensity of staining, while staining in the invasive portions of the tumor was weak and variable. These findings were of interest, since combination chemotherapy of invasive transitional cell carcinoma of the bladder often is ineffective against carcinoma in situ. Normal uroepithelium stained strongly in all 3 patients who experienced disease progression and death, and in only 1 of the 5 who are currently without evidence of disease.

Aged

Ex-vivo microvascular reconstruction before renal allograft and autograft transplantation.

Microvascular reconstruction was performed ex vivo on 50 kidneys that had vascular anomalies or had sustained vascular injury during procurement before allograft transplantation or autotransplantation. The authors review the various surgical techniques used to facilitate the in-situ vascular anastomoses during transplantation and to salvage otherwise an unusable allograft. The complications associated with the microvascular repair were negligible. The authors conclude from the results of their study that ex-vivo microvascular reconstruction is a valuable adjunct to renal transplantation.

Anastomosis, Surgical

Microvascular reconstructive "bench" surgery for donor kidneys before transplantation: techniques and results.

Forty kidneys (10 from live donors) with either multiple renal arteries or damaged vasculature were reconstructed accurately ex vivo with microsurgical techniques before transplantation. The end product in all cases was a kidney requiring a single arterial and venous in situ anastomosis. The warm ischemia time was minimized by this adjunctive "bench" microsurgery. There was no surgical complication relating to the vascular reconstruction. The potential technical and hemodynamic benefits of this surgical approach to kidneys with multiple vessels are discussed. In addition, some kidneys with damaged vasculature can be salvaged for transplantation with microvascular reconstruction.

Anastomosis, Surgical