Biomedical subjects

S S Chen

Publications and source records attributed to S S Chen.

At least 37 records · Page 2Linked to original sources

PubMed2001

Percutaneous transluminal angioplasty as an adjunct to treat the carotid-cavernous fistula.

We report a case of the direct carotid-cavernous fistula (CCF) with high-grade stenosis of the internal carotid artery (ICA) and treatment via the transarterial route after percutaneous transluminal angioplasty (PTA). A 46-year-old man was found to have a CCF after a motorcycle accident. Transarterial embolization was attempted, but it failed due to stenosis of the left cervical ICA. After the procedure of PTA for dilatation of the stenotic ICA, the fistula was successfully obliterated by detachable balloon subsequently. There were no complications or recurrence of the fistula at the three-year clinical follow up.

Angioplasty, Balloon↗

PubMed2001

Magnetic resonance imaging appearance of intradural spinal lipoma.

Intradural spinal lipoma not associated with spinal dysraphism is a rare tumor often presenting with nonspecific symptoms and indolent clinical course. Its intradural location and fat component is the key for proper preoperative diagnosis, which could hardly be made by traditional imaging studies including plain film and myelography. Both CT and MRI can reveal the fat component of the tumor, but MRI is superior to CT in demonstrating its relationship with adjacent normal nerve tissue. We report a 32-year-old man who had back pain for years and the symptom progressed rapidly in recent two months. MRI revealed an intradural tumor at T12 level with high signal intensity on both T1- and T2-weighted images. The signal intensity dropped dramatically with fat saturation technique, which confirmed fat as its main component. The patient received surgery and the tumor was proved to be an intraspinal lipoma.

Adult↗

PubMed2001

[Construction and expression of a new humanized salmon calcitonin variant].

OBJECTIVE: To study the reduction of immunogenicity of salmon calcitonin (sCT). METHODS: A new (11-17) humanized salmon calcitonin variant gene (11-17) hsCT was designed and synthesized to construct recombinant expression vector and express in E.coli G1724 with tryptophan. The fusion protein of humanized salmon calcitonin and thioredoxin (Trx-hsCT) obtained from the bacterial by means of osmotic pressure; The bioactivity of Trx-hsCT was estimated by serum calcium reduction method in rat; The quantitative Western blot analysis was used for detecting the immunogenicity of hsCT. RESULTS: Recombinant expressing vector pTrxFus-hsCT was expressed in high level and soluble in E.coli G1724, reaching 46% of total bacterial protein and obtaining the fusion protein of 90% purity; Special bioactivity of hsCT was preserved that of half pre-sCT and its immunogenicity reduced over 50% that of pre-sCT. CONCLUSION: Obtain a new humanized salmon calcitonin variant(11-17) hsCT which maintains a rather high bioactivity over pre-sCT and decreases distinctly its immunogenicity.

Animals↗

PubMed2000

Assembly and release of human immunodeficiency virus type 1 Gag proteins containing tandem repeats of the matrix protein coding sequences in the matrix domain.

We have constructed human immunodeficiency virus (HIV) gag mutants by increasing the matrix protein (MA) sequences via tandemly repeated duplication of the central 107-MA codons. Instead of a total of 132 amino acid residues for the wild-type MA, the resultant mutants designated as MA2, MA3, and MA4 contained a total of 242, 352, and 462 codons in the MA domains, respectively. Analysis indicated that the addition of 110 or 220 amino acid residues to the MA did not significantly affect the assembly, release, and processing of particles; however, particle production was markedly reduced when another copy of 110 residues was added to the MA. Subcellular fractionation analysis suggested that the MA tandem repeat mutations enhanced the Gag membrane affinity, in a manner which correlated with the copy number of MA sequences. The effects of enhanced membrane affinity were substantially reduced when sequences downstream of the capsid (CA) domain were deleted. Sucrose density gradient fractionation analysis showed that particles produced by the large insertion mutants possessed wild-type (wt) HIV particle density. Truncation of sequences downstream of the nucleocapsid (NC) domains of the mutants did not influence the budding of particles. In contrast, particle budding was severely impaired when sequences downstream of the CA domain were truncated. Particle densities for the large Gag proteins, which were truncated at the C-terminus of CA, were about 1.12-1.14 g/ml lower than that for wt. Our results suggest that the HIV MA domain could adopt insertions of large protein sequences, and strongly support the proposal that the NC and p2 domains play a crucial role in the process of correct Gag protein packing.

Cell Line↗

PubMed2000

Evaluating the protective role of the olivocochlear bundle against acoustic overexposure in rats by using Fos immunohistochemistry.

Efferent inhibition on the cochlea is suggested as a possible function of the olivocochlear bundle (OCB). Substantial evidence supports the finding that the OCB may protect the inner ear from noise-induced damage. However, there is relatively less known about the effects of noise on the central auditory transmission compared to the effects on the periphery. In the present animal study, two experimental paradigms were designed to analyze the influence of OCB lesion on the central auditory transmission following acoustic overexposure. In order to evaluate the animal's auditory function, its hearing threshold and the tone-evoked Fos expression shown in auditory nuclei were examined. Fos is a protein product of proto-oncogene c-fos. Via appropriate acoustic stimulation, Fos expression reveals the activated neuronal elements along the ascending auditory pathway. Thus, in experiment 1, no exposure sound was introduced and therefore no significant differences were shown in hearing thresholds and Fos expression among all rats, regardless of the status of their OCB. This result indicates that, without acoustic overexposure, OCB lesion caused no significant effect on brainstem auditory transmission. In contrast, in experiment 2, rats were exposed to continuous 8 kHz tones at 85 dB sound pressure level (SPL). A significantly increasing threshold was observed in rats with OCB lesion following an exposure period of 5 or 10 days. In addition, Fos expression was invisible first in rats with OCB lesion following 5-day exposure and almost no Fos expression could be examined in all rats after 10-day exposure. Taken together, the present data demonstrate that damaging the OCB renders an animal more easily vulnerable to acoustic damage than that of rat with intact OCB, and then reduces its cochlear activities, which eventually leads to increasing difficulty to induce tone-evoked Fos expression along the ascending auditory pathway.

Animals↗

PubMed2000

Multimerization potential of the cytoplasmic domain of the human immunodeficiency virus type 1 transmembrane glycoprotein gp41.

We previously demonstrated that an envelope mutant of human immunodeficiency virus type 1 lacking the entire cytoplasmic domain interferes in trans with the production of infectious virus by inclusion of the mutant envelope into the wild-type envelope complex. We also showed that the envelope incorporation into virions is not affected when the wild-type envelope is coexpressed with the mutant envelope. These results suggest that an oligomeric structure of the cytoplasmic domain is functionally required for viral infectivity. To understand whether the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 has the potential to self-assemble as an oligomer, in the present study we fused the coding sequence of the entire cytoplasmic domain at 3' to the Escherichia coli malE gene, which encodes a monomeric maltose-binding protein. The expressed fusion protein was examined by chemical cross-linking, sucrose gradient centrifugation, and gel filtration. The results showed that the cytoplasmic domain of gp41 assembles into a high-ordered structural complex. The intersubunit interaction of the cytoplasmic domain was also confirmed by a mammalian two-hybrid system that detects protein-protein interactions in eucaryotic cells. A cytoplasmic domain fragment expressed in eucaryotic cells was pulled down by glutathione-Sepharose 4B beads via its association with another cytoplasmic domain fragment fused to the C terminus of the glutathione S-transferase moiety. We also found that sequences encompassing the lentiviral lytic peptide-1 and lentiviral lytic peptide-2, which are located within residues 828-856 and 770-795, respectively, play a critical role in cytoplasmic domain self-assembly. Taken together, the results from the present study indicate that the cytoplasmic domain of gp41 by itself is sufficient to assemble into a multimeric structure. This finding supports the hypothesis that a multimeric form of the gp41 cytoplasmic domain plays a crucial role in virus infectivity.

ATP-Binding Cassette Transporters↗

PubMed2000

Evidence of selective processing of immunodominant epitopes in virally infected cells.

Recent advances in clarifying the molecular mechanisms involved in Ag processing and presentation have relied heavily on the use of somatic cell mutants deficient in proteasome subunits, TAP transporter, and cell surface expression of MHC class I molecules. Of particular interest currently are those mutants that lack specific protease activity involved in the generation of antigenic peptides. It is theoretically possible that deficiencies of this nature could selectively prevent the cleavage of certain peptide bonds and thus generate only a subset of antigenic peptides. Gro29/Kb cell line is derived from the wild-type murine Ltk- cell line. This cell line is one example of a mutant that lacks specific protease activities. This deficiency manifests itself in an inability to generate a subset of immunodominant peptide epitopes derived from vesicular stomatitis virus and herpes simplex virus. This in turn leads to a general inability to present these viral epitopes to cytotoxic T lymphocytes (CTL). These studies describe a unique Ag processing deficiency and provide new insight into the role of proteasome-independent proteases in MHC class I-restricted peptide generation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Chitinous materials inhibit nitric oxide production by activated RAW 264.7 macrophages.

Chitinous materials have been studied in wound healing and artificial skin substitutes for many years. Nitric oxide (NO) has been shown to contribute to cytotoxicity in cell proliferation during inflammation of wound healing. In this study, we examined the effect of chitin and its derivatives on NO production by activated RAW 264.7 macrophages. Chitin and chitosan showed a significantly inhibitory effect on NO production by the activated macrophages. Hexa-N-acetylchitohexaose and penta-N-acetylchitopentaose also inhibited NO production but with less potency. However, N-acetylchitotetraose, -triose, -biose, and monomer of chitin, N-acetylglucosamine and glucosamine had little effect on NO production by the activated cells. These results suggest that the promotive effect of chitinous material on wound healing be related, at least partly, to inhibit NO production by the activated macrophages.

Animals↗

PubMed2000

Transtentorial cerebellar c-jun expression after focal cerebral cortical injury in mice.

Delayed and remote effect of focal cerebral cortical lesion on cerebellum remains unclear. The c-Jun, an inducible transcription factor of cellular immediate early gene, is the predominant transcription factor and consistent marker for neurons that respond to stress or injury. We use a mouse cryogenic injury model to study the spatial and temporal changes of c-jun in the cerebellum after focal neocortical lesion. A transient and moderate expression of c-jun mRNA was found in the cerebellum with central dominance since 3 day postinjury and gradually subsided within 2 weeks. A distinct increment of c-Jun protein expression in Purkinje cells of the bilateral cerebellar hemispheres with focal connotation in the vermis was detected since 1 week postinjury. These findings suggest that the delayed and remote c-jun expression of the cerebellum, functionally connected with the cerebral cortex, indicate transneuronal gene activation.

Animals↗

PubMed2000

Role for IgE in airway secretions: IgE immune complexes are more potent inducers than antigen alone of airway inflammation in a murine model.

IgE is present in airway secretions from human patients with allergic rhinitis and bronchial asthma. However, the contribution of IgE present locally to the overall airway inflammation is not well understood. We hypothesize that Ag-specific IgE can capture airborne Ags and form immune complexes. These immune complexes may function as potent inducers of immune responses in the lung, contributing to the perpetuation of airway inflammation. BALB/c mice were first sensitized with OVA in alum systemically and then challenged with nebulized OVA. Bronchoalveolar lavage (BAL) fluid from these mice contained significant amounts of IgE, of which >50% was Ag specific. The IgE levels in airway secretions remained elevated for more than 15 days after the termination of Ag exposure. Significant amounts of IgE-OVA immune complexes were detected in BAL fluid from the OVA-challenged mice. For comparison of IgE immune complexes vs Ag alone, we treated OVA-immunized mice with intranasal administration of trinitrophenyl-OVA or trinitrophenyl-OVA-anti-DNP IgE. Those treated with the immune complexes showed significantly higher levels of IL-4 and more pronounced eosinophilia in BAL fluid than did those receiving the Ag alone. The IgE immune complexes did not augment the inflammatory response in high affinity IgE receptor (FcepsilonRI)-deficient mice. We conclude that IgE present in the airways can capture the Ag and that the immune complexes thus formed may augment allergic airway response in an FcepsilonRI-dependent manner. Thus, IgE present in airway secretions may facilitate Ag-mediated allergic airway inflammation.

Aerosols↗

PubMed2000

PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo .

BACKGROUND: Management of prostate cancer that has spread beyond the capsule is a difficult problem. Innovative and nontoxic approaches to the disease are urgently required. Recently, a commercially available herbal mixture called PC-SPES showed potent antitumor activities on a variety of malignant cells in vitro. METHODS: PC-SPES was evaluated for its ability to inhibit clonal growth, and to induce cell cycle arrest of three human prostate cancer cell lines (LNCaP, PC-3, and DU 145). Western blot analysis examined the effect of PC-SPES on levels of p21(waf1), p27(kip1), Bcl-2, and E-cadherin in the three cell lines; and telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay. Furthermore, the effect of oral PC-SPES (250 mg/kg/day) on growth of PC-3 and DU 145 tumors present in male BNX nu/nu triple immunodeficient mice was studied. LNCaP cells were not analyzed in mice because they grow only with difficulty in these immunodeficient mice. RESULTS: PC-SPES markedly inhibited clonal growth of LNCaP, PC-3, and DU 145 prostate cancer cells, with a 50% inhibition (ED50) at approximately 2 microl/ml. Pulse-exposure studies showed that a 5-day pulse-exposure to PC-SPES (2 microl/ml) in liquid culture achieved a 50% inhibition of PC-3 clonal growth in soft agar, suggesting that the growth inhibition mediated by the extracts remained after removal of PC-SPES. Cell cycle analysis using the prostate cancer cell lines found that PC-SPES induced a significant increase in the number of cells in G0-G1 and G2/M, with a concomitant decrease in the number of cells in S phase. PC-SPES (2 microl/ml, 4 days) increased slightly the levels of p21(waf1) in the three cell lines, decreased by 40% the levels of Bcl-2 in PC-3, and the levels of p27(kip1) and E-cadherin and telomerase were unchanged in each of the lines. In vivo treatment with oral PC-SPES of male BNX mice having DU 145 tumors produced significant inhibition of their growth (P < 0.001), with no objective side effects including blood chemistries, weights, or autopsy analysis. The PC-SPES showed no statistical effect on the in vivo growth of PC-3 cells. CONCLUSIONS: PC-SPES inhibits clonal proliferation of human prostate cancer cells both in vitro and in vivo, using a murine model.

Androgens↗

PubMed2000

Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in the nasal mucosa of patients with rhinitis.

Since nitric oxide (NO) can be involved in multiple physiological and pathological functions, we evaluated its possible involvement and that of peroxynitrite in the pathogenesis of rhinitis. Inferior nasal turbinates were obtained from allergic rhinitis and nonallergic rhinitis patients during corrective nasal surgery. The expressions of the inducible form of nitric oxide synthase (iNOS) and the production of peroxynitrite and its metabolite 3-nitrotyrosine were examined by immunohistochemistry in consecutive tissue sections. Each section (or tissue compartment) was given a score of 0-4 according to the labeling intensity seen, with the highest number representing the highest labeling intensity. The results showed that iNOS expression was present mainly in the mucosal epithelium, vascular endothelium, and submucosal glands. A significant difference was only observed in the labeling scores of glandular tissues of the allergic group, which had a higher iNOS labeling score. We also found that sections with a higher iNOS level did not necessarily exhibit a higher 3-nitrotyrosine labeling intensity. These data suggest that iNOS-derived NO may have a role in the pathophysiology of rhinitis, especially the glandular function of allergic nasal mucosa. Moreover, our findings suggest that the production of peroxynitrite in rhinitis patients is not dependent on the level of iNOS alone.

Adolescent↗

PubMed2000

TAP expression provides a general method for improving the recognition of malignant cells in vivo.

A major class of tumors lack expression of the transporters associated with antigen processing (TAP). These proteins are essential for delivery of antigenic peptides into the lumen of the endoplasmic reticulum (ER) and subsequent assembly with nascent major histocompatibility complex (MHC) class I, which results in cell surface presentation of the trimeric complex to cytolytic T lymphocytes. Cytolytic T lymphocytes are major effector cells in immunosurveillance against tumors. Here we have tested the hypothesis that TAP downregulation in tumors allows immunosubversion of this effector mechanism, by establishing a model system to examine the role of TAP in vivo in restoring antigen presentation, immune recognition, and effects on malignancy of the TAP-deficient small-cell lung carcinoma, CMT.64. To test the potential of providing exogenous TAP in cancer therapies, we constructed a vaccinia virus (VV) containing the TAP1 gene and examined whether VV-TAP1 could reduce tumors in mice. The results demonstrate that TAP should be considered for inclusion in cancer therapies, as it is likely to provide a general method for increasing immune responses against tumors regardless of the antigenic complement of the tumor or the MHC haplotypes of the host.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

The correlation between clinical outcome and residual prostatic weight ratio after transurethral resection of the prostate for benign prostatic hyperplasia.

OBJECTIVE: To assess in a prospective study the use of a new variable, the residual prostatic weight ratio (RPWR), for evaluating the clinical outcome after transurethral resection of the prostate (TURP). PATIENTS AND METHODS: From April 1996 to June 1997, 40 men (mean age 70.4 years, range 53-85) with symptomatic benign prostatic hyperplasia were evaluated using the American Urological Association (AUA) symptom score, measurements of the mean and maximum urinary flow rate (Qave and Qmax), and by transrectal ultrasonography (TRUS) before and 16 weeks after TURP. The estimated total prostate weight was derived as 0.52 x length x width x height x the specific gravity of the prostate (1.010). The RPWR was calculated as the prostate weight after TURP divided by the initial weight, where the value after TURP was the initial weight minus that of the TURP specimen. The clinical outcome was evaluated by the difference (Delta) in AUA score, Qmax and Qave before and 16 weeks after surgery. RESULTS: There was a close correlation between the estimated prostate weight and the actual weight of the TURP specimen (r = 0.82 and 0.80 for the adenoma and total prostate, respectively). The mean (SD) RPWR, DeltaAUA score, DeltaQmax and DeltaQave were 50.1 (17.1)%, 11.5 (5. 3), 9.0 (4.2) mL/s and 6.2 (2.9) mL/s, respectively. There was a negative correlation between the RPWR and the DeltaAUA, DeltaQmax and DeltaQave (r = -0.81, -0.68, and -0.70, respectively, P < 0.05). The prostate volume estimated by TRUS decreased significantly 16 weeks after TURP. CONCLUSIONS: TRUS is a useful tool for estimating prostate weight before surgery. The smaller the RPWR at 16 weeks after TURP, the better the clinical outcome.

Aged↗

PubMed2000

Blocked transport of soluble K(b) molecules containing connecting peptide segment involved in calnexin association.

The molecular event governing the assembly of the MHC class I heavy chain-beta(2)-microglobulin-peptide complex is still not fully understood. In order to characterize the transport properties of MHC class I molecules, several truncated H-2K(b) genes were constructed and expressed in COS7 cells. Surprisingly, the expressed soluble molecule containing connecting peptide (CP) segment (sK(b)(CP)) did not secrete as efficiently as the one without CP (sK(b)(CYT)). When the sK(b)(CP) gene was transfected into a calnexin-deficient cell line CEM.NK(R), the amount of soluble K(b) molecules in the supernatant was comparable with sK(b)(CYT)-transfected CEM.NK(R). To further demonstrate the different transport of sK(b)(CP) and sK(b)(CYT) within living cells, we attached green fluorescent protein (GFP) to the C-termini of both molecules and, as a comparison, to the full-length transmembrane counterpart (mK(b)-GFP). While the mK(b)-GFP-transfected cells showed the green fluorescence in the reticular network and the nuclear envelope, sK(b)(CP)-GFP showed obviously lump fluorescence of high intensity within cells. However, the distribution of sK(b)(CYT)-GFP was fairly uniform. Furthermore, GFP-tagged molecules allow us to analyze their interaction with other proteins in a direct, simple and quantitative method, designated immunofluorescence precipitation. The results showed that 60% of sK(b)(CP)-GFP molecules were associated with calnexin, while <10% with tapasin. Taken together with the results from sK(b)(CYT)-GFP and mK(b)-GFP, it is reasonable to deduce that the CP segment is involved in the association of class I molecules with calnexin and the transmembrane region might play a dynamic role in the dissociation from calnexin. The suggested kinetic association of class I molecules with calnexin is likely to contribute to the different maturation rate between several class I alleles.

Animals↗

PubMed2000

C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue.

Knockout of C/EBPalpha causes a severe loss of liver function and, subsequently, neonatal lethality in mice. By using a gene replacement approach, we generated a new C/EBPalpha-null mouse strain in which C/EBPbeta, in addition to its own expression, substituted for C/EBPalpha expression in tissues. The homozygous mutant mice C/ebpalpha(beta/beta) are viable and fertile and show none of the overt liver abnormalities found in the previous C/EBPalpha-null mouse line. Levels of hepatic PEPCK mRNA are not different between C/ebpalpha(beta/beta) and wild-type mice. However, despite their normal growth rate, C/ebpalpha(beta/beta) mice have markedly reduced fat storage in their white adipose tissue (WAT). Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebpalpha(beta/beta) mice. In addition, expression of the non-adipocyte-specific genes for transferrin and cysteine dioxygenase is reduced in WAT but not in liver. Our study demonstrates that when expressed from the C/ebpalpha gene locus, C/EBPbeta can act for C/EBPalpha to maintain liver functions during development. Moreover, our studies with the C/ebpalpha(beta/beta) mice provide new insights into the nonredundant functions of C/EBPalpha and C/EBPbeta on gene regulation in WAT.

Adipose Tissue↗

PubMed2000

Hyperinsulinemia compensates for infection-induced impairment in net hepatic glucose uptake during TPN.

In animals receiving total parenteral nutrition (TPN), infection impairs net hepatic glucose uptake (NHGU) by 40% and induces mild hyperinsulinemia. In the normal animal, the majority of the glucose taken up by the liver is diverted to lactate, but in the infected state, lactate release is curtailed. Because of the hyperinsulinemia and reduced NHGU, more glucose is utilized by peripheral tissues. Our aims were to determine the role of infection-induced hyperinsulinemia in 1) limiting the fall in NHGU and hepatic lactate release and 2) increasing the proportion of glucose disposed of by peripheral tissues. Chronically catheterized dogs received TPN for 5 days via the inferior vena cava. On day 3, a fibrin clot with a nonlethal dose of E. coli was placed into the peritoneal cavity; sham dogs received a sterile clot. On day 5, somatostatin was infused to prevent endogenous pancreatic hormone secretion, and insulin and glucagon were replaced at rates matching incoming hormone concentrations observed previously in sham or infected dogs. The TPN-derived glucose infusion was adjusted to maintain a constant arterial plasma glucose level of approximately 120 mg/dl. after a basal blood sampling period, the insulin infusion rate was either maintained constant (infected time control, Hi-Ins, n = 6; sham time control, Sham, n = 6) or decreased (infected + reduced insulin, Lo-Ins; n = 6) for 180 min to levels seen in noninfected dogs (from 23 +/- 2 to 12 +/- 1 microU/ml). Reduction of insulin to noninfected levels decreased NHGU by 1.4 +/- 0.5 mg x kg(-1) x min(-1) (P < 0.05) and nonhepatic glucose utilization by 4.8 +/- 0.8 mg x kg(-1) x min(-1) (P < 0.01). The fall in NHGU was caused by a decline in HGU (Delta-0.6 +/- 0.4 mg x kg(-1) x min(-1)) and a concomitant increase in hepatic glucose production (HGP, Delta0.8 +/- 0.5 mg x kg(-1) x min(-1)); net hepatic lactate release was not altered. Hyperinsulinemia that accompanies infection 1) primarily diverts glucose carbon to peripheral tissues, 2) limits the fall in NHGU by enhancing HGU and suppressing HGP, and 3) does not enhance hepatic lactate release, thus favoring hepatic glucose storage. Compensatory hyperinsulinemia plays a critical role in facilitating hepatic and peripheral glucose disposal during an infection.

Animals↗

PubMed2000

Expression of transforming growth factor-beta1 and its receptors related to the ureteric fibrosis in a rat model of obstructive uropathy.

PURPOSE: Transforming growth factor (TGF-beta) is a multifunctional cytokine that may stimulate fibroblast proliferation and regulate the synthesis of matrix components. To elucidate the role of TGF-beta1 in the process of ureteric fibrosis in obstructive uropathy, we conducted this study. MATERIALS AND METHODS: The expression of TGF-beta1 and TGF-beta receptors I, II, III were studied in 54 rats by the method of immunohistochemistry. RESULTS: The degree of smooth muscle hypertrophy and serosa thickening aggravated gradually along the course of ureteric ligation. The expression of TGF-beta1 in the serosa layer was noticed from day 7 after ligation. The expression of TGF-beta1 and receptors in the serosa layer progressively increased during the period of ureteric obstruction, reached a peak on day 21 after ligation, and then declined. The expression of TGF-beta1 and TGF-beta receptors (II and III) in the serosa layer was correlated significantly (r = 0.8048 and 0.7974, respectively; p values both <0.0001). The expression of TGF-beta1 also correlated significantly with the thickening of serosa layer and the severity of hydroureter (r = 0.6921 and 0.5394, respectively; p values both <0.005). The expression of TGF-beta1 and TGF-beta receptors in the smooth muscle layer was transient and weak, and the expression of TGF-beta1 and TGF-beta receptors was accompanied with the fibrosis in the muscle layer. CONCLUSIONS: We conclude that TGF-beta1 might participate in the progression ofureteric fibrosis in obstructed ureters.

Animals↗