PubMed Health⌕ Search

Biomedical subjects

Hong Ling

Publications and source records attributed to Hong Ling.

At least 19 recordsLinked to original sources
PubMed2006

Mechanism of template-independent nucleotide incorporation catalyzed by a template-dependent DNA polymerase.

Numerous template-dependent DNA polymerases are capable of catalyzing template-independent nucleotide additions onto blunt-end DNA. Such non-canonical activity has been hypothesized to increase the genomic hypermutability of retroviruses including human immunodeficiency viruses. Here, we employed pre-steady state kinetics and X-ray crystallography to establish a mechanism for blunt-end additions catalyzed by Sulfolobus solfataricus Dpo4. Our kinetic studies indicated that the first blunt-end dATP incorporation was 80-fold more efficient than the second, and among natural deoxynucleotides, dATP was the preferred substrate due to its stronger intrahelical base-stacking ability. Such base-stacking contributions are supported by the 41-fold higher ground-state binding affinity of a nucleotide analog, pyrene nucleoside 5'-triphosphate, which lacks hydrogen bonding ability but possesses four conjugated aromatic rings. A 2.05 A resolution structure of Dpo4*(blunt-end DNA)*ddATP revealed that the base and sugar of the incoming ddATP, respectively, stack against the 5'-base of the opposite strand and the 3'-base of the elongating strand. This unprecedented base-stacking pattern can be applied to subsequent blunt-end additions only if all incorporated dAMPs are extrahelical, leading to predominantly single non-templated dATP incorporation.

Binding Sites↗
PubMed2006

[Stereotactic biopsy for non-palpable breast lesions: evaluation and choice of minimal invasive and excisional biopsy].

OBJECTIVE: To evaluate three biopsy methods which are currently used in stereotactic breast biopsy. METHODS: A total of 361 cases of stereotactic breast biopsies were carried out since 2000, including 73 cases of true cut core needle biopsies (ST-CNB), 74 cases of vacuum assisted biopsies (ST-VAB) and 214 cases of excisional biopsies. After medium follow-up time of 18 months (6 to 66 months), the accuracy as well as the clinical benefits of the three stereotactic biopsy procedures were analyzed retrospectively. RESULTS: The cancer miss rate of stereotactic wire localized excisional biopsy, ST-CNB and ST-VAB is 0, 2.7% and 0 respectively. Under-estimate rate of minimal invasive biopsy was 33% in atypical ductal hyperplasia (ADH) and 53% in ductal carcinoma in situ (DCIS). The minimal invasive procedure is superior to surgical procedure in terms of operation time, breast cosmetic outcome and complications, etc. Furthermore, 69% of the surgeries for suspicious lesion were waived. CONCLUSIONS: Stereotactic minimal invasive breast biopsy, especially ST-VAB, is an accurate, safty and convenient diagnosis technique and could be considered as the first line choice for mammographic moderate suspicious breast lesions (BIRADS-4). However, further excisional biopsy is recommended for atypical hyperplasia. Stereotactic excisional biopsy could be directly used for diagnosis of mammographic highly suspicious breast lesions (BIRADS-5).

Biopsy↗
PubMed2006

A numerical simulation method and analysis of a complete thermoacoustic-Stirling engine.

Thermoacoustic prime movers can generate pressure oscillation without any moving parts on self-excited thermoacoustic effect. The details of the numerical simulation methodology for thermoacoustic engines are presented in the paper. First, a four-port network method is used to build the transcendental equation of complex frequency as a criterion to judge if temperature distribution of the whole thermoacoustic system is correct for the case with given heating power. Then, the numerical simulation of a thermoacoustic-Stirling heat engine is carried out. It is proved that the numerical simulation code can run robustly and output what one is interested in. Finally, the calculated results are compared with the experiments of the thermoacoustic-Stirling heat engine (TASHE). It shows that the numerical simulation can agrees with the experimental results with acceptable accuracy.

Journal Article↗
PubMed2006

[Value of magnetic resonance imaging in diagnosing breast lesions which need biopsy].

OBJECTIVE: To evaluate MRI in diagnosing breast lesions which need biopsy. METHODS: One hundred and eight patients were admitted to hospital for biopsies due to one hundred and sixteen suspicious lesions detected in their breasts. These lesions were detected by physical examination, mammography or ultrasonography. They were also administrated MRI examination before biopsy. The sensitivity and specificity of each diagnostic method were obtained and the radiologic-pathologic correlation was meanwhile calculated. RESULTS: Seventy (60.3%) breast lesions were diagnosed malignancy. The sensitivity, specificity, accuracy, positive prognostic value and negative prognostic value of ultrasonography were 83.3%, 62.0%, 74.1%, 74.3% and 73.8%. Such data of mammography were 86.8%, 68.1%, 78.0%, 75.4% and 82.1%. And those of MRI were 97.1%, 73.9%, 87.9%, 85.0% and 94.4%. CONCLUSION: MRI is superior to ultrasonography and mammography in diagnosing breast lesions, especially for the nonpalpable lesions.

Adult↗
PubMed2006

Competitive study of monoclonal antibodies against the HIV-1 Gp41 core structure.

Monoclonal antibodies (MAbs) 50.69, 98.6, and T26 bind specifically to the core structure of the human immunodeficiency virus type 1 (HIV-1) envelope transmembrane glycoprotein (gp41). To clarify the specificity of the anti-core structure MAbs, we performed competitive assays using the MAbs to the H9 human T cell line infected with the IIIB strain of HIV-1 (H9/IIIB). Bound MAb 50.69 inhibited MAb 98.6 binding unidirectionally. The reason for the unidirectional cross competition between MAbs 50.69 and 98.6 is not clear, but these results help to define the antigenic structure of gp41 on the surface of infected cells.

Antibodies, Monoclonal↗
PubMed2005

Fidelity of Dpo4: effect of metal ions, nucleotide selection and pyrophosphorolysis.

We report the crystal structures of a translesion DNA polymerase, Dpo4, complexed with a matched or mismatched incoming nucleotide and with a pyrophosphate product after misincorporation. These structures suggest two mechanisms by which Dpo4 may reject a wrong incoming nucleotide with its preformed and open active site. First, a mismatched replicating base pair leads to poor base stacking and alignment of the metal ions and as a consequence, inhibits incorporation. By replacing Mg2+ with Mn2+, which has a relaxed coordination requirement and tolerates misalignment, the catalytic efficiency of misincorporation increases dramatically. Mn2+ also enhances translesion synthesis by Dpo4. Subtle conformational changes that lead to the proper metal ion coordination may, therefore, be a key step in catalysis. Second, the slow release of pyrophosphate may increase the fidelity of Dpo4 by stalling mispaired primer extension and promoting pyrophosphorolysis that reverses the polymerization reaction. Indeed, Dpo4 has robust pyrophosphorolysis activity and degrades the primer strand in the presence of pyrophosphate. The correct incoming nucleotide allows DNA synthesis to overcome pyrophosphorolysis, but an incorrect incoming nucleotide does not.

Base Pair Mismatch↗
PubMed2005

[The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing ESRD patients from microinflammation and arteriosclerosis].

OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and end stage renal disease (ESRD) patients microinflammatory state and arteriosclerosis (AS). METHODS: We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and arteriosclerosis. RESULTS: Compared with the control group, CRP, TNF-alpha, CH50, C3, IL-10 and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with IL-10A/A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum CRP and Fib. CONCLUSION: The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk.

Arteriosclerosis↗
PubMed2005

Properties of anti-gp41 core structure antibodies, which compete with sera of HIV-1-infected patients.

To determine the correlation between the immunoreaction against the core structure of human immunodeficiency virus type (HIV-1) transmembrane protein gp41 epitopes and the disease progression, it is essential to evaluate the anti-core structure antibody epitopes and the humoral immunity against the epitopes. For this purpose we evaluated monoclonal antibodies (mAbs) against the gp41 core structure such as mAbs 50.69, 98.6 and T26, by Western blotting (WB) and flow cytometry. WB showed mAbs 50.69 and 98.6 bound to both monomeric and oligomeric gp41, and mAb T26 exclusively bound to oligomeric gp41. We evaluated the sera from Pneumocystis pneumonia patients (PCP; n=7) and long-term survivors (LTS; n=7). Competition assay with sera and mAbs for binding to H9 cells infected with HIV-1 IIIB virus was done using flow cytometry. The results revealed that PCP sera as well as LTS sera inhibited the binding of all the three mAbs, and the PCP sera inhibited mAb T26 binding more efficiently than LTS. Therefore, PCP patients retain competing immunity to antibodies against not only the shared epitopes of the core structure (binding sites of mAbs 50.69 and 98.6) but also against oligomeric gp41 specific epitope (binding site of mAb T26).

Adolescent↗
PubMed2004

Investigating the role of the little finger domain of Y-family DNA polymerases in low fidelity synthesis and translesion replication.

Dpo4 and Dbh are Y-family polymerases that originate from two closely related strains of Sulfolobaceae. Quite surprisingly, however, the two polymerases exhibit different enzymatic properties in vitro. For example, Dpo4 can replicate past a variety of DNA lesions, yet Dbh does so with a much lower efficiency. When replicating undamaged DNA, Dpo4 is prone to make base pair substitutions, whereas Dbh predominantly makes single-base deletions. Overall, the two proteins are 54% identical, but the greatest divergence is found in their respective little finger (LF) domains, which are only 41% identical. To investigate the role of the LF domain in the fidelity and lesion-bypassing abilities of Y-family polymerases, we have generated chimeras of Dpo4 and Dbh in which their LF domains have been interchanged. Interestingly, by replacing the LF domain of Dbh with that of Dpo4, the enzymatic properties of the chimeric enzyme are more Dpo4-like in that the enzyme is more processive, can bypass an abasic site and a thymine-thymine cyclobutane pyrimidine dimer, and predominantly makes base pair substitutions when replicating undamaged DNA. The converse is true for the Dpo4-LF-Dbh chimera, which is more Dbh-like in its processivity and ability to bypass DNA adducts and generate single-base deletion errors. Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member.

Amino Acid Sequence↗
PubMed2004

Snapshots of replication through an abasic lesion; structural basis for base substitutions and frameshifts.

Dpo4 from S. Solfataricus, a DinB-like Y family polymerase, efficiently replicates DNA past an abasic lesion. We have determined crystal structures of Dpo4 complexed with five different abasic site-containing DNA substrates and find that translesion synthesis is template directed with the abasic site looped out and the incoming nucleotide is opposite the base 5' to the lesion. The ensuing DNA synthesis generates a -1 frameshift when the abasic site remains extrahelical. Template realignment during primer extension is also observed, resulting in base substitutions or even +1 frameshifts. In the case of a +1 frameshift, the extra nucleotide is accommodated in the solvent-exposed minor groove. In addition, the structure of an unproductive Dpo4 ternary complex suggests that the flexible little finger domain facilitates DNA orientation and translocation during translesion synthesis.

Amino Acid Substitution↗
PubMed2004

Crystal structure of a benzo[a]pyrene diol epoxide adduct in a ternary complex with a DNA polymerase.

The first occupation-associated cancers to be recognized were the sooty warts (cancers of the scrotum) suffered by chimney sweeps in 18th century England. In the 19th century, high incidences of skin cancers were noted among fuel industry workers. By the early 20th century, malignant skin tumors were produced in laboratory animals by repeatedly painting them with coal tar. The culprit in coal tar that induces cancer was finally isolated in 1933 and determined to be benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon. A residue of fuel and tobacco combustion and frequently ingested by humans, BP is metabolized in mammals to benzo[a]pyrene diol epoxide (BPDE), which forms covalent DNA adducts and induces tumor growth. In the 70 yr since its isolation, BP has been the most studied carcinogen. Yet, there has been no crystal structure of a BPDE DNA adduct. We report here the crystal structure of a BPDE-adenine adduct base-paired with thymine at a template-primer junction and complexed with the lesion-bypass DNA polymerase Dpo4 and an incoming nucleotide. Two conformations of the BPDE, one intercalated between base pairs and another solvent-exposed in the major groove, are observed. The latter conformation, which can be stabilized by organic solvents that reduce the dielectric constant, seems more favorable for DNA replication by Dpo4. These structures also suggest a mechanism by which mutations are generated during replication of DNA containing BPDE adducts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2004

Thrombin activates envelope glycoproteins of HIV type 1 and enhances fusion.

To elucidate the roles of serine proteases, including thrombin, in HIV infection, we treated H9 cells infected with HIV-1 LAI virus (H9/IIIB) with four different proteases (thrombin, cathepsin G, trypsin and chymotrypsin) and observed their effects on functional epitopes on both gp120 and gp41 by using flow cytometry. Monoclonal antibodies (MAbs) against the V3 loop, V2 loop, CD4 binding site, coreceptor binding site and gp41 were used. It was found that trypsin decreased the binding of all MAbs except for one MAb against the V3 loop (IIIB-V3-21). Chymotrypsin and cathepsin G did not show any remarkable effect on the antigen expression. On the other hand, thrombin decreased the reactivities of two out of four anti-V3 MAbs and increased the exposure of functional gp120 epitopes including the coreceptor binding site and CD4 binding site. Thrombin also increased the expression of 2F5 antigen (a neutralizing epitope of gp41) but had no effect on other gp41 epitopes. The effect of trypsin or thrombin on HIV-induced cell fusion was examined through co-culturing H9/IIIB and MAGI cells. Trypsin slightly inhibited fusion. Fusion was significantly enhanced in a dose-dependent manner by thrombin, and a 280% increase at 5 U/ml (P < 0.001) was observed. In conclusion, thrombin, one of the major inflammatory molecules in blood, facilitates HIV-induced cell fusion, probably by activating gp120.

Antibodies, Monoclonal↗
PubMed2004

The N-terminal of the V3 loop in HIV type 1 gp120 is responsible for its conformation-dependent interaction with cell surface molecules.

The V3 loop of HIV-1 gp120 plays an important role in the interaction of the viral envelope with cellular coreceptors and/or with other cell surface molecules. To clarify this interaction we used a panel of monoclonal antibodies (MAbs) against V3 loop and synthetic looped V3 peptides V3-BH10, V3-ADA, and V3-89.6, derived from the V3 regions of the BH10 clone of IIIB (X4-tropic), ADA (R5-tropic), and 89.6 (R5X4-tropic), respectively. A linear mutant peptide, V3-BH10/CA, was also synthesized as a control. Biotinylated V3-BH10, -BH10/CA, and-ADA were also made. The binding abilities of the biotinylated and nonbiotinylated peptides to various types of cells were investigated by using flow cytometry. Subsequently, the principal region of the V3 loop involved in cell surface binding was analyzed by using MAbs against the tip (447-52D and 694-98D), N-termini (IIIB-V3-21) or C-termini (IIIB-V3-01) of the V3 loop in flow cytometry and enzyme-linked immunoabsorbent assay. We demonstrate that looped V3 peptides of both X4 and R5X4 HIV (V3-BH10 and V3-89.6) can bind to various types of cells irrespective of their CD4 and/or coreceptor expression in a conformation-dependent manner. In contrast, the V3 loop of R5 HIV (V3-ADA) can scarcely bind to the cells. Using MAbs whose epitopes cover the entire V3 loop we found that MAb IIIB-V3-21 can react with platebound but not cell-bound peptides, and the MAb blocked biotin-V3-BH10 binding suggesting that the N-terminal of the V3 loop interacts directly with cell surface molecule(s).

Amino Acid Sequence↗
PubMed2004

Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats.

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates immune/inflammatory cells, promotes extracellular matrix (ECM) accumulation, and is increased in fibrotic organs. Here we report the effects of administering a puromycin aminonucleoside nephropathy (PAN)-specific TGF-beta neutralizing antibody on glomerulosclerosis in vivo. METHODS: Adult male Sprague-Dawley rats underwent uninephrectomy (Nx) followed by intraperitoneal PAN at weeks 2, 6, 7 and 8. Rats were treated with either high (5 mg/kg body weight) (N= 9) or low (0.5 mg/kg body weight) (N= 7) dose TGF-beta antibody intraperitoneally three times weekly until sacrifice at week 10. A PAN untreated control group (N= 7) was dosed with an isotype specific, null antibody. The nephrectomy samples were studied as normal kidney control (NL) (N= 5). Rats undergoing left kidney Nx (N= 5) only were also included as age-matched control. Renal function and morphology were assessed, and molecular studies performed. RESULTS: Systolic blood pressure was increased in parallel over time in all groups (at 10 weeks, control 137 +/- 10 mm Hg; high 129 +/- 4 mm Hg; low 137 +/- 3 mm Hg) (P= NS). Both TGF-beta antibody treatments decreased renal cortex mRNA expressions similarly for TGF-beta1, TGF-beta2, and collagen III (TGF-beta1, control 0.36 +/- 0.02 mm Hg; high 0.19 +/- 0.01 mm Hg; low 0.19 +/- 0.02 mm Hg; P < 0.01 low and high vs. control; TGF-beta2, control 0.38 +/- 0.03 mm Hg; high 0.19 +/- 0.02 mm Hg; low 0.20 +/- 0.03 mm Hg; P < 0.01 low and high vs. control; and collagen III, control 0.33 +/- 0.01 mm Hg; high 0.14 +/- 0.01 mm Hg; low 0.19 +/- 0.01 mm Hg; P < 0.01 low and high vs. control; P < 0.05 low vs. high, data expressed as mRNA normalized density units vs. 18S RNA). However, only low dose TGF-beta antibody improved renal function and sclerosis measured by serum creatinine and creatinine clearance (serum creatinine, control 2.3 +/- 0.5 mg/dL; high 2.5 +/- 0.5 mg/dL; low 0.8 +/- 0.1 mg/dL; P < 0.05 low vs. control and high; creatinine clearance, control 0.44 +/- 0.11 mL/min; high 0.70 +/- 0.26 mL/min; low 1.34 +/- 0.30 mL/min; P < 0.05 low vs. control, P= NS vs. high). In parallel, sclerosis index (0 to 4+ scale) was improved in low dose (control 2.67 +/- 0.27; high 2.37 +/- 0.30; low 1.78 +/- 0.24; P < 0.05 low vs. control). This improved function and structure was linked to decreased glomerular infiltrating macrophages (0 to 4+ score, control 2.3 +/- 0.2; high 1.8 +/- 0.4; low 0.8 +/- 0.1; P < 0.01 low vs. control; P < 0.05 low vs. high; P= NS high vs. control). Further, plasminogen activator inhibitor-1 (PAI-1) mRNA expression in renal cortex was attenuated after low dose TGF-beta antibody treatment compared to control and high dose group (PAI-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio, NL 0.18 +/- 0.003; control 0.45 +/- 0.03; high 0.40 +/- 0.04; low 0.23 +/- 0.01; P < 0.05 low vs. control and high). Matrix metalloproteinase-9 (MMP-9) activity was maintained at higher levels in kidneys of the low dose TGF-beta antibody-treated group. CONCLUSION: These results show an in vivo dose-response with an agent that blocks the biologic activity of TGF-beta. Higher dose of TGF-beta antibody was without beneficial effect, suggesting that TGF-beta-mediated effects on PAI-1 and macrophage influx are bimodal and closely regulated. Given that both antibody doses reduced the expression of TGF-beta isoforms and collagen III production, but only low dose ameliorated histologic sclerosis, it appears that pharmacologic effects of anti-TGF-beta antibody on matrix synthesis and degradation are not equivalent.

Animals↗
PubMed2003

Replication of a cis-syn thymine dimer at atomic resolution.

Ultraviolet light damages DNA by catalysing covalent bond formation between adjacent pyrimidines, generating cis-syn cyclobutane pyrimidine dimers (CPDs) as the most common lesion. CPDs block DNA replication by high-fidelity DNA polymerases, but they can be efficiently bypassed by the Y-family DNA polymerase pol eta. Mutations in POLH encoding pol eta are implicated in nearly 20% of xeroderma pigmentosum, a human disease characterized by extreme sensitivity to sunlight and predisposition to skin cancer. Here we have determined two crystal structures of Dpo4, an archaeal pol eta homologue, complexed with CPD-containing DNA, where the 3' and 5' thymine of the CPD separately serves as a templating base. The 3' thymine of the CPD forms a Watson-Crick base pair with the incoming dideoxyATP, but the 5' thymine forms a Hoogsteen base pair with the dideoxyATP in syn conformation. Dpo4 retains a similar tertiary structure, but each unusual DNA structure is individually fitted into the active site for catalysis. A model of the pol eta-CPD complex built from the crystal structures of Saccharomyces cerevisiae apo-pol eta and the Dpo4-CPD complex suggests unique features that allow pol eta to efficiently bypass CPDs.

Amino Acid Sequence↗
PubMed2003

Therapeutic role of TGF-beta-neutralizing antibody in mouse cyclosporin A nephropathy: morphologic improvement associated with functional preservation.

TGF-beta is believed to play a central role in the development of Cyclosporin A (CsA)-induced nephropathy. This study investigated the effects of 1D11, a murine pan-specific TGF-beta-neutralizing monoclonal antibody, in an ICR mouse model of chronic CsA nephropathy. Mice were administered a low-salt diet (0.01% sodium) for 1 wk followed by CsA treatment (30 mg/kg, subcutaneously, daily) for 4 wk. 1D11 was administered (2.5 mg/kg, intraperitoneally, 3 times/wk) beginning immediately after the termination of CsA dosing and continued through 8 wk. CsA caused extensive renal histopathologic alterations, including tubular damage, interstitial infiltrates and fibrosis, deposition of collagen III, and apoptosis of tubular epithelial cells. 1D11 ameliorated the CsA-induced histopathologic alterations, with significant reduction in collagen III expression and deposition. Additionally, elevated levels of mRNA encoding TGF-beta1 and TGF-beta2 were significantly reduced. 1D11 also protected tubular epithelial cells from apoptosis by 48% (P < 0.05). In contrast, 13C4 (a control antibody) had no significant effect on any of the endpoints described above. Importantly, the effects of 1D11 on the CsA-induced morphologic alterations were followed by a reduction in serum creatinine level when compared with CsA mice treated with 13C4 (13C4, 0.45 +/- 0.09; 1D11, 0.30 +/- 0.08; P < 0.05) after 8 wk of treatment. Endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), nitrotyrosine, and tissue hypoxia were examined by immunostaining using specific antibodies. eNOS was significantly reduced in the endothelium of arterioles in the kidneys of mice treated with CsA, whereas iNOS was induced in the cortical tubules. Tissue hypoxia was found in both the arterioles and tubules, whereas nitrotyrosine was localized in the tubules. Administration of 1D11 improved tissue hypoxia and reduced nitrotyrosine formation. Moreover, the reciprocal changes in iNOS and eNOS expression were normalized by 1D11. This study demonstrates that 1D11 administration ameliorated morphologic alterations and preserved renal function in the context of existing chronic CsA nephropathy.

Animals↗