Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by progressive renal atrophy, renal interstitial fibrosis, an increase in renal transforming growth factor-beta (TGF-beta), and renal tubular apoptosis. The present study was undertaken to determine the effect of a monoclonal antibody to TGF-beta (1D11) in UUO. METHODS: Mechanical stretch was applied to tubular epithelial cells (NRK-52E) by a computer-assisted system. Three doses of 1D11 (either 0.5, 2, or 4 mg/rat) were administered to rats one day prior to UUO and every two days thereafter, and kidneys were harvested at day 13. Fibrosis was assessed by measuring tissue hydroxyproline and mRNA for collagen and fibronectin. Apoptosis was assessed with the terminal deoxy transferase uridine triphosphate nick end-labeling assay. TGF-beta levels were determined by bioassay. Western blot and immunostaining were used to identify proliferating cell nuclear antigen (PCNA), p53, bcl-2, and inducible nitric oxide synthase (iNOS). RESULTS: Stretch significantly induced apoptosis in NRK-52E cells, which was accompanied by an increased release of TGF-beta; 1D11 (10 microg/mL) totally inhibited stretch-induced apoptosis. Control obstructed kidney contained 20-fold higher TGF-beta as compared with its unobstructed kidney; 1D11 neutralized tissue TGF-beta of the obstructed kidney. Control obstructed kidney exhibited significantly more fibrosis and tubular apoptosis than its unobstructed counterpart, which was blunted by 1D11. In contrast, 1D11 significantly increased tubular proliferation. p53 immunostaining was localized to renal tubular nuclei of control obstructed kidney and was diminished by 1D11. In contrast, bcl-2 was up-regulated in the 1D11-treated obstructed kidney. Total NOS activity and iNOS activity of the obstructed kidney were increased by 1D11 treatment. CONCLUSION: The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.

Changing testicular histology in AIDS: its implication for sexual transmission of HIV.

OBJECTIVES: The understanding of testicular histology in acquired immunodeficiency syndrome (AIDS) is essential, because the sexual route is one of the main means of transmission of the human immunodeficiency virus, which is localized primarily in the germ cells of the testes. It is important to determine whether any changes have occurred in the testicular histologic patterns in the course of the AIDS epidemic. METHODS: One hundred forty testicular specimens were available from AIDS autopsies during the AIDS epidemic (1981 to 1998). The epidemic was divided into pre-zidovudine (pre-AZT) therapy (1981 to 1987) and antiviral therapy (1988 to 1998) periods; the latter period was further subdivided on the basis of the particular treatment used. Testicular histology was evaluated and correlated with patient age, CD4 T-cell counts, and pathologic findings in other parts of the body. RESULTS: Testicular histologic findings were categorized into three groups: hypospermatogenesis (group S), spermatogenic arrest (group A), and Sertoli cell only (group O). The percentage of AIDS patients with group S histologic findings remained constant throughout the study period: 26% in the pre-AZT and 28% in the antiviral therapy periods. However, there was a reversal in the percentages of patients in groups A and O: group A decreased from 48% (pre-AZT) to 28% (antiviral) and group O increased from 26% (pre-AZT) to 44% (antiviral). There was no correlation between testicular histologic results and patient age or CD4 count. Opportunistic infections and testicular neoplasms were also identified. CONCLUSIONS: This study demonstrates that current therapy and prolongation of survival in AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. However, 28% of patients still show significant spermatogenesis at the time of death from AIDS and this subgroup cannot be identified by age or CD4 T-cell counts. The presence of large numbers of residual germ cells in these patients suggests that they may continue to be infectious throughout their disease course.

Cardiac hemangioma. A case report and discussion.

A cardiac hemangioma is a rare form of primary cardiac tumor. To our knowledge, only 34 cases of cardiac hemangioma have been discussed in the literature at the time of this writing. We report the case of a patient who presented with 1 episode of exertional dyspnea. The medical history, physical exam, work-up, surgical approach, and outcome are discussed. Other published reports on this topic are also reviewed.

A review of revision functional endoscopic sinus surgery.

For some patients, traditional or functional endoscopic sinus surgery (FESS) fails to relieve persistent or recurrent sinus disease. This subset of patients may require revision surgery. The objective of this study was to define and evaluate which features of sinus disease and prior treatment were characteristic of patients requiring revision FESS. Within a series of 295 consecutive FESS procedures, 43 patients who had prior sinus surgery and required revision FESS were studied and followed for a mean 14.1-month period. The characteristics of 13 patients with persistent disease following revision FESS and the potential technical risks and complications encountered were also evaluated. This study concludes that revision FESS is a safe technique that was effective in 69.8% of the patients, and that certain factors may predict a poor surgical outcome.