Unilateral testicular metastasis of low PSA level prostatic adenocarcinoma.

A 71-year-old man presented with a firm left testicle 15 years after being diagnosed with prostatic adenocarcinoma. After the initial diagnosis, the patient underwent a radical prostatectomy. He received radiation therapy 5 years after surgery for a slightly elevated prostate-specific antigen (PSA) level and a negative metastatic workup. Eight years later, the patient's PSA rose to 3.38 ng/mL and he was started on intermittent Lupron therapy. It was then 3 years later when the patient discovered the testicular mass. At that time, his PSA level was 2.98 ng/mL. He underwent a left orchiectomy which demonstrated metastatic prostatic adenocarcinoma. Currently, the patient is doing well 3 months postorchiectomy and is now receiving continuous testosterone suppression therapy. This case report discusses the unique modes of spread from the prostate to the testicle as well as the importance of follow-up care in patients with prostate cancer, especially in the setting of low PSA levels.

Endosalpingiosis in conjunction with ovarian serous cystadenoma mimicking metastatic ovarian malignancy.

PATIENT: Female, 26. FINAL DIAGNOSIS: Endosalpingiosis. SYMPTOMS: Chronic pelvic pain. MEDICATION: -. CLINICAL PROCEDURE: Diagnostic laproscopy (conservative management). SPECIALTY: Obstetrics and Gynecology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Interesting and unusual case of endosalpingiosis mimicking ovarian malignancy presentation. CASE REPORT: A 26-year-old G0P0 white female presented to our office with chronic pelvic pain. On vaginal examination, a nontender mass in left the adnexal region was palpable. Transvaginal ultrasound showed a left ovarian cyst. Laparoscopy was performed, which revealed diffuse bilateral ovarian excrescences with unusual multiple studdings throughout the peritoneum and abdominal cavity. Due to a suspicion of malignancy, a biopsy specimen was obtained for frozen sectioning. The specimen proved to be consistent with benign papillary serous cystadenofibroma. Gross appearance was still suspicious for malignancy and therefore left paraovarian cystectomy was performed. Additional specimens showed ovarian adenofibroma and endosalpingiosis. The patient's complaint of pelvic pain improved after laparoscopy. Due to diffuse presentation of endosalpingiosis in the peritoneum, serial CT scan of abdomen and pelvis at 6-month intervals was recommended. CONCLUSIONS: To our knowledge, this is an unusual case of a young, nulliparous female presenting with diffuse-presentation endosalpingiosis in the abdomen and peritoneum, which on gross examination was suspicious for malignancy. By following a conservative approach and performing serial CT scans, the patient will be clinically monitored.

Impact of mutations in the coreceptor binding site on human immunodeficiency virus type 1 fusion, infection, and entry inhibitor sensitivity.

An increasingly large number of antiviral agents that prevent entry of human immunodeficiency virus (HIV) into cells are in preclinical and clinical development. The envelope (Env) protein of HIV is the major viral determinant that affects sensitivity to these compounds. To understand how changes in Env can impact entry inhibitor sensitivity, we introduced six mutations into the conserved coreceptor binding site of the R5 HIV-1 strain YU-2 and measured the effect of these changes on CD4 and coreceptor binding, membrane fusion levels and rates, virus infection, and sensitivity to the fusion inhibitors enfuvirtide (T-20) and T-1249, the CCR5 inhibitor TAK-779, and an antibody to CD4. The mutations had little effect on CD4 binding but reduced CCR5 binding to various extents. In general, reductions in coreceptor binding efficiency resulted in slower fusion kinetics and increased sensitivity to TAK-779 and enfuvirtide. In addition, low CCR5 binding usually reduced overall fusion and infection levels. However, one mutation adjacent to the bridging sheet beta21 strand, P438A, had little effect on fusion activity, fusion rate, infectivity, or sensitivity to enfuvirtide or T-1249 despite causing a marked reduction in CCR5 binding and a significant increase in TAK-779 sensitivity. Thus, our findings indicate that changes in the coreceptor binding site of Env can modulate its fusion activity, infectivity, and entry inhibitor sensitivity by multiple mechanisms and suggest that reductions in coreceptor binding do not always result in prolonged fusion kinetics and increased sensitivity to enfuvirtide.

Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells.

Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the proapoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier. Low-passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control, under similar conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol. Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase release, compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha production, compared with cells treated with ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.

Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics.

HIV entry inhibitors include coreceptor antagonists and the fusion inhibitor T-20. T-20 binds the first helical region (HR1) in the gp41 subunit of the viral envelope (Env) protein and prevents conformational changes required for membrane fusion. HR1 appears to become accessible to T-20 after Env binds CD4, whereas coreceptor binding is thought to induce the final conformational changes that lead to membrane fusion. Thus, T-20 binds to a structural intermediate of the fusion process. Primary viruses exhibit considerable variability in T-20 sensitivity, and determinants outside of HR1 can affect sensitivity by unknown mechanisms. We studied chimeric Env proteins containing different V3 loop sequences and found that gp120coreceptor affinity correlated with T-20 and coreceptor antagonist sensitivity, with greater affinity resulting in increased resistance to both classes of entry inhibitors. Enhanced affinity resulted in more rapid fusion kinetics, reducing the time during which Env is sensitive to T-20. Reduced coreceptor expression levels also delayed fusion kinetics and enhanced virus sensitivity to T-20, whereas increased coreceptor levels had the opposite effect. A single amino acid change (K421D) in the bridging sheet region of the primary virus strain YU2 reduced affinity for CCR5 and increased T-20 sensitivity by about 30-fold. Thus, mutations in Env that affect receptor engagement and membrane fusion rates can alter entry inhibitor sensitivity. Because coreceptor expression levels are typically limiting in vivo, individuals who express lower coreceptor levels may respond more favorably to entry inhibitors such as T-20, whose effectiveness we show depends in part on fusion kinetics.