Focal testicular infarction from laparoscopic inguinal hernia repair.

A 53-year-old Caucasian male underwent laparoscopic total extraperitoneal repair of a right indirect inguinal hernia. Postoperatively, the patient developed right testicular swelling and pain that increased over the course of a week. On examination, the patient was found to have a tender, swollen, high-riding testicle, and testicular torsion was of main concern. Doppler sonography and testicular scan suggested an infarction only to the upper pole of the right testicle. Subsequent exploration of the right testicle revealed a hydrocele and focal ischemia to the upper pole of the right testicle. Intraoperative Doppler study and a urology consultation were obtained with an initial impression of possible intermittent torsion. This report describes a rare complication seen in laparoscopic inguinal hernia repairs.     

Blood Transfusion and Immunomodulation: A Possible Mechanism

To induce an immunogenic response in vivo, an antigen-presenting (stimulator) cell must present both antigen-specific (class II MHC) and an accessory signal to the CD4 T cell. Failure to express the accessory signal has been shown in vitro to induce a state of specific unresponsiveness (anergy) in the T cell. We have shown that although stimulator cells in blood continue to express class II MHC molecules during refrigerated storage, their ability to present the accessory signal diminishes, reaching zero in all units tested by about 13 days. This implies that blood in excess of 2 weeks old should not alloimmunize but could induce some degree of immunosuppression. UV-B irradiation and, to a lesser extent, gamma-irradiation, were also shown to inhibit expression of the accessory signal by stimulator cells in blood.     

Induction of primary mixed leukocyte reactions with ultraviolet B or chemically modified stimulator cells

Treatment of stimulator cells with 0.1% paraformaldehyde for 60 sec or ultraviolet-B (UV-B) irradiation (1000 J/m2) eliminates their ability to elicit T cell proliferation in a primary mixed leukocyte reaction. However, a T cell response equal to 20-40% of control value could be elicited by paraformaldehyde fixed or UV-B irradiated cells providing the latter are incubated at 37 degrees C for 18 hr prior to treatment. The incubation also induces a one-log increase in the density of fluorescence when the cells are stained with monoclonal antibodies against class II molecules DR and DP as well as the intercellular adhesion molecule -1 (ICAM-1). We interpret this as an increase in the membrane expression of these structures following incubation. Chloroquine and cerulenin, known to inhibit protein degradation and antigen processing and presentation do not influence the upregulation in membrane expression of these class II and adhesion molecules, but do prevent incubation from overriding the effect of paraformaldehyde treatment. Colchicine, which reduces the traffic through tubular lysosomes, also has no effect on the upregulation but enhances allopresentation. We propose that incubation of stimulator cells in the presence of chloroquine and cerulenin results in the membrane expression of class II molecules without associated peptides. The inability of stimulator cells expressing such "nude" MHC molecules to elicit T cell proliferation after chemical modification could be due to easier crosslinking of the allodeterminants by paraformaldehyde when the binding site is empty but could also mean that nude MHC molecules are not per se immunogenic and become so only after acquisition of a peptide. It is also possible that chloroquine, NH4Cl, and cerulenin block the expression of signals other than the class II and cell adhesion molecules that are essential for induction of T cell proliferation.     

Immune responses against PSMA after gene-based vaccination for immunotherapy-A: results from immunizations in animals

Two plasmid DNA vaccines, encoding either products that are retained in the cytosol and degraded in the proteasome (tVacs; hPSMAt), or secreted proteins (sVacs; hPSMAs) were evaluated for stimulation of cytotoxic cell or antibody responses. Immunization with both vectors led to generation of cell cytotoxicity providing granulocyte-macrophage colony-stimulating factor was administered with the vaccine. Spleen cells from animals immunized with hPSMAt demonstrated stronger cytotoxicity to the target cells. Priming with a vector that encoded a xenogeneic protein (hPSMAt; 'xenogeneic' construct) and boosting with a vector that encoded an autologous protein (rPSMAt; 'autologous' construct) gave the best protection against tumor challenge. Immunization with tVacs did not lead to formation of antibodies to the target protein as detected by Western blot or ELISA, while immunization with sVacs or with the protein did. Antibodies were of mixed Th1-Th2 isotype. Priming with tVacs and boosting with protein also resulted in antibody formation, but in this case the antibodies were from the cytotoxic, Th1 isotype. The best strategy to obtain a strong cellular cytotoxic response, therefore, seems to be gene-based vaccinations with tVacs, priming with the 'xenogeneic' and boosting with the 'autologous' constructs. When cytotoxic antibody production is the goal, priming should be performed with the tVacs while boosting with the protein.     

Depletion of CD25+ cells from human T-cell enriched fraction eliminates immunodominance during priming with dendritic cells genetically modified to express a secreted protein

The ability of dendritic cells (DCs), genetically modified with one of two types of plasmid DNA vaccines to stimulate lymphocytes from normal human donors and to generate antigen-specific responses, is compared. The first type, also called "secreted" vaccine (sVac), encodes for the full length of the human prostate-specific antigen (PSA) with a signal peptide sequence so that the expressed product is glycosylated and directed to the secretory pathway. The second type, truncated vaccines (tVacs), encodes for either hPSA or human prostate acidic phosphatase (hPAP), both of which lack signal peptide sequences and are retained in the cytosol and degraded by the proteasomes following expression. Monocyte-derived dendritic cells are transiently transfected with either sVac or one of two tVacs. The DCs are then used to activate CD25+-depleted or nondepleted autologous lymphocytes in an in vitro model of DNA vaccination. Lymphocytes are boosted following priming with transfected DCs, peptide-pulsed DCs or monocytes. Their reactivity is tested against tumor cells or peptide-pulsed T2 target cells. Both tVacDCs and sVacDCs generate antigen-specific cytotoxic T-cell responses. The immune response is restricted towards one of the three antigen-derived epitopes when priming and boosting is performed with sVacDCs. In contrast, tVac-transfected DCs prime T cells towards all antigen-derived epitopes. Subsequent repeated boosting with transfected DCs, however, restricts the immune response to a single epitope due to immunodominance. While CD25+ cell depletion prior to priming with sVacDCs alleviates immunodominance, cotransfection of dendritic cells with GITR-L does so in some but not all cases.     

Fundamental Role of microRNAs in Androgen‐Dependent Male Reproductive Biology and Prostate Cancerogenesis

Male reproductive failure has been linked to successive development of various urologic diseases including prostate cancer. There is strong epidemiologic data in support of this association, it is important therefore to identify the fundamental grounds that lay beneath such a connection. Male reproductive biology, as sex determined, is significantly dependent upon the hormonal regulation of androgens. With the advancement of knowledge on androgen receptivity and epigenetic regulation, the role of new regulatory factors such as microRNAs becomes essential. This review focuses on unraveling the role of microRNA tight incorporation in androgen‐dependent male reproductive biology in the context of recent prostate cancer data.     

Fas and Fas Ligand Expression on Human Peripheral Blood Leukocytes

Objectives : Study of Fas and Fas ligand(Fas-L) expression, as well as sFas–L release, by fresh human peripheral blood leukocytes. Methods : Flow cytometry, cytotoxicity, immunofluorescence staining of fresh smears, Western blotting, Results : Granulocytes and monocytes express a low level of Fas receptor, but no Fas–L. These cells, as well as NK cells, contain presynthesized depots of Fas–L which they express following activation by brief storage (60 min) at room temperature or during separation from whole blood. Such activation also leads to Fas receptor upregulation. NK cells do not express Fas receptor. Once expressed on blood leukocytes, fully functional Fas–L can be released from the membrane and can be detected in plasma–free cell supernatants. Conclusion : Human peripheral blood granulocytes, monocytes and NK cells contain intracellular presynthesized Fas–L which they readily express following blood anticoagulation, blood storage or cell separation. Soluble Fas–L is released from those cells and can be detected in protein–free supernatants by immunoblotting.     

Costimulatory signals necessary for induction of T cell proliferation

Two separate signals are required for induction of T cell proliferation. In an attempt to identify them we used polyclonal T cell activation with Con A, which requires costimulation with autologous accessory cells. The costimulatory activity is not constitutively expressed on accessory cells since such cells fixed immediately after separation from whole blood are unable to provide the necessary signal(s), although such activity is readily expressed after activation by incubation and such cells subsequently fixed will support Con A-induced T cell proliferation. Addition of recombinant IL-1 plus IL-6 to T cell cultures in the absence of accessory cells does not result in T cell proliferation but addition of these factors to cultures containing fixed activated accessory cells results in further increase in proliferation. The expression of the costimulatory activity during incubation is inhibited in the presence of cycloheximide or tunicamycin. The costimulatory activity of fixed activated cells is partially inhibited by antibody against ICAM-1. This inhibition is not reversed by the addition of recombinant IL-1 and IL-6. When accessory cells are preactivated in the presence of chloroquine, they are unable to provide costimulation to T cells but addition of recombinant IL-1 and IL-6 restores their ability to support T cell proliferation. Accessory cells preactivated in the presence of colchicine show an increased ability to provide costimulation to T cells in culture.     

Ruptured mycotic aneurysm presenting initially with bacterial meningitis

Infections of the major vessels can result in the formation of mycotic aneurysms, which can ultimately rupture and can be associated with a high mortality rate. Mycotic aneurysms can pose a diagnostic dilemma for the clinicians and successful treatment of this condition often requires a very high index of suspicion. We report an unusual case of a 65-year-old black female who initially presented with bacterial meningitis due to Streptococcus pneumoniae and 1 week later died from a ruptured undetected mycotic aneurysm. A similar case, in which a mycotic aneurysm initially presented with bacterial meningitis, could not be found in the literature.     

Metastatic spread to a percutaneous gastrostomy site from head and neck cancer: case report and literature review.

BACKGROUND: The placement of percutaneous endoscopic gastrostomy tubes is a common procedure in patients with head and neck cancer who require adequate nutrition because of the inability to swallow before or after surgery and adjuvant therapies. A potential complication of percutaneous endoscopic gastrostomy tubes is the metastatic spread from the original head and neck tumor to the gastrostomy site. METHODS: This is a case of a 59-year-old male with a (T4N2M0) Stage IV squamous cell carcinoma of the oropharynx who underwent percutaneous endoscopic gastrostomy tube placement at the time of his surgery and shortly thereafter developed metastatic spread to the gastrostomy site. A review of the published literature regarding the subject will be made. RESULTS: Twenty-nine cases of percutaneous endoscopic gastrostomy site metastasis occurring in patients with head and neck cancer have been previously reported in the literature. The pull-through method of gastrostomy tube placement had been used in our patient as well as in the majority of the other cases reviewed in the literature. CONCLUSION: The metastatic spread of head and neck cancer to the percutaneous endoscopic gastrostomy site is a very rare occurrence. The direct implantation of tumor through instrumentation is the most likely explanation for metastasis; however, hematogenous seeding is also a possibility. To prevent this rare complication, other techniques of tube insertion need to be considered.