Pathologic progression of autochthonous prostate cancer in the TRAMP model.

The ability to manipulate gene expression in specific cell types at specific times utilizing transgenic technology has allowed the development of novel mouse model systems that can mimic human disease. We have previously established the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model for prostate cancer using the rat probasin promoter to direct expression of the SV40 early genes to prostate epithelium. Male TRAMP mice exhibit consistent prostate-specific patterns of expression and develop prostatic intraepithelial neoplasia that will become invasive and metastasize primarily to the lymph nodes and lungs.

Prostate cancer gene therapy.

Numerous gene therapy trials in the United States and throughout the world using various strategies are in progress for the treatment of locally advanced and metastatic prostate cancer. Although vector technology advances at a rapid pace, progress in elucidating the molecular pathways critical for the development and progression of prostate cancer has been slower and more deliberate. Thus far, prostate gene therapy appears to be safe and well tolerated.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation.

Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long-term HBIG/3TC has been shown to prevent short-term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short-term HBIG, long-term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups.

Effects of dynorphin on rat entopeduncular nucleus neurons in vitro.

The entopeduncular nucleus (EP) receives dense neostriatal afferent axons that contain dynorphin (DYN, an endogenous kappa-receptor agonist), in addition to GABA and substance P. To examine the role of DYN in the EP, whole-cell recordings were performed in rat brain slice preparations. Based on the physiological and morphological characteristics, all the neurons recorded were similar to the Type-I EP neuron described in a previous study.

Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience.

Purpose: To review the safety and efficacy of thymoglobulin in pancreas transplant patients receiving tacrolimus and mycophenolate mofetil.

Methods: Retrospective, single centre analysis of 45 patients transplanted between 1995 and 2000 who received 54 courses of thymoglobulin, including 36 courses in 29 solitary pancreas transplant recipients (16 pancreas alone, 13 pancreas after kidney transplants) and 18 courses in 16 simultaneous kidney-pancreas transplant patients. Thirty-two patients (71%) were primary pancreas transplants, 10 (22%) were second transplants and three (7%) were third transplants.

Utility of the case-method approach for the integration of clinical and basic science in surgical education.

Background: Although students develop experience in integrating clinical and basic scientific knowledge, it may be difficult for them to do so in patient management. Formalized instructions using case discussions that involve the integration of basic science concepts may facilitate their incorporation into practice.

Methods: Third-year surgical clerkship students were pretested for baseline knowledge of information relevant to the case being discussed.

Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina.

Purpose: To measure the concentrations of polyamines, determine their cellular and subcellular localization, and analyze effects of their depletion in developing rabbit retina.

Methods: Isolated retinas at different developmental stages were analyzed for polyamine content by high-performance liquid chromatography (HPLC). An antibody against polyamines was used to localize endogenous stores in both freshly harvested retinas and neonatal retinal explants.

Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor.

While nonsteroidal androgen receptor (AR) antagonists have been known for many years, and used in the clinic for the treatment of hormone dependent prostate cancer, very little is known about nonsteroidal AR agonists. We designed and synthesized a series of chiral bicalutamide analogs, which bear electron-withdrawing groups (either a cyano or a nitro group at the 4-position and a trifluoromethyl group at the 3-position) in the aromatic A ring, and different substituents at the para position in the aromatic B ring of the parent molecule. We also synthesized a series of racemic bicalutamide analogs, which have a trifluoromethyl group instead of a methyl group at the R(2) position.

Rhodococcus equi pulmonary infection in a pancreas-alone transplant recipient: consequence of intense immunosuppression.

We report the case of a pancreas-alone transplant recipient who developed Rhodococcus equi pneumonia after receiving multiple courses of antilymphocyte therapy for the treatment of recurrent acute pancreas allograft rejection. We also review and discuss the diagnosis, clinical course, and treatment of 18 cases of R. equi infection reported in solid organ transplant recipients.

Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice.

The cellular localization and development of neuronal intranuclear inclusions (NIIs) in cortex and striatum of R6/2 HD transgenic mice were studied to ascertain the relationship of NIIs to symptom formation in these mice and gain clues regarding the possible relationship of NII formation to neuropathology in Huntington's disease (HD). All NIIs observed in R6/2 mice were ubiquitinated, and no evidence was observed for a contribution to them from wild-type huntingtin; they were first observed in cortex and striatum at 3.5 weeks of age.

Extensive stage small cell lung cancer.

Small cell lung cancer is a rapidly proliferating, biologically aggressive form of lung cancer that has a short survival without treatment. Chemotherapy is the foundation of the therapeutic approach to patients with small cell lung cancer. Most patients present with extensive disease, and, although few patients are cured, significant improvement in survival is possible with modern chemotherapy.

Expression of PH-20 in normal and neoplastic breast tissue.

Background: Tumor metastasis involves a sequence of interrelated steps, of which penetration beyond the basement membrane is an essential component. Hyaluronic acid (HA) is a major structural component of the complex proteoglycans found in extracellular matrices and basement membranes. Hyaluronidase (PH-20) degrades HA, resulting in the disruption of basement membrane integrity and possible tumor dissemination.

Functional circuitry of the avian basal ganglia: implications for basal ganglia organization in stem amniotes.

Histochemical, pathway tracing, and neuropeptide/neurotransmitter localization studies in birds, reptiles and mammals during the 1970s and 80s clearly showed that the telencephalon in all amniotes consists of a prominent ventrally situated subpallial region termed the basal ganglia, and a large overlying region involved in higher order information processing termed the pallium or cortex. These studies also showed that the basal ganglia in all extant amniote groups possessed neurochemically and hodologically distinct striatal and pallidal territories. More recently, studies of the localization of genes controlling regional brain development have confirmed the homology of the basal ganglia among amniotes.

Initial clinical experience with interleukin-2 receptor antagonist induction in combination with tacrolimus, mycophenolate mofetil and steroids in simultaneous kidney-pancreas transplantation.

Since 1996, our standard immunosuppressive protocol for simultaneous kidney-pancreas transplantation (SKPT) has been tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids without antibody induction. When basiliximab and daclizumab, monoclonal antibodies directed against the interleukin-2 receptor (IL-2R), became available, we selectively added these agents to our standard protocol. The purpose of this prospective, open-label study was to evaluate the safety and efficacy of IL-2 receptor antagonists in SKPT.

Magnetic resonance imaging of the paranasal sinuses: incidental abnormalities and their relationship to patient symptoms.

Objectives: Magnetic resonance imaging (MRI) is able to demonstrate a wide range of abnormalities in the paranasal sinuses, which are often reported as incidental findings on scans performed for indications other than the evaluation of paranasal sinus pathology. However, the clinical significance of these findings remains undefined. We present a prospective study that determines the prevalence of abnormalities in the paranasal sinuses in a population undergoing MRI scans for suspected intracranial disease.

Mechanisms by which AC leakage currents cause complete hemodynamic collapse without inducing fibrillation.

Introduction: The first study of weak alternating current (AC) stimulation in closed chest humans showed that complete hemodynamic collapse can occur below the threshold for inducing ventricular fibrillation (VF), a heretofore unknown danger to patients. This article, and the accompanying simulation article, explore the mechanisms responsible for the collapse.

Methods And Results: A quadripolar pacing catheter was placed in the right ventricle (RV) of six dogs.

Death, hospitalization, and economic associations among incident hemodialysis patients with hematocrit values of 36 to 39%.

Anemia treatment with epoetin has led to dramatic increases in hematocrit levels since 1989. Studies have demonstrated that morbidity and mortality rates are lower when hematocrit values are within the Disease Outcomes Quality Initiative (DOQI) target range (33 to 36%). Recently, clinical studies demonstrated that patients without cardiovascular disease exhibited lower morbidity rates and improved cognitive function with hematocrit values of >36%.

Renal allograft outcomes in African American versus Caucasian transplant recipients in the tacrolimus era.

Methods: Between January 1995 and December 1999, 185 kidney transplants were performed with tacrolimus (TAC)-based immunosuppression including 120 African American (AA, 65%) and 65 Caucasian recipients (C, 35%). Mean follow-up was 34 months. The AA group was characterized by a higher incidence of renal disease due to hypertension (72% AA vs 37% C, P <.

Neostriatal and globus pallidus stimulation induced inhibitory postsynaptic potentials in entopeduncular neurons in rat brain slice preparations.

Recent anatomical studies revealed that the entopeduncular nucleus of the rat receives GABAergic inputs from both the neostriatum and the globus pallidus. The present study was undertaken to reveal the physiological features of these inputs using the intracellular recording method in rat brain slice preparations. Most of the entopeduncular nucleus neurons generated repetitive firing without spike accommodation with intracellular current stimulation and thus were classified as Type-I.

Portal-enteric pancreas transplantation at the University of Tennessee, Memphis.

The UT Memphis group has made a number of important contributions to the field of PTX, including: 1) pioneering studies on the effects of PTX on autonomic neuropathy, 2) comprehensive reports dealing with quality of life after PTX, 3) seminal studies on the metabolic effects of PTX with portal venous delivery of insulin, 4) refining and perfecting a novel technique of PTX with portal venous drainage of insulin and primary enteric drainage of the exocrine secretions, 5) describing a safe outpatient percutaneous technique of pancreas allograft biopsy, 6) developing the use of glucose tolerance for rejection surveillance, and 7) managing PTX patients with biopsy-directed immunosuppression and no anti-lymphocyte induction therapy. The P-E technique has the potential to become the standard of care in the near future because it is more physiologic, normalizes carbohydrate and lipid metabolism, and minimizes complications attributed to the transplant procedure. In addition, we have been actively involved in studying new immunosuppressive regimens in order to improve and simplify the care of the PTX recipient.

Number, origins, and chemical types of rat pallidostriatal projection neurons.

The dorsal globus pallidus (GP) receives major inputs from the dorsal neostriatum (Str), the subthalamic nucleus (STN) and the dorsal thalamus. The GP projects to multiple basal ganglia nuclei. One of the GP projection sites is the Str.

Familial adenomatous polyposis: a case report and review of the literature.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition characterized by diffuse intestinal polyposis, specific gene mutation, and predisposition for developing colon cancer. Left untreated, patients with FAP will develop colorectal carcinoma during early adulthood. Hence, early detection and surgical intervention are of the utmost importance.

Long-term outcomes in simultaneous kidney-pancreas transplant recipients with portal-enteric versus systemic-bladder drainage.

We retrospectively reviewed long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients with portal-enteric (P-E) versus systemic-bladder (S-B) drainage. Forty-five patients were alive with functioning grafts 1 year after SKPT and were followed up for a minimum of 3 years (mean, 5.9 years), including 26 patients with P-E drainage and 19 patients with S-B drainage.