Tissue transglutaminase interacts with protein kinase A anchor protein 13 in prostate cancer

We have previously described that tissue transglutaminase (tTG) is a high level phenotypic biomarker in prostate cancer, which is down regulated in prostate cancer and surrounding premalignant field compared to benign prostate glands. To understand the function of tTG in prostate cancer, we sought to identify proteins that interact with the transglutaminase moiety of tTG using a human prostate cancer complementary deoxyribonucleic acid library in a Yeast 2-Hybrid system. The Yeast 2-Hybrid experiments identified a strong and novel interaction between the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13), which was quantified by β-galactosidase assay, confirmed in vitro by immunoprecipitation experiments using PC3 prostate cancer cell lysates, and in vivo colocalization was confirmed by immunofluorescence studies in PC3 cells. Because AKAP plays a major role in protein kinase A and Rho protein mediated signaling, functional studies are underway to elucidate the significance of tTG-AKAP13 interaction in prostate cancer.     

Intracerebral penetration and tissue distribution of 2,5-diaziridinyl 3,6-bis(carboethoxyamino) 1,4-benzoquinone (AZQ,NSC-182986)

[¹⁴C]AZQ (2–4 mg/m², 100–200 mCi) was administered at varying times to five patients undergoing surgical resection of intracerebral tumors. Plasma, cerebrospinal fluid (CSF), edematous brain, and tumor specimens were obtained during surgery and the concentration of AZQ was determined radiochemically and chromatographically. Total [¹⁴C]AZQ equivalent concentration in tumor for two patients was determined to be 47.5% and 85% of concurrent plasma concentration which was similar to that found in normal brain (60.4% and 75.5% respectively). Only 18–45% of the total radioactivity in tumor tissue and 30–56% in plasma were accounted for by unchanged AZQ. These findings suggest that AZQ may be metabolized to a certain extent. Tissue samples from various organs were obtained during autopsy in a patient who expired ten days after AZQ administration. The highest AZQ concentration was found in the liver, followed by the kidney. Comparable amounts were found in normal brain and brain tumor (22 ng/ g vs. 31 ng/ g respectively). These results indicate that AZQ penetrates readily into the normal brain and brain tumor with a tendency to persist.     

Tracheal agenesis: diagnosis and management

Tracheal agenesis (TA) is a rare congenital anomaly that typically has fatal consequences. Its rarity, lack of prenatal symptoms, and emergent presentation usually lead to a failure to arrive at the correct diagnosis and manage the airway properly before the onset of irreversible cerebral anoxia. We report the case history of an infant born with immediate respiratory failure who was diagnosed with tracheal agenesis. The clinical features, embryology, classification schemes and surgical management are discussed with the hope that increased awareness and earlier diagnosis may lead to better chances of survival for affected individuals.     

Age-related mitochondrial DNA mutations in the human larynx

OBJECTIVE: To determine whether age-related mitochondrial DNA mutations occur in the human larynx. STUDY DESIGN: Genetic study of cadaveric larynx specimens. METHODS: Vocal fold mucosa, thyroarytenoid muscle, and cricoarytenoidjoint tissue were harvested from 13 fresh postmortem larynges (age range, 2 d-82 y). DNA was extracted from each sample, and the polymerase chain reaction (PCR) was used to amplify a target DNA sequence resulting from the common age-associated, 4977-base-pair (bp) mitochondrial DNA deletion. PCR products were visualized by agarose gel electrophoresis. Automated sequencing determined the sequence of identified PCR products. SUBJECTS: Thirteen cadaveric larynges were obtained through the University of Kentucky Medical Center (Lexington, KY). Specimens from patients with a history of head and neck cancer, previous laryngeal trauma, or surgery were excluded. RESULTS: Strongly positive bands were identified in samples from three individuals. Weaker bands were seen in samples from four other samples. No band was noted from the two pediatric larynges. Different band patterns were seen among the three different tissue sites in the larynges with positive PCR products, but no consistent pattern was seen. Sequencing of the identified PCR products from selected samples confirmed that they were products of the age-associated, 4977-bp mitochondrial DNA deletion. CONCLUSIONS: An age-associated mitochondrial DNA deletion was detected in several post-mortem human larynges. Its presence seemed to increase in appearance with age. In the larynges in which the deletion occurred, there were individual regional differences in the occurrence of the deletion, but no consistent pattern was noted across all individuals who carried the deletion.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.     

Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets

AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life-long treatment is indicated. PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature--were given testosterone pellets (8-10 mg/kg) every six months for 18 months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys.