Localization of soluble guanylyl cyclase in the superficial dorsal horn

Nitric oxide (NO) has been implicated in pain processing at the spinal level, but the mechanisms mediating its effects remain unclear. In the present work, we studied the organization of the major downstream effector of NO, soluble guanylyl cyclase (sGC), in the superficial dorsal horn of rat. Almost all neurokinin 1 (NK1) receptor-positive neurons in lamina I (a major source of ascending projections) were strongly immunopositive for sGC. Many local circuit neurons in laminae I-II also stained for sGC, but less intensely. Numerous fibers, presumably of unmyelinated primary afferent (C fiber) origin, stained for calcitonin gene-related peptide or isolectin B4, but none of these was immunopositive for sGC. These data, along with immunoelectron microscopy results, imply that unmyelinated primary afferent fibers terminating in the superficial dorsal horn lack sGC. Double labeling showed that neuronal nitric oxide synthase (nNOS) seldom colocalized with sGC, but nNOS-positive structures were frequently closely apposed to sGC-positive structures, suggesting that in the superficial dorsal horn NO acts mainly in a paracrine manner. Our data suggest that the NK1 receptor-positive projection neurons in lamina I are a major target of NO released in superficial dorsal horn. NO may also influence local circuit neurons, but it does not act on unmyelinated primary afferent terminals via sGC.     

Thromboembolic complications in children with cancer

Thrombosis is a significant problem in patients with cancer. The impact of thromboembolism in association with childhood cancer is not clearly defined. Similarly the information of prevention and management of thromboembolic events in children receiving cancer-therapy is limited. This review aims to examine current knowledge regarding the epidemiology, pathophysiology and management of thrombosis in association with cancer in children.     

Genetic background of type I protein C deficiency in Finland

In contrast to other populations the usually rare type II form of protein C deficiency is as common in Finland as type I deficiency. We recently reported that a single mutation explained virtually all cases of type II protein C deficiency in Finland, indicating strong founder effect. We now investigated in the same population the genetic background of type I protein C deficiency. Thirty-eight apparently unrelated families were studied. They represent the vast majority of all families with type I deficiency in Finland. A genetic defect was identified in 23 (61%) families who carried 13 different mutations. Only three of the 13 mutations have been reported in other populations. Unlike in type II deficiency, considerable heterogeneity in mutations was found in type I deficiency. Our results indicate interesting differences in mutational histories of these two different forms of protein C deficiency in Finland.     

Prenatal ethanol exposure alters sensitivity to the effects of corticotropin-releasing factor (CRF) on behavior in the elevated plus-maze

Animals prenatally exposed to ethanol (E) exhibit behavioral alterations in a wide variety of stressful or challenging tasks. The hypothalamic peptide corticotropin-releasing factor (CRF) is known to play a crucial role in integrating an organism's behavioral responses to environmental stressors or challenges. Previous research indicates that E animals exhibit increased hypothalamic-pituitary-adrenal (HPA) reactivity, including increased hypothalamic CRF expression under both basal and stress conditions. However, the possible role of CRF in mediating the behavioral changes observed in E animals remains to be determined. The current study investigated the hypothesis that E animals may be differentially sensitive to the effects of CRF on behavior in the elevated plus-maze, a task widely used to assess anxiety-like behavior in rodents. Sprague-Dawley offspring from prenatal E, pair-fed (PF), and ad lib-fed control (C) groups were tested at 60-90 days of age. Thirty minutes prior to a 5 min test on the elevated plus-maze, animals received an icv infusion of vehicle (VEH) or CRF (males: 0.75 microg or 1.5 microg ; females: 1.0 microg or 2.0 microg ). Under VEH conditions, E males showed greater activity (more total arm entries) than PF and C males and both E males and E and PF females showed less anxiety-like behavior (more open arm entries) than their PF and/or C counterparts. As expected, CRF treatment resulted in fewer open arm, closed arm and total arm entries, and total rears in both males and females in all prenatal groups, and increased time in the closed arms in males compared to that in their VEH-treated counterparts. Importantly, the effects of CRF were most pronounced in E animals. That is, when normalized for prenatal group differences following VEH treatment, CRF-treated E males showed fewer total arm entries and total rears than PF and C males, and CRF-treated E and PF females showed fewer open arm entries than C females. These results support and extend previous findings demonstrating that E animals show altered behavior in aversive or stressful situations. While some effects of CRF in females may be mediated partially by nutritional effects of ethanol, the data overall suggest that the behavioral alterations observed in E animals may be due, at least in part, to increased sensitivity to CRF.     

Asymptomatic near-total airway obstruction by a cylindrical tracheal foreign body

OBJECTIVES/ HYPOTHESIS: The objective was to present the unique case of previously unreported asymptomatic cylindrical tracheal foreign body causing near-total airway obstruction. The asymptomatic nature of the case made diagnosis and management challenging. STUDY DESIGN: A retrospective case review at an urban health maintenance organization medical center. METHODS: A 3.5-year-old asymptomatic boy was incidentally discovered to have a metallic foreign body in his mid trachea on a screening scoliosis roentgenogram. He underwent rigid bronchoscopic retrieval the following day. RESULTS: The foreign body was found to be a corroded, 9 x 6-mm metallic cylinder with a narrowed luminal diameter of 2.0 mm. Intubation was maintained in the pediatric intensive care unit for 48 hours, and extubation was performed in the operating room under direct bronchoscopy. Mitomycin C was applied to a circumferential area of denuded tracheal mucosa. CONCLUSION: Tracheal foreign bodies are distinctly different clinical entities from bronchial foreign bodies. Asymptomatic bronchial foreign bodies are relatively common, but to the authors' knowledge, an asymptomatic tracheal foreign body had not been reported previously. Discussion focused on pathophysiology with reference to Poiseuille's law, diagnosis, and management of asymptomatic tracheal foreign bodies, including the possibility of elective bronchoscopic retrieval.     

Outcome analysis of patients with squamous cell carcinoma of the head and neck and hepatitis C virus

Objective/Hypothesis: Infection with the hepatitis C virus (HCV) is a global problem with over 170 million people infected. Recently, we have noticed that a large number of patients diagnosed with squamous cell carcinoma of the head and neck (SCCHN) have also been diagnosed with HCV. A review of the literature reveals little information concerning this patient population. The objective of this study was to compare the outcome of SCCHN patients who have been exposed to HCV with naïve SCCHN patients. Study Design: Retrospective chart review. Methods: A retrospective chart review from June 1991 through December 2002 was performed to identify patients diagnosed with SCCHN who were screened for HCV. Patients were stratified into two groups (HCV positive and HCV negative). Data were recorded on patients for status of disease at last clinic visit, pretreatment serum albumin and hematocrit levels, and RNA quantities of HCV. Statistical analysis was performed using paired t test to compare serum albumin and hematocrit levels. Kaplan‐Meier survival curves were used to compare outcomes. The log‐rank test was used to determine significance. Cox regression was used to examine the association of prognostic predictor variables with overall survival and disease‐free survival. Results: There was no difference noted in 5 year survival between hepatitis C positive and hepatitis C negative groups in overall outcomes (66.7% vs. 67.9%, P = 1.000) or 5 year disease‐free survival (90.5% vs. 80.8%, P = .514). The two groups, HCV positive versus HCV negative, also had similar serum albumin levels (3.62 g/dL vs. 3.72 g/dL, P = .37) as well as serum hematocrit levels (42.9% vs. 41.0%, P = .12). Serum levels of hepatitis C RNA were obtained in seven patients, with only one being undetectable. The only prognostic predictor variable that was significantly associated with overall survival was age. None of the predictor variables were significantly associated with disease‐free survival. Conclusion: Co‐infection with HCV, although prevalent in the Veterans Administration Hospital population, did not affect patient outcome as defined by disease‐free survival. Patients who were seropositive for HCV had comparable serum albumin levels as well as serum hematocrit when compared with HCV negative patients.     

Prevention of anterior glottic stenosis after transoral microresection of glottic lesions involving the anterior commissure with mitomycin C

OBJECTIVE: To evaluate the effectiveness of topical mitomycin C (MMC) in preventing anterior glottic stenosis (AGS) after transoral microresection of glottic lesions involving the anterior commissure (AC). STUDY DESIGN: Prospective clinical study. METHODS: Sixteen patients with benign or malignant glottic lesions involving the AC were studied. The lesions were removed by transoral microsurgery using a CO2 laser or cold microinstruments. In all patients, the anterior glottis was treated topically with 0.4 mg/mL MMC for 5 minutes at the end of surgery. The postoperative vocal folds and voice quality of patients were evaluated using video strobolaryngoscopy and voice recordings. RESULTS: Four patients had local recurrences after surgery and were treated with repeat microsurgery. Postoperatively, five patients (31%) developed acceptable small webs in the anterior glottis; one resolved with web lysis and a second with topical MMC. Postoperative vocal quality was affected mainly by the extent of vocal fold resection and the subsequent wide glottal gaps and extensive scarring, rather than by MMC use per se. Significant local side effects or atrophy of the vocal folds owing to MMC were not found. CONCLUSION: Topical MMC may be useful for preventing AGS and subsequent dysphonia after transoral microresection of glottic lesions involving the AC.     

Analysis of BDNF in Brain Structures of Inbred Mice with Different Phenotypes of Mental and Stress Reaction

The content of BDNF was measured in cerebral structures of intact C57Bl/6 and BALB/c mice in winter and spring. The level of cerebral neurotrophic factor in laboratory mice depended on genetic characteristics and chronobiological factors. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 11, pp. 549–551, November, 2005     

Neurobiology of TRPC2: from gene to behavior

The mammalian vomeronasal organ (VNO), a part of the accessory olfactory system, plays an essential role in the sensing of pheromonal signals. The VNO has emerged as an excellent model to investigate the functional role of transient receptor potential (TRP) channels in intact neurons and intact physiological systems. TRPC2, a member of the (canonical) TRPC subfamily, is highly localized to the dendritic tip of vomeronasal sensory neurons. Phenotypic analysis of mice exhibiting a targeted deletion in the TRPC2 gene has established that TRPC2 occupies a fundamental role in the transduction machinery underlying the detection of pheromone signals by the VNO. TRPC2-deficient mice exhibit striking behavioral defects in the regulation of sexual and social behaviors. A previously unknown Ca²⁺-permeable, diacylglycerol (DAG)-activated cation channel found at the dendritic tip of vomeronasal neurons is severely defective in TRPC2 mutants, providing the first clear example for the existence of native DAG-gated cation channels in the mammalian nervous system. The experimental strategy employed in the mouse VNO now serves as a powerful model for examining the native functions of other TRP genes.     

Comparing capsid assembly of primate lentiviruses and hepatitis B virus using cell-free systems

Many viruses that assemble their capsids in the eukaryotic cytoplasm require a threshold concentration of capsid protein to achieve capsid assembly. Strategies for achieving this include maintaining high levels of capsid protein synthesis and targeting to specific sites to raise the effective concentration of capsid polypeptides. To understand how different viruses achieve the threshold capsid protein concentration required for assembly, we used cell-free systems to compare capsid assembly of hepatitis B virus (HBV) and three primate lentiviruses. Capsid formation of these diverse viruses in a common eukaryotic extract was dependent on capsid protein concentration. HBV capsid assembly was also dependent on the presence of intact membrane surfaces. Surprisingly, not all of the primate lentiviral capsid proteins examined required myristoylation and intact membranes for assembly, even though all contain a myristoylation signal. These findings reveal significant diversity in how different capsid proteins assemble in the same cellular extract.