Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle

Human Molecular Genetics     

Neurofibroma in a patient with von Recklinghausen's disease seen as a malignant schwannoma. A case report

A rapidly growing, malignant schwannoma occurred in a 46-year-old woman with neurofibromatosis. Computed tomography, isotope bone scan, chest roentgenogram, and angiogram are helpful in determining the local extent and distant spread of such musculoskeletal tumors and are useful in planning appropriate surgical management. A well-planned biopsy, however, is essential to accurately determine the histologic diagnosis of the tumor. Clinical and roentgenographic presentation of some benign lesions may mimic malignant tumors. To confirm the diagnosis of a malignant or benign tumor, it is advisable to examine the musculoskeletal tumor histologically before proceeding with the definitive treatment, even if the clinical presentation strongly suggests malignancy.     

Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment.

Adult hippocampal neurogenesis has been demonstrated in several species and is regulated by both environmental and pharmacological stimuli. The present study seeks to determine whether hippocampal proliferation and neurogenesis are altered in adult animals exposed to inescapable shock (IS) in the learned helplessness model of depression. We report that exposure to avoidance testing, regardless of pre-exposure to IS, decreases cell proliferation in the hippocampus, extending previous studies demonstrating downregulation of neurogenesis by exposure to acute stressors. In addition, when the analysis was conducted 9 days after exposure to IS we observed a significant decrease in cell proliferation compared to nonshocked animals. Administration of fluoxetine, a serotonin selective reuptake inhibitor, from days 2-8 blocked the downregulation of cell proliferation resulting from IS. Fluoxetine treatment also reversed the deficit in escape latency observed in animals exposed to IS. Finally, at the 9 day time point, there was no significant difference in blood levels of corticosterone between nonshocked and IS exposed animals, indicating that the decreased cell proliferation that is observed is not due to increased levels of this adrenal steroid. These findings demonstrate that exposure to IS, which results in a state of behavioral despair, decreases hippocampal cell proliferation and that this effect can be reversed by fluoxetine treatment.     

Limitations of a thermal camera in measuring surface temperature of laser-irradiated tissues

Thermal cameras are used in research laboratories to measure tissue temperature during laser irradiation. This study was an evaluation of the accuracy of a 3-5 microns thermal camera and two 8-12 microns cameras in detecting the maximum temperatures of small targets. The size of the targets was within the range of laser spot diameters which are used for vessel welding, angioplasty, and dermatology. The response to a sharp thermal edge was measured and analyzed for the three cameras, which had a scanning rate of 30 frames per second. The response of the 3-5 microns camera to reference black body targets of different sizes was also studied. It was found that the detector system required an average of 2.44 microseconds to reach 90% of maximum step response for the 8-12 microns system and 5.85 microseconds for the 3-5 microns system. With a 3 x telescope and a 9.5 inch focal distance close-up lens, the 3-5 microns camera underestimated the temperature of targets smaller than 2.0 mm because of its slow detector response. Although the 8-12 microns camera provides more accurate measurements due to its faster detector response, it still underestimates the temperature of targets smaller than 900 microns, when similar magnification and focal distance are used. Methods to compensate for the inaccuracies are discussed, including empirical correction factors and the inverse filtering technique.     

Recent trends in early outcome of adult patients after heart transplantation: a single-institution review of 251 transplants using standard donor organs.

Older age, prior transplantation, pulmonary hypertension, and mechanical support are commonly seen in current potential cardiac transplant recipients. Transplants in 436 consecutive adult patients from 1994 to 1999 were reviewed. There were 251 using standard donors in 243 patients (age range 18-69 years). To emphasize recipient risk, 185 patients who received a nonstandard donor were excluded from analysis. The indications for transplant were ischemic heart disease (n = 123, 47%), dilated cardiomyopathy (n = 82, 32%), and others (n=56, 21%). One hundred and forty-nine (57%) recipients were listed as status I; 5 and 6% were supported with an intra-aortic balloon and an assist device, respectively. The 30-d survival and survival to discharge were 94.7 and 92.7%, respectively; 1-year survival was 89.1%. Causes of early death were graft failure (n = 6), infection (n = 4), stroke (n = 4), multiorgan failure (n = 3) and rejection (n = 2). Predictors were balloon pump use alone (OR= 11.4, p =0.002), pulmonary vascular resistance > 4 Wood units (OR = 5.7, p = 0.007), pretransplant creatinine > 2.0 mg/dL (OR = 6.9, p = 0.004) and female donor (OR = 8.3, p = 0.002). Recipient age and previous surgery did not affect short-term survival. Heart transplantation in the current era consistently offers excellent early and 1-year survival for well-selected recipients receiving standard donors. Early mortality tends to reflect graft failure while hospital mortality may be more indicative of recipient selection.     

Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease

Recent experimental studies and one clinical case have suggested that grafting tissue from the adrenal medulla into the brain may ameliorate the signs of Parkinson's disease. We describe the treatment of two young patients (35 and 39 years old) with intractable and incapacitating Parkinson's disease, in whom fragments of the adrenal medulla were autotransplanted to the right caudate nucleus. Clinical improvement was noted in both patients at 15 and 6 days (respectively) after implantation and has continued in both. Rigidity and akinesia had virtually disappeared in the first patient at 10 months after surgery, and his tremor was greatly reduced. A similar degree of improvement was present in the second patient at three months. We conclude that autografting of the adrenal medulla to the right caudate nucleus was associated with a marked improvement in the signs of Parkinson's disease in two patients, but our results are preliminary and further work is necessary to see whether this procedure will be applicable over the long term in other types of patients with Parkinson's disease.