Substrate phosphorylation in the protein kinase Cgamma knockout mouse

The phosphorylation state of three identified neural-specific protein kinase C substrates (RC3, GAP-43/B-50, and MARCKS) was monitored in hippocampal slices of mice lacking the gamma-subtype of protein kinase C and wild-type controls by quantitative immunoprecipitation following 32Pi labeling. Depolarization with potassium, activation of glutamate receptors with glutamate, or direct stimulation of protein kinase C with a phorbol ester increased RC3 phosphorylation in wild-type animals but failed to affect RC3 phosphorylation in mice lacking the gamma-subtype of protein kinase C. Our results suggests the following biochemical pathway: activation of a postsynaptic (metabotropic) glutamate receptor stimulates the gamma-subtype of protein kinase C, which in turn phosphorylates RC3. The inability to increase RC3 phosphorylation in mice lacking the gamma-subtype of protein kinase C by membrane depolarization or glutamate receptor activation may contribute to the spatial learning deficits and impaired hippocampal LTP observed in these mice.     

Genitourinary anomalies in the CHARGE association

PURPOSE: We identified the incidence and types of genital and urinary anomalies, and established a plan for evaluating the urinary system in the CHARGE association. MATERIALS AND METHODS: We retrospectively reviewed the charts of 32 patients in whom the CHARGE association was diagnosed. RESULTS: Of the 32 patients identified 22 (69%) had genitourinary abnormalities. Genital anomalies, including micropenis, penile agenesis, hypospadias, chordee, cryptorchidism, a bifid scrotum, atresia of the uterus, cervix and vagina, and hypoplastic labia majora, labia minora and clitoris, were present in 18 patients (56%). Of the 24 patients who underwent renal ultrasound 10 (42%) were diagnosed with urinary tract anomalies including a solitary kidney, hydronephrosis, renal hypoplasia and duplex kidneys. Further evaluation revealed vesicoureteral reflux, neurogenic bladder secondary to spinal dysraphism, nephrolithiasis, ureteropelvic junction obstruction and a nonfunctioning upper pole in both duplex kidneys. CONCLUSIONS: There is a high incidence of genitourinary anomalies in the CHARGE association. Because of this high incidence of anomalies, patients with this condition should undergo a careful genitourinary evaluation, including renal and bladder ultrasound, and voiding cystourethrography screening.     

Memory improvement following cardiac transplantation

Seventeen patients with severe cardiomyopathy underwent neuropsychological evaluation prior to and at least 1 year after successful heart transplantation. Study candidates were screened, and individuals with a history of stroke, cardiac arrest, or medical and neurological conditions which might affect brain function were excluded. Pre-transplant testing revealed normal intelligence and normal attentional, language, and executive abilities but impaired recent memory. Following heart transplant, memory functioning improved significantly, reaching normal levels. Other cognitive abilities remained unchanged. Results suggest that cardiomyopathy is associated with mesial temporal dysfunction, possibly attributable to inadequate or reduced cerebral blood flow and related hypometabolism. This cerebral dysfunction is potentially reversible following successful transplantation, which restores cardiac output and cerebrovascular perfusion.     

Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

Lanepitant is a high-affinity, selective neurokinin-1 receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine-associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant. Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.     

Interactions of spatial frequency and unequal monocular contrasts in stereopsis

Increasing the contrast of just one eye's image degrades stereothresholds; this phenomenon is referred to as the stereo contrast paradox. In experiment one, this paradox was found to be absent in dynamic random-element stereograms; thresholds were simply limited by the lower of the two eyes' contrasts. In experiment two, in which narrowband Gabor targets were used, the paradox was found to be strongest at relatively low spatial frequencies (1 cycle deg-1). As spatial frequency was increased, the paradox gradually disappeared. At relatively high spatial frequencies (5 cycles deg-1), thresholds were generally limited by the lower of the two eyes' contrasts, as was found for the dynamic noise targets. These results demonstrate the interactions of spatial frequency and contrast in binocular image combination and yield clues as to the different roles which high and low spatial frequencies may play in stereopsis.