An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans

During sexual reproduction in most animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. Despite progress in delineating mitogen-activated protein kinase (MAPK) and CDK/cyclin activation pathways involved in meiotic maturation, it is less clear how these pathways are regulated at the cell surface. The Caenorhabditis elegans major sperm protein (MSP) signals oocytes, which are arrested in meiotic prophase, to resume meiosis and ovulate. We used DNA microarray data and an in situ binding assay to identify the VAB-1 Eph receptor protein-tyrosine kinase as an MSP receptor. We show that VAB-1 and a somatic gonadal sheath cell-dependent pathway, defined by the CEH-18 POU-class homeoprotein, negatively regulate meiotic maturation and MAPK activation. MSP antagonizes these inhibitory signaling circuits, in part by binding VAB-1 on oocytes and sheath cells. Our results define a sperm-sensing control mechanism that inhibits oocyte maturation, MAPK activation, and ovulation when sperm are unavailable for fertilization. MSP-domain proteins are found in diverse animal taxa, where they may regulate contact-dependent Eph receptor signaling pathways.     

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Myelinated and nonmyelinated nerves: comparison of proton MR properties

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.     

Blunt injury to mesentery and small bowel: CT evaluation

Helical CT now allows rapid acquisition of sections through the abdomen and pelvis with optimal vascular opacification and minimal motion artifact. Oral contrast may aid in the identification of subtle bowel and mesenteric injuries and does not have any significant deleterious effects. CT findings of extraluminal enteric contrast, active hemorrhage, or free intraperitoneal-retroperitoneal air allow accurate diagnosis of SBMI in the setting of blunt abdominal trauma. Mesenteric hematoma in association with bowel wall thickening or the presence of significant amounts of free fluid without solid organ injury is highly suspicious for SBMI requiring laparotomy. CT alone or in concert with DPL and physical examination is a valuable tool in the timely diagnosis and treatment of bowel and mesenteric injury caused by blunt trauma.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

CIRCADIAN PREFERENCE AND COGNITIVE FUNCTIONING AMONG REHABILITATION INPATIENTS

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n = 28) and noncognitive (n = 28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta² .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e.g., complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, an index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.     

The effect of age on sciatic nerve block duration

The physiologic changes that occur with advancing age and their effect on the duration of peripheral nerve blocks have yet to be defined. We prospectively studied the duration of sciatic nerve block using mepivacaine in younger and older patients. Eighty ASA physical status I-III patients, aged 18-35 (n = 40) or 55-80 (n = 40) yr, having outpatient knee arthroscopy with a femoral block and a standardized sciatic nerve block were enrolled; 37 in each group completed the study. All patients received a Labat sciatic nerve block using 20 mL of 1.0% mepivacaine with 0.1 mEq/mL sodium bicarbonate and 1:400,000 (2.5 microg/mL) epinephrine and a femoral nerve block. The duration of sensory block (sensation of pinprick, temperature, and vibration), motor block (plantar and dorsi flexion), and complete sensory and motor block in the sciatic nerve distribution of the operative extremity were measured. The time for complete return of both sensory and motor function was longer in the older group, 329 +/- 47 min compared with 306 +/- 46 min (mean +/- sd) in the younger group (P = 0.04). The difference was small under the conditions of this study and would not be perceived clinically. Age also increased the time to return of vibratory sensation (younger = 292 +/- 58 min, older = 257 +/- 50 min; P = 0.007). The other measurements did not differ between groups. We conclude that age may affect peripheral nerve blocks and that more investigation is needed to determine the pharmacologic, physiologic, and chronologic factors behind these findings.     

Practical and technical considerations in establishing an intraoperative radiation therapy program in the community practice

The Radiation Oncology Center in Sacramento, California, has developed a procedure for establishing an intraoperative radiation therapy facility in a community practice. The logistics pertaining to personnel, equipment, physical measurements, and quality assurance are presented. Particular emphasis is given to the most effective means of acquiring the large quantity of data needed to ensure a program of acceptable quality.