5-HPETE is a potent inhibitor of neuronal Na+, K(+)-ATPase activity

The effects of 1 microM concentrations of arachidonic acid hydroperoxide (HPETES) products of 5-, 12- and 15-lipoxygenase on Na+, K(+)-ATPase activity were investigated in synaptosomal membrane preparations from rat cerebral cortex. 5-HPETE inhibited Na+, K(+)-ATPase activity by up to 67 %. In contrast, 12-HPETE and 15-HPETE did not inhibit Na+, K(+)-ATPase activity. In addition, neither 5-HETE or LTA4 inhibited Na+, K(+)-ATPase activity. Dose-response studies indicated that 5-HPETE was a potent (IC25 = 10(-8) M) inhibitor of Na+, K(+)-ATPase activity. These findings indicate that 5-HPETE inhibits Na+, K(+)-ATPase activity by a mechanism that is dependent on the hydroperoxide position and independent of further metabolism by 5-lipoxygenase. It is proposed that 5-HPETE production by 5-lipoxygenase and subsequent inhibition of neuronal Na+, K(+)-ATPase activity may be a mechansim for modulating synaptic transmission.     

Characterization method of thermomechanical parameters for microelectronic materials

Reliability of thermomechanical simulations is critically linked to the accuracy of the mechanical properties that govern the behaviour of structure, like Young's modulus (E) and coefficient of thermal expansion (CTE). For many cases, the values found in literatures are dealing with bulk properties without detailed information on temperature effects. To address such issues, it is necessary to measure the materials parameters as a function of temperature. The measurement of CTE is usually accomplished by evaluating the thermal deflections of a subjected material layer deposited on a substrate, providing that E is known at a specific temperature of experiment. A bilayer method, based on theory of elasticity, is proposed to determine both E and CTE for a given temperature with a good resolution. This paper presents the theoretical analysis, the design and process of the microsystem test structures, and the main calculation results.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities

We reviewed the cases of sixty-two patients who had had a subcutaneous sarcoma to determine the effect of tumor and treatment-related variables on the rates of survival and local recurrence. Fifty-nine (95 per cent) of the patients had had an operation at another hospital before being referred to us. Twenty-nine (47 per cent) of the sixty-two tumors were high-grade, forty-two (68 per cent) were small (five centimeters or less), and thirty (48 per cent) were malignant fibrous histiocytomas. We followed a treatment strategy that consisted of repeat excision with the goal of obtaining wide margins. Excluding thirteen patients who had had a palpable local recurrence at the time of presentation, twenty (49 per cent) of forty-one patients who had had a marginal excision at another hospital had microscopic residual tumor on repeat excision. At a median of fifty-six months after the repeat excision, fifty (81 per cent) of the sixty-two patients had been continuously disease-free, one had no evidence of disease, eight had died of the disease, and three had died of other causes. The five-year rate of disease-free survival was 85 per cent (fifty-three of sixty-two patients). There were three local recurrences, all in patients who had had a marginal resection. No recurrences were noted in patients who had had a wide local excision of the tumor or of the previous operative field. Multivariate analysis revealed that a large tumor (greater than five centimeters), a marginal excision, and adjuvant radiation therapy were associated with a worse prognosis. Excellent rates of survival for patients who have a subcutaneous sarcoma, including those who have a large or high-grade tumor and those who have residual tumor following a previous operation, can be obtained with carefully planned operative treatment alone. We recommend operative excision or repeat excision with wide margins because of the high prevalence of residual tumor. Size is the most important tumor-related factor, and the operative margin is the most important treatment-related factor. The additional value of adjuvant radiation therapy remains unproved.     

Signal attenuation as a function of integrator time constant and signal duration

In some laboratories, eyeblink electromyogram is rectified and smoothed before the analog signal is digitized. The relationship among the integrator time constant, the duration of the response, and the attenuation of the data was investigated by passing a number of signals at durations of 5, 10, 20, 50, and 100 ms into a contour-following integrator (Coulbourn model S76-01), which first rectifies and then smooths (integrates) the signal. Integrator time constants of 10, 42, 70, 144, and 300 ms were used. The output of the integrator was sampled (1,000 Hz) and stored on a Macintosh SE computer. The integrator attenuated the signal, and the amount of attenuation increased as the duration of the signal decreased and as the time constant of the integrator increased. For brief inputs, the integrator does not charge fully, so only the early portion of the charge limb is present, and this early portion is the steepest part of the charge limb. Therefore, the longer the time constant, the less likely that small or brief responses will be detected.     

Homogeneity of fruits and vegetables comminuted in a vertical cutter mixer

The homogeneity of comminuted composites of 20 lb samples of apples, cabbage, and green beans containing field-incurred residues of p, p'-methoxychlor was studied to determine whether a 5 min comminution in a 40 qt vertical cutter mixer produces a homogeneous composite and whether the size of test portions used accurately represents the composite. Duplicate test portions of 100, 50, 25, 10, 5, and 2 g taken from each of 6 separate sections of the mixer were analyzed by standard pesticide residue methodology for p, p'-methoxychlor. Results of this study confirmed that comminution of fresh produce in a 40 qt vertical cutter mixer, according to instructions described in the U.S. Food and Drug Administration's Pesticide Analytical Manual, Volume I, Section 203B, produces a homogeneous composite. No significant differences were found in the data for the 3 crops taken from the 6 sections of the mixer. Test portion weights of 100, 50, and 25 g produced equivalent results for all 3 crops. Statistically significant differences were observed for cabbage at 2, 5, and 10 g and for green beans at 2 g.     

Developmental and behavioral effects of prenatal primidone exposure in the rat

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.