Pathogenesis of chronic allograft nephropathy

We found normal individuals whose aspartoacylase gene Y231X mutation site consistently gave no signal in a primer extension assay. We determined the nucleotide sequence of the relevant region of the gene in those individuals, and found a new allele with a thymidine residue at the mutation site instead of a cytidine. Since both TAC and TAT code for tyrosine, this sequence polymorphism has no effect on the amino acid sequence of the ASPA protein. We found the relative frequencies of the 693C and the 693T alleles in the tested population to be 0.75 and 0.25 respectively.     

Approach and avoidance strength during goal attainment: regulatory focus and the "goal looms larger" effect

Three studies tested the hypothesis that regulatory focus, both as a chronic person variable and as a manipulated situational variable, differentially affects the strength of participants' approach and avoidance strategic motivations as they get closer to the goal. In 2 studies, flexion and extension arm pressure were used as on-line measures of approach and avoidance intensity, respectively. As predicted, the approach gradient was steeper for participants with a promotion focus on aspirations and gains than for participants with a prevention focus on responsibilities and nonlosses, whereas the reverse was true for the avoidance gradient. In a third study, the same pattern of results was found on a persistence measure of motivational strength. Participants with a promotion focus worked longer on anagrams closer to the goal when they were approach means for goal attainment than when they were avoidance means, whereas the reverse was true for participants with a prevention focus.     

Epidemiology of work-related aviation fatalities in Alaska, 1990-94

Alaska, with less than one-half of 1% of the United States workforce, accounts for 9% of all occupational aviation fatalities nationally; 30% of all occupational fatalities in Alaska are related to aviation. To understand this high mortality, we investigated occupational aviation crashes to identify risk factors. Occupational aviation fatalities in Alaska during 1990-94 were examined using National Transportation Safety Board reports and merged with records from the Alaska Occupational Injury Surveillance System. There were 876 aircraft crashes; 407 (46%) were work-related. Occupational crashes were 2.2 times (CI: 1.5, 3.2) more likely to result in fatalities than non-occupational crashes. Risk factors identified included poor weather conditions defined as Instrument Meteorological Conditions (IMC). A crash during IMC was 5.3 times (CI: 3.5, 7.9) more likely to result in fatalities than crashes in other conditions. Of aircraft involved in fatal occupational incidents, 33% were not completely destroyed, allowing the potential for survivors. An estimated 30% reduction in fatalities could have occurred if current technology in occupant protection had been used.     

Strain gauge plethysmography and Doppler ultrasound in the measurement of limb blood flow

The maintenance of adequate oxygen delivery (DO2) and tissue uptake (VO2) has become central dogma in the management of the critically ill. However, these parameters are derived using gas tensions measured in mixed venous blood and may not reflect changes in regional blood flow. Therefore, it has become necessary to provide estimates of blood flow to specific organs and to evaluate the most adequate techniques available. In order to define the best means of assessing blood flow to the lower limb noninvasively in normal subjects, measurements of superficial femoral arterial blood flow using Doppler ultrasound (DU) and strain gauge plethysmography (SGP) were compared in 10 normal volunteers at rest and during exercise. To evaluate the effect of strain gauge positioning, results of measurements made under four different combinations of cuff/strain gauge placement were compared in 15 other volunteers. The correlation of the limb blood flow obtained using the two methods at rest and exercise was 0.57 and 0.62 and the limits of agreement (d +/- 2SD) were 0.40 +/- 2.49 and -0.86 +/- 5.22 ml 100 ml-1 tissue min-1 at rest and on exercise, respectively. Results obtained using SGP were more reproducible (Coef. repeat. 0.45 vs. 0.94 ml 100 ml-1 tissue min-1, for SGP and DU, respectively). The various combinations of cuff/strain gauge positioning showed a tendency to over-read when the latter was placed on the thigh, but were not significantly different (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Month of birth and schizophrenia in Taiwan: effect of gender, family history and age at onset

Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method to compare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset.     

Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).     

Severing of F-actin by the amino-terminal half of gelsolin suggests internal cooperativity in gelsolin

Gelsolin is a Ca2+-regulated actin-binding protein that can sever, cap, and nucleate growth from the pointed ends of actin filaments. In this study we have measured the binding of the amino-terminal half of gelsolin, G1-3, to pyrene-labeled F-actin as a function of Ca2+ concentration. The rate of binding is shown to be dependent on micromolar concentrations of Ca2+. Independent experiments demonstrate that conformational changes in G1-3 are induced by micromolar concentrations of Ca2+. Titrations of pyrene-F-actin with G1-3 and gelsolin show that the quenching of pyrene fluorescence is identical in extent and stoichiometry for both G1-3 and gelsolin. In contrast, severing of F-actin by G1-3 is found to be much less efficient than is severing by gelsolin. In experiments in which F-actin severing is quantitatively measured, the filament number is found to be proportional to the 1.35 power of the G1-3 concentration. This deviation from linearity may be explained by cooperativity; the binding of two G1-3 molecules in close proximity may lead to cooperative severing of the polymer, thus increasing the severing efficiency. This model is supported by experiments that show that the efficiency of G1-3 severing of F-actin increases with increasing G1-3:F-actin ratios. Extrapolating from these results, we conclude that G4-6, the carboxyl-terminal half of gelsolin, has an active role in the severing of F-actin by intact gelsolin. Whereas F-actin severing by G1-3 is enhanced by cooperative binding of two separate G1-3 molecules, cooperativity is inherent to intact gelsolin because the cooperative partners are covalently linked.     

Clinical presentation of experimentally induced rabies in horses

Twelve naive and nine test-vaccinated horses which developed clinical signs of rabies as a result of the required protocol of a vaccine trial were prospectively observed. Nineteen of the 21 cases were confirmed positive for rabies infection of the brain by fluorescent antibody test. The two horses with negative results had ganglioneuritis of the trigeminal ganglion or lymphocytic perivascular cuffing in the brain stem in addition to clinical signs. Average incubation period was 12.3 days and average morbidity was 5.5 days. Naive animals had significantly shorter incubation and morbidity periods (P < 0.05). Muzzle tremors were the most frequently observed (81%) and most common initial sign. Other common signs were pharyngeal spasm or pharyngeal paresis (71%), ataxia or paresis (71%), lethargy or somnolence (71%). The furious form was manifested in 43% of rabid horses and some of these furious animals initially manifested the dumb form. The paralytic form was not observed. Histopathology was characteristics for rabies. The results of this trial do not reflect on the efficacy of commercially licensed equine rabies vaccines.