Inactivation of human synovial fluid phospholipase A2 by the marine natural product, manoalide

The marine natural product, manoalide (MLD), was investigated to determine if this drug inhibited purified human synovial fluid phospholipase A2 (HSF-PLA2). Utilizing classical Michaelis-Menten kinetics, apparent Km and Vmax values for HSF-PLA2 of 1.34 mM and 0.47 mumol [3H]palmitic acid released/min/mg protein were obtained using dipalmitoylphosphatidylcholine (DPPC) as the substrate, and 38.0 microM and 18.8 mumol [3H]arachidonic acid released/min/mg protein with Escherichia coli as a natural substrate. These kinetic parameters were utilized subsequently to evaluate the inhibitory effects of manoalide on HSF-PLA2. Inhibition of HSF-PLA2 by MLD was concentration and time dependent with IC50 values of 0.2 and 0.02 microM for DPPC and E. coli respectively. Dialysis studies and examination of DPPC or E. coli hydrolysis versus enzyme concentration indicate that MLD is an irreversible inhibitor of HSF-PLA2. Substrate specificity was also examined in the absence and presence of MLD using dipalmitoylphosphatidylethanolamine (DPPE) as a substrate. MLD inhibited the hydrolysis of DPPE (greater than 90% inhibition at 2 microM), and preliminary results indicate that DPPC was more readily hydrolyzed than DPPE under the substrate conditions of the assay. While the cellular source of secreted HSF-PLA2 is unknown, these studies indicate that MLD can inactivate secreted phospholipase A2 isolated from patients with inflammatory joint disease.     

Management of hypertension in Mamre women

A follow-up study was conducted in December 1987 on all 136 women between the ages of 25 and 64 years who had been recorded as being on treatment for hypertension in the Mamre Community Health Project in December 1986. A further 136 women were randomly selected from the same age category to determine the overall prevalence of hypertension. The repeatability and validity of the 1986 project questionnaire were satisfactory. The overall prevalence of hypertension in Mamre women was 25.9% (16.1% for the age group 25-44 years and 38.4% for the age group 44-64 years). The extent of underdiagnosis of hypertension in the community on the basis of the 1986 survey was 56.8%. Despite a good reported compliance rate of 72.7%, 56.3% of hypertensives were not adequately controlled. The Mamre community presents an ideal setting for an interventive study in the management of hypertension.     

Integration of bilateral whisker stimuli in rats: role of the whisker barrel cortices.

Recently, we demonstrated that neural responses within the whisker region of the primary somatosensory cortex (SIw) of rats are profoundly influenced by the spatiotemporal attributes of ipsilateral, as well as contralateral, whisker stimuli. As inactivation of one SIw eliminates in the intact SIw both ipsilaterally evoked responses and the influence of ipsilateral stimulation on contralaterally evoked activity, we proposed that interhemispheric interactions between the SIws may be important for integrating bilateral whisker information. To test whether rats can recognize the bilateral nature of a whisker stimulus, we developed a tactile discrimination task that required rats to conjointly determine distances to a left and a right discriminandum as equidistant or non-equidistant using only their facial whiskers. All rats trained in this task achieved performance levels indicative of an ability to integrate bilateral whisker information. Testing during unilateral, as well as bilateral, inactivation of the SIws indicated that rats rely on both SIws for detecting the bilateral nature of a whisker stimulus. Rats were unable to perform the task without both sets of whiskers, a fact that indicates that the whiskers (and not other modalities) were used to perform this task. The findings presented here indicate that rats can solve a task that requires the conjoint detection of left and right whisker-mediated distance information and implicate the SIws as central to this ability.     

Endoscopic reconstruction of traumatic membranous urethral transection

Newer endoscopic techniques derived from percutaneous renal manipulations are well suited for endoscopic reconstruction of traumatic short total membranous urethral transections. Four men and 1 child underwent successful endoscopic membranous urethral reconstruction. All 4 men are voiding with good flow and normal control more than 1 year after any endoscopic manipulation.     

Progression of self-reported symptoms in laboratory animal allergy

BACKGROUND: Laboratory animal allergy is a common illness among workers exposed to laboratory animals and can progress to symptoms of asthma. OBJECTIVES: This study evaluates the continuum of disease from allergy symptoms to asthma symptoms in a dynamic cohort of workers exposed to animals in a pharmaceutical company. METHODS: Data arose from annual questionnaires administered to workers in a surveillance program established to monitor exposure to animals and the development of allergy. The life-table method was used to compare asthma-free survival between workers with and without symptoms of allergy. A Cox proportional hazards model was used to examine the effects of covariates on the development of asthma. RESULTS: A total of 603 workers contributed 2527.4 person-years to the study over the 12.3-year period. The probabilities of experiencing asthma symptoms by the 11th year of follow-up were 0.367 for workers with allergy symptoms and 0.052 for those without allergy symptoms. The hazard ratio for asthma symptoms when comparing workers with and without allergy symptoms was 7.39 (95% CI, 3.29-16.60) after adjustment for sex and family history of allergy. Female subjects developed asthma at a rate 3.4 times that of male subjects. CONCLUSIONS: This study supports the hypothesis that laboratory animal allergy symptoms are a major risk factor for the development of asthma. It also suggests a heightened risk of asthma for women who work with laboratory animals, a finding that has not been previously reported.     

Multilocular renal cysts in adults. Possible relationship to renal adenocarcinoma

Three grossly typical multilocular renal cysts are described. In one case, results from cytologic examination of a cyst aspirate were suggestive of malignancy. In this and the second case, histologic examination revealed cysts lined by attenuated to pump epithelium, with mild cytologic atypia and clear cytoplasm. The third case, arising in the clinical setting of chronic renal insufficiency, had the above histologic features as well as papillary proliferations and septal invasion by clear cells, interpreted as a renal adenocarcinoma. Although the preoperative evaluations in each case were suggestive of a multilocular cyst, a cystic or partially necrotic adenocarcinoma could not be ruled out. The concept of renal adenocarcinoma arising in a multilocular cyst is controversial. Because the natural evolution of multilocular cysts is indolent, these papillary and clear cell changes may represent a malignant neoplasm or a peculiar atypical hyperplasia.