The eucaryal tRNA splicing endonuclease recognizes a tripartite set of RNA elements

The tRNA splicing endonuclease cleaves intron-containing tRNA precursors on both sides of the intron. The prevailing belief has been that the enzyme binds only to the mature domain through the invariant bases. We show instead that, for recognition, the endonuclease utilizes distinct sets of structural elements, several of which are within the intron. One subset of recognition elements, localized in the mature domain, is needed for recognition of both cleavage sites, while two other subsets, localized at the exon-intron boundaries, are used for recognition of either one or the other cleavage site. The two cleavage sites are essentially independent: neither is required by the other for cleavage to take place. These results support a two-active-site model for the eucaryal endonuclease.     

Interactions of monoamine oxidase inhibitors, N-acetylenic analogues of tryptamine, with rat liver microsomal cytochrome P450

Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time-dependent manner. Only tertiary aliphatic amines constituted the substrate for P450-dependent N-demethylase activity, with comparable kinetic parameters. The N-demethylated metabolites were identified by thin-layer chromatography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.     

Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs

This article describes the nucleotide sequence of a porcine circovirus (PCV) which possesses a high degree of association with postweaning multisystemic wasting syndrome (PMWS), a newly described disease of young pigs. The DNA sequence of this PMWS-associated PCV (pmws PCV) has 68% homology with that of a previously published nonpathogenic strain of PCV. The strains appear to be closely related yet distinct from one another.     

MAP Kinase in the rat adrenal gland

Commercial citrus pectin containing galacturonic acid and rhamnose in a ratio of approximately 40:1 was saponified and then exhaustively digested with endopolygalacturonase (EPG). The products were separated by ultrafiltration into low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions. The LMW fraction accounted for 80% of the starting material, but for only 10% of the total rhamnose. The molar ratio of galacturonic acid to rhamnose of the LMW fraction was 236, suggesting that very few small Rha-containing oligomers were generated by the EPG digestion. No distinct Rha-containing oligomers were found by various chromatographic analyses of the LMW fraction. The HMW fraction, which only accounted for 10% by weight of the starting pectin, contained more than 85% of the rhamnose. The ratio of GalA to Rha in the HMW fraction was 1.7:1 and partial acid hydrolysis of this fraction produced a series of oligomers consisting of GalA-Rha repeating units, suggesting that it contained rhamnogalacturonan, which has a backbone composed of GalA-Rha disaccharide repeating units. The HMW fraction also contained large amounts of arabinose and galactose, which probably originated from side chains linked to some of the rhamnose residues. We propose that commercial citrus pectin is composed of two regions: the predominant region consists of chains of uninterrupted 1,4-linked alpha-D-GalA residues with between 60-70% of the residues methyl esterified; and the other region consists of rhamnogalacturonan with a backbone composed of GalA-Rha disaccharide repeating units and neutral sugar side chains.     

US national survey of physician practices for the secondary and tertiary prevention of ischemic stroke. Design, service availability, and common practices

BACKGROUND AND PURPOSE: Stroke is largely a preventable disease. However, there are little data available concerning the use of stroke prevention diagnostic and treatment modalities by practicing physicians. These data are critical for the rational allocation of resources and targeting of educational efforts. The purposes of this national survey were to gather information about physicians' stroke prevention practice patterns and their attitudes and beliefs regarding secondary and tertiary stroke prevention strategies. METHODS: We conducted a national survey of stroke prevention practices among a stratified random sample of 2000 physicians drawn from the American Medical Association's Physician Masterfile. The survey focused on the availability of services and the use of diagnostic and preventive strategies for patients at elevated risk of stroke. RESULTS: Sixty-seven percent (n = 1006) of eligible physicians completed the survey. Diagnostic studies considered readily available by at least 90% of physicians included carotid ultrasonography, transthoracic echocardiography, Holter monitoring, and brain CT and MRI scans. MR angiography was perceived as being readily available by 68% and transesophageal echocardiography by 74% of respondents. Twelve percent of physicians reported cerebral arteriography and 10% reported carotid endarterectomy as not being readily available. Multiple logistic regression analyses showed that the availability of services varied with physician specialty (noninternist primary care, internal medicine, neurology, surgery), practice setting (nonmetropolitan versus small metropolitan or large metropolitan areas), and for carotid endarterectomy, region of the country (South, Central, Northeast, and West). The odds of carotid endarterectomy being reported as readily available were approximately 2.5 to 3.5 times greater for physicians practicing in the central, northeastern, and western regions compared with those practicing in the South, independent of practice setting and specialty. With regard to stroke prevention practices, 61% of physicians reported prescribing 325 mg of aspirin for stroke prevention, while 33% recommend less than 325 mg and 4% use doses of 650 mg or more. Seventy-one percent of physicians using warfarin reported monitoring anticoagulation with international normalized ratios, and 78% reported monitoring anticoagulated patients at least once a month. Fewer than 20% of physicians reported knowing the perioperative carotid endarterectomy complication rates at the hospital where they perform the operation themselves or refer patients to have the procedure done. CONCLUSIONS: Although all routine and most specialized services for secondary and tertiary stroke prevention are readily available to most physicians, variation in availability exists. The use of international normalized ratios for monitoring warfarin therapy has not yet become universal. Physician knowledge of carotid endarterectomy complication rates is generally lacking. Depending on their causes, these problems may be addressed through targeted physician education efforts and systematic changes in the way in which services are provided.     

Timing of pedicle thrombosis and flap loss after free-tissue transfer

A series of 990 consecutive free flaps was reviewed to determine how often pedicle thrombosis occurred, when it occurred, and if the timing of thrombosis detection had any relationship to the probability of flap salvage. The overall thrombosis rate was 5.1 percent, and the flap loss rate was 3.2 percent. The majority (80 percent) of thrombi occurred within the first 2 postoperative days. Only 5 thrombi (10 percent) were known to have occurred after the third postoperative day. No flaps that developed thrombosis after the third postoperative day were salvaged successfully. Had flap monitoring been discontinued after the first 3 postoperative days, our results in this series would have been unchanged. Thrombosis of the vein (54 percent) was more common than arterial thrombosis (20 percent) or thrombosis of both artery and vein (12 percent). Almost all purely arterial thrombi (90 percent) occurred before the end of the first postoperative day, whereas 41 percent of all venous thrombi occurred later. We conclude that arterial monitoring is most critical immediately after surgery. Beginning on the second postoperative day, venous monitoring becomes progressively more important to flap success. The cost-effectiveness of postoperative monitoring of free flaps is greatest during the first 2 days, after which it decreases significantly.     

Pelvic exenteration for malignant melanomas of the vagina or urethra with over 3 mm of invasion

Pelvic exenteration has usually been employed as salvage treatment for gynecologic malignancies which have failed primary radiotherapy. The therapeutic mainstay for vulvar melanomas has become wide local excision with or without concurrent regional node dissection. Patients with primary melanoma of the vagina who undergo exenteration as primary therapy may experience 50% 5-year survival if the pelvic nodes are free of metastases. However, the overall 5-year survival for vaginal melanoma is 15%. In our patient population, there have been four patients with vaginal or urethral melanomas treated primarily with pelvic exenteration. The purpose of this study was to report that patients with vaginal or urethral melanomas over 3 mm in thickness may benefit from primary pelvic exenteration. Four patients underwent pelvic exenteration at Indiana University Medical Center for malignant melanoma of the vagina or urethra between 1986 and 1992. The pathologic specimens of all patients were analyzed for thickness, growth pattern, and nodal metastases. Patient age ranged from 50 to 71. Thickness of the melanomas ranged from > 3 to 12 mm. All four patients underwent exenterations, three total and one anterior. All patients had negative pelvic and inguinal nodes at the time of surgery. None of the patients has experienced a recurrence. Three of four patients are alive without evidence of disease at 31 to 97 months following their exenteration. One patient died postoperatively of cardiopulmonary complications. Patients with melanomas of the vagina and female urethra, greater than 3 mm in thickness, may benefit from primary pelvic exenteration.