Electrospray ionisation mass spectrometry facilitates detection of fibrinogen (Bbeta 14 Arg --> Cys) mutation in a family with thrombosis

We report the first direct detection of a fibrinogen mutation by electrospray ionisation mass spectrometry. The propositus, from a family with a history of thrombosis, came to attention after a pulmonary embolism subsequent to a spontaneous abortion. Prolonged thrombin (41 s) and reptilase times (26 s) together with an impairment of fibrinopeptide B release suggested a mutation at the thrombin cleavage site of the Bbeta chain. Direct mass analysis of purified fibrin chains from a thrombin induced clot showed that 50% of the Bbeta chains remained uncleaved. The measured mass of the mono sialo isoform of this uncleaved chain was 54150 Da, compared to a value of 54198 Da for normal Bbeta chains. This decrease of 48 Da in the intact protein is indicative of either a Bbeta 14 Arg to Cys, or Arg to Leu substitution. Heterozygosity for the Bbeta 14 Arg --> Cys mutation was verified by PCR amplification and DNA sequence analysis.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Appendiceal and peri-appendiceal air at CT: prevalence, appearance and clinical significance

AIM: Appendiceal air has been reported as both a sign of appendicitis and of a normal appendix both at plain radiography and computed tomography (CT). It is the aim of this investigation to determine the prevalence, range of appearances, and significance of appendiceal and peri-appendiceal air at CT. PATIENTS AND METHODS: Appendiceal CT scans of 100 patients with proven appendicitis and 100 patients with a normal appendix were reviewed for the presence of appendiceal and peri-appendiceal air. All cases were correlated with surgical and pathological findings or clinical follow-up. RESULTS: In 100 CT cases of appendicitis, appendiceal and/or peri-appendiceal air was present in one or more forms in 31% of cases. When present, it appeared as intraluminal air bubbles (38.7%) or air-fluid levels (22.6%), appendolith air (41.9%), intramural air (16.1%), peri-appendiceal air bubbles (12.9%), or extraluminal air-fluid level(s) (29.0%). Intramural and extraluminal air correlated with perforation in 60% and 100%, respectively. In 100 CT cases of a normal appendix, air was present in 57%. It was always intraluminal and appeared as small bubbles of air (52.6%), a tubular-shaped air collection (43.9%), or as an air-fluid level (3.5%). The appendiceal lumen was either airless (43%), or minimally (32%), moderately (18%), or completely filled with air (7%). CONCLUSION: Air is a common finding at appendiceal CT in both the normal and inflamed appendix. Intraluminal air is seen in both appendicitis and normal appendices, and cannot be presumed to indicate a patent lumen and thus a normal appendix. Appendolith, intramural and peri-appendiceal air appear diagnostic of appendicitis.     

Nests, tree holes, and the evolution of primate life histories

In contrast to the majority of primates, many prosimians, some New World monkeys, and the great apes rest in tree holes or self-constructed nests during their inactive periods. The goal of this comparative study was to examine possible functions of this interspecific variation. Information on resting behavior, maternal behavior, and basic life-history traits was gleaned from the literature and mapped onto a phylogenetic tree of primates for various comparative tests. Parsimony-based reconstructions revealed that only the use of nests or tree holes as shelters for young infants can be unequivocally reconstructed for various higher taxa, suggesting that it is functionally different from the use of shelters by adults (who may be accompanied by infants). Further reconstructions revealed that the ancestral primate was most likely nocturnal and solitary and produced a single infant that was initially left in a shelter and later carried orally to a parking place in the vegetation--a combination of traits exhibited by many living galagos. Evolutionary losses of the use of nests were concentrated among diurnal and nonsolitary taxa and weakly associated with evolutionary increases in body size. Thus, protective functions of nests or tree holes used by prosimians are either secondary or there are alternative ways of obtaining protection. Because the evolution of larger litters was significantly associated with the presence of shelters, the presence of relatively altricial young among prosimians best explains the use of nests and tree holes, which are in most but not all cases also used by adults. These shelters therefore play an integral part in the life-history strategies of primitive primates and their ancestors and evolved secondarily among anthropoids for other purposes.     

Nodular duodenum after pediatric renal transplant due to Brunner''s gland hyperplasia

We studied mortality related to peptic ulcer bleed in a well defined cohort of patients in the month after the episode of peptic ulcer bleed. Our objective was to assess the contribution of peptic ulcer antecedents and other predictive factors on the risk of dying. The study cohort comprised 1,020 patients hospitalized for an episode of peptic ulcer bleed between January 1991 and March 1994 and identified in the General Practice Research Database in the United Kingdom. Six hundred twenty-three patients had no prior episode of peptic ulcer disease, and 384 had peptic ulcer antecedents; for 13 patients, information was not available. Forty-five patients died (mortality rate = 4.4 per 100 person-months; 95% confidence interval = 3.3-5.9) within 1 month of the peptic ulcer bleed. Patients with no peptic ulcer antecedent faced a greater risk of dying than patients with antecedents (relative risk = 3.0; 95% confidence interval = 1.2-7.1). Elderly patients, those undergoing surgery, and current users of acid-suppressing drugs or nonsteroidal antiinflammatory drugs all had an increased mortality risk. Patients presenting with their first-ever episode of peptic ulcer bleed have a higher case fatality rate than those with previous episodes of peptic ulcer.     

Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9

Ubiquitin conjugating enzymes (UBCs) are a family of proteins directly involved in ubiquitination of proteins. Ubiquitination is known to be involved in control of a variety of cellular processes, including cell proliferation, through the targeting of key regulatory proteins for degradation. The ubc9 gene of the yeast Saccharomyces cerevisiae (Scubc9) is an essential gene which is required for cell cycle progression and is involved in the degradation of S phase and M phase cyclins. We have identified a human homolog of Scubc9 (termed hubc9) using the two hybrid screen for proteins that interact with the human papillomavirus type 16 E1 replication protein. The hubc9 encoded protein shares a very high degree of amino acid sequence similarity with ScUBC9 and with the homologous hus5+ gene product of Schizosaccharomyces pombe. Genetic complementation experiments in a S.cerevisiae ubc9ts mutant reveal that hUBC9 can substitute for the function of ScUBC9 required for cell cycle progression.