Concordance between ANSI occupational back injury codes and claim form diagnoses and a lower bound estimate of the fraction associated with disc displacement/herniation

The current BLS Annual Survey of Occupational Illnesses and Injuries and several recent analyses of factors affecting missed worktime in occupational back injuries rely on ANSI-based injury codes derived from injury narratives to classify occupational injuries and estimate incidence and outcome. No population-based studies of the concordance between back injury codes and clinical diagnoses have been reported. Back injury cases were identified in two large work-injured populations totaling almost 80,000 cases in the states of Michigan and Minnesota. In both populations, cases had been coded by the single nature-of-injury and part-of-body-injured codes assigned by an ANSI-based injury-coding system and by as many as four (Michigan) or three (Minnesota) clinical diagnoses according to the International Classification of Diseases-Clinical Modification, 9th Revision. Concordance was measured by the sensitivity and predictive value positive (PVP, aka PV+ or PPA) of the injury coding scheme for related diagnostic groups. We also used an algorithm based on the limited clinical information available to corroborate the diagnosis of displaced/herniated disc for cases that underwent spinal surgery. Cases identified by the algorithm were then used to obtain a lower bound estimate of the fraction with disc injury. The injury coding scheme had PVPs of 82.9-90.1% and overall sensitivities of 69.7-75.9%. Sensitivities for individual diagnostic groups show that their distribution in ANSI-coded injury groups is skewed slightly toward cases with sprain and disc displacement/herniation, but these shifts are modest. The lower bound estimate of the fraction of cases with disc displacement/herniation in a population of cases with back injuries producing at least 1 day of missed worktime is 5.8%. The demographic comparisons indicate that, as the time between injury and cohort ascertainment increases during the first 8 days of missed worktime following injury, the proportion of younger workers in an injury cohort decreases. The relationship between increasing age and increasing missed worktime disability, reported in various outcome studies, is also present during the first few days following injury. The use of ANSI injury codes underestimates the contribution of back injuries to missed worktime because 24-30% of cases are missed by the ANSI coding system. However, the distribution of diagnostic groups in the injury-coded groups approximates that observed with all diagnosed cases and supports the use of such data to study outcome. Our estimate, and one from Quebec, suggest that disc displacement/herniation occurs more frequently in the subset of occupational back injuries compared to the set of back injuries from all sources.     

The carcinogenicity of environmental tobacco smoke

Male strain A/J mice were exposed for 6 h a day, 5 days a week to environmental tobacco smoke (ETS) generated from Kentucky 1R4F reference cigarettes. Chamber concentrations were 87 mg/m3 of total suspended particulate matter (TSP), 246 p.p.m. of CO and 16 mg/m3 of nicotine. After 5 months, 33% of the ETS exposed and 11% of the control animals had one or several lung tumors; the difference was statistically not significant. A second group of animals exposed for 5 months to ETS was allowed to recover for another 4 months in filtered air. When they were killed, 85% of the ETS animals had lung tumors (average number per lung: 1.4 +/- 0.2), whereas in the control group 38% had lung tumors (average number of lung tumors in all animals 0.5 +/- 0.2). The differences in tumor incidence and multiplicity were statistically significant. More than 80% of all tumors were adenomas, the rest adenocarcinomas. When animals were pretreated with a carcinogen, lung tumor multiplicity was lower in the ETS exposed animals after 5 months compared with controls injected with a carcinogen and kept in air. However, after an additional 4 month recovery period in air, lung tumor multiplicities were the same in ETS plus carcinogen exposed mice as in carcinogen-treated air-exposed controls. Histopathologic and morphometric analysis of the lung tissue failed to reveal any differences between ETS exposed and control animals. However, immediately after ETS exposure, immunohistochemistry revealed increased staining for CYP1A1 in airway epithelia and lung parenchyma; following recovery in air, the staining disappeared again. Analysis of cell kinetics showed an initial burst of increased DNA synthesis in the epithelial cells of the airways and a smaller early positive response in the parenchyma. Feeding of butylated hydroxytoluene during ETS exposure did not modulate lung tumor development. It was concluded that ETS is a pulmonary carcinogen in strain A/J mice.     

Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases

Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.     

Detection of congenital müllerian duct anomalies using three-dimensional ultrasound

PURPOSE: The purpose of this study was to assess the value of 3-dimensional sonography in the diagnosis of congenital müllerian duct anomalies, which cause infertility, preterm labor, and first trimester abortion. METHODS: A prospective study was undertaken in which 40 patients with histories of repeated spontaneous abortions or infertility were first examined using conventional 2-dimensional sonography or hysterosalpingography. Three-dimensional transvaginal sonography was then performed. RESULTS: Twenty-eight women had müllerian duct abnormalities, and 12 women had normal uterine anatomy. Müllerian duct defects detected in this study were unicornuate uterus (3), bicornuate uterus (3), complete or partial septate uterus (12), arcuate uterus (9), and didelphic uterus (1). The diagnosis of müllerian duct anomalies in these patients was confirmed by laparoscopic and/or hysteroscopic examinations. Three-dimensional sonography demonstrated all congenital uterine abnormalities with a sensitivity and specificity of 100%. Separate uterus and bicornuate uterus could be correctly diagnosed using 3-dimensional sonography in 11 (92%) of 12 cases and 3 (100%) of 3 cases, respectively. These 2 abnormalities were commonly confused with each other using hysterosalpingography and conventional sonography. CONCLUSIONS: Three-dimensional sonography with image reconstruction is less expensive and less invasive than hysterosalpingography for the assessment of uterine anatomy and diagnosis of müllerian duct abnormalities. The ability to visualize both the uterine cavity and the myometrium on a 3-dimensional scan facilitates the diagnosis of uterine anomalies and enables the differentiation of septate from bicornuate uteri for preoperative surgical planning.     

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.     

The effect of verbal elaborations on memory in young and older adults

The Stein paradigm was used to examine the circumstances under which verbal elaborations enhance memory in young and older adults. Subjects studied target adjectives that were embedded in one of three sentence contexts that varied in elaboration of the subject-adjective relationship: (1) nonelaborated base sentences; (2) base sentences with semantically consistent, but arbitrary verbal, elaborations; and (3) base sentences with explanatory verbal elaborations that clarified the significance of the subject-adjective relationship. The presence of the elaborations was varied at encoding and retrieval, and cued recall of the target adjectives was tested with incidental and intentional learning procedures. In Experiments 1A and 1B, explanatory elaborations at encoding and retrieval yielded the largest memorial facilitation for both young and older adults, and the benefit was comparable for the incidental and intentional learning measures. In Experiment 2, age-related differences in recall were minimal with explanatory elaborations at encoding and retrieval, but larger age differences occurred in the nonelaborated comparison conditions. In Experiment 3, explanatory elaborations present at encoding but not at retrieval enhanced recall when the original Stein stimuli were used, but not with the present stimuli. The implications of these results with regard to the mnemonic efficacy of verbal elaborations for young and older adults are discussed.     

Simultaneous measurement of opiate-induced histamine release in the periaqueductal gray and opiate antinociception: an in vivo microdialysis study

Histamine release and the subsequent activation of H2 receptors in the periaqueductal gray (PAG) are thought to be important components of morphine antinociception. In vivo microdialysis and antinociceptive testing were simultaneously applied in rats to characterize the effects of morphine on PAG histamine release and determine the relationship between histamine release and antinociception. In the absence of nociceptive (tail pinch) testing, morphine (12.8 mg/kg) induced a delayed, long-lasting release of histamine in the PAG. This effect of morphine was abolished by the opiate antagonist naltrexone (1 mg/kg) but was not mimicked by the mu-preferring agonist fentanyl (0.3 mg/kg), suggesting that activation of an opiate receptor other than, or in addition to, the mu receptor is necessary. In contrast to the findings with fentanyl in untested animals, fentanyl combined with nociceptive testing increased histamine release, even though testing alone had no such effect. Unexpectedly, tail pinch testing inhibited morphine-induced histamine release. These results show that the test procedure alters the action of opiates on histamine release, an effect likely to be the result of the stress of repeated tail pinch testing. Therefore, although histamine release may not be obligatory for all types of opiate antinociception, histamine in the PAG may function as a mediator of stress-induced potentiation of opiate antinociception. Even though the microdialysis technique has been acclaimed for its ability to assess neurochemical and behavioral characteristics simultaneously, the introduction of nociceptive testing clearly can alter the neurochemical systems under study.