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.     

Serial cytological assay of micronucleus induction: a new tool to predict human cancer radiosensitivity

The role of the propeptide sequence and a disulfide bridge between sites 1 and 122 in chymotrypsin has been examined by comparing enzyme activities of wild-type and mutant enzymes. The kinetic constants of mutants devoid of the Cys1-Cys122 disulfide-linked propeptide show that this linkage is not important either for activity or substrate specificity. However this linkage appears to be the major factor in keeping the zymogen stable against non-specific activation. A comparison of zymogen stabilities showed that the trypsinogen propeptide is ten times more effective than the chymotrypsinogen propeptide in preventing non-specific zymogen activation during heterologous expression and secretion from yeast. This feature can also be transferred in trans to chymotrypsinogen; i.e. the chymotrypsin trypsin propeptide chimera forms a stable zymogen.     

Toward successful compliance with JCAHO standard NC.1

Recommendations resulting from a JCAHO survey can be a true blessing as they force nursing departments to assess critically their professional practice and documentation systems. Systematic preparation, begun at least two years prior to the survey, includes Nursing Administration, a Nursing Documentation Task Force and all staff nurses. Educational consultants assigned to each unit bring nurses up-to-date on nursing process and nursing diagnosis. Mock surveys and cross-training in chart review prepare staff nurses for confident participation in the accreditation process.     

Desensitization of mutant acetylcholine receptors in transgenic mice reduces the amplitude of neuromuscular synaptic currents

While the slow onset of desensitization of nicotinic acetylcholine receptors (AChRs), relative to the rate of acetylcholine removal, excludes this kinetic state from shaping synaptic responses in normal neuromuscular transmission, its role in neuromuscular disorders has not been examined. The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder caused by point mutations in the AChR subunit-encoding genes leading to kinetically abnormal (slow) channels, reduced miniature endplate current amplitudes (MEPCs), and degeneration of the postsynaptic membrane. Because of this complicated picture of kinetic and structural change in the neuromuscular junction, it is difficult to assess the importance of the multiple factors that may be responsible for the reduced endplate current amplitudes, and ultimately the clinical syndrome. In order to address this we have used a transgenic mouse model for the SCCMS that has slow AChR ion channels and reduced endplate responsiveness in the absence of any of the degenerative changes. We found that the reduction in MEPC amplitudes in these mice could not be explained by either reduced AChR number or by reduced AChR channel conductance. Rather, we found that the mutant AChRs in situ manifested an activity-dependent reduction in sensitivity that caused diminished MEPC and endplate current amplitude with nerve stimulation. This observation demonstrates that the basis for the reduction in MEPC amplitudes in the SCCMS may be multifactorial. Moreover, these findings demonstrate that, under conditions that alter their rate of desensitization, the kinetic properties of nicotinic AChRs can control the strength of synaptic responses.     

Beyond the interpersonal circumplex in group psychotherapy: the structure and relationship to outcome of the Individual Group Member Interpersonal Process Scale

Development of a new scale to measure patient behavior in group psychotherapy, the Individual Group Member Interpersonal Process Scale (IGIPS), is described. This scale captures clinically important aspects of how patients act in group, including how they respond to the other group members. The IGIPS was applied to videotapes of the first four sessions of seven 15-session outpatient therapy groups (52 patients) in the Mental Health Department of a health maintenance organization. The scale was found to have five factors (Activity, Interpersonal Sensitivity, Comfort with Self, Self-Focus, and Psychological Mindedness). Patient behavior that was moderate on two IGIPS dimensions was connected with better outcome than was that of patients with more extreme behavior in either direction.     

Adopting a policy of reuse

In many firms' experience, reusing elements of proven systems designs and software is best done through a companywide program. Reuse means savings in design, testing, manufacturing and support. The author gives the basic information a company needs to get started. The author discusses the context for reuse, planning and strategy involved in a reuse program     

A neural network that predicts psychiatric length of stay

One hundred and twelve bilateral thyroidectomies for solitary thyroid nodules with suspected malignancy were performed. The incidence of malignancy in the 112 primary nodules was 42%. Twenty-nine of the 112 contralateral lobes (26%) contained malignancy, which was unsuspected in 80%. Of these 29, 20 were foci of papillary cancer < or = 5 mm and 9 were larger papillary tumors or follicular carcinoma. We analyzed these 112 patients to determine whether there was a simple method to identify those patients at risk for contralateral, unsuspected malignancy. With use of the AMES clinical staging retrospectively, 70 of the 112 patients were classified as having low-stage disease. Fifty percent (35) had cancers on the primary side and 27% (19) on the contralateral side. Of these 19 contralateral cancers, 14 were papillary cancers < or = 5 mm, 4 were papillary cancer > 5 mm and one was a 1.5 cm follicular carcinoma, a similar distribution as in the whole group of 112. When the AMES analysis then excluded those thought to be at risk for multicentricity or papillary carcinoma and examined female patients only with nonpapillary frozen sections, nonpapillary aspiration cytological results, and no history of radiation exposure, no further reduction in the proportion of contralateral cancers (7 of 26, 27%) was found. Fifty-five of the 112 patients underwent preoperative ultrasound scans. In those cases in whom the contralateral lobe had no intraoperative palpable or preoperative sonographic mass, 5 of 20 still had contralateral cancers, but all were papillary < or = 5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetic analysis of the crystallization of poly(p-phenylene sulphide)

Growth rates of spherulites were measured in poly(p-phenylene sulphide) crystallized from the melt and the quenched glass over the temperature range 100°C–280°C, possibly the most extensive overall range yet reported for any polymer and, as such, most propitious for study of régime III crystallization. For a medium M.wt. polymer, a régime II → III transition was obtained at 208°C using values of transport parameters common to many polymers ($\text{U1 = 1400}\text{cal mol}{}^{\mathrm{?1}}$, T_∞ ? T_g = 30°C) together with experimentally determined values of T⁰_m(315°C) and T_g(92°C). Under these conditions, the régime III/II slope ratio was found to be 2.07 (i.e. only 3.5% higher than predicted by régime theory), and reasonable estimates of surface free energies and of the work of chain folding were obtained. Other choices of the transport terms, including WLF and zero values, did not allow successful kinetic analyses. Although a régime I → II transition is predicted to occur at the high-temperature end of our growth-rate data, we found no experimental evidence for it. For a low M.wt. polymer, our analysis showed that régime III kinetics is obeyed at low temperatures, while at higher ones there is a continuous departure from that behaviour without, however, full attainment of régime II kinetics.     

Outcomes related to burn-related child abuse: a case series

Nationally, approximately 10% of child abuse cases involve burning, and up to 20% of pediatric burn admissions involve abuse or neglect. Historically, these cases have been more difficult to prosecute than nonburn cases for multiple reasons. Between 1995 and 1999, there were 285 pediatric (under 18) patients admitted to the Spectrum Health Regional Burn Center. Of these cases, 18 of the alleged perpetrators were legally investigated for suspicion of child abuse, and 7 received punitive sentences. We found that men tended to be prosecuted and convicted more often than women and that cases involving multiple instances of injury tended to be prosecuted more frequently. Similarly, we found that cases involving more severe injuries tended to be prosecuted more successfully. There are many psychological and social factors involved in handling burn abuse cases. However, by successful prosecution of these crimes, victims tend to fare better both socially and psychologically.