Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

Estimation of actinide skeletal content in humans based on bone samples collected at autopsy.

The USTUR has developed simple linear and multiple regression models for estimating skeletal actinide concentrations on the basis of bone samples collected at autopsies of non-whole body tissue donors. Bone samples usually collected include a clavicle, the patella(e), one or more ribs, the sternum, and a vertebral wedge cut from within the abdominal cavity. The described models were derived by regression analyses with the analytical results from those bones and the entire skeletons of eight whole body donations to the USTUR. With the model, skeletal concentrations of 238Pu, (239+240)Pu, and 241Am can be estimated from wet or ashed actinide concentrations in one to five of the bones usually collected at autopsy and analyzed. Application of the models to a selected USTUR non-whole body donation (Case 0240) indicated that the skeletal actinide concentration estimates were reasonably precise and that there was good agreement between the results from individual bones with wet or ashed actinide concentrations. The USTUR will apply the model that is based on wet concentrations of bones to estimate skeletal concentrations of actinides in all non-whole body autopsy cases for the sake of consistency because of the large number of early cases for which ashed weights of bones were not recorded.

Emergency airway management in penetrating neck injury.

STUDY OBJECTIVES: Airway management in the context of penetrating neck injury is a challenging scenario. Management decisionmaking has not been well studied and the initial airway approach remains controversial. We examined various initial emergency airway techniques and their success in the setting of penetrating neck trauma. METHODS: A retrospective study was conducted of emergency department intubations in penetrating neck injury from January 1, 1993, to December 31, 1996, at a Level I trauma center. Cases of out-of-hospital traumatic arrest or out-of-hospital intubation were excluded. Successful airway management was defined as endotracheal tube placement confirmed by clinical evaluation, pulse oximetry, chest radiography, and end-tidal CO(2) detection. RESULTS: During the study period, 748 consecutive patients with penetrating neck injury were evaluated in the ED. Of these, 82 (11%) were deemed to require immediate airway management. Twenty-four of the 82 were excluded because of out-of-hospital traumatic arrest or out-of-hospital intubation, resulting in a study population of 58 patients. Of these 58 patients, 39 had initial rapid sequence intubation using succinylcholine with a 100% success rate. Five comatose patients had successful orotracheal intubation without paralysis, and 2 patients underwent successful emergency tracheostomy. The remaining 12 patients had initial fiberoptic intubation by otolaryngology clinicians, which was unsuccessful in 3 patients. All 3 of these patients were subsequently successfully orotracheally intubated using the rapid sequence intubation technique. Therefore, oral endotracheal intubation was the definitive method of airway management in 47 (81%) of the 58 patients and was successful in all cases. CONCLUSION: Rapid sequence intubation was the most commonly performed initial technique by emergency physicians and was safe and effective in all cases attempted. Furthermore, rapid sequence intubation methodology resulted in successful intubation of the fiberoptic intubation failures. Physicians with airway expertise should consider using rapid sequence intubation as an initial airway technique in managing patients with penetrating neck injury who require airway control.

Intracranial hemorrhage associated with tangential gunshot wounds to the head.

UNLABELLED: Tangential gunshot wounds (TGSWs) to the head are gunshot wounds in which the bullet or bullet fragments do not penetrate the inner table of the skull. OBJECTIVES: To determine the occurrence of intracranial hemorrhage (ICH) associated with TGSW to the head and to assess the ability of selected clinical criteria to predict ICH in this patient population. METHODS: A retrospective chart review of patients diagnosed as having TGSWs to the head presenting to the ED of Los Angeles County + University of Southern California Medical Center from October 1, 1993, to May 31, 1996. RESULTS: Four hundred twenty patients with gunshot wounds to the head presented to the ED. CT confirmed the diagnosis of TGSWs in 154 patients (36.7%). Head CT of patients with TGSWs revealed 25 (16.2%) skull fractures and 37 (24.0%) ICHs. Fourteen (56.0%) skull fractures were depressed. Of patients with a CT-documented TGSW to the head, 23 (16.1%) had a history of a loss of consciousness (LOC), 129 (84.3%) had a normal neurologic examination in the ED, 17 (11.1%) had a Glasgow Coma Scale score (GCS) < 15, and 75 (48.7%) had retained extracranial bullets or bullet fragments. Of all patients with TGSWs to the head, 113 had a GCS of 15 with no LOC and a normal neurologic examination, with 17 of these 113 patients (15.0%) having ICH. One patient died while hospitalized. Fifty-six (36.6%) patients were released home directly from the ED. Five clinical criteria (history of LOC, GCS < 15 on ED presentation, skull fracture, location of TGSW on the skull, and presence of extracranial bullet fragments) were examined to determine their ability to predict ICH. None of these criteria either alone or in combination were adequately predictive of ICH. CONCLUSION: In this series, 1 in 4 patients with a TGSW to the head had an ICH. All patients with TGSWs to the head should undergo head CT to rule out depressed skull fractures and ICH.

Standards for psychological services in long-term care facilities.

Psychologists in Long-Term Care (PLTC), a national network established in 1983, has developed, with input from colleagues and consumers, standards for psychological practice in long-term care facilities. These standards address provider characteristics, methods of referral, assessment practices, treatment, and ethical issues. This article describes the document's development and offers suggestions for its use.

Determination of taxanes in Taxus brevifolia extracts by tandem mass spectrometry and high-performance liquid chromatography.

A tandem mass spectrometric (ms/ms) method using desorption chemical ionization is described for the quantitation of taxol [1], cephalomannine [2], and baccatin III [3] found in Taxus brevifolia bark and needle extracts. A parent ion scan was used to simultaneously determine the weight percentages of 1-3 in bark and needle samples by the method of standard addition. In an alternative experiment, the concentration of 1 in the same samples was determined by ms/ms using trideuterated 10-acetyltaxol [7a] as an internal standard. High-performance liquid chromatography (hplc) was also used to determine the weight percentages of 1-3 in the same T. brevifolia bark and needle extracts with an external standard. The ms/ms method of quantitation by internal standard is the best overall method of analysis examined. With this method, 1 was quantitated in the T. brevifolia extracts at the low picomole level with a relative standard deviation of 17% or better for all samples analyzed with an analysis time of less than five min per sample. The precision, level of quantitation, and speed of analysis of the three methods of taxane quantitation are compared.

Help-seeking behaviors of people with sexual problems.

Help-seeking activities associated with the sexual problems of community respondents (N = 503) were studied. Major findings include (i) a majority of respondents reported some form of social help-seeking from predominantly informal rather than professional helpers; (ii) a significant increase over early adulthood in the likelihood of reporting a dyadic sexual problem was evidenced, however there was no parallel change in help-seeking behaviors with age; (iii) help-seeking from intimates was associated with obtaining help from other informal contacts; (iv) help-seeking from extrafamilial, but not familial, supports was found to covary with income, and (v) a "normative" sequence to help-seeking behaviors was identified. Also discussed is the present work's relevance to research on human immunodeficiency virus transmission.

Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients.

Thyrotropin (TSH) concentrations were measured in 1580 hospitalized patients and 109 normal persons. Using the mean +/- 3 SD limits of the log values for the controls (0.35-6.7 milli-int. units/L), the proportion of abnormal TSH results in the hospitalized patients was 17.2%. TSH was undetectable (less than 0.1 milli-int. unit/L) in 3.1% of patients, suggesting hyperthyroidism, and high (greater than 20 milli-int. units/L) in 1.6%, suggesting hypothyroidism. On follow-up of 329 patients, 62% with abnormal TSH (less than 0.35 or greater than 6.7 milli-int. units/L) and 38% with normal TSH concentrations, only 24% of those with undetectable TSH had thyroid disease: 36% of them were being treated with glucocorticoids and 40% had nonthyroidal illness (NTI). Although half the patients with TSH greater than 20 milli-int. units/L had thyroid disease, 45% of patients had high TSH values associated with NTI. TSH concentrations usually returned towards normal when patients' therapy with glucocorticoids was discontinued or they recovered from NTI. TSH test sensitivity appeared good when the mean +/- 3 SD limits of the reference population were used, i.e., no cases of hyper- or hypothyroidism, as identified by free thyroxin index (FT4I), were missed. However, TSH test specificity was inferior to that of the FT4I test (90.7% vs 92.3%), although specificity could be improved to 97.0% if the wider TSH reference limits of 0.1 to 20 milli-int. units/L were used--limits considered pathological if applied to outpatients. Evidently, different reference intervals for TSH are needed for hospitalized and nonhospitalized patients. We conclude that a "sensitive TSH assay" is not a cost-effective thyroid screening test for hospitalized patients as compared with the FT4I.

Testicular cultivation of Treponema pallidum (Nichols strains) facilitated by sustained-release steroid administration.

Treponema pallidum cultivation is facilitated by substitution of methylprednisolone acetate suspension for hydrocortisone administration during rabbit testicular infection. Methylprednisolone suspension reduces testicular mononuclear cell infiltration and should benefit future studies of virulent T. pallidum.