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Biomedical subjects

J McGrew

Publications and source records attributed to J McGrew.

13 recordsLinked to original sources
PubMed2001

Nucleocytoplasmic shuttling of the thyroid hormone receptor alpha.

The thyroid hormone receptor alpha (TR alpha) exhibits a dual role as an activator or repressor of gene transcription in response to thyroid hormone (T(3)). Our studies show that TR alpha, formerly thought to reside solely in the nucleus tightly bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. The finding that TR alpha shuttles reveals an additional checkpoint in receptor control of gene expression. Using Xenopus oocyte microinjection assays, we show that there are two coexisting mechanisms for nuclear entry of TR alpha. First, nuclear import of TR alpha (molecular mass 46 kDa) was not sensitive to general inhibitors of signal-mediated transport, indicating that TR alpha can enter the oocyte nucleus by passive diffusion. Second, when TR alpha was tagged with glutathione-S:-transferase, import of the fusion protein (molecular mass 73 kDa) was completely blocked by these inhibitors, demonstrating that an alternative, signal-mediated import pathway exists for TR alpha. Nuclear retention of TR alpha in oocytes is enhanced in the presence of T(3), suggesting that more intranuclear binding sites are available for the ligand-bound receptor. Using mammalian cells, we show that shuttling of green fluorescent protein (GFP)-tagged and untagged TR alpha is inhibited in both chilled and energy-depleted cells, suggesting that there is an energy-requiring step in the nuclear retention/export process. Nuclear export of TR alpha is not blocked by leptomycin B, a specific inhibitor of the export receptor CRM1, indicating that TR alpha does not require the CRM1 pathway to exit the nucleus. Dominant negative mutants of TR with defects in DNA binding and transactivation accumulate in the cytoplasm at steady state, illustrating that even single amino acid changes in functional domains may alter the subcellular distribution of TR. In contrast to TR alpha, nuclear export of its oncogenic homolog v-ErbA is sensitive to leptomycin B, suggesting that the oncoprotein follows a CRM1-mediated export pathway. Acquisition of altered nuclear export capabilities may contribute to the oncogenic properties of v-ErbA.

Animals↗
PubMed1999

Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus.

Most poxviruses, including variola, the causative agent of smallpox, express a secreted protein of 35 kDa, vCCI, which binds CC-chemokines with high affinity. This viral protein competes with the host cellular CC-chemokine receptors (CCRs), reducing inflammation and interfering with the host immune response. Such proteins or derivatives may have therapeutic uses as anti-inflammatory agents. We have determined the crystal structure to 1.85-A resolution of vCCI from cowpox virus, the prototype of this poxvirus virulence factor. The molecule is a beta-sandwich of topology not previously described. A patch of conserved residues on the exposed face of a beta-sheet that is strongly negatively charged might have a role in binding of CC-chemokines, which are positively charged.

Amino Acid Sequence↗
PubMed1996

An estimate and comparison of MMPI and MMPI-2 concurrent validity. Predicting DSM-III-R diagnoses among college students.

The ability of the MMPI and MMPI-2 to identify persons who were either free or not free from DSM-III-R-defined psychopathology was assessed and compared. University students completed either the MMPI (N = 388) or the MMPI-2 (N = 302) along with a computerized version of the Diagnostic Interview Schedule, which was scored according to the criteria of the DSM-III-R. MMPI profiles were categorized with several different rules as being within normal limits or not. DSM-III-R status served as the criterion variable, and 189 (27%) study participants met criteria for a current axis I disorder. Although MMPI profiles were more elevated than MMPI-2 profiles, the proportion of profiles categorized as either normal or abnormal did not differ. Both the MMPI and MMPI-2 demonstrated a statistically reliable degree of relation with the broadly applied DSM-III-R standard of current disorder or not. Predictive relationships were modest. The variance in DSM-III-R-measured psychopathology accounted for by MMPI or MMPI-2 categorizations averaged gamma 2 = .12. Contrary to hypotheses, our results did not demonstrate improved MMPI-2 discrimination.

Adult↗
PubMed1995

Regulated expression of Ly-6A.2 is important for T cell development.

Ly-6A.2 is a surface protein on T cells that may play a role in lymphocyte activation. The regulation of Ly-6A.2 expression during T cell lymphopoiesis has been intriguing. It is one of the earliest markers expressed on pluripotent hemopoietic stem cells and is present on both primitive and mature T cells, but its expression is extinguished in the thymus during key developmental stages. To determine whether Ly-6A.2 is active on developing T cells, as well as the significance of its developmental regulation, Ly-6A.2 was expressed throughout T cell development under control of the T cell-specific human CD2 enhancer in transgenic mice. The constitutive overexpression of Ly-6A.2 in vivo led to a marked impairment in the generation of thymocytes. Development was arrested at the time in thymic development when Ly-6A.2 expression is normally turned off. These results indicate that the regulated expression of Ly-6A.2 in thymocytes may be important for normal development. Moreover, these findings demonstrate that Ly-6A.2 is active in the thymic microenvironment.

Animals↗
PubMed1994

Validity of the substance abuse scales of the MMPI-2 in a college student sample.

This study assessed the validity of three Minnesota Multiphasic Personality Inventory-2-based (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) substance abuse scales. The scales were the MacAndrew Alcoholism Scale-Revised (MAC-R; Butcher et al., 1989) and the recently developed Addiction Acknowledgment Scale and Addiction Potential Scale (AAS & APS; Weed, Butcher, McKenna, & Ben-Porath, 1992). Study participants were 308 male and female college students who completed the MMPI-2 and the substance use disorder modules of the Diagnostic Interview Schedule. The MAC-R and the APS had a nonsignificant-to-weak relationship with substance dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1980). The AAS had a moderate ability to identify the 33 study participants who met DSM-III-R criteria for a substance use disorder, primarily alcoholism. Broadening the definition of substance abuse to a continuum of alcohol/drug problems did not alter the character of findings. These results highlight the relative superiority of direct (AAS) versus subtle (APS, MAC-R) scales to detect substance dependence and support studies that question the overall utility of traditional MMPI scales to identify substance abuse.

Adolescent↗
PubMed1993

Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast.

It is widely assumed that degradation of mitotic cyclins causes a decrease in mitotic cdc2/CDC28 kinase activity and thereby triggers the metaphase to anaphase transition. Two observations made on the budding yeast Saccharomyces cerevisiae are inconsistent with this scenario: (i) anaphase occurs in the presence of high levels of kinase in cdc15 mutants and (ii) overproduction of a B-type mitotic cyclin causes arrest not in metaphase as previously reported but in telophase. Kinase destruction is therefore implicated in the exit from mitosis rather than the entry into anaphase. The behaviour of esp1 mutants shows in addition that kinase destruction can occur in the absence of anaphase completion. The execution of anaphase and the destruction of CDC28 kinase activity therefore appear to take place independently of one another.

Anaphase↗
PubMed1993

Familial resemblance of schizotypic traits.

The goal of this study was to examine the familial resemblance of schizotypic traits, and to explore whether different schizotypic traits are familially related to one another. Several of the Chapmans' psychosis proneness scales were administered to a group of college students and their families. Evidence of at least some familial resemblance was found for both physical anhedonia and perceptual aberration, though it was stronger for anhedonia. Anhedonia and perceptual aberration appeared to be familially influenced independently of one another. Finally, the results indicated that offspring resembled their mothers more than they resembled their fathers on both anhedonia and perceptual aberration.

Adolescent↗
PubMed1987

The changing smoking environment for middle and high school students: 1980-1983.

Cultural-historical changes in smoking prevalence and in smoking-related attitudes and beliefs were examined as part of a cohort-sequential study of 6th- to 12th-grade midwestern adolescents (N = 8681) between 1980 and 1983. Smoking prevalence decreased over the 4 years for the younger cohorts and remained unchanged for high school students. Paradoxically, however, some specific beliefs and attitudes about smoking (including health beliefs) became less negative with time. It is suggested that continuing negative social beliefs about smoking are supporting declines in smoking prevalence among younger cohorts. Implications of these cultural-historical changes for smoking behavior and smoking control are discussed.

Adolescent↗
PubMed1986

Single base-pair mutations in centromere element III cause aberrant chromosome segregation in Saccharomyces cerevisiae.

In this paper we show that a 211-base pair segment of CEN3 DNA is sufficient to confer wild-type centromere function in the yeast Saccharomyces cerevisiae. We used site-directed mutagenesis of the 211-base pair fragment to examine the sequence-specific functional requirements of a conserved 11-base pair segment of centromere DNA, element III (5'-TGATTTATCCGAA-3'). Element III is the most highly conserved of the centromeric DNA sequences, differing by only a single adenine X thymine base pair among the four centromere DNAs sequenced thus far. All of the element III sequences contain specific cytosine X guanine base pairs, including a 5'-CCG-3' arrangement, which we targeted for single cytosine-to-thymine mutations by using sodium bisulfite. The effects of element III mutations on plasmid and chromosome segregation were determined by mitotic stability assays. Conversion of CCG to CTG completely abolished centromere function both in plasmids and in chromosome III, whereas conversion of CCG to TCG decreased plasmid and chromosome stability moderately. The other two guanine X cytosine base pairs in element III could be independently converted to adenine X thymine base pairs without affecting plasmid or chromosome stability. We concluded that while some specific nucleotides within the conserved element III sequence are essential for proper centromere function, other conserved nucleotides can be changed.

Base Composition↗
PubMedDate not supplied

Prospective screening of substance dependence: the advantages of directness.

This study evaluated the ability of several subtle and direct alcoholism screening scales to identify DSM-III-R-defined substance dependence in a university setting. Study participants were university students (N = 495) who completed the substance use disorder modules of the Diagnostic Interview Schedule along with the Michigan Alcoholism Screening Test (MAST), the Substance Abuse Subtle Screening Inventory (SASSI), and five direct screening questions concerning the consequences of alcohol and drug use. Results indicated that the SASSI had no appreciable ability to identify the 57 study participants who met criteria for a substance use disorder. The MAST also demonstrated limited predictive ability, and results suggested that this is because many MAST items assess the more advanced features of alcoholism, features less common in the substance abuse found among university students. The five direct screening questions were modestly useful, and it is argued that there are advantages to directness when screening for substance use disorders.

Adolescent↗
PubMedDate not supplied

Alexithymia and the interpretation of hostile-provoking situations.

BACKGROUND: To examine the relationship between alexithymia and the interpretation of hostility-provoking situations. METHODS: Sixty-two college students completed the TAS-20 and the Test for the Interpretation of Provoking Situations (TIPS). The TIPS measures how accurately participants can select the most likely explanation for the occurrence of a hypothetical, potentially provoking situation; it also measures how accurately participants judge whether explanations for events are innocent or noninnocent. RESULTS: Higher levels of alexithymia were associated with greater degrees of accuracy in interpreting the innocence of interpersonal information. The facets of alexithymia that were most strongly associated with interpretation accuracy varied by gender. CONCLUSIONS: Alexithymia is not associated with a general affect recognition deficit. The results are consistent with social factors playing a central role in alexithymia.

Adolescent↗