Structural Characterization of Variant Forms of Arylsulfatase A that Associate with Alcoholism

Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type III_a and normal type IV_a, have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type III_a compared with nonalcoholic psychiatric and normal controls. Individuals with the III_a enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the III_a and IV_a individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from III_a individuals lacks an N -linked glycan found in ASA from IV_a individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N -linked carbohydrate or phosphorylation exist between the fibroblast ASA from III_a and IV_a individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.     

Inhibitory effects of amitriptyline on the stimulation-induced Ca2+ increase in parotid acini

The present study demonstrates the effects of the antidepressant, amitriptyline, and the acetylcholine antagonist, atropine, on the stimulation-induced rise in cytosolic, free Ca2+ (Cai2+). The changes in Cai2+ of collagenase-isolated rat parotid acini were measured by means of the Ca2(+)-sensitive dye, fura-2. It was found that stimulation by carbachol resulted in a maximal increase of 582 +/- 34 nM (mean +/- S.E.) in Cai2+ with a ks of 5.8 +/- 1.3 microM. Adrenaline caused a rise of 380 +/- 22 nM in Cai2+ with a ks of 0.5 +/- 0.2 microM. Amitriptyline and atropine were found to inhibit the carbachol-induced rise in Cai2+ with dissociation constants (kI) of 105 and 1.25 nM, respectively, in the absence of agonist. The adrenergic-induced rise in Cai2+ was inhibited by amitriptyline with a kI of 45 nM. Amitriptyline was found to inhibit both receptor classes by a competitive or mixed type of inhibition. Similarly, atropine exerted the same type of inhibition on the acetylcholine receptor. Amitriptyline and atropine were found to be mutually exclusive for competing for substrate binding on the receptor. These findings are consistent with a common binding site for amitriptyline and atropine on the acetylcholine receptor, possibly in close proximity with, but different from the substrate binding site. The stimulation-induced cell shrinkage evoked by the loss of electrolytes and water from the acini was measured by a 90 degree light scattering signal. It was found that this method makes possible the detection of autonomic side-effects of antidepressants on acini suspended in protein-containing media.     

Sociotropy and Autonomy as Vulnerabilities to Specific Life Events: Issues in Life Event Categorization

This study examined the relations betweensociotropy, autonomy, and stress severity ratings forhypothetical life events that were objectivelycategorized as interpersonal or achievement-related infocus. The hypothesis that sociotropy and autonomyserve as vulnerability factors to dysphoria in thepresence of life stress that matches the theme of thevulnerability was also examined in 6-week and 12-week follow-up evaluations. Results provided onlypartial support for the predicted relations amongsociotropy, autonomy, and perceived stress severityratings of interpersonal and achievement-related events. Longitudinal results failed to support thehypothesis that sociotropy and autonomy serve asvulnerability factors for matching interpersonal andachievement-related stress. It was concluded thatobjectively categorizing life events as interpersonal orachievement-related is problematic given that themeaning of life events can vary across individuals, andthat these meanings are likely to vary partly as a function of sociotropy and autonomy.     

C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

Internal fixation of children's fractures of the lower extremity

Lower grade fractures are by definition stable and almost always treated with casting or functional splinting. The best kind of fixation for the higher grade fractures, however, differs between adults and children. Appropriate treatments are discussed, and case-study illustrations are provided. Background on the anatomy of the tibia and femur is included.     

Patterns of Cocaine Use Among Cocaine-Dependent Outpatients

The authors systematically evaluated the frequency patterns of cocaine use in 85 cocaine-dependent outpatients and found four patterns of use: continuous (27%), intermittent patterned (35%), intermittent nonpatterned (25%), and occasional (13%). Few subjects reported consistent cycling between binges and crashes. There were no significant differences in patterns of use associated with gender, race, educational level, route of administration, or recency of heroin use. Continuous users and occasional users were older than intermittent users. Because different contingencies may control patterned vs. nonpatterned cocaine use, pattern of use may have implications for treatment, even in individuals reporting similar amounts of cocaine use.     

Stress on the Farm: A Test of the life-Events Perspective Among Iowa Farm Operators*

Although a great deal is known about the nature and severity of the recent financial crisis in agriculture, there has been little systematic study of the social and psychological effects of this crisis upon farm operators and their families. Using data from a statewide sample of Iowa farmers, this study tests some hypotheses about correlates of psychological stress. The findings suggest that many farm operators find their situations to be stressful and that such stress is related to the severity of their financial problems. In addition, the life-events perspective is examined in its utility to explain how adverse economic changes impact psychological well-being.     

Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 4l of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this “elevated apoB” allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL. © 1993 Wiley-Liss, Inc.