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Biomedical subjects

D A Adler

Publications and source records attributed to D A Adler.

At least 19 recordsLinked to original sources
PubMed2000

Patient-based health status assessments in an outpatient psychiatry setting.

OBJECTIVE: The reliability, validity, and feasibility of the routine use of a generic health status instrument, the Short-Form-36 Health Survey (SF-36), were examined in a psychiatric outpatient clinic of a general hospital. METHODS: The sample comprised 411 patients referred to an outpatient psychiatry department between April 1994 and March 1995. They filled out the SF-36 along with their admission forms. Scores and reports were generated, and the results were returned to the charts and used at weekly clinical conference discussions. Feasibility was evaluated using subjective and objective data on administration of the instrument, its psychometric properties, and costs. Results from the outpatient psychiatry patients were compared with those from patients scheduled for elective surgery and a healthy normative sample. RESULTS: Routine administration of the SF-36 was successfully achieved with minimal resistance from staff and patients. The SF-36 provided reliable and valid data. As predicted, patients with emotional disorders scored lower, indicating more impairment, on scales measuring mental health than did the elective surgery patients and the normative sample. However, the psychiatric patients' scores on the physical health scale were lower than clinicians expected. Compared with the elective surgery patients, the psychiatric patients were less impaired on only the physical functioning and bodily pain scales; no difference was found between the two groups in role functioning due to physical problems. CONCLUSIONS: Routine use of the SF-36 in a general hospital psychiatric outpatient clinic was feasible, and the results were reliable, valid, and helpful to clinicians. Psychiatric patients' significantly lower scores in physical health and social and role functioning provided additional information about their difficulties.

Adolescent↗
PubMed1999

The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression.

Acid ceramidase (AC) is the lysosomal enzyme that degrades ceramide into sphingosine and fatty acid. A deficiency in human AC activity leads to the lysosomal storage disorder, Farber disease (FD). The human AC gene (HGMW-approved symbol ASAH) was cloned and characterized, revealing an organization similar to that of the murine AC gene. The human gene spans about 30 kb in length and contains 14 exons ranging in size from 46 to 1201 bp. The exon/intron junctions were determined and found to follow the GT-AG rule. The putative promoter region had a GC content over 60%, lacked a TATA box, and contained several sequences matching transcription factor binding sites, including nine SP-1 sites, one AP-1 site, and three CACC boxes. The promoter activity of a 475-bp fragment from within this region was demonstrated by chloramphenicol acyltransferase assays. Northern blotting revealed variable expression of the human AC RNA; i.e., expression of the major 2.4-kb transcript was high in heart and kidney, followed by lung and placenta, but low in pancreas, liver, brain, and skeletal muscle. Two minor AC transcripts of 1.7 and 1.2 kb also were detected in heart and skeletal muscle. The human AC gene was mapped to the chromosomal region 8p21.3-p22 by in situ hybridization and FISH analyses, syntenic with the mouse chromosomal location. Finally, three new missense mutations, E138V, R254G, and P362R, were identified in the human AC gene from FD patients. Mutant AC cDNAs containing these point mutations were constructed and examined using the FLAG-tagged expression system. Although the levels of protein expression for these mutant ACs were about equivalent to that of the controls, their enzymatic activity was markedly reduced, confirming their authenticity.

3T3 Cells↗
PubMed1997

Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus.

Previous studies have shown that the chloride channel gene Clc4 is X-linked and subject to X inactivation in Mus spretus, but that the same gene is autosomal in laboratory strains of mice. This exception to the conservation of linkage of the X chromosome in one of two interfertile mouse species was exploited to compare expression of Clc4 from the X chromosome to that from the autosome. Clc4 was found to be highly expressed in brain tissues of both mouse species. Quantitative analyses of species-specific expression of Clc4 in brain tissues from mice resulting from M. spretus x laboratory strain crosses, demonstrate that each autosomal locus has half the level of Clc4 expression as compared with the single active X-linked locus. In contrast expression of another chloride channel gene, Clc3, which is autosomal in both mouse species is equal between alleles in F1 animals. There is no evidence of imprinting of the Clc4 autosomal locus. These results are consistent with Ohno's hypothesis of an evolutionary requirement for a higher expression of genes on the single active X chromosome to maintain balance with autosomal gene expression [Ohno, S. (1967) Sex Chromosomes and Sex-Linked Genes (Springer, Berlin)].

Animals↗
PubMed1996

The entire genomic sequence and cDNA expression of mouse alpha-galactosidase A.

The full-length cDNA and genomic sequences encoding mouse alpha-galactosidase A (alpha-Gal A; EC 3.2.1.22), a lysosomal galactohydrolase, were isolated and characterized. The cDNA's open reading frame encoded 419 amino acids and had 82% nucleotide (nt) and 78% amino acid identity with the human sequence, although the carboxy terminus of the mouse alpha-Gal A polypeptide was 10 amino acids shorter. The functional integrity of the mouse cDNA was demonstrated by transient expression in COS-1 cells. Northern analysis revealed two mRNA species of about 1.6 and 3.4 kb due to alternative polyadenylation signals. The entire 14.4-kb mouse genomic sequence was determined; each of its seven exons was interrupted by intronic sequence at the identical positions as the exons in the human gene. The mouse 5' flanking region (250 nt) had one Sp1, site, five CAAT boxes, and no TATA box and had 67% identity with the human promoter region. The gene contained 18 complete or partial Alu-repetitive elements (13 type 1 and 5 type 2 repeats), and three putative functional AATAAA consensus polyadenylation signals were identified 72, 1668, and 1682 nt after the TAA termination codon. Use of the 72-nt site and the 1866 and/or 1682 sites were consistent with the shorter and longer transcripts. The availability of the full-length cDNA and genomic sequence encoding mouse alpha-Gal A should facilitate structure/function studies of this lysosomal glycosidase and the construction of alpha-Gal A-deficient mice by targeted gene disruption.

Amino Acid Sequence↗
PubMed1996

Possible paroxetine-induced bruxism.

OBJECTIVE: To report the case of a patient with possible paroxetine-induced bruxism that was effectively treated with buspirone. CASE SUMMARY: A 20-year-old woman with no active medical conditions besides acne and no history of dental problems was seen in an outpatient psychiatry clinic for the evaluation of ongoing depression. The patient was prescribed paroxetine 10 mg every morning. After 5 days of therapy the patient reported no adverse effects, and the paroxetine dosage was increased to 20 mg every morning. Due to increased somnolence, the dosing schedule was subsequently changed to 20 mg hs. Two months later during a dental visit for a tooth extraction, the dentist noted that the patient's teeth appeared damaged in what he believed to be a pattern consistent with the grinding and clenching of teeth. Prior to this time, dental examinations had not revealed any tooth damage. The patient was thought to have paroxetine-induced bruxism and, based on earlier case reports, was treated with buspirone 5 mg hs. On day 4 of buspirone therapy the patient reported a significant reduction in the extent of gritting, tooth pain, and jaw tenderness. DISCUSSION: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline have been associated with bruxism in previous reports. This case suggests paroxetine-induced bruxism. The exact mechanism of SSRI-induced bruxism remains unclear. Many theories have been proposed, including sleep disturbance, serotonergic-mediated inhibition of dopamine manifesting as akathisia, and SSRI-induced anxiety. According to published reports, SSRI-induced bruxism may respond to therapy with buspirone. Consistent with these reports, this patient responded favorably to buspirone therapy. CONCLUSIONS: Clinicians should be aware that the potential for paroxetine-induced bruxism exists and that buspirone may be an appropriate therapeutic intervention.

Adult↗
PubMed1995

The X-linked methylated DNA binding protein, Mecp2, is subject to X inactivation in the mouse.

DNA methylation at the promoter region of X-linked genes is associated with the maintenance of X inactivation in mammals. One of the methylated DNA binding proteins, MECP2, that binds to methylated bases in DNA is encoded by a gene (Mecp2) located on the mouse X Chromosome (Chr). To determine whether this gene was expressed from the inactive X Chr, and X-autosome translocation (T(X;16)16H) system in which expression from the Mecp2 allele on the inactive X Chr could be assayed was used. Results from these experiments indicate that Mecp2 is subject to X inactivation in mouse.

Animals↗
PubMed1995

Schizophrenia and the life cycle.

We reframe the longitudinal treatment of persons with schizophrenia from the perspective of phases in adult development. This approach articulates the need for different interventions of varying intensities over the person's lifetime. The paper discusses the implications of an adult developmental perspective in managing pharmacologic treatment and psychosocial interventions, and in reallocating financial resources for improved long-term outcomes. This perspective is especially useful in the context of a comprehensive community mental health program permitting access to a continuum of services throughout the lifecycle.

Adolescent↗
PubMed1995

Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice.

We report the unprecedented finding of a gene with a different map position in two mouse strains. The Clcn4 gene was found to map to the X chromosome in the wild Mediterrean mouse, Mus spretus but to chromosome 7 in the inbred strain of laboratory mouse C57BL/6J. These data indicate that a recent evolutionary rearrangement occurred on the mouse sex chromosomes, very close to the pseudoautosomal region. Our data provide molecular evidence for a major divergence near the pseudoautosomal region, consistent with the hypothesis that hybrid sterility in these species results from abnormal pairing of sex chromosomes during male meiosis.

Amino Acid Sequence↗
PubMed1995

The mouse Sb1.8 gene located at the distal end of the X chromosome is subject to X inactivation.

The mouse homolog of the human DXS423E (SB1.8) gene has been isolated by screening a mouse cDNA library. Like its human counterpart, the mouse Sb1.8 gene is X-linked, as shown by Southern blot analysis and by in situ hybridization to metaphase chromosomes. Sb1.8 was sublocalized to band F of the mouse X chromosome, distal to Alas2 and proximal to DXPas1, which confirms a region of conservation between band Xp11.21-p11.22 in human and band XF in mouse. In situ hybridization also showed that the Smcx (Xe169) gene maps near Sb1.8 in band F. The Sb1.8 gene was shown to be highly conserved in mammals; partial DNA sequence analysis indicates 92% identity between the mouse and human genes. In contrast to the human DXS423E gene, the mouse Sb1.8 gene is subject to X inactivation, as shown by restriction enzyme and sequence analysis of mRNA from mice with Searle's translocation (T(X;16)16H). Absence of Sb1.8 expression from the inactive mouse X chromosome in vitro was confirmed by analysis of a cell line (Hobmski) in which the M. spretus X chromosome is inactivated. The Sb1.8 gene is a new member of a group of genes that escape X inactivation in human, but are inactivated in mouse.

Animals↗
PubMed1994

Chromosomal mapping and expression levels of a mouse soluble epoxide hydrolase gene.

The chromosomal location of a murine soluble epoxide hydrolase gene was determined using in situ mapping, restriction fragment length polymorphism (RFLP) and simple sequence length polymorphism (SSLP) analysis. In situ hybridization to mouse metaphase chromosomes using a soluble epoxide hydrolase cDNA probe showed that soluble epoxide hydrolase maps at band D of chromosome 14. An RFLP found between Mus castaneus (CAST) and Mus musculus (MEV) was used to map the soluble epoxide hydrolase gene in CAST x MEV intersubspecific testcross progeny to 14 cM from the Np-1 locus on mouse chromosome 14. SSLP markers were then used to confirm the location of soluble epoxide hydrolase at 14.0 +/- 3.7 cM distal to Np-1 and 19.2 +/- 4.3 cM proximal to D14Mit7. This region of mouse chromosome 14 is homologous with human chromosomes 8, 13 and 14. Enzyme assays and immunoblotting results suggest significant quantitative differences in expression of soluble epoxide hydrolase among three mouse strains. Northern blotting analysis showed that soluble epoxide hydrolase mRNA levels were correlated with the relative level of soluble epoxide hydrolase enzyme activity and soluble epoxide hydrolase protein in all three mouse strains.

Animals↗
PubMed1993

Maintenance of X inactivation of the Rps4, Zfx, and Ube1 genes in a mouse in vitro system.

Several genes, including RPS4X (ribosomal protein subunit 4), ZFX (zinc finger on the X chromosome), and UBE1 (ubiquitin-activating enzyme), have been shown to be expressed from the inactive X chromosome of cultured human cells. By contrast, these genes are subject to X-chromosome inactivation in tissues from adult mice. We have now examined the inactivation status of these genes in cultured mouse cells to determine whether the differences in X-chromosome inactivation between species is due to an intrinsic difference between human and mouse X-chromosome genes or whether it is a function of gene reactivation in cell culture per se. The expression of three mouse X-chromosome genes, Rps4, Zfx, and Ube1 was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in heterozygous cultured cells from a cross of a laboratory mouse by Mus spretus, which were selected to uniformly express the X chromosome from the laboratory mouse parent. No expression of the M. spretus alleles of these genes was observed in the cell line (Hobmski), which is consistent with the patterns of expression previously observed in mouse in vivo and indicates that these genes remain stably inactivated in an immortalized mouse cell line. By cytogenetic and RT-PCR analyses the Hobmski cell line was shown to retain a late-replicating X chromosome from M. spretus, which expressed the M. spretus allele of the X (inactive) specific transcript (Xist). The Hobmski cell line will be a useful resource for studying the features that maintain X-chromosome genes inactive.

Animals↗
PubMed1993

Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification.

Human and rabbit paraoxonases/arylesterases were purified to homogeneity by chromatographic and gel electrophoretic/isofocusing procedures coupled with activity stains. N-terminal and peptide sequence analysis suggested retention of the secretion signal sequence and allowed design of oligonucleotide probes. The probes were used to isolate a 1294-bp rabbit paraoxonase cDNA clone, which, in turn, was used to isolate three human cDNA clones. Comparison of rabbit and human protein and cDNA sequences indicated a high degree of sequence conservation (approximately 85% identity) and verified that paraoxonase retains its signal sequence (except for the N-terminal Met). The rabbit cDNA encodes a protein of 359 amino acids and the human a protein of 355 amino acids. In situ hybridization demonstrated, as expected, that the paraoxonase gene maps to the long arm of human chromosome 7. Arginine at position 192 specifies high activity paraoxonase and glutamine low activity human paraoxonase. Variation in protein levels explains the variation of enzyme activity observed within a genetic class. Toxicity studies showed that raising rat plasma paraoxonase levels by i.v. administration of partially purified rabbit paraoxonase protected animals against cholinesterase inhibition by paraoxon and chlorpyrifos oxon. Protection correlated with the relative rates of hydrolysis of these two compounds.

Amino Acid Sequence↗
PubMed1993

The molecular basis of the human serum paraoxonase activity polymorphism.

The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.

Aryldialkylphosphatase↗
PubMed1993

The case for a services-based approach to payment for mental illness under national health care reform.

In this position paper drafted by the committee on psychopathology of the Group for the Advancement of Psychiatry, the authors discuss merits and disadvantages of three different approaches to equitable coverage of mental illness: coverage for selected psychiatric diagnoses, coverage based on severity of impairment, and coverage of services. They believe that coverage of selected disorders has political appeal but is discriminatory and arbitrary; it is also impractical because clinicians may overdiagnose conditions covered by insurance and underdiagnose excluded conditions. Coverage based on severity of impairment, or disability, has similar limitations. The authors believe services should be the principal basis for coverage, as under general medical insurance. The approach is nondiscriminatory, and costs can be controlled through such means as managed care, changes in the payment system, or benefit design.

Community Mental Health Services↗
PubMed1992

The gene for B7, a costimulatory signal for T-cell activation, maps to chromosomal region 3q13.3-3q21.

B7 is an activation antigen expressed on activated B cells and gamma-interferon-stimulated monocytes. The B7 antigen is the natural ligand for CD28 on T cells. After engagement of T-cell receptor with antigen in association with major histocompatibility complex class II, a second signal mediated through the binding of B7 to CD28 greatly upregulates the production of multiple lymphokines. We have now mapped the B7 gene to human chromosome 3 using the technique of polymerase chain reaction on a panel of hamster x human somatic cell hybrid DNAs. We have further localized the gene to 3q13.3-3q21 using in situ hybridization on human metaphase chromosomes. Trisomy of chromosome 3 is a recurrent chromosome change seen in various lymphomas and lymphoproliferative diseases, particularly diffuse, mixed, small, and large cell lymphomas, human T-cell lymphotropic virus type I-induced adult T-cell leukemia, and angioimmunoblastic lymphadenopathy. A number of chromosomal defects involving 3q21 have been described in acute myeloid leukemia and also in myelodysplastic and myeloproliferative syndromes. The mapping of B7 may permit further insight into disease states associated with aberrant lymphocyte activation and lymphokine synthesis.

Animals↗
PubMed1992

Expression of the receptor-linked protein tyrosine phosphatase LAR: proteolytic cleavage and shedding of the CAM-like extracellular region.

The human transmembrane molecule LAR is a protein tyrosine phosphatase (PTPase) with a cell adhesion molecule-like extracellular receptor region. The structure of LAR hinted at its involvement in the regulation of tyrosine phosphorylation through cell-cell or cell-matrix interactions. We show here that LAR is expressed on the cell surface as a complex of two non-covalently associated subunits derived from a proprotein. The LAR E-subunit contains the cell adhesion molecule-like receptor region, while the LAR P-subunit contains a short segment of the extracellular region, the transmembrane peptide and the cytoplasmic PTPase domains. Proprotein processing occurs intracellularly. Analysis of LAR mutants suggested that cleavage occurs in the LAR extracellular region at a paired basic amino acid site by a subtilisin-like endoprotease. A single amino acid substitution at this site blocked LAR proprotein cleavage. The LAR E-subunit is shed during cell growth, suggesting that LAR receptor shedding may be a mechanism for regulating PTPase function. The use of immunohistochemistry techniques on human tissues demonstrated the expression of LAR by various cell lineages, including epithelial cells, smooth muscle cells and cardiac myocytes. The LAR gene is mapped to chromosome 1, region p32-33, which contains candidate tumor suppressor genes.

Amino Acid Sequence↗
PubMed1992

Mapping and expression of the ubiquitin-activating enzyme E1 (Ube1) gene in the mouse.

The nucleotide sequence of the human cDNA encoding ubiquitin-activating enzyme E1 is more than 99% identical with the human A1S9T cDNA, a gene that has been shown to complement the temperature-sensitive mutant mouse cell line, tsA1S9. The amino acid sequences of the proteins encoded by these two cDNA sequences are identical, and both cDNAs were previously shown to be located in the same region of the human X chromosome; thus, ubiquitin-activating enzyme E1 and A1S9T appear to be the same gene, designated UBE1. By in situ hybridization to metaphase chromosomes from male mice and by Southern blot analysis of male and female mouse DNA, we show that, in the mouse, a human UBE1 cDNA probe identified both X- and Y-linked loci. Ube1 is located at band A2 of the mouse X Chromosome (Chr) and Ube2 on the short arm of the Y Chr. This is in contrast to the situation in the human, where there is no evidence for Y-linked sequences related to UBE1. Mapping of the Ube1 gene in interspecific backcrosses between Mus spretus and C57BL/6 shows that the Ube1 locus maps close to Timp, in a conserved region of the mouse and human X Chrs that include Otc, Cybb, Syn1, Timp, and Araf. Expression of Ube1 on the inactive X Chr was examined to determine whether this gene is subject to X-Chr inactivation in the mouse, as there is previous evidence that the human UBE1 gene escapes, at least partially, X inactivation. Sequencing of reverse transcriptase polymerase chain reaction (RT-PCR) products from M. spretus, C57BL/6J, and T(X;16)16H x M. spretus F1 female mice indicates that the mouse Ube1 gene is subject to X-Chr inactivation in vivo. This represents a new example of differences between the sex chromosomes of mouse and human.

Animals↗