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T Singer

Publications and source records attributed to T Singer.

21 records · Page 2Linked to original sources

Is dysthymia a different disorder in the elderly?

OBJECTIVE: This study evaluated elderly dysthymic patients in a late life depression clinic and compared their clinical features to previous findings in young adult dysthymic patients. METHOD: Of 224 consecutive elderly outpatients, 40 (17.9%) met criteria for dysthymic disorder. A semistructured interview was used to obtain history, the Structured Clinical Interview for DSM-III-R--Patient Version and the Structured Clinical Interview for DSM-III-R Personality Disorders were used to make DSM-III-R diagnoses, and standard rating instruments for depression were administered. RESULTS: The gender distribution was equal and major stressors were common. The mean age at onset of dysthymia was 55.2 years (SD = 15.4), with an average illness duration of 12.5 years (SD = 14.2). Early onset (before 21 years of age) and secondary dysthymia were rare. A history of major depression earlier during the course of dysthymic illness, comorbid anxiety disorders, and personality disorders were relatively uncommon. Cross-sectionally, cognitive and functional symptoms were more prominent than vegetative symptoms. CONCLUSIONS: Dysthymia is not uncommon among depressed elderly outpatients who present for treatment. Elderly dysthymic patients differ from young adult dysthymic patients, who are mostly female with an early onset and who frequently have comorbid axis I and axis II disorders. Most elderly dysthymic patients do not appear to be young dysthymic patients who simply grew older, and the DSM-III-R subtyping of dysthymia into early/late onset and primary/secondary may not apply to the elderly. Further clinical studies of "pure" dysthymic disorder appear feasible in the elderly, and these are clearly needed.

Adult↗

The PRE4 gene codes for a subunit of the yeast proteasome necessary for peptidylglutamyl-peptide-hydrolyzing activity. Mutations link the proteasome to stress- and ubiquitin-dependent proteolysis.

Proteinase yscE, the yeast proteasome, is a member of the nonlysosomal, high molecular mass (approximately 700 kDa) multifunctional proteinase complexes that are highly conserved from yeast to man. We have isolated mutants defective in one of the three proteolytic activities of the enzyme complex, i.e. in cleavage of peptide bonds after acidic amino acids. Using one of these mutants (pre4-1), we cloned the PRE4 gene and uncovered an open reading frame with 266 amino acids coding for a predicted protein of 29.4 kDa. The protein proved to be a subunit of proteinase yscE. The Pre4 amino acid sequence shows strong homology to the beta-subunit of the Xenopus laevis proteasome. Chromosomal deletion of the PRE4 gene is lethal. The pre4-1 mutant allele was cloned and sequenced. The mutant protein is shortened by 15 amino acids at the carboxyl terminus. Mutations (pre1-1, pre2-2) in the chymotrypsin-like activity of proteinase yscE uncovered the enzyme to be involved in ubiquitin-linked and stress-dependent proteolytic pathways. In contrast to these mutants, pre4-1 mutants did not exhibit any apparent stress-dependent phenotypes. However, pre1-1 pre4-1 double mutants showed enhanced canavanine sensitivity and increased accumulation of ubiquitin protein conjugates, as compared with pre1-1 single mutants.

Amino Acid Sequence↗