The role of comorbidities in duration of untreated illness for bipolar spectrum disorders.

BACKGROUND: Growing interest has been given to the construct of Duration of untreated illness (DUI) on the outcome of bipolar disorder (BD), due to its potentially modifiable nature. The aim of this study was to identify possible clinical correlates of DUI in a sample of BD patients. METHOD: 119 BD spectrum patients included. DUI rate was calculated and dichotomized into short DUI and long DUI subgroups, cut-off 24 months. These subgroups were compared for socio-demographic and clinical variables. Significant results were included into direct logistic regressions to assess their impact on the likelihood of presenting with long DUI. RESULTS: Mean DUI±SD was 75.6±98.3 months. Short DUI subgroup comprised 56 (47.1%), long DUI 60 (52.9%) patients. Age at onset of BD was lower in the long DUI subgroup (p=0.021), illness duration longer (p=0.011). Long DUI subgroup showed significantly more comorbidity with Axis I (p=0.002) and personality disorders (p=0.017), less interepisodic recovery (p<0.001) and less Manic Predominant Polarity (p=0.009). Direct logistic regression as a full model was significant, correctly classifying 76.7% of cases. A unique statistically significant contribution was made by: Manic Predominant Polarity, Personality Disorder Comorbidity, and Total Changes in Medications. LIMITATIONS: Partial retrospective data, cross sectional study. CONCLUSIONS: DUI was longer than 24 months in half of the sample. Psychotic /Manic onset contributed to a quick diagnostic classification. Personality disorders in depressed patients could delay a correct diagnosis of BD, factors associated with an increased likelihood of BD must be considered. More research on personality disorder comorbidities is needed.

Amino acid sequence of k Sci, the Bence Jones protein isolated from a patient with light chain deposition disease.

Light chain Sci was isolated from the urine of a patient affected by light chain deposition disease with an apparent exclusive localization to the kidney. Sci protein is an intact light chain: it consists of 214 amino acid residues and has an Mr of 23.65. Its complete primary structure has been determined by sequence analysis of the corresponding tryptic peptides and by partially sequencing the intact protein. Sequence comparison shows that Sci protein is strictly related to the light chains of kIIIa family (88% structural identity) which are usually expressed in autoimmune rheumatoid syndromes. Computer graphics model suggests a perturbation in k Sci three-dimensional structure due to the unusual replacement of residues 53 and 77.

Chloroplast glyceraldehyde-3-phosphate dehydrogenase (NADP): amino acid sequence of the subunits from isoenzyme I and structural relationship with isoenzyme II.

The structural relationship between isoenzymes I and II of chloroplast glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NADP+ oxidoreductase (phosphorylating) EC 1.2.1.13) has been established at the protein level. The complete primary structure of subunits A and B of glyceraldehyde-3-phosphate dehydrogenase I from Spinacia oleracea has been determined by sequence analysis of the corresponding tryptic peptides, aligned by fragments derived from cyanogen bromide and Staphylococcus proteinase V8 digestions and by partially sequencing each intact subunit. Subunit A has an Mr of 36,225 and consists of 337 amino acid residues, whilst subunit B (Mr 39,355) consists of 368 residues. The amino acid sequence of subunit B, as determined through direct analysis of the protein, is identical to that recently deduced at cDNA level (Brinkmann et al. (1989) Plant Mol. Biol. 13, 81-94). The two subunits share a common portion of amino acid sequence which differs by 66 amino acid residues. Subunit B has an extra C-terminal sequence of 31 amino acid residues. Chloroplast glyceraldehyde-3-phosphate dehydrogenase II was partially characterized by sequencing the N-terminal portion of the intact protein and some of its tryptic peptides. The sequences of all the examined fragments fit precisely that of the corresponding regions of subunit A from glyceraldehyde-3-phosphate dehydrogenase I.

The bovine plasma retinol-binding protein. Amino acid sequence, interaction with transthyretin, crystallization and preliminary X-ray data.

1. The primary structure of bovine plasma retinol-binding protein (RBP) has been determined and found to be more than 90% identical to human and rabbit RBPs, and more than 80% identical to rat RBP. Main changes in amino acid sequence are observed in two regions on the surface of the protein molecule (residues 138-148 and 169-183). 2. The interactions of bovine RBP with bovine and human transthyretins were investigated using the technique of fluorescence polarization. Bovine RBP was able to form high affinity complexes (K'd = 0.34 +/- 0.02 microM) with both bovine and human transthyretins, displaying a stoichiometry of approximately 2 molecules RBP/molecule transthyretin in both cases. The sites that participate in protein-protein interactions are thus very similar, and this tends to exclude the involvement of the superficial regions more significantly substituted in mammalian RBPs (residues 138-151 and 167-183) in the protein-protein recognition. 3. Bovine RBP has been crystallized (space group P2(1)2(1)2(1), with a = 4.61 nm, b = 4.91 nm, c = 7.61 nm) and the crystals are suitable for high-resolution X-ray diffraction studies.

Separation of fragments from human serum albumin and its charged variants by reversed-phase and cation-exchange high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) and ion-exchange chromatography on poly(2-sulphoethylaspartamide)-silica (SCX) were compared as alternative approaches in characterizing charged genetic variants of human serum albumin. The chromatographic behaviour of cyanogen bromide (CNBr), tryptic and V8 protease digests from normal and mutant albumins were examined. The results showed that substituted site-containing CNBr fragments are successfully resolved by RP-HPLC; in most instances SCX and RP-HPLC are equally adequate in identifying the modified tryptic peptides from CNBr fragments; although generally useful, SCX chromatography is specifically needed in all instances where amino acid replacement is occurring in a small hydrophilic tryptic fragment and choosing Staphylococcus aureus V8 protease instead of tryptic digestion is advantageous.

The molecular defect in a COOH-terminal-modified and shortened mutant of human serum albumin.

Albumin Venezia is a fast migrating genetic variant of human serum albumin which, in heterozygous subjects, represents about 30% of the circulating protein. The molecular defect in this variant was studied in a subject possessing an atypical level of the mutant (80% of the total protein) and in other members of his family. Albumins, isolated from the sera of the propositus and his heterozygous relatives, were treated with CNBr and the resulting fragments analyzed by isoelectric focusing. The peptides were then isolated in a homogeneous form by reverse-phase high performance liquid chromatography and submitted to sequence analysis. The results show that albumin Venezia possesses a shortened polypeptide chain, 578 residues instead of 585, completely variant from residue 572 to the COOH-terminal end: sequence: (see text). This extensive modification may be accounted for by the deletion of exon 14 and translation to the first terminator codon of exon 15, which normally does not code for protein. The absence of a basic COOH-terminal dipeptide in the mature molecule can be explained by the probable action of serum carboxypeptidase N. Additional support for such action comes from examination of the remaining 20% of the total albumin of the propositus, which is found to contain an extra Arg at its COOH terminus, probably due to partial digestion by carboxypeptidase N. The low serum level of the variant in heterozygous subjects suggests that the COOH-terminal end of the molecule is critical for albumin stability.

High-performance liquid chromatography of complex mixtures of cyanogen bromide-produced peptides from different proteins.

A variety of approaches have been required in order to achieve the resolution of large fragments from cyanogen bromide (CNBr) digests of Inc k chain (an immunoglobulin light chain), human serum albumin (HSA) and four of its mutants. Reversed-phase high-performance liquid chromatography (RP-HPLC) under different conditions failed to resolve the Inc k chain digest; the three CNBr fragments (3.1, 6.7 and 13.7 kDa) were separated in a homogeneous form by gel HPLC. Five of the seven CNBr fragments (ranging from 3.4 to 20.0 kDa) obtained from CNBr cleavage of HSA can be resolved by a single reversed-phase HPLC step; separation of the other two requires modification of the eluent composition. Some structural features of the peptides seem to influence their chromatographic behaviour; by examining the elution patterns from albumin mutants, the sequence-related contribution of single amino acid residues is apparent.