Conserved cholecystokinin receptor transmembrane domain IV amino acids confer peptide affinity

The Cholecystokinin type 1 and type 2 receptors (CCK-1R and CCK-2R) share >50% amino acid identity, as well as subnanomolar affinity for the endogenous peptide cholecystokinin octapeptide (CCK-8). Although it is likely that these two receptor subtypes share amino acids that confer CCK-8 affinity, it has been difficult to identify such residues. We have examined the role of several transmembrane domain (TMD) IV residues that are common to both CCK receptor subtypes. In both the CCK-1R and CCK-2R, we demonstrate that alanine substitution of two TMD IV residues, which are highly conserved among all known CCK receptor subtypes and species homologs, significantly decrease CCK-8 affinity. Despite the observed decrease in peptide binding, the mutant receptors maintain close to wild-type affinity for the respective subtype selective nonpeptide ligands, 3H-labeled L-364,714 (CCK-1R) and 3H-labeled L-365,260 (CCK-2R), suggesting conserved tertiary structure of these mutants. Assessment of CCK-8-induced inositol phosphate production at each of the mutant CCK receptors revealed normal peptide efficacy. In contrast, peptide potencies are reduced in parallel with the observed decreases in affinity. Taken together, these findings suggest that important peptide affinity determinants are localized on TMD IV, a region that has not previously been considered a major contributor to ligand affinity in either CCK receptors or other G protein-coupled peptide receptors.     

A prospective 4-5 year follow-up of juvenile onset bipolar disorder

OBJECTIVE: Data on outcome of juvenile onset bipolar disorder is limited. This study examined the course and outcome of bipolar disorder and assessed the rate and predictors of recovery and relapse in a sample of children and adolescents over a 4-5 year period. METHOD: Twenty-five consecutively ascertained subjects (9-16 years) with a diagnosis of mania (mean duration at intake of 4.6 +/- 3.9 weeks), were comprehensively assessed at baseline and at 6-month intervals using the Diagnostic Interview for Children and Adolescents (revised) (DICA-R), the Missouri Assessment for Genetic Interview in Children (MAGIC), the Young's Mania Rating Scale (YMRS) and the Children's Global Assessment (CGAS). The study phenotype required DSM-IV criteria of mania with elation and/or grandiosity as a criterion to distinguish them from those with attention deficit hyperactivity disorder. Subjects received the standard treatment as prescribed by their primary treating team. RESULTS: During the course of the study period, all 25 subjects (100%) recovered from the index episode. The mean time to recovery was 44 +/- 46 days. The mean duration of follow-up was 51.6 +/- 4.1 months. Sixteen subjects (64%) relapsed after a mean period of 18 +/- 16.4 months. A majority of the relapses (72.4%) were while the subjects were on treatment. CONCLUSIONS: Acute juvenile onset mania has a high rate of recovery and low chronicity. The relapse rate was high and most of these occurred in the first 3 years despite aggressive prophylactic treatment. The effectiveness of currently used thymoleptics, in particular lithium, in the prophylaxis of juvenile bipolar disorder needs to be evaluated in controlled studies.     

Teratoma of the placenta

Primary non-trophoblastic tumours of the placenta reported to date are chorioangioma and teratoma, both of which are extremely rare. A case of teratoma in a term placenta is reported.     

Genetic variation observed at two tetrameric short tandem repeat loci on chromosome 12 (D12S66 and D12S67) among five distinct ethnic groups of India: detection of two new alleles

OBJECTIVE: The present investigation reports the genetic variation observed at two tetrameric short tandem repeat (STR) loci on chromosome 12 (D12S66 and D12S67) among five anthropologically distinct population groups of India. SUBJECTS AND METHODS: A total of 277 random, normal and healthy volunteers were investigated for the D12S66 locus, and 236 for the locus D12S67, from five ethnic groups of India. Two of these belong to the state of Maharashtra in western India (Konkanastha Brahmins and Marathas) and three from the state of Kerala in South India (Nairs, Ezhavas and Muslims). DNA was extracted from peripheral blood samples, amplified by duplex polymerase chain reaction (PCR) and electrophoresed on 6% denaturing urea (7 M) gel electrophoresis. The analysis was performed on ALF Express DNA sequencer (Amersham Pharmacia Biotech) using Fragment Manager software. Statistical analysis was done by using Arlequin ver. 1.1. RESULTS: At D12S66 locus, a total of nine alleles (8-17 repeats) and 27 genotypes were detected with an observed heterozygosity ranging from 0.55 to 0.91. At the D12S67 locus, nine alleles (36-44 repeats) and 33 genotypes were observed with a heterozygosity ranging from 0.74 to 0.89. Both the loci displayed high Power of Discrimination (PD) which ranged from 0.81 to 0.91 and Polymorphic Information Content (PIC) ranging from 0.68 to 0.84. At D12S66, two alleles were detected for the first time in these population groups which were not reported earlier. The level of gene differentiation (G(ST) value, 0.02) was moderate at these two loci, indicating a close relationship among the population groups. CONCLUSIONS: From this investigation, it is concluded that both the tetrameric loci are highly polymorphic and informative, and can be used for the characterization of the Indian population groups in addition to other well-studied STR loci.     

A tip on using the appropriate wire passer in orthopaedic surgery

The authors present a technical tip on using the appropriate wire passer while passing cerclage wires around long bones in orthopaedic surgery.