A binary/digital approach to amino acid identification and its application to peptide sequencing and protein identification.

A binary/digital method is proposed in theory for the identification of single amino acids (AAs) in the bulk or with a few molecules from a single binary measurement. Combined with Edman degradation (or other cleaving method), it can be used to sequence a peptide or identify the parent protein from a partial sequence. The approach is centered on the superspecificity property of transfer RNAs (tRNAs). Markedly different from conventional and recent single molecule (SM) sequencing methods based on analog measurements, it changes the analytical question 'Which AA is it?' to the much simpler one 'Is there an AA in the detection space?'. Each of 20 terminal residues cleaved from 20 copies of a peptide enters a different cavity with a unique tRNA; tRNA charging (or binding with AA) occurs only in the cavity with the cognate AA. The bound AA or the AA separated from the tRNA is detected with a single binary measurement; its identity is known from the position of the single high bit in the resulting 20-bit output. Alternatively, a 20-stage pipeline can be used with sparse samples. Detection of the bound AA can be done optically by tagging the AAs with a fluorescent dye, or of the freed AA electrically with a nanopore. Necessary conditions for accurate AA identification are satisfied in principle; related computations and simulation results are presented. A modified version that can be used for de novo sequencing in parallel of large numbers of peptides immobilized on a glass slide with the tRNAs carrying a fluorescent tag is also proposed. Both methods can be used for protein identification from partial sequences containing 2 or 3 AA types by using only the corresponding tRNAs. Experiments may be performed to validate them, followed by translation into practice with existing technology; potential implementation issues are discussed. Binary/digital amino acid identification for peptide sequencing.

A rare case of posterior vaginal wall cyst.

A 42-year-old multi para, presented with a mass protruding from vagina since 1 year. The mass was cystic in nature arising from the posterior vaginal wall. It was insidious in growth, gradually increasing in size to 8×8 cm. Surgical excision of the cyst was done by sharp and blunt dissection. The cyst was filled with mucoid material and histopathology confirmed a mullerian cyst. Cystic lesions of vagina are relatively uncommon and they are an incidental finding during gynaecological examination. Mullerian cysts are congenital cysts of vagina, usually reported during childbearing age group. These cysts usually arise at the level of cervix and extend anteriorly in relation to bladder, but very rarely they may also extend posteriorly. This paper illustrates a rare case of large posterior vaginal wall cyst of Mullerian origin.

Rationalizing neuroleptic polypharmacy in chronic schizophrenics: effects of changing to a single depot preparation.

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

Radio receptor assay of serum neuroleptic levels in psychiatric patients.

The radioreceptor assay for the measurement of neuroleptic drugs in serum has been used to study the relationship between dose and serum level in schizophrenic patients receiving these drugs. The assay was found to be reproducible and capable of detecting neuroleptics in the sera of patients receiving a range of both oral and depot drugs, with the exception of trifluoperazine spansules. Linear correlations were obtained between daily dose and serum level for each drug both in individual patients on different doses and between patients on a stable dose. Extrapyramidal side effects were related to the serum neuroleptic level within, but not between, patients. The assay may be of use in clinical practice, including the assessment of compliance or poor response to neuroleptics.