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Biomedical subjects

D B Mitchell

Publications and source records attributed to D B Mitchell.

At least 19 recordsLinked to original sources

A new approach to the safety assessment of pharmaceutical excipients. The Safety Committee of the International Pharmaceutical Excipients Council.

This article presents a set of proposed guidelines for the safety assessment of new pharmaceutical excipients. These guidelines were developed by the Safety Committee of the International Pharmaceutical Excipients Council and represent a new, scientifically based approach to establishing conditions for the safe use of proposed pharmaceutical excipients utilizing various routes of human exposure. They are based upon the best currently available toxicological science and have taken the deliberations of the International Conference on Harmonization into consideration. These guidelines were developed because there are no regulatory agency guidelines currently available which specifically address the toxicological testing of a material intended for use as an excipient in pharmaceutical preparations. Only materials which have been previously permitted for use in a pharmaceutical preparation or which have been permitted for use in foods may be considered safe under current practices. If implemented, these guidelines should expedite the review of a proposed new excipient by regulatory agencies.

Chemistry, Pharmaceutical

Single and multiple test repetition priming in implicit memory.

Using a picture naming task, we compared the magnitude of repetition priming after one prior study episode (single test priming) versus multiple prior study presentations (multiple test priming). Pictures were repeated either one, two, or three times, and the interval between tests was either several minutes (blocked test) or one week (spaced test). Priming increased with additional prior presentations (beyond one) in the multiple test format. In addition, single test priming decreased within one hour after initial exposure, with little change from one hour to two weeks. Priming was unaffected by a simultaneous recognition task, suggesting that picture naming is an implicit task relatively immune from explicit memory contamination.

Humans

A reevaluation of semantic versus nonsemantic processing in implicit memory.

A number of investigations have purported to demonstrate that semantic processing does not produce a memorial advantage over nonsemantic processing on implicit tests, as contrasted with the typical advantage of semantic over nonsemantic processing on explicit tests. A review of 166 outcomes from 38 studies that have manipulated processing on implicit tests reveals that on 131 occasions (79%), priming was greater following semantic than it was following nonsemantic processing. This difference was found in both perceptual and conceptual implicit memory tests, as well as in within- and between-subjects designs. It suggests that implicit tests reflect the involvement of both conceptual and perceptual processes. Although explicit contamination may account for some of the processing difference in implicit tests, the pervasiveness of the phenomenon, especially in perceptual implicit tests, makes it an unlikely account for the entire effect.

Attention

Detection of hog cholera virus and differentiation from other pestiviruses by polymerase chain reaction.

Reverse transcription coupled with the polymerase chain reaction (RT-PCR) was used for the detection and differentiation of pestiviruses. For this purpose, one primer pair was selected from a highly conserved region of the genome of pestiviruses. Using these primers (PEST 1-PEST 2), DNA fragments of between 72 and 74 bp could be amplified from all pestivirus isolates tested. In order to differentiate hog cholera virus (HCV) from bovine viral diarrhea virus (BVDV) and border disease virus (BDV), we selected a primer pair from a conserved region in the genome of HCV strains that differed from that sequenced in the genome of BVDV strains. By using these primers (HCV 1-HCV 2), a DNA fragment of 478 bp could be specifically amplified from HCV isolates. By these means, viral RNA was detected in extracts of lymph node, spleen, tonsil, and lung. Such extracts were used directly for RT-PCR without prior RNA isolation. We also performed multiplex PCR by using both the PEST 1-PEST 2 and HCV 1-HCV 2 primer pairs in a single reaction. This allowed the differentiation of HCV from BVDV and BDV in one step. To assess the sensitivity of the method, RT-PCR was compared with virus propagation in tissue culture and subsequent detection by immunofluorescence staining. The results show that RT-PCR is useful for the rapid detection and differentiation of pestiviruses.

Animals

Emergency treatment of tracheal tear during pharyngolaryngectomy.

Longitudinal tracheal tear (of the trachealis muscle), an unusual but acknowledged complication of pharyngolaryngectomy, was encountered during a total pharyngo-oesophagolaryngectomy with gastric replacement. Due to serious ventilatory difficulties a rapid repair was required to obtain an airtight seal to allow continued mechanical ventilation. A reinforced polytetrafluoroethylene (PTFE) vascular graft was used as an intratracheal stent to seal the air leak. This technique proved effective and the tracheal defect had healed by the time the stent was removed 10 days later.

Carcinoma, Squamous Cell

Expression of rotavirus proteins encoded by alternative open reading frames of genome segment 11.

The nucleotide sequence of rotavirus genome segment 11 shows that this gene contains three potential open reading frames. We used several approaches to determine whether any polypeptides other than NS26, the primary protein product, are expressed. In particular, we sought to determine whether the strong out-of-phase start codon present at nucleotides 80-82, which would encode a protein of 92 amino acids, is used in vivo or in cell-free systems. Several modifications of gene 11 were made and found to produce proteins from the different initiation codons in cell-free transcription-translation systems. The protein from the out-of-phase open reading frame was shown to be expressed in rotavirus-infected MA104 cells; this was demonstrated using monospecific sera prepared to this protein expressed in Spodoptera frugiperda insect cells infected with a baculovirus recombinant containing only the out-of-phase open reading frame. The origin of some of the lower-molecular-weight bands serologically related to the primary product of gene 11, NS26, was also studied by selective immunoprecipitation using two different sera made from recombinant baculovirus lysates. All of these polypeptides are present in infected cells in a complex which is still incompletely defined.

Amino Acid Sequence

Iodide mumps following intravenous urography with iopamidol.

We report a case of bilateral submandibular and parotid sialadenitis subsequent to the injection of 100 ml of iopamidol (Niopam 370, Bracco) for an intravenous urogram. Iodide 'mumps' has previously been reported as a rare sequela of ionic contrast media injection. It is a mild and short lived condition, usually requiring no treatment.

Aged

Submucous resection of the nasal septum as an outpatient procedure.

We report our experience of submucous resection of the nasal septum under local anaesthesia as an outpatient procedure. We have audited 50 consecutive cases and compared the results with a similar group of patients in whom the operation was carried out in the usual way under general anaesthesia. We have found the procedure to be safe, effective and economically advantageous.

Adolescent

Transfer of processing in repetition priming: some inappropriate findings.

Transfer effects in repetition priming were found with both picture and word naming, but varied with the type of prime list. Unmixed lists of word or picture primes produced equivalent intra-modal and cross-modal repetition priming in both picture-naming (Experiment 1) and word-naming (Experiment 5) tasks. However, mixing word and picture primes resulted in greater intra-modal than cross-modal priming for both picture-naming (Experiment 2) and word-naming (Experiment 6) tasks. This mixed-list difference between intra-modal and cross-modal priming was reduced by blocking prime types at input (Experiment 3). These findings suggest that differences in priming as a function of prime stimulus format should be cautiously interpreted when mixed prime lists are used.

Adult

Age differences in retrieval consistency and response dominance.

The probability of generating dominant responses and producing the same response on two occasions was compared for older and younger adults over three different intervals. Continuous retrieval from broadly defined semantic and orthographic categories was examined in Experiment 1; single-word retrieval from restricted categories was tested in Experiment 2 using a picture-naming task. There was no age difference in the tendency to generate normatively dominant responses in either experiment, but there were age differences in consistency. For broad categories, older were less consistent than younger adults at each intersession interval. With restricted categories, older adults showed a systematic decline in consistency over increasing intersession interval, while younger adults showed no change. Unlike prior research, we failed to find evidence for a positive relationship between verbal ability and response dominance.

Adolescent

The interaction of CD4 with HIV-1 gp120.

CD4 is an integral cell surface glycoprotein that is able to enhance T cell specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). Infection by HIV-1 is initiated by the binding of the envelope glycoprotein, gp120, to the first domain of CD4. The binding of CD4 to class II MHC is inhibited by gp120, one possible mechanism for immunosuppression in AIDS patients. In addition, the CD4/gp120 interaction may directly inhibit T cell function. Recently we have synthesized small molecules (CPFs) that specifically inhibit this interaction. CPFs bind to gp120 and prevent the binding of gp120 to CD4, and also inhibit the infectivity of HIV-1.

Animals

Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120.

Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.

Animals

Conservation of a potential metal binding motif despite extensive sequence diversity in the rotavirus nonstructural protein NS53.

The nucleotide sequence for the simian rotavirus SA11 gene segment 5 has been determined. The gene is 1611 nucleotides in length and contains a single open reading frame of 1485 nucleotides. The segment codes for the nonstructural protein NS53 which is predicted to be a polypeptide of 495 amino acids with a molecular weight of 58,484. When compared to the sequence of bovine RF gene segment 5 there are homologies of only 49 and 36% at the nucleotide and amino acid levels, respectively. This is in marked contrast to the situation with other rotavirus nonstructural proteins which are highly conserved between isolates. Nevertheless, there is a conserved region between amino acids 37-81 which contains a generalized motif for a metal binding domain. All eight cysteine and two histidine residues in this short sequence are conserved between the simian and bovine NS53 proteins. The conservation of this domain despite extensive sequence diversity in the remainder of the protein suggests that this region is functionally important.

Amino Acid Sequence

Completion of the genomic sequence of the simian rotavirus SA11: nucleotide sequences of segments 1, 2, and 3.

The nucleotide sequences for gene segments 1, 2, and 3 of the simian rotavirus SA11 genome, coding for the structural polypeptides VP1, VP2, and VP3, respectively, have been determined. Comparison of the VP1 and VP2 amino acid sequences with those determined for other strains indicates that certain features of these proteins are conserved. The possible functions of the viral polypeptides VP1, VP2, and VP3 are discussed in the light of enzyme functions known to be present in the rotavirus particle. The complete sequence of the entire SA11 genome, which consists of 11 segments of dsRNA totaling 18,555 nucleotides, has now been determined. This is the first complete sequence available for a rotavirus genome. Each genome segment appears to code for only one primary product; there are no significant, alternative open reading frames which are conserved between strains. Relevant data for each genome segment are tabulated.

Amino Acid Sequence