PubMed HealthSearch

Biomedical subjects

B Ferguson

Publications and source records attributed to B Ferguson.

At least 37 records · Page 2Linked to original sources

Liaison psychiatry in general practice: the comprehensive collaborative model.

A model of liaison psychiatry in general practice is described and its impact assessed using data from the Nottingham psychiatric case register. The model incorporates a comprehensive network of general practice psychiatric clinics for both psychiatrists and other mental health professionals, associated with mainly informal liaison with general practitioners and others in the primary care team, and a reduction in psychiatric outpatient clinics. Following the introduction of this model, the proportion of new and referred patients seen in primary care settings rose from 1% to 18% in Nottingham over an 8-year period. Over this period admission rates significantly fell in Nottingham compared with the rest of England and evidence is given that the growth of primary care psychiatry contributed significantly to this reduction.

Adolescent

Patterns of sperm allocation across successive ejaculates in four species of voles (Microtus).

This study was designed to determine testes masses, total number of spermatozoa ejaculated per copulatory episode, and the pattern of sperm numbers in successive ejaculates in prairie voles (Microtus ochrogaster), montane voles (M. montanus), pine voles (M. pinetorum), and meadow voles (M. pennsylvanicus). Prairie voles displayed mean totals of 2.7 ejaculations and 30.5 X 10(6) spermatozoa before reaching a satiety criterion; montane voles 3.4 ejaculations and 19.0 X 10(6) spermatozoa, pine voles 2.4 ejaculations and 3.3 X 10(6) spermatozoa, and meadow voles 2.5 ejaculations and 25.5 X 10(6) spermatozoa. In all species the number of spermatozoa decreased in successive ejaculates. Significant species differences were noted for the total number of spermatozoa ejaculated and number of spermatozoa ejaculated in each of the first 3 ejaculates. Species differences also were noted for testes mass, with meadow voles having the largest testes and pine voles having the smallest. These data can be compared to similar data on laboratory rats and deer mice and related to recent theory regarding sperm numbers, testes sizes, and mating systems. In general, the species with large testes appear to ejaculate more spermatozoa. The significance of species differences in testes mass and total sperm numbers remains unclear, but may relate to the occurrence of multiple mating by females during a single receptive period.

Animals

A comparison of time delay and decreasing prompt hierarchy strategies in teaching banking skills to students with moderate handicaps.

Four students with moderate handicaps were taught to cash checks and to use an automatic teller through either a decreasing prompt hierarchy or time delay procedure. The strategies were compared within a multielement design. Results indicated that both strategies led to the acquisition of the target tasks; however, the decreasing prompt hierarchy was more efficient. Four and 8-week follow-up probes indicated that the strategies were equally effective in producing maintenance of performance.

Activities of Daily Living

The Nottingham study of neurotic disorder: comparison of drug and psychological treatments.

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

Adult

Synthesis and evaluation of multisubstrate inhibitors of an oncogene-encoded tyrosine-specific protein kinase. 2.

Tyrosine-specific protein kinases that transfer the terminal phosphate from ATP to protein acceptors are associated with certain transforming viruses and cell surface growth factor receptors. Here we describe the synthesis and testing of potential multisubstrate inhibitors of this class of enzymes. The inhibitors were prepared by covalent attachment of the terminal phosphate of ATP or its tetraphosphate analogue to tyrosine mimics. Testing against p60v-abl, the tyrosine kinase from the Abelson murine leukemia virus, showed that the series of inhibitors was moderately potent (IC50 values as low as 13 microM). However, structural modification of the tyrosine mimic, including replacement with a serine-like moiety, had little effect on potency. It is therefore concluded that the ATP moiety is largely responsible for binding and that the enzyme requires additional structural features for recognition of the tyrosine-containing substrate.

Abelson murine leukemia virus

Sexual activity and satiety over an extended observation period in prairie voles (Microtus ochrogaster).

This study was designed to delineate the course of sexual satiation in prairie voles (Microtus ochrogaster). Fourteen male-female pairs were allowed to copulate freely for 24 hr under continuous observation. Copulations occurred predominantly during the first few hours and decreased in frequency thereafter. The mean number of ejaculations per pair was 5.6 (range, 2-9). Two thirds of the ejaculations occurred during the first 3 hr, and over 90% took place within the first 7 hr after the first intromission. No ejaculations were observed during the last 8 hr. These results suggest that male capacity to deliver ejaculations to a female is limited and that direct observations reveal a more limited capacity than observations made with time-lapse videotape.

Animals

Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5.

The binding sites for the 300-, 107-, and 105-kilodalton cellular proteins which associate with human adenovirus type 5 E1A products were studied with E1A deletion mutants. All appeared to bind to the amino-terminal half of E1A products in regions necessary for oncogenic transformation. These results suggest that these cellular species may be important for the biological activity of E1A products.

Adenovirus Early Proteins

Binding of cellular polypeptides to human adenovirus type 5 E1A proteins produced in Escherichia coli.

Cellular proteins of 300, 107, 105, 68 and 65 kDa have previously been shown to associate specifically with the early region 1A (E1A) proteins of human adenovirus type 5. In the present study we report that, to varying degrees, these proteins also were capable of binding to E1A products produced in Escherichia coli from plasmids carrying cDNAs corresponding to the 1.1- and 0.9-kb E1A mRNAs. When these purified E1A proteins were mixed in solution with extracts from mock-infected human cells, the 68- and 65-kDa species bound very efficiently to the 1.1-kb mRNA product and somewhat less so with that of the 0.9-kb mRNA. The 107-, 105-, and 300-kDa species bound poorly, if at all, to both E1A products. Using the E1A 1.1-kb mRNA product which had been covalently attached to Sepharose beads, the 68-, 65-, and 300-kDa species bound efficiently, and binding of protein which migrated in SDS gels in the region of the 107- and 105-kDa species was also observed. In addition to these proteins, several other cellular polypeptides of 30, 33, 75, 95, 150, 180, and greater than 300 kDa were shown to bind to E1A-Sepharose and thus may also be E1A-binding proteins. The present data confirm the specificity of the previously identified cellular proteins for E1A products and show that binding of the 300-, 65-, and 68-kDa species does not require the presence of any other viral polypeptide. In contrast, the inefficient binding of the 107- and 105-kDa species to Escherichia coli-expressed E1A protein may suggest that these interactions require either eukaryotic-specific post-translational modifications of the E1A protein, or the presence of additional Ad5 gene products.

Adenovirus Early Proteins

Transfer of functional adenovirus E1A transcription activator proteins into mammalian cells by protoplast fusion.

Human adenovirus 2/5 E1A proteins were used to evaluate protoplast fusion as a method of transferring functional proteins into mammalian cells. Both the E1A 13 and 12 S mRNA products expressed in Escherichia coli are shown to activate in trans adenovirus gene expression following transfer into monkey kidney cells by protoplast fusion. Approximately 20% of the recipient mammalian cells exhibited positive nuclear E1A-specific immunofluorescence following fusion with protoplasts containing E1A protein. E. coli-expressed E1A protein was modified post-translationally in Vero cells following protoplast fusion, as evidenced by its shift in sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility. These results establish protoplast fusion as a simple rapid method for examining the functional activity, intracellular distribution, and post-translational modification of E. coli-expressed proteins in intact mammalian cells.

Adenovirus Early Proteins

Induction of cellular DNA synthesis by purified adenovirus E1A proteins.

The purified Escherichia coli-expressed products of the human subgroup-C adenovirus E1A 13 S and 12 S mRNAs are shown to induce cellular DNA synthesis when introduced by microinjection into quiescent, G0-arrested mammalian cells from immortalized cell lines. The E1A proteins stimulated cellular DNA synthesis in mouse Swiss 3T3 cells, when microinjected either individually or in combination. A truncated E1A protein, in which 169 carboxyl terminal residues of the 289-amino acid E1A 13 S mRNA product are deleted, was unable to induce cellular DNA synthesis in these cells. Our results provide evidence that E1A proteins can function, independent of other viral functions, in the stimulation of cellular DNA synthesis in certain cell types. The present results are consistent with the E1A gene products acting to modulate the expression of the cellular genes which control cell cycle progression into S phase.

Adenovirus Early Proteins

Prevalence of speech and language disorders in 5-year-old kindergarten children in the Ottawa-Carleton region.

A representative sample of 5-year-old kindergarten children was assessed for speech and/or language disorder. Of the 1,655 children tested, 180 were identified as having speech or language impairment. It is estimated that within the total reference population, between 16.2% and 21.8% would show some impairment; for the boys, the rate would be 15.5% to 20.7% and for the girls, between 19.1% and 25.1%. Most of these children would show some language impairment as opposed to speech problems only. Approximately 36% of the identified boys and 30% of the girls would have speech problems only, the remainder having speech and language problems or language problems only. Followup studies of these children are needed to ascertain their outcome and language status in middle childhood.

Articulation Disorders

Structure and activity of recombinant human interferon-gamma analogs.

We have prepared interferon-gamma (IFN-gamma) analogs to study the structural role of particular amino acids in relation to their effects on antiviral activity. Three IFN-gamma analogs were prepared on the basis of predicted secondary structure. In two of the analogs, [Gln25]IFN-gamma and [Thr45]IFN-gamma, changes were made at residue 25 (Asn to Gln) and at residue 45 (Met to Thr), respectively. [Gln25Lys78]IFN-gamma had two changes, at residue 25 (Asn to Gln) and residue 78 (Asn to Lys). Another analog, [Cys-Tyr-Cys]IFN-gamma, incorporated Cys-Tyr-Cys at the amino terminus. Comparison of the structure and activity of these analogs with that of the natural sequence protein suggested that residues 25 and 78 are at the protein surface and play an important role in antiviral activity. The residue at position 45 was found to be important for maintaining the protein structure, as assessed by circular dichroism spectroscopy. The addition of Cys-Tyr-Cys resulted in a small perturbation of protein structure and a small decrease in antiviral activity.

Amino Acid Sequence

Detection of physical disorder in newly admitted psychiatric patients.

Screening tests for the detection of physical illness in 650 newly admitted psychiatric patients were examined critically. Almost 17% of these investigations were found to be abnormal and certain high risk groups were identified. These included patients suffering from significant weight loss, substance abuse, disorientation and self-neglect in addition to the elderly and patients with clinical evidence of physical disorder on examination. The young and physically fit had the least number of abnormalities, and it is suggested that more clinical common sense should determine the screening procedure and that no test is rightly "routine".

Diagnostic Tests, Routine

Adenovirus type 12 E1A protein expressed in Escherichia coli is functional upon transfer by microinjection or protoplast fusion into mammalian cells.

We efficiently expressed, in Escherichia coli, and purified the protein product encoded by the human adenovirus type 12 (Ad12) 13S mRNA. The functional properties of the E1A protein were analyzed by introducing the protein by microinjection or protoplast fusion into living mammalian cells. We showed that the E. coli-expressed E1A protein induces gene expression of the adenovirus type 5 (Ad5) E1A deletion mutant Ad5dl312. The purified E1A protein rapidly and quantitatively localized to the cell nucleus after microinjection into the cytoplasm. In addition, we raised high-titered monospecific antibodies to the purified Ad12 E1A protein. Using deleted forms of an adenovirus type 2 and Ad5 hybrid (Ad2/5) E1A protein, we showed that all of the epitopes conserved between Ad2/5 E1A and Ad12 E1A protein that are recognized by the Ad12 E1A-specific antiserum map to within the first exon-encoded amino-terminal half of the protein.

Adenovirus Early Proteins

An immunodominant domain in adenovirus type 2 early region 1A proteins.

Six independent rat hybridoma cell lines producing monoclonal antibodies to human subgroup C adenovirus early region 1A (E1A) proteins were isolated. Competition binding experiments revealed that each of the monoclonal antibodies was directed against the same epitope or overlapping cluster of epitopes on the E1A proteins. Viral E1A deletion mutants and deleted forms of E1A proteins expressed in Escherichia coli were used to localize the antibody recognition sites to sequences between amino acids 23 and 120, encoded within the first exon of the E1A gene. Similarly, polyclonal antisera raised against the trpE-E1A fusion protein, as well as against the native, biologically active E1A protein, were also directed primarily against this immunodominant region.

Adenoviridae