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Biomedical subjects

J Drew

Publications and source records attributed to J Drew.

At least 37 records · Page 2Linked to original sources
PubMed1996

Instability of long inverted repeats within mouse transgenes.

Various sequences in the mammalian genomes are unstable. One class of sequence arrangement is long inverted repeats, which are known to be unstable in bacteria and yeast. While in mammals some evidence suggests that short inverted repeats (<10 bp long) may show instability, nothing is known about the stability of long inverted repeats. Here we describe two unrelated multicopy transgenes in the mouse (loci 109 and OX1-5), each of which contains a long inverted repeat that shows substantial mitotic instability. This instability also occurs in the germline so that mutant transgenes appear within pedigrees at a high frequency. The mutation processes acting at these two inverted repeats are complex and can involve insertion or deletion, and can result in stabilization of the transgene. At transgene 109 mutational events range from very small rearrangements at the centre of the inverted repeat to complete transgene deletion. In addition we show that the rates of mutation at the inverted repeat of transgene OX1-5 can vary between the male and female germlines and between inbred strains of mice, suggesting the possibility of a genetic analysis to identify loci that modulate inverted repeat instability.

Animals↗
PubMed1995

Polyadenylic-polyuridylic acid enhances the natural cell-mediated cytotoxicity in patients with breast cancer undergoing mastectomy.

BACKGROUND: Surgical procedures suppress host antitumor defense mechanisms, which may increase the risk of metastatic tumor dissemination. We have evaluated the effects of the biologic response modifier polyadenylic-polyuridylic acid (PAPU) on natural cytotoxicity in patients with breast cancer undergoing operation. METHODS: PAPU (150 mg) or placebo was given intravenously during the perioperative period (preoperative, days -1 and 0; postoperative, days 1, 3, 5, 7, and 14). The function (chromium release assay) and number (flow cytometry) of natural killer (NK) cells were measured before operation (days -2 and -1), on the day of operation (day 0), and after operation (days 1, 2, 4, 6, and 18). RESULTS: Surgical procedures suppressed NK cell cytotoxicity in the placebo group on postoperative days 1 (p < 0.001), 4, 6, and 18 (p < 0.05), whereas inhibition on postoperative day 2 failed to reach significance. PAPU abolished this immunosuppression after operation. The NK cell activity was elevated when compared with the control group; it was significant (p < 0.05) on postoperative days 1, 2, 4, 6, and 18. Surgical procedures also reduced circulating NK cell numbers during the first postoperative week in the placebo group; the decrease was statistically significant on day 4. The decrease in NK cell numbers in the PAPU group was insignificant. CONCLUSIONS: PAPU prevented the decrease in the circulating number and cytotoxic activity of NK cells that occurred after operation and enhanced NK cell cytotoxicity. This may have important implications for patients with cancer undergoing major operation.

Adult↗
PubMed1995

Use of component analyses to identify active variables in treatment packages for children with feeding disorders.

We evaluated the separate components in treatment packages for food refusal of 4 young children. First, treatment packages were implemented until food acceptance improved. Next, a component analysis was conducted within a multielement or reversal design to identify the active components that facilitated food acceptance. The results indicated that escape extinction was always identified as an active variable when assessed; however, other variables, including positive reinforcement and noncontingent play, were also identified as active variables for 2 of the children. The results suggest that the component analysis was useful for identifying variables that affected food acceptance.

Child, Preschool↗
PubMed1995

Two measures of preference during forced-choice assessments.

A forced-choice preference assessment was conducted in which two dependent measures were used to select preferred stimuli: (a) approach responding and (b) latency to the first aberrant response. Stimuli identified as preferred based on both dependent measures were then evaluated during treatment. The results suggested that latency may be a useful measure in the selection of preferred stimuli during forced-choice assessments.

Child↗
PubMed1994

Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein.

We describe the construction of a plasmid (pCAT2AGUS) encoding a polyprotein in which a 19 amino acid sequence spanning the 2A region of the foot-and-mouth disease virus (FMDV) polyprotein was inserted between the reporter genes chloramphenicol acetyl transferase (CAT) and beta-glucuronidase (GUS) maintaining a single, long open reading frame. Analysis of translation reactions programmed by this construct showed that the inserted FMDV sequence functioned in a manner similar to that observed in FMDV polyprotein processing: the CAT2AGUS polyprotein underwent a cotranslational, apparently autoproteolytic, cleavage yielding CAT-2A and GUS. Analysis of translation products derived from a series of constructs in which sequences were progressively deleted from the N-terminal region of the FMDV 2A insertion showed that cleavage required a minimum of 13 residues. The FMDV 2A sequence therefore provides the opportunity to engineer either whole proteins or domains such that they are cleaved apart cotranslationally with high efficiency.

Amino Acid Sequence↗
PubMed1994

trans complementation by RNA of defective foot-and-mouth disease virus internal ribosome entry site elements.

A region of about 435 bases from the 5' noncoding region of foot-and-mouth disease virus RNA directs internal initiation of protein synthesis. This region, termed the internal ribosome entry site (IRES), is predicted to contain extensive secondary structure. Precise deletion of five predicted secondary structure features has been performed. The mutant IRES elements have been constructed into vectors which express bicistronic mRNAs and assayed within cells. Each of the modified IRES elements was defective in directing internal initiation when assayed alone. However, coexpression of an intact foot-and-mouth disease virus IRES complemented four of these defective elements to an efficiency of up to 80% of wild-type activity. No complementation was observed with the structurally analogous element from encephalomyocarditis virus. The role of RNA-RNA interactions in the function of the picornavirus IRES is discussed.

Amino Acid Sequence↗
PubMed1993

A comparison of children's performance on two recognition memory tasks: delayed nonmatch-to-sample versus visual paired-comparison.

Although 4- to 6-month-old children have a significant tendency to look at new stimuli in a visual paired-comparison task (VPC), they have difficulty in consistently choosing novel objects in a delayed nonmatch-to-sample task (DNMS). To evaluate which factors could account for this difficulty, we tested human infants (10-107 months) and adults (17-25 years) in a DNMS task while monitoring eye fixations. The results indicated that children at all ages reliably looked at (VPC scores) or chose (DNMS scores) the new stimuli about 60% of the time, indicating that both tasks measure visual recognition memory. A videotape analysis of visual attention revealed that children younger than 22 months, but not older children, spent significantly more time visually exploring the objects rather than looking at the food reward under it. Although this visual attraction to objects in children younger than 22 months of age may have impaired the formation of stimulus-reinforcer association needed to solve the DNMS task, this was not the case for older children, since beyond 22 months of age children consistently looked at the reward while displacing the objects. These results suggest that other cognitive abilities required by the DNMS task may not be fully functional even in children 22 months and older.

Adolescent↗
PubMed1993

The cost of improving the outcome for infants of birthweight 500-999 g in Victoria. The Victorian Infant Collaborative Study Group.

The aim of this study was to conduct an economic evaluation of neonatal intensive care for extremely low birthweight (ELBW) infants born in the state of Victoria. Two distinct eras (1979-80 and 1985-87) were compared. Follow-up data at 2 years of age were available for all 89 survivors from the 351 live births in 1979-80, and for 211 of 212 survivors from the 560 live births in 1985-87. The overall cost-effectiveness for ELBW infants during 1985-87 compared with 1979-80 was $104,990 ($A 1987) per additional survivor, or $5390 ($A 1987) per additional life year gained. Cost-effectiveness improved with increasing birthweight. If the quality of life of the survivors was considered, the economic outlook was more favourable. The cost per quality-adjusted life year gained was $5090 ($A 1987), approximately one-tenth of that obtained from the only previous full economic evaluation of neonatal intensive care. Although neonatal intensive care is expensive, it compares favourably with some other health care programmes, particularly as the outcome for ELBW infants continues to improve.

Birth Weight↗
PubMed1993

Establishment of a quality assurance program for human immunodeficiency virus type 1 DNA polymerase chain reaction assays by the AIDS Clinical Trials Group. ACTG PCR Working Group, and the ACTG PCR Virology Laboratories.

An independent quality assurance program has been established by the Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring polymerase chain reaction (PCR) assays for human immunodeficiency virus type 1 (HIV-1) DNA that are performed by 11 laboratories participating in multicenter clinical trials in the United States. To perform HIV-1 DNA PCR for patients in AIDS Clinical Trials Group protocols, each laboratory was initially certified by correctly testing a coded certification panel consisting of eight well-defined clinical whole-blood specimens and 30 cell pellets containing 0, 2, 5, 10, 20, or 50 8E5/LAV cells per 125,000 uninfected peripheral blood mononuclear cells. PCR was performed by one of two standardized commercial assays for amplification and nonisotopic detection of HIV-1 proviral DNA. For continuing certification, each laboratory must correctly test eight coded whole-blood samples per quarter and run three or four coded cell pellets and HIV-1 DNA copy standards with every PCR assay in real time. The PCR results for the coded pellets on each run are entered into an encrypted computer file, which immediately assesses the validity of the run. To date, 10 of 11 laboratories have correctly tested all HIV-1-positive and -negative samples in the initial certification panel on their first or second attempt. Subsequently, 9 of these 11 laboratories have continued to maintain their certified status. The use of commercial HIV-1 DNA PCR assays and an external quality assurance program have ensured that results from different laboratories are comparable and that problems with sensitivity and specificity are quickly identified.

Certification↗
PubMed1993

A brief component analysis of potential treatment packages in an outpatient clinic setting with young children.

The purpose of this study was to develop outpatient clinic assessments that allowed us to assess multiple treatment variables, produce relatively quick effects, and isolate active treatment components. Assessment began by evaluating a treatment package consisting of antecedent and consequence variables followed by a component analysis to determine the separate effects of the treatment variables. Three examples of the findings are presented.

Ambulatory Care↗
PubMed1992

Tachyarrhythmia, cardiac rhabdomyomata and fetal hydrops in a premature infant with tuberous sclerosis.

An hydropic infant was delivered at 32 weeks gestation by emergency Caesarean section for acute polyhydramnios. A diagnosis of cardiac rhabdomyomata was made on echocardiography. The baby survived 10 days, during which time repeated episodes of supraventricular tachycardia occurred. She eventually died of cardiac failure following an episode of septicaemia, convulsions and aspiration pneumonia. Necropsy showed multiple cardiac rhabdomyomata and numerous cerebral germinal layer and periventricular white matter nodules. This case stresses the importance of clinical investigations and perinatal necropsy in non-immune hydrops fetalis (NIHF) in determining the causes of clinical presentation and the underlying pathology.

Female↗
PubMed1991

Spectrofluorometric determination of lipase activity.

A fluorescent triglyceride, 1(3)-pyrenylbutanoyl-2,3(1,2)-dipalmitoyl-sn-glycerol, was synthesised, characterised by NMR and mass spectrometry, incorporated into a lipid emulsion and used as a fluorescent substrate for pancreatic lipase. It is shown that the product of the reaction, pyrene butyric acid, diffuses into the aqueous phase resulting in a decrease in the excimer fluorescence of the pyrene fluorophore in the emulsion and an increase in its monomer fluorescence. The phenomenon can be used to assay the enzyme thereby cirumventing the need to extract the fatty acid product.

Fluorescent Dyes↗
PubMed1990

Resolution of heterogeneous fluorescence into component decay-associated excitation spectra. Application to subtilisins.

Direct and indirect methods are described to combine steady-state and picosecond time-resolved fluorescence decay data to generate decay-associated excitation spectra. The heterogeneous fluorescence from a fluorophore mixture that models protein fluorescence was resolved into individual component excitation spectra. The two methods were also used to determine the excitation spectra associated with each of the decay time components for the proteins subtilisin Carlsberg and BPN'. On the basis of associated spectra, the decay components of both proteins were assigned to individual (or groups of) emitting species. The two approaches used to generate the decay-associated excitation spectra are compared and their general application to protein fluorescence studies is discussed.

Kinetics↗
PubMed1990

Preparation of lipid emulsions by pressure extrusion.

Lipid emulsions consisting of a surface monolayer of phospholipid enclosing a core of neutral lipids have been prepared by repeated extrusion through polycarbonate filters of defined pore size. Particle size, as measured by photon correlation spectroscopy, decreases on successive passes through a 100 nm filter, reaching a near constant value (130-150 nm) after 4 passes. A corresponding decrease in the standard deviation of the particle size distribution occurs during this process. The recovery of lipids, especially of cholesterol and cholesterol ester, is improved if the emulsion is sonicated before extrusion through filters. [31P]-NMR and fluorescence techniques are used to confirm that the resulting structures are emulsions rather than lipid bilayers.

Cholesterol↗
PubMed1990

Anticipation of future food: suppression and facilitation of saccharin intake depending on the delay and type of future food.

A series of studies examined the (Sprague-Dawley) rat's tendency to suppress intake of .15% saccharin when it was followed by a second food after 4-, 16-, or 32-min delays. The second foods examined were 32% sucrose, 64% sucrose, lab chow, a Nutrasweet solution, skim milk, and chocolate milk. Saccharin intake was influenced by both the delay and the specific food available. Subsequent analysis showed that saccharin intake before the 4-min delay was an inverse function of the caloric value of the second food. However, saccharin intake before the 16-min delay was better predicted as an inverse function of the hedonic value of the second food. The results suggest that the caloric and hedonic values of a food may influence food selection across different time courses, and that the effective time horizon for the sequential comparison of foods depends on the specific foods that are compared.

Animals↗