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R Garlick

Publications and source records attributed to R Garlick.

13 recordsLinked to original sources
PubMed2000

Positional cloning utilizing genomic DNA microarrays: the Niemann-Pick type C gene as a model system.

A major obstacle in positional cloning is identifying the specific mutated gene from within a large physical contig. Here we describe the application of DNA microarray technology to a defined genomic region (physical map) to identify: (i) exons without a priori sequence data and (ii) the disease gene based on differential gene expression in a recessive disorder. The feasibility was tested using resources from the positional cloning of the Neimann-Pick Type C (NP-C) disease gene, NPC1. To identify NPC1 exons and optimize the technology, an array was generated from genomic fragments of the 110-kb bacterial artificial chromosome, 108N2, which encodes NPC1. First, as a test case for blindly identifying exons, fluorescently labeled NPC1 cDNA identified 108N2 fragments that contained NPC1 exons, many of which also contained intronic sequences and could be used to determine part of the NPC1 genomic structure. Second, to demonstrate that the NPC1 disease gene could be identified based upon differential gene expression, subarrays of 108N2 fragments were hybridized with fluorescently labeled cDNA probes generated from total RNA from hamster cell lines differentially expressing NPC1. A probe derived from the NP-C cell line CT60 did not detect NPC1 exons or other genomic fragments from 108N2. In contrast, several NPC1 exons were detected by a probe generated from the non-NP-C cell line 911D5A13, which was derived from CT60, and expressed NPC1 as a consequence of stable transduction with a YAC that contains NPC1 and encompasses 108N2. Thus, the array technology identified NPC1 as a candidate gene based on a physical contig and differential NPC1 expression between NP-C and non-NP-C cells. This technique should facilitate gene identification when a physical contig exists for a region of interest and mutations result in changes in the mRNA level of the disease gene or portions thereof.

Animals↗
PubMed1998

Lowering the language barrier in an acute psychiatric setting.

OBJECTIVES: The aim of this paper is to investigate the effectiveness of a training and policy strategy to improve communication opportunities in an acute inpatient unit for patients of non-English-speaking background (NESB) with low English proficiency. METHOD: A pre- and post-intervention design involved: (i) a survey of the multilingual skills of 80 clinical staff; (ii) recording of patients' ethnic background and proficiency; (iii) pre- and post-intervention data collection of the main outcome measure (communications with patients in a language other than English [LOTE]); and (iv) staff training, and active encouragement, in interpreter use. English proficiency was assessed using the population census proficiency question. RESULTS: Of 257 admissions, 33% were of NESB and 19% preferred to speak a LOTE. The staff survey yielded a 49% return rate and showed that, of 11 LOTEs spoken by patients, seven were also spoken by 17 of the staff. Twenty-nine percent of staff were not clinically proficient in these languages. Compared to the NESB population, a higher proportion of NESB patients rated low on proficiency. Following the intervention, interpreter bookings and booking duration increased significantly. CONCLUSIONS: A standard training package and a policy promoting interpreter use improved communication opportunities in an acute setting where language needs are typically poorly met. Failure to ensure effective communicate raises risks of misdiagnosis and inappropriate treatment. By measuring patients' proficiency directly, the present study identified a higher level of need for interpreter services than estimated by past reports.

Acute Disease↗
PubMed1993

The UPA score and teenage pregnancy.

Teenage motherhood is often said to be the result of deficient contraceptive and abortion services. Using data from the Public Health Common Data Set (PH CDS) we demonstrate two important effects in a Regional Health Authority: higher rates of conception are related to a live birth rather than an abortion pregnancy outcome; District Health Authorities (DHAs) with high underprivileged area scores (UPA) are more likely to have high rates of conception in the teenage years than those districts with low scores.

Abortion, Induced↗
PubMed1990

Regulation of surface expression of the granulocyte/macrophage colony-stimulating factor receptor in normal human myeloid cells.

Recombinant human granulocyte/macrophage colony-stimulating factor (GM-CSF) exerts stimulatory effects on hematopoietic cells through binding to specific, high-affinity receptors (Kd = 30-100 pM). By using radiolabeled GM-CSF with high specific activity, we have investigated the factors and mechanisms that regulate GM-CSF receptor expression in normal human neutrophils, monocytes, and partially purified bone marrow myeloid progenitor cells. The neutrophil GM-CSF receptor was found to rapidly internalize in the presence of ligand through a mechanism that required endocytosis. Out of a large panel of naturally occurring humoral factors tested, only GM-CSF itself, tumor necrosis factor, and formyl-Met-Leu-Phe were found to down-regulate neutrophil GM-CSF receptor expression after a 2-hr exposure at biologically active concentrations (95% +/- 1%, 34% +/- 5%, 48% +/- 8% receptor down-regulation, respectively). GM-CSF also down-regulated its own receptor on monocytes and myeloid progenitor cells. Since formyl-Met-Leu-Phe is known to stimulate neutrophil protein kinase C activity, we also tested the ability of protein kinase C agonists to modulate GM-CSF receptor expression. Phorbol 12-myristate 13-acetate, bryostatin-1, and 1,2-dioctanoylglycerol were found to induce rapid down-regulation of the GM-CSF receptor in neutrophils, monocytes, and partially purified myeloid progenitor cells, suggesting that this effect may be at least partially mediated by protein kinase C. These data suggest that certain activators of neutrophil function may negatively regulate their biological effects by inducing down-regulation of the GM-CSF receptor.

Colony-Stimulating Factors↗
PubMed1990

Medical audit: assessment of surgical performance in a low volume specialty.

We describe a simple technique for auditing one aspect of the activity of a neurosurgical unit--the surgical operations performed. A proforma completed by the surgeon at the time of operation was brought up-to-date on subsequent daily ward rounds. Each week, the medical staff of the unit met to review the data sheets of those patients discharged during the previous seven days. This meeting served to ensure the completeness of the data and to discuss any problems in management before the records were computerized. At the end of the first year, problems which had become apparent in the system were identified and corrected. The revised system involves a comprehensive and prospective audit of relevant clinical information. It has led to the accumulation of a considerable quantity of reliable data and it involves frequent positive feedback which appears to be leading to an improvement in treatment outcome. The system is simple to administer and is economical of time. It should be suitable for any surgical specialty which resembles neurosurgery in dealing with a relatively small volume of major procedures, and it could easily be adapted to audit other aspects of the activity of a unit.

Evaluation Studies as Topic↗
PubMed1987

The use of intermittent and continuous recordings of jugular venous bulb oxygen saturation in the unconscious patient.

Monitoring clinical signs in unconscious patients provides only late information about cerebral deterioration. Ischaemia and hypoxia are the mechanisms of much of the damage. Cerebral blood flow (CBF) measurements provide direct evidence of ischaemia but are intermittent values for what may be an unstable situation. Continuous recordings of CBF and oxygenation are more likely to reveal harmful tendencies to ischaemia and hypoxia at an early stage than intermittent readings. We report our experience with intermittent and also continuous recording of the jugular venous bulb oxygen saturation (JVO2Sat) obtained by fibreoptic oximetry in a group of 10 head injured and 7 septic patients. Simultaneous measurements of CBF by an isotopic xenon clearance method were also made. The JVO2Sat has been suggested to be a reliable indicator of cerebral oxygenation, a low value being indicative of ischaemia. We discuss whether our findings support this statement. There are also variations in JVO2Sat with mean arterial blood pressure and intracranial pressure. These variations have important implications in the interpretation that can be made of one single value of JVO2Sat.

Adolescent↗
PubMed1986

Subdural empyema.

Explore the source record for details and available documents.

Empyema, Subdural↗
PubMed1985

Retention of biological activity following radioiodination of human interleukin 2: comparison with biosynthetically labeled growth factor in receptor binding assays.

Human interleukin 2 (IL-2) was radioiodinated by a modified form of the chloramine-T reaction. Comparison with biosynthetically radiolabeled IL-2 demonstrated that the iodinated molecule retained similar receptor binding characteristics and proliferation-inducing ability. The iodinated molecule also possessed the distinct advantages of a higher specific radioactivity and a reduced processing time for the assay samples. The majority of the iodine was incorporated at the tyrosine in position 45 of the polypeptide chain. Evidently, this residue is unimportant for the molecule's association with its receptor. The development of active radioiodinated IL-2 should facilitate routine measurement of the high-affinity IL-2 binding sites which mediate the physiological response to this lymphokine.

Binding Sites↗