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J Young

Publications and source records attributed to J Young.

At least 163 records · Page 9Linked to original sources
PubMed1999

Sequence-tagged connectors: a sequence approach to mapping and scanning the human genome.

The sequence-tagged connector (STC) strategy proposes to generate sequence tags densely scattered (every 3.3 kilobases) across the human genome by arraying 450,000 bacterial artificial chromosomes (BACs) with randomly cleaved inserts, sequencing both ends of each, and preparing a restriction enzyme fingerprint of each. The STC resource, containing end sequences, fingerprints, and arrayed BACs, creates a map where the interrelationships of the individual BAC clones are resolved through their STCs as overlapping BAC clones are sequenced. Once a seed or initiation BAC clone is sequenced, the minimum overlapping 5' and 3' BAC clones can be identified computationally and sequenced. By reiterating this "sequence-then-map by computer analysis against the STC database" strategy, a minimum tiling path of clones can be sequenced at a rate that is primarily limited by the sequencing throughput of individual genome centers. As of February 1999, we had deposited, together with The Institute for Genomic Research (TIGR), into GenBank 314,000 STCs ( approximately 135 megabases), or 4.5% of human genomic DNA. This genome survey reveals numerous genes, genome-wide repeats, simple sequence repeats (potential genetic markers), and CpG islands (potential gene initiation sites). It also illustrates the power of the STC strategy for creating minimum tiling paths of BAC clones for large-scale genomic sequencing. Because the STC resource permits the easy integration of genetic, physical, gene, and sequence maps for chromosomes, it will be a powerful tool for the initial analysis of the human genome and other complex genomes.

Chromosome Mapping↗
PubMed1999

Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices.

We used ouabain (100 microM) to block Na+,K(+)ATPase of in vitro rat hippocampal slices. This treatment was sufficient to cause the sudden depolarization that is the hallmark of both spreading depression (SD) and of the SD-like anoxic depolarization (AD). This depolarization was accompanied by a large and sudden increase in [K](o), also reminiscent of that observed during both SD and AD. Ouabain-induced SD did not require a complete inactivation of Na+,K(+)ATPase, as it occurred when the enzyme was still capable of providing recovery of both V(o) and [K](o). The data indicate that functional inactivation of Na+,K(+)ATPase per se initiates events that lead to an SD-like AD. This ouabain-induced depolarization was not affected by block of synaptic transmission, instead it was abolished by hyperosmolarity of the extracellular space. The possible relevance of these findings to the pathophysiology of AD is discussed.

Animals↗
PubMed1999

[Diagnosis and treatment of hypogonadotropism in males and females].

Hypogonadotropic hypogonadism is the consequence of FSH and LH deficiency leading to testicular or ovarian dysfunction. The diagnosis should be considered when there is a complete absence of pubertal development in both sexes. Hypogonadotropism, that occurs after puberty, is revealed by secondary amenorrhea in women, decreased libido in men. The hormonal diagnosis is easy in the complete forms with usually undetectable plasma LH, FSH and sex steroid levels. In the partial forms, plasma gonadotropin levels may be in the low normal range with slightly decreased plasma sex steroid levels. Gonadotropin deficiency may be isolated, congenital and of genetic origin. In acquired forms, panhypopituitarism and mass lesions of the hypothalamic pituitary sites must be diagnosed by magnetic resonance imaging and hormonal testing. Treatment requires only substitution when fertility is not sought. In the treatment of infertility, the use of pulsatile modes of GnRH administration is remarkably successful in women, as well as exogenous gonadotropins in both sexes.

Female↗
PubMed1999

Otoacoustic emission criteria for neonatal hearing screening.

Transient evoked otoacoustic emission measures are gaining acceptance as a technique in new-born hearing screening. At present a wide variety of pass-fail screening criteria are used in otoacoustic emission screening programs. In a study of 100 special care neonates and 35 well, full term babies, a number of screening criteria were examined for sensitivity and specificity characteristics when compared to a standard auditory brainstem response protocol. Results indicate that, for normal and special care neonates with a gestational age at test of 38-41 weeks, high sensitivity ( > 80%) could be obtained when a pass-fail criterion involving analysis of emission reproducibility, or emission reproducibility and emission response level, was set. Sensitivity was reduced for special care neonates who fell outside this age range. Specificity was found to be relatively low overall (always < 65%) and may relate to clinical factors in special care neonates not investigated in this study.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1999

Systematic review of day hospital care for elderly people. The Day Hospital Group.

OBJECTIVE: To examine the effectiveness of day hospital attendance in prolonging independent living for elderly people. DESIGN: Systematic review of 12 controlled clinical trials (available by January 1997) comparing day hospital care with comprehensive care (five trials), domiciliary care (four trials), or no comprehensive care (three trials). SUBJECTS: 2867 elderly people. MAIN OUTCOME MEASURES: Death, institutionalisation, disability, global "poor outcome," and use of resources. RESULTS: Overall, there was no significant difference between day hospitals and alternative services for death, disability, or use of resources. However, compared with subjects receiving no comprehensive care, patients attending day hospitals had a lower odds of death or "poor" outcome (0.72, 95% confidence interval 0.53 to 0.99; P<0.05) and functional deterioration (0.61, 0.38 to 0.97; P<0.05). The day hospital group showed trends towards reductions in hospital bed use and placement in institutional care. Eight trials reported treatment costs, six of which reported that day hospital attendance was more expensive than other care, although only two analyses took into account cost of long term care. CONCLUSIONS: Day hospital care seems to be an effective service for elderly people who need rehabilitation but may have no clear advantage over other comprehensive care. Methodological problems limit these conclusions, and further randomised trials are justifiable.

Aged↗
PubMed1999

Expression of Bcl-2 protein is decreased in colorectal adenocarcinomas with microsatellite instability.

Bcl-2 is known to inhibit apoptosis and is thought to play a role in colorectal tumour development. Studies of the promoter region of bcl-2 have indicated the presence of a p53 responsive element which downregulates bcl-2 expression. Since p53 is commonly mutated in colorectal cancers, but rarely in those tumours showing microsatellite instability (MSI), the aim of this study was to examine the relationship of bcl-2 protein expression to MSI, as well as to other clinicopathological and molecular variables, in colorectal adenocarcinomas. Expression of bcl-2 was analysed by immunohistochemistry in 71 colorectal cancers which had been previously assigned to three classes depending upon their levels of MSI. MSI-high tumours demonstrated instability in three or more of six microsatellite markers tested, MSI-low tumours in one or two of six, and MSI-null in none of six. Bcl-2 expression in tumours was quantified independently by two pathologists and assigned to one of five categories, with respect to the number of cells which showed positive staining: 0, up to 5%; 1, 6-25%; 2, 26-50%; 3, 51-75%; and 4, > or =76%. Bcl-2 negative tumours were defined as those with a score of 0. Bcl-2 protein expression was tested for association with clinicopathological stage, differentiation level, tumour site, age, sex, survival, evidence of p53 inactivation and MSI level. A significant association was found between bcl-2 expression and patient survival (P = 0.012, Gehan Wilcoxon test). Further, a significant reciprocal relationship was found between bcl-2 expression and the presence of MSI (P = 0.012, Wilcoxon rank sum test). We conclude that bcl-2 expressing colorectal cancers are more likely to be MSI-null, and to be associated with improved patient survival.

Adenocarcinoma↗
PubMed1999

Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two important determinants of angiogenesis in human cancers. Expression of VEGF and bFGF was examined by immunohistochemistry in 120 colorectal cancers. Neoplasms were classified according to the presence or absence of microsatellite instability determined at six microsatellite loci and labelled as a high microsatellite instability (MSI-H), low microsatellite instability (MSI-L) or microsatellite stable (MSS). Only 4/30 MSI-H cancers expressed VEGF (13 per cent), compared with 24/64 MSS cancers (38 per cent; p< 0.01). Fewer MSI-H cancers showed bFGF expression (38 per cent) than MSS cancers (53 per cent; p< 0.09). MSI-L cancers showed the same pattern as MSS cancers. Western blotting and immunohistochemistry showed that the tumour suppressor gene p53 was mutated infrequently in MSI-H cancers (8 per cent; p< 0. 001). Microvessel density counts using CD31 and UEA-1 demonstrated no difference in the number of blood vessels in MSI-H and MSS cancers. Although these results are consistent with the known role of wild-type p53 in down-regulating VEGF, no association was found between a mutation in p53 and VEGF or bFGF levels in all colonic neoplasms. This is the first evidence that MSI-H cancers may follow a different pathway to angiogenesis. The low frequency of VEGF expression amongst MSI-H cancers may partially explain why these cancers are less aggressive, with a better overall prognosis.

Adenocarcinoma↗
PubMed1999

Outcome of de novo hepatitis C virus infection in heart transplant recipients.

The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 +/- 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P =.04) and high viral load at onset of acute liver disease (P =.02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P =.20). Development of ACH (P =.02) and MMF use (P =.0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.

Actuarial Analysis↗
PubMed1999

Influence of phospholipid composition on the properties of reconstituted surfactants.

The influence of phospholipids on the ultrastructure and metabolism of reconstituted surfactants has not been well defined. The aim of this study was to determine if changes in the phospholipid composition of reconstituted surfactants altered their biophysical properties, ultrastructure, and conversion to light subtype by cycling. We prepared various surfactants containing radiolabeled dipalmitoylphosphatidylcholine ([14C]DPPC). The addition of phosphatidylglycerol (PG) or dipalmitoylphosphatidic acid (PA) to DPPC increased conversion to light subtype. In contrast, the addition of dipalmitoylphosphatidylglycerol (DPPG) to DPPC markedly reduced conversion to light subtype on cycling. DPPC and DPPC+PG produced large liposomes ( approximately 1,000 nm), whereas DPPC+PA or DPPC+DPPG formed multilamellar membranes. Mixtures of DPPC and PA were highly surface active in vitro, whereas the surface activity of DPPC+DPPG was similar to that of DPPC. In conclusion, the ultrastructure, metabolism, and surface active properties of DPPC+PG mixtures were influenced markedly by alterations in the fatty acid composition or polar head group of PG.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Antibody analysis of the localisation, expression and stability of HlyD, the MFP component of the E. coli haemolysin translocator.

HlyD has a single transmembrane domain (residues 59-80) and a large periplasmic domain, and is essential for the secretion of haemolysin from Escherichia coli. Using an antibody raised against HlyD, the protein was localised to the cell envelope by immunofluorescence and to the cytoplasmic membrane by sucrose gradient analysis. We have examined the stability of this protein in the presence and absence of other putative components of the translocator, HlyB and TolC. HlyD is normally highly stable but in the absence of TolC, the steady-state level of HlyD is greatly reduced and the protein has a half-life at 37 degrees C of 36 min. In the absence of HlyB, HlyD is also unstable and specific degradation products are detected, which co-fractionate with the inner membrane, indicating in this case limited cleavage at specific sites. However, the effect of removing both HlyB and TolC is not additive. On the contrary, in the absence of both HlyB and TolC the half-life of HlyD is approximately 110 min. This result shows that in the presence of HlyB removal of TolC renders HlyD more unstable than it is in the absence of both HlyB and TolC. This suggests that the presence of HlyB induces a structural change in HlyD. In addition, HlyB itself appears to be less stable in the absence of HlyD. These results are consistent with an interaction between HlyD/TolC and HlyB/HlyD. A derivative of HlyD, HlyD22, lacking the 40 N-terminal residues of HlyD assembles into the inner membrane displaying the same stability with and without HlyB as wild type HlyD does. This N-terminal region therefore appears to play no role in stable localisation but is involved in secretion, since HlyD22 is completely secretion defective. Modification of the C-terminus on the other hand completely destabilised the molecule and HlyD was not detectable in the envelope. Secretion of active haemolysin is limited to a brief period during mid to late exponential phase. In contrast, HlyD is apparently synthesised constitutively throughout the growth phase, demonstrating that the production of this component of the translocator is not the limiting factor for growth phase-dependent secretion.

Antibodies, Monoclonal↗
PubMed1999

The prolonged hematologic effects of a single injection of PEG-rHuMGDF in normal and thrombocytopenic mice.

A single injection of > or =10 microg/kg PEG-rHuMGDF in mice causes a dose-dependent increase in circulating platelets beginning on day 3 and peaking on days 5-6. The mean platelet volume and platelet distribution width at doses > or =100 microg/kg initially increase in a dose-dependent fashion and later decrease. However, the mean platelet volume does not change when platelets are incubated with PEG-rHuMGDF in vitro. The number of marrow megakaryocytes increases in a dose-dependent fashion as early as day 1 and peaks on day 3. Marrow megakaryocyte colony-forming units (CFU-Meg) do not increase on days 1-3 at a dose of 100 microg/kg (a dose that increases platelet numbers two- to threefold and may be clinically relevant), but the relative frequency of high ploidy megakaryocytes and the proportion of large marrow megakaryocytes (29-50 microm in diameter) increases. After a dose of 1,000 microg/kg the percentage of megakaryocytes in mitosis peaks at 24-48 hours and the percentage of megakaryocytes incorporating BrdU is maximal at 48 hours, the relatively delayed peak of BrdU incorporation most likely representing endomitosis. The relative frequency of type II and III megakaryocytes peaks on days 3 and 4, respectively. Pharmacokinetic analysis of PEG-rHuMGDF shows peak serum concentrations at 2-4 hours and a terminal half-life of 11.4+/-2.5 hours. A single injection of PEG-rHuMGDF ameliorates carboplatin-induced megakaryocytopenia and thrombocytopenia in a dose-response dependent fashion. In conclusion, a single injection of PEG-rHuMGDF increases megakaryocyte and platelet production in normal and myelo-suppressed mice.

Acetylcholinesterase↗
PubMed1999

Night-time non-nutritive sucking in infants aged 1 to 5 months: relationship with infant state, breastfeeding, and bed-sharing versus room-sharing.

AIM: Epidemiological studies suggest that pacifier use may be protective against SIDS but little is known of the relationship between pacifier use and other forms of non-nutritive sucking (NNS) in infancy, or of patterns of NNS during the night, when most SIDS deaths occur. We report the first longitudinal study of NNS by direct overnight observations in healthy infants in a sleep laboratory. METHODS: Healthy, breast fed term infants (n = 10) were enrolled at birth, and sequential overnight polygraphic and infrared video recordings of infants with their mothers performed at monthly intervals from 1 to 5 months. Each month, mother baby pairs were randomized to 1 night bed-sharing (BN) then 1 room-sharing (RN), or vice versa. 'Episodes' of pacifier, own digit and mother's digit sucking (> 1 min) were identified and compared with state-matched control periods without sucking or feeding before and after each such episode. RESULTS: 329 episodes of NNS were identified in 749 h of video recording. The prevalence of pacifier sucking decreased with age, whilst digit sucking increased. Routine pacifier users rarely sucked their digits. There were temporal differences throughout the night in the distribution of different types of sucking and in infant state during and around sucking episodes. Sleeping in the 'non-routine' location was associated with a larger percentage of nights with sucking episodes and increased sleep latency. Bed sharing (routinely or on a given night) was associated with less sucking behavior and more breastfeeding. Non-nutritive sucking was not, however, associated with decreased total time breastfeeding per night or number of feeds per night. CONCLUSION: Patterns of NNS during the night change with age and are affected by maternal proximity. Digit sucking has state modulating effects, and may be suppressed by pacifier use. Thus any benefits of pacifier use must be set against the potential loss of a self-directed ability to modulate state during the night, and possible shortening of breastfeeding duration.

Beds↗
PubMed1999

Hypoglycemia in multiple trauma victims.

The typical presentation of hypoglycemia involves a diaphoretic patient with a history of diabetes mellitus who is found with an altered mental status. The hypoglycemic patient's presentation may lead the physician to believe that the altered mentation may have been caused by some other condition. Hypoglycemia occurs rarely in the traumatic setting, yet is easily and rapidly diagnosed with bedside testing. A retrospective review was conducted in a university hospital emergency department (ED) (level 1 trauma center) of adult trauma patients with a Glasgow Coma Scale (GCS) score of <15 who had presented from July 1995 through August 1996. Hypoglycemia was defined as a serum glucose level of <60 mg/dL. A total of 926 patients (49% of all trauma cases encountered in the period) met entry criteria. Four (0.4%) cases of hypoglycemia were encountered in 1 nondiabetic and 3 diabetic patients; no patient had medical alert warnings. Rapid bedside screening identified 2 cases within a mean of 7 minutes after arrival; 1 patient had an improvement in mental status after dextrose therapy. Two cases were identified by formal laboratory analysis a mean of 35 minutes after ED arrival; dextrose therapy improved the mental status in 1 patient. These results show that hypoglycemia, rare in trauma patients with abnormal GCS scores, may mimic significant traumatic injury with mental status alterations. Physicians should consider such a diagnosis in patients with an abnormal GCS score and known risk situations for hypoglycemia, including diabetes mellitus and chronic alcohol use; in such cases, appropriate bedside screening should be performed after initial stabilization.

Adult↗
PubMed1999

ED use of flexion-extension cervical spine radiography in the evaluation of blunt trauma.

Dynamic cervical spine radiography (CSR) is used to detect ligamentous instability. We investigated the ED use of dynamic CSR through a retrospective descriptive review using a convenience sample study design at a university emergency department. Adult blunt trauma patients with static (lateral, AP, odontoid) and dynamic (flex, extend) CSR participated. 451 patients (52% male with mean age of 33.6 years) met entry criteria. Injury mechanisms were 74% MVA, 12% fall, 8% direct trauma, and 6% other. Indications for dynamic CSR were 100% traumatic mechanism, 86% neck pain, 70% midline neck tenderness, and 18% abnormal static CSR. Static CSR were normal in 372, 5 of which had abnormal dynamic CSR (5 cervical contour line disruption [CCLD], 2 posterior element abnormality [PEA]); of these 5 patients, none required invasive stabilization. Static CSR were abnormal in 79 patients (38 CCLD, 30 lordotic curve reversal, 17 PEA, 4 soft tissue swelling) of which 16 had abnormal dynamic CSR (9 increased CCLD, 4 PEA, and 4 fracture); of these 16 patients, 4 required invasive stabilization. Final diagnoses were 428 cervical soft tissue injury, 11 subluxation, 8 fracture, 2 fracture-subluxation, and 2 spinal cord injury without radiographic abnormality. Spine consultation was made in 12%. Stabilization therapy was required: 21 soft collar, 4 surgical, 3 halo-device, and 5 other. No complications of dynamic CSR were noted. The blunt trauma patient with neck complaints and an abnormal static CSR was more likely to have an abnormal dynamic CSR demonstrating a cervical injury requiring stabilization compared to patients with normal static CSR.

Adult↗
PubMed1999

Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin.

OBJECTIVE: Functional hypothalamic amenorrhoea (FHA) is a consequence of low dietary intake as observed in two major pathophysiological conditions, anorexia nervosa and/or intensive physical exercise. The aim of the present study was to assess in women with FHA and normal body mass index (BMI) and apparently normal daily activities, the degree of impairment of GnRH secretion, its nutritional origin and its reversibility. PATIENTS: Twelve women (22-35 years) with FHA not related with exercise and 12 age and BMI matched menstruating controls (NC) were studied. Six women with congenital hypothalamic hypogonadism (CHH), representative of complete gonadotrophin deficiency, were also enrolled for comparison. DESIGN: Plasma oestradiol (E2) and androstenedione (A) levels were measured and the pulsatile profile of LH was studied. A GnRH agonist test, using 100 micrograms S/C of DTrp6 GnRH (Triptorelin) was performed (sampling every 2 h for 24 h). Dietary intake, body composition and nutritional markers (FT3, ferritin, retinol binding protein (RBP), SHBG, IGF-1 and leptin) were measured. All the women with FHA were advised to normalize their diet during four months. The same studies were performed if nutritional markers and body composition were normalized. RESULTS: In FHA, mean plasma E2 and A levels were low. LH pulse frequency and amplitude were significantly reduced compared to NC (P < 0.005). FSH/LH ratio increased rapidly after triptorelin with a significant increase in plasma E2 levels between 18 and 24 h. In contrast, no response to triptorelin was observed in women with CHH. The fat body mass was lower and the lean body mass higher in FHA than in NC. Marked differences in nutritional intake were identified, with altered dietary composition. FHA consumed significantly less fat (P < 0.001) and less carbohydrate (P = NS) than the BMI-matched controls. Mean plasma levels of SHBG were increased whereas mean plasma levels of FT3, ferritin, RBP, IGF-1, and leptin were significantly decreased. Only three patients with FHA kept a balanced diet and improved their body composition after 4 months. LH pulsatile profile and response to triptorelin challenge were normalized in these patients. CONCLUSION: Mild dieting, close to normal but prolonged and characterized by an important fat restriction, is able to interfere with gonadotrophin secretion. Assessment of nutritional markers allows recognition of mild nutritional insufficiency as a common cause of FHAs. The gonadotrophin deficiency is partial and may be reversible after improvement of nutritional intake and body composition.

Adult↗
PubMed1999

Recovering from stroke: a qualitative investigation of the role of goal setting in late stroke recovery.

This article examines the role of goal setting in the continuing relationship between specialist nurse and patients recovering from stroke. The nurse intervention was intended to ease the patient through the stages of recovery from stroke, focusing on emotional and social recovery rather than physical function. Literature on the use of goals in the nursing process is discussed. The article uses data from contemporary nurse records and from interviews with nurses and with patients and caregivers. The data from each of these elements were subjected to content analysis and were then synthesized using a grounded theory approach to interpret their significance. The perspective of patients and caregivers provides an additional insight into the use and limitations of goal setting which is largely developed in the literature from a nursing perspective. Nurses were found to have different interpretations of the use of goal setting. Some used it explicitly in their relationships with patients, whilst others used the concept to inform their actions whilst being less explicit and more informal. In all cases they demonstrate the tension between establishing and supporting progress towards realistic recovery goals and recognizing the limitations now placed on stroke victims.

Adaptation, Psychological↗
PubMed1999

The development of a collaborative stroke training programme for nurses.

The effectiveness of multidisciplinary stroke rehabilitation may be enhanced by nurses and therapists adopting a single consistent approach to the positioning and mobilizing of patients. As patients can spend as little as 4% of the waking day receiving 'therapy' there is considerable potential for a more dynamic nursing intervention, which may contribute to improving patient care. We aimed to investigate whether physiotherapists could step back from direct patient treatment in order to participate in a structured training programme for nurses involved with patients recovering from stroke on an established elderly care rehabilitation ward in a district general hospital. Qualitative methods were used within a participatory action research framework to describe the development process and content of the training programme. Nursing staff, physiotherapists and their respective managers were interviewed to identify perceived training needs. This informed the structure and content of the training course and allowed insight into interprofessional working.

Attitude of Health Personnel↗