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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 271 records · Page 15Linked to original sources
PubMed1998

Demented and chronic depressed patients attending a day hospital: stress experienced by carers.

OBJECTIVE: The main hypothesis was that carers of elderly patients attending a day hospital with chronic depression experience considerable stress. A subsidiary hypothesis was that this stress is equivalent to that experienced by carers of dementia patients attending the same day hospital. DESIGN: All attenders of the day hospital with a diagnosis of depression or dementia coresident with their principal carers. SETTING: An urban psychogeriatric day hospital in the UK. PATIENTS: A consultant diagnosis of dementia or depression with a history of present illness in excess of 12 months in patients over 65. The total sample was 57, 32 dementia and 25 depression (19 major depressive episode). MEASURES: Dementia patients: Mini-Mental State Examination (MMSE), Clifton Assessment Schedule (CAPE). Depressed patients: MMSE, Montgomery-Asberg Depression Rating Scale (MADRS) and Brief Psychiatric Rating Scale (BPRS). Carers: Semi-structured questionnaire, General Health Questionnaire (GHQ-30) and Relatives Stress Scale (RSS). RESULTS: Dementia patients were older than depressed (75.66 vs 71.84). The two groups were of comparable severity. The dementia carers were significantly more stressed on the GHQ and RSS than depression carers but these carers also exceeded the threshold for psychiatric 'caseness'. Important negative views about life upset and carer burden were expressed by both groups. CONCLUSIONS: The main hypothesis but not the subsidiary one is supported. More sophisticated study of the burden of caring for chronic depressive illness is required.

Aged↗
PubMed1997

Mitosin (a new proliferation marker) correlates with clinical outcome in node-negative breast cancer.

Tumor proliferation rate is an important prognostic factor in breast cancer, and S-phase fraction (SPF), as measured by flow cytometry, is the most clinically validated of several methods for measuring it. However, flow cytometry is not well suited to evaluating the formalin-fixed, paraffin-embedded tumors that are routinely available or to the increasing number of small breast cancers. These and other limitations have motivated research into alternative methods for measuring proliferation, including immunohistochemistry (IHC) against cell cycle-related antigens, which are better suited for the evaluation of small archival tissue samples. Mitosin is a recently described 350 kD nuclear phosphoprotein that is expressed in the late G1, S, G2, and M phases of the cell cycle but not in G0. Using a new monoclonal antibody (14C10), this pilot study evaluated mitosin expression by IHC in a series of 386 node-negative, formalin-fixed, archival breast cancers and correlated the results with several prognostic factors and clinical outcome (median follow-up, 78 months; range 3-214 months). The median and range of mitosin positive cells were 7% and 1-47%, respectively. There was a strong positive correlation between mitosin and SPF (r = 0.57; P = 0.0001), and there were significant negative correlations with estrogen receptor, progesterone receptor, and patient age. Mitosin was not related to overall survival in this pilot study. However, in a univariate cutpoint analysis of disease-free survival (DFS), patients with high levels of mitosin (>9% positive cells) had significantly worse DFS than did patients with lower levels (68% versus 84% at 5 years, respectively). In a multivariate analysis of DFS, large tumor size (>2 cm) and high mitosin were the only independently significant predictors of recurrence (relative risks = 2.47 and 1.72, respectively) in a model containing the additional factors estrogen receptor, progesterone receptor, patient age, and SPF. These preliminary results suggest that mitosin as assessed by IHC may be superior to SPF as a prognostic factor in node-negative breast cancer, but additional studies are necessary to validate these promising findings.

Animals↗
PubMed1997

Prediction of the tertiary structure and substrate binding site of caspase-8.

The caspases represent a family of sulfhydryl proteases that play important regulatory roles in the cell. The tertiary structure of the protease domain of caspase-8, also called FLICE, has been predicted by a segment match modeling procedure. First, the atomic coordinates of the catalytic domain of caspase-3, also called CPP32, a member of the family that is closely related to caspase-8, were determined based upon the crystal structure of human caspase-1 (interleukin converting enzyme). Then, the caspase-3 structure was used as a template for modeling the protease domain of caspase-8. The resulting structure shows the expected level of similarity with the conformations of caspases-1 and -3 for which crystal structures have been determined. Moreover, the subsite contacts between caspase-8 and the covalently linked inhibitor, Ac-DEVD-aldehyde, are only slightly different from those seen in the caspase-3 enzyme/inhibitor complex. The model of caspase-8 can serve as a reference for subsite analysis relative to design of enzyme inhibitors that may find therapeutic application.

Amino Acid Sequence↗
PubMed1997

CTL responses induced by a single immunization with peptide encapsulated in biodegradable microparticles.

A synthetic peptide representing a measles virus (MV) cytotoxic T cell epitope (CTL) when encapsulated in poly (D,L-lactide co-glycolide) (PLG) 50:50 microparticles induced a strong CTL response after a single intraperitoneal immunization of mice which was greater than that following administration of the peptide in Freund's complete adjuvant. A 100 micrograms dose of encapsulated peptide was shown to be more effective for CTL priming than 50 and 25 micrograms doses. A vaccine formulation prepared by simply mixing empty 50:50 PLG microparticles with the peptide resulted in the induction of CTL responses comparable to those induced by the encapsulated peptide. Moreover, a CTL response against MV-infected target cells was observed. These findings highlight the potential immunostimulatory effect of PLG microparticles for the induction of MV and peptide-specific CTL responses.

Amino Acid Sequence↗
PubMed1997

Patterns of failure in children with medulloblastoma: effects of preirradiation chemotherapy.

PURPOSE: To evaluate the effects of preirradiation chemotherapy on patterns of failure in children with medulloblastoma. METHODS AND MATERIALS: Fifty-three patients (pts) with medulloblastoma were given preirradiation chemotherapy as initial postoperative treatment at St. Jude Children's Research Hospital from November 1984 to September 1993. Patients < or = 3 years of age (n = 23) received chemotherapy (CH) with delayed craniospinal irradiation (CSI). Children > or = 3 years with more advanced disease (T3b-T4, M+ or measurable residual after resection) were given CH followed by CSI (30 patients). Chemotherapy regimen depended on protocol, but usually included cis- or carboplatin and etoposide, +/- cyclophosphamide and vincristine. RESULTS: Actuarial overall survival and event-free survival rates are 60% (95% confidence interval [41,79]) and 37% [19,55] at 5 years. Children < or = 3 at diagnosis: six of 23 pts completed CH without progression and received consolidative CSI; all six are alive with no evidence of disease (NED) at 2.4-9.1 years. Seventeen patients progressed during CH and were then given CSI. Sites of progression during CH were posterior fossa (PF) in 11 patients, neuraxis (NEUR) in 4, and PF+NEUR in 2. Following CSI, 7 patients are alive NED at 2.0-8.6 years; 10 patients died of progressive disease. Eleven patients had M0 disease at diagnosis; 8 (73%) progressed during CH, 3 in the neuraxis. Children > or = 3 at diagnosis: 20 of 30 patients completed pre-CSI CH without progression; 15 are alive NED at 1.3-9.2 years, and 5 showed post-CSI progression in the PF (n = 3), in the NEUR (n = 1) and in bone marrow (n = 1). Ten of the 30 (33%) patients progressed on CH (6 in NEUR, 4 in PF); 5 are alive and NED or with stable disease. Seventeen patients had M0 disease at diagnosis; 3 out of 17 (18%) progressed during CH, 2 in NEUR and 1 in an extraneural site. In the total group of 30 patients, 11 have had disease recurrence after completion of XRT. The actuarial rate of failure was 23 +/- 9% for the patients < or = 3 years of age and 21 +/- 8% for the older children when evaluated at 4 months after diagnosis (at the completion of chemotherapy in the older children but during the ongoing chemotherapy in the younger children). CONCLUSIONS: In patients presenting with M0 disease and receiving pre-CSI chemotherapy, the risk of neuraxis progression seems to increase with duration of chemotherapy. The sites of progression during preirradiation chemotherapy are nearly equally divided between posterior fossa and other neuraxis sites. CSI salvage of patients progressing on chemotherapy is possible in approximately 50% of patients. Following CSI, neuraxis progression is more frequent than posterior fossa relapse.

Adolescent↗
PubMed1997

His own private hospital.

Dr. Brian Day had a simple solution when it became increasingly difficult to book operating room time in Vancouver. He built his own hospital. The Cambie Surgical Centre, which treats patients from BC and around the world, has 2 main operating rooms, 10 recovery beds and 5 private rooms for extended stays. "What I've done," says Day, "is say that if there are no operating rooms at UBC, I'll build my own."

British Columbia↗
PubMed1997

The first 5 amino acids of the carboxyl terminus of phosphatidylinositol transfer protein (PITP) alpha play a critical role in inositol lipid signaling. Transfer activity of PITP is essential but not sufficient for restoration of phospholipase C signaling.

Phosphatidylinositol transfer protein (PITP) is essential for phospholipase C signaling and for constitutive and regulated vesicular traffic. PITP has a single lipid-binding site that can reversibly bind phosphatidylinositol (PI) and phosphatidylcholine (PC) and transfer these lipids between membrane compartments in vitro. The role of the carboxyl terminus was examined by comparing wild-type PITPalpha with PITPalpha in which 5, 10, and 20 amino acids were deleted from the C terminus. Delta5- and Delta10-PITP had reduced PI and PC transfer activities compared with wild-type PITP, with the effect on PI transfer being more marked than that on PC transfer. Delta20-PITP was inactive at all concentrations tested. All three truncated mutants were unable to restore G-protein-mediated phospholipase Cbeta stimulation in HL-60 cells. Delta5- and Delta10-PITP, but not Delta20-PITP, inhibited the signaling function of wild-type protein without any effect on lipid transfer in vitro. We conclude that (a) the carboxyl terminus of PITP plays a critical role in phospholipase C signaling; (b) the transfer activity is not the only determining factor that dictates the restorative function of PITP in inositol lipid signaling; and (c) the dominant inhibitory effects of Delta5- and Delta10-PITP on wild-type PITP in phospholipase C signaling suggest the existence of a receptor for PITP.

Amino Acid Sequence↗
PubMed1997

Metabolic effects of blocking tone conditioning on the rat auditory system.

The Kamin blocking phenomenon occurs when behavioral expression of conditioning to a novel stimulus fails in the presence of a previously conditioned stimulus (CS). Neural metabolic effects of a tone conditioned as an excitor were compared to the effects of the same physical tone when excitatory conditioning was blocked by previous conditioning with a light. We examined the metabolic activity of the auditory system to test the hypothesis that auditory processing of a tone CS changes during blocking. Quantitative histochemistry of cytochrome oxidase (C.O.), the final mitochondrial enzyme for oxidative metabolism, was used to evaluate cumulative changes in the metabolic capacity of the auditory system resulting from blocking. Rats (Long-Evans) in the Blocking group received pairings of a light CS with a mild footshock unconditioned stimulus (US) during Phase 1 training. Rats in the Control group received random presentations of the same stimuli during Phase 1. Both groups then received the same Phase 2 training consisting of simultaneous tone and light presentations paired with footshock. The Control group exhibited significant suppression of drinking to tone alone presentations after training, whereas the Blocking group did not. Metabolic mapping results demonstrated that blocking effects were localized to auditory regions receiving direct US somatosensory projections. Significantly greater C.O. activity in the inferior colliculus and the dorsal cochlear nucleus was found for the Blocking group relative to the Control group. Input cell layers of secondary auditory cortex also demonstrated a group difference, in that layers II/III and IV had lower levels of C.O. activity in the Blocking group. These specific changes in C.O. activity linked to behavioral training demonstrated that the blocking phenomenon produced distinct neural metabolic changes in CS processing in the auditory system localized to regions with CS-US interactions.

Animals↗
PubMed1997

Generation of a contig comprising YACs and BACs within chromosome region 1p13.1.

Chromosome region 1p13 is known to show loss of heterozygosity (LOH) in a number of human tumor types, including breast. We have generated a contig comprising YACs and BACs spanning part of 1p13.1 which includes the smallest region of overlapping loss identified in our earlier studies. The contig is anchored to the genetic map by a number of microsatellite markers, and by the use of CEPH YACs. We have excluded a number of candidate genes from this region, and we have oriented the contig with respect to the centromere and a number of other genes and markers on 1p13. This resource will be valuable in mapping the target for LOH in breast and other tumors, and may also be useful for the genetic analysis of other genes or diseases known to map to this region.

Chromosome Mapping↗
PubMed1997

Use of stress-inducible transgenic nematodes as biomarkers of heavy metal pollution in water samples from an english river system.

Transgenic strains of the nematode Caenorhabditiselegans, which carry stress-inducible lacZ reporter genes, aremeasurably stressed by exposure to heavy metals in aqueous solution. Thisstress response can be quantified, using enzymatic assays for the reportergene-product (Escherichia coli beta-galactosidase), or estimatedapproximately by in situ staining for beta-galactosidase in exposedworms. Stress responses to heavy metals have been demonstrated both inlaboratory tests using Cd2+ or Hg2+, and also in watersamples taken from a metal-polluted river system in southwest England. TheRiver Carnon flows through an area with an ancient mining history,principally for Sn, but also for Cu and other metals; As, Cd, Al, Mn, and Zn,as well as large amounts of Fe, are all present in these ore bodies. Foursites in the Carnon river basin were compared with respect to theirmacroinvertebrate diversity, physical and chemical characteristics (includingthe concentrations of As, Cd, Al, Cu, Mn, Zn, and Fe). Transgenic worms wereexposed to water samples from these four sites, and also to a 0.33%(v/v) dilution of metal-laden minewater from the principal local mine (WhealJane). Transgene expression was induced in all five cases, though markedlyless so for the least polluted of the sites (which also supported a richermacroinvertebrate fauna). Two different transgenic strains were tested inthis study; strain PC72 (using a homologous hsp16 promoter) isslightly more sensitive to most metal-containing water samples than strainCB4027 (using a heterologous Drosophila hsp70 promoter). Bothtransgenic strains and two different assay methods gave essentially similarresults. These findings demonstrate that transgenic nematodes could provide arapid and simple assessment of aquatic pollution, in that the transgeneresponse is inducible by mixtures of dissolved metals at concentrationsactually encountered in metal-polluted watercourses.

Animals↗
PubMed1997

Effects of intrauterine position on the metabolic capacity of the hypothalamus of female gerbils.

The intrauterine position that a rodent fetus occupies relative to members of the same or opposite gender affects both its reproductive physiology and behavior when adult. Cytochrome oxidase histochemistry was used to assess regional differences in the oxidative metabolic capacity of the hypothalamus of female Mongolian gerbils that developed in utero between 2 female fetuses (n = 15) or between 2 male fetuses (n = 14). Cytochrome oxidase reactivity was measured densitometrically by experimenters unaware of subject intrauterine position. Gray-to-white matter ratios of optical density in 11 brain regions were used as a normalized index of metabolic capacity. Significant group differences in the metabolic capacity of the medial and the posterior parts of the anterior hypothalamus were revealed. Females that developed in utero between 2 male fetuses showed significant increases (19-22%) in cytochrome oxidase reactivity in these brain regions compared to that in females that developed between 2 female fetuses. The medial part of the anterior hypothalamus contributes to copulatory behavior, whereas the posterior part of the anterior hypothalamus may be involved in the control of pituitary gonadotropin secretion. Both these functions are influenced by intrauterine position during fetal life. To our knowledge, this is the first demonstration of metabolic changes in hypothalamic areas of the adult related to the differences in intrauterine position.

Animals↗
PubMed1997

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo.

The goal of this study was to determine the expected normal range of variation in spin-lattice relaxation time (T1) of brain tissue in vivo, as a function of age. A previously validated precise and accurate inversion recovery method was used to map T1 transversely, at the level of the basal ganglia, in a study population of 115 healthy subjects (ages 4 to 72; 57 male and 58 female). Least-squares regression analysis shows that T1 varied as a function of age in pulvinar nucleus (R2 = 56%), anterior thalamus (R2 = 51%), caudate (R2 = 50%), frontal white matter (R2 = 47%), optic radiation (R2 = 39%), putamen (R2 = 36%), genu (R2 = 22%), occipital white matter (R2 = 20%) (all p < 0.0001), and cortical gray matter (R2 = 53%) (p < 0.001). There were no significant differences in T1 between men and women. T1 declines throughout adolescence and early adulthood, to achieve a minimum value in the fourth to sixth decade of life, then T1 begins to increase. Quantitative magnetic resonance imaging provides evidence that brain tissue continues to change throughout the lifespan among healthy subjects with no neurologic deficits. Age-related changes follow a strikingly different schedule in different brain tissues; white matter tracts tend to reach a minimum T1 value, and to increase again, sooner than do gray matter tracts. Such normative data may prove useful for the early detection of brain pathology in patients.

Adolescent↗