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Biomedical subjects

J M Jones

Publications and source records attributed to J M Jones.

At least 37 records · Page 2Linked to original sources
PubMed2001

A province-wide needs assessment of oncology health care professionals in psychosocial oncology.

BACKGROUND: Oncology professionals still lack the knowledge and skills to provide effective psychosocial care. Continuing education (CE) aimed at addressing this lack may improve the provision of psychosocial care to patients and their families. METHODS: The authors conducted a province-wide cross-sectional mail survey of oncology health care professionals [oncologists (MDs), nurses (RNs) and radiation therapists (RTs)] and assessed psychosocial orientation, self-assessed knowledge, and motivation to learn about psychosocial oncology. In addition, they sought factors that might influence professionals' willingness to attend CE programs. RESULTS: In total, 241 surveys were completed and returned. Psychosocial orientation was highest in the RN subgroup. MDs rated their knowledge to deal with specific psychosocial issues higher than did RNs and RTs, while their motivation to learn more about providing psychosocial care was significantly lower. Seventy-three percent of respondents indicated that they would like CE in psychosocial oncology. Self-reported motivation to learn was the most significant factor associated with this interest. CONCLUSION: These findings raise questions about perceived learning needs and aided in the development of an interprofessional curriculum in psychosocial oncology.

Adult↗
PubMed2000

Consequences of cAMP and catalytic-subunit binding on the flexibility of the A-kinase regulatory subunit.

A combination of site-directed labeling and time-resolved fluorescence anisotropy was used to further elucidate the structure and underlying dynamic features of the type I regulatory (R(I)(alpha)) subunit of the cAMP-dependent protein kinase. Specifically, the consequences of cAMP and the catalytic (C)-subunit binding on the backbone flexibility around seven sites of cysteine substitution and fluorescein maleimide labeling (Thr(6)Cys, Leu(66)Cys, Ser(75)Cys, Ser(81)Cys, Ser(99)Cys, Ser(145)Cys, and Ser(373)Cys) in the R(I)(alpha) subunit were assessed. Focusing on the fast rotational correlation time, the results indicate that most of the interdomain segment connecting the dimerization/docking (D/D) and tandem cAMP-binding domains is probably weakly associated with the latter domain. Also, this segment becomes more tightly bound to the C subunit upon holoenzyme formation. The results also suggest that there is a short 'hinge' segment (around Leu(66)Cys) that could allow the structured interdomain/cAMP-binding and D/D domains to pivot about each other. Finally, cAMP binding dramatically reduces the backbone flexibility around only the two sites of cysteine substitution in the cAMP-binding domains, suggesting a selective structural stabilization caused by cAMP and a "tight" coupling of low-nanosecond fluctuations selectively within the tandem cAMP-binding domains.

Catalysis↗
PubMed2000

Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.

Computer-based approaches identified PTE2 as a candidate human peroxisomal acyl-CoA thioesterase gene. The PTE2 gene product is highly similar to the rat cytosolic and mitochondrial thioesterases, CTE1 and MTE1, respectively, and terminates in a tripeptide sequence, serine-lysine-valine(COOH), that resembles the consensus sequence for type-1 peroxisomal targeting signals. PTE2 was targeted to peroxisomes and recombinant PTE2 showed intrinsic acyl-CoA thioesterase activity with a pH optimum of 8.5. A comparison of PTE2 and PTE1 thioesterase activities across multiple acyl-CoA substrates indicated that while PTE1 was most active on medium-chain acyl-CoAs, with little activity on long-chain acyl-CoAs, PTE2 displayed high activity on medium- and long-chain acyl-CoAs. The identification of PTE2 therefore offers an explanation for the observed long-chain acyl-CoA thioesterase activity of mammalian peroxisomes.

Acyl Coenzyme A↗
PubMed2000

Eating disorders in adolescent females with and without type 1 diabetes: cross sectional study.

OBJECTIVE: To determine the prevalence of eating disorders in adolescent females with type 1 diabetes mellitus compared with that in their non-diabetic peers. DESIGN: Cross sectional case-control led study. SETTING: Diabetes clinics and schools in three Canadian cities. SUBJECTS: 356 females aged 12-19 with type 1 diabetes and 1098 age matched non-diabetic controls. MAIN OUTCOME MEASURE: Eating disorders meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. RESULTS: Eating disorders that met DSM-IV criteria were more prevalent in diabetic subjects (36, 10%) than in non-diabetic controls (49, 4%) (odds ratio 2.4, 95% confidence interval 1.5 to 3.7; P<0.001). Subthreshold eating disorders were also more common in those with diabetes (49, 14%) than in controls (84, 8%) (odds ratio 1.9, 95% confidence interval 1.3 to 2.8; P<0.001). Mean haemoglobin A(1c) concentration was higher in diabetic subjects with an eating disorder (9.4% (1.8)) than in those without (8.6% (1.6)), P=0.04). CONCLUSIONS: DSM-IV and subthreshold eating disorders are almost twice as common in adolescent females with type 1 diabetes as in their non-diabetic peers. In diabetic subjects, eating disorders are associated with insulin omission for weight loss and impaired metabolic control.

Adolescent↗
PubMed2000

Identification and characterization of HAOX1, HAOX2, and HAOX3, three human peroxisomal 2-hydroxy acid oxidases.

Computer-based approaches identified three distinct human 2-hydroxy acid oxidase genes, HAOX1, HAOX2, and HAOX3, that encode proteins with significant sequence similarity to plant glycolate oxidase, a prototypical 2-hydroxy acid oxidase. The products of these genes are targeted to peroxisomes and have 2-hydroxy acid oxidase activities. Each gene displays a distinct tissue-specific pattern of expression, and each enzyme exhibits distinct substrate preferences. HAOX1 is expressed primarily in liver and pancreas and is most active on the two-carbon substrate, glycolate, but is also active on 2-hydroxy fatty acids. HAOX2 is expressed predominantly in liver and kidney and displays highest activity toward 2-hydroxypalmitate. HAOX3 expression was detected only in pancreas, and this enzyme displayed a preference for the medium chain substrate 2-hydroxyoctanoate. These results indicate that all three human 2-hydroxy acid oxidases are involved in the oxidation of 2-hydroxy fatty acids and may also contribute to the general pathway of fatty acid alpha-oxidation. Primary hyperoxaluria type 1 (PH1) is caused by defects in peroxisomal alanine-glyoxylate aminotransferase, the enzyme that normally eliminates intraperoxisomal glyoxylate. The presence of HAOX1 in liver and kidney peroxisomes and the ability of HAOX1 to oxidize glyoxylate to oxalate implicate HAOX1 as a mediator of PH1 pathophysiology.

Alcohol Oxidoreductases↗
PubMed2000

The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a.

Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a). The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes.

Amino Acid Sequence↗
PubMed2000

PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.

Peroxisomes are components of virtually all eukaryotic cells. While much is known about peroxisomal matrix protein import, our understanding of how peroxisomal membrane proteins (PMPs) are targeted and inserted into the peroxisome membrane is extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes. Furthermore, mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane. This hypothesis is supported by the observation that the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.

Animals↗
PubMed2000

Transfer of nonassisted hatched and hatching human blastocysts after in vitro fertilization.

OBJECTIVE: To determine the feasibility of performing blastocyst transfer 6 days after oocyte insemination. DESIGN: Retrospective clinical study. SETTING: University-based IVF center. PATIENT(S): All cases of IVF over a 1-year span of time (June 1998-1999) in which seven 2PN embryos were available for transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and multiple pregnancy rates. RESULT(S): Transfer of blastocysts on days 5 and 6 resulted in implantation rates of 69% and 33% (P=0.0006), clinical pregnancy rates of 89% and 59% (P=0.05), and multiple pregnancy rates of 39% and 10% (P=0.03), respectively. In cases in which blastocysts were spontaneously hatching or hatched on day 6 (9% of embryos), implantation and pregnancy rates were 52% and 80%, respectively. Embryos were successfully frozen in the hatched or hatching state with resultant clinical pregnancies. CONCLUSION(S): Transfer of embryos can be delayed to day 6 after oocyte insemination at which time a small percentage of embryos will hatch. Hatching of embryos by day 6 is a favorable prognostic factor for IVF outcome. Embryos that fail to hatch by day 6 may have a lower implantation potential. Difficulty with hatching embryos sticking to the transfer catheter was not encountered. Furthermore, hatching and hatched embryos can be frozen and with subsequent transfer result in pregnancies.

Adult↗
PubMed2000

Using videotaped specimens to test quality control in a computer-assisted semen analysis system.

OBJECTIVE: To determine the feasibility of using semen samples previously recorded on videotape for intralaboratory and interlaboratory quality control of computer-assisted semen analysis (CASA) systems. DESIGN: Blinded, controlled study. SETTING: Pooled semen specimens from two normal human volunteers in an academic research environment. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen parameters from a videotape analyzed internally and by four external laboratories. RESULT(S): Preliminary experiments designed to examine intralaboratory variation by repeated analysis of semen samples recorded on videotape revealed some significant differences for every variable examined. When these data were analyzed by using the larger biologic error caused by subsampling, no significant differences were found for any of the variables examined. When either a standard set or the specific laboratories' sets of parameters were used to analyze the same videotaped semen specimen, no statistically significant differences were detected for sperm concentration for motility among the five laboratories after the biological error caused by subsampling was applied to results. CONCLUSION(S): These data strongly suggest that videotaped semen specimens can serve as quality control for intralaboratory and interlaboratory testing of CASA equipment as long as the biologic error caused by subsampling is used to compare results.

Cytological Techniques↗
PubMed2000

Comparison of three salivary flow rate assessment methods in an elderly population.

Measuring salivary flow rates among the frail elderly is a challenge. The currently used spit collection method requires levels of time and cooperation that often may exclude the frail elderly who are at high risk for salivary compromise. A measurement method that is not only valid and reliable, but also feasible and acceptable is needed for use in population studies of compromised adults. This study compared two salivary flow rate assessment methods using a suction machine against the currently accepted spit collection method in an elderly population aged 75 and older. Three methods of flow rate (g/min) assessment were compared at three time periods among 16 elders (mean age 86.6 years). Flow rates using the 2-min open suction method compared well with the 10-min spit method (r=0.778) but the 2-min closed suction method did not (r=0.158). Reliability evaluation of the open suction method and the spit method was assessed using a test/retest with a 1-week interval. Both methods demonstrated good comparable reliability (spit method r=0.566, P=0.01); open suction method, (r= 0.861, P<0.01). Based on a short survey questionnaire about the three methods, 11 of the 16 elderly subjects preferred the use of the suction machine to the spit method. These results indicate that the 2-min open suction method technique is a valid and reliable means of measuring salivary flow. The lower level of patient cooperation needed, the shorter time period required, and this preliminary report of its acceptability support the use of this method in future population studies of frail elders.

Aged↗
PubMed2000

PriA and phage T4 gp59: factors that promote DNA replication on forked DNA substrates microreview.

The initiation of DNA synthesis on forked DNA templates is a vital process in the replication and maintenance of cellular chromosomes. Two proteins that promote replisome assembly on DNA forks have so far been identified. In phage T4 development the gene 59 protein (gp59) assembles replisomes at D-loops, the sites of homologous strand exchange. Bacterial PriA protein plays an analogous function, most probably restarting replication after replication fork arrest with the aid of homologous recombination proteins, and PriA is also required for phage Mu replication by transposition. Gp59 and PriA exhibit similar DNA fork binding activities, but PriA also has a 3' to 5' helicase activity that can promote duplex opening for replisome assembly. The helicase activity allows PriA's repertoire of templates to be more diverse than that of gp59. It may give PriA the versatility to restart DNA replication without recombination on arrested replication forks that lack appropriate duplex openings.

Bacteriophage T4↗
PubMed2000

Human embryonic stem cell technology.

Undifferentiated human embryonic stem (ES) cells can be cultured indefinitely and yet maintain the potential to form almost every cell in the adult human body. Therefore ES cells provide a model for understanding the differentiation and function of human tissue, offer new strategies for drug discovery and testing, and have the potential to provide new transplantation therapies for the treatment of a wide variety of human diseases. In this article, we describe the origin and properties of human ES cells, distinguish ES cells from other pluripotent stem cell lines, and discuss their implications for basic research and human medicine.

Animals↗
PubMed2000

A prospective study of primary care patients with musculoskeletal pain: the identification of predictive factors for chronicity.

Primary care faces the challenge of reducing the proportion of patients continuing with musculoskeletal pain beyond the acute phase. This study assessed patients presenting in general practice with a four- to 12-week history of pain and re-assessed them 12 weeks later. Patients whose pain was described as 'none' or 'slight' were allocated to the 'acute group', and those whose pain continued to be 'moderate' or 'severe' were allocated to the 'chronic group'. Comparative analysis of the two groups' responses at initial assessment identified pain intensity, active coping score, and previous pain episode to be factors independently predictive of chronicity.

Acute Disease↗
PubMed2000

Clinical and hemodynamic performance of the Toronto SPV bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: By providing a superior hemodynamic profile, the stentless valve design allows ventricular remodeling and may improve patient survival after aortic valve replacement (AVR). Compared with stent-mounted prostheses, implantation is more complex and requires a longer ischemic time; this may adversely affect surgical risk, especially if patients are elderly or require a concomitant procedure. The mid-term clinical and hemodynamic performance of the Toronto SPV bioprosthesis in a predominantly elderly patient group was analyzed. METHODS: A total of 123 patients (median age 72 years) underwent AVR with the Toronto SPV. Concomitant procedures (mainly coronary artery bypass grafting, CABG), were performed in 60 patients (49%). Clinical details were recorded, with 100% follow up (total 317 patient-years). Hemodynamic evaluation, by serial echocardiography, was performed at four and 18 months after implantation. RESULTS: The early mortality rate was low (0.8%). Mean (+/- SD) actuarial survival at 53 months was 78 +/- 5.9%, with most patients (91%) in NYHA classes I and II. Freedom from valve-related complications were: endocarditis 93.8 +/- 2.3%, thromboembolism 90.3 +/- 3.7% and bleeding 95.8 +/- 1.8%; there were no structural failures. The valve hemodynamic profile was excellent for all sizes: peak gradient 8.8 +/- 4.3 mmHg, effective orifice area 1.9 +/- 0.54 cm2 with significant improvement in left ventricular fractional shortening. CONCLUSION: In this patient population the Toronto SPV was a suitable choice. Advanced age, a requirement for concomitant procedures and increased ischemic times did not adversely affect surgical risk. AVR with the Toronto SPV provided an excellent hemodynamic profile, and improved both left ventricular function and NYHA functional class.

Adult↗
PubMed2000

'The falling sickness' in literature.

Seizures have been described in literature since early times. Since classical literature reflects the attitudes of society, a review of "the falling sickness" in literature provides some insights into the profound affect of epilepsy. This article explores some great writings describing epilepsy and the changing view of an epileptic as a person being "possessed" to that of one with a medical condition.

Bible↗
PubMed1999

Duplex opening by primosome protein PriA for replisome assembly on a recombination intermediate.

PriA and other primosome assembly proteins of Escherichia coli recruit the major replicative helicase DnaB for replisome assembly during bacteriophage Mu transposition and replication. MuA transposase catalyzes the transfer of Mu ends to target DNA, forming a potential replication fork that provides the assembly site for the replisome. However, this fork lacks the single-stranded DNA needed to load DnaB. Although no pre-existing primosome assembly sites that bind PriA were found within the Mu end sequences, PriA was able to bind to the forked DNA structure created by MuA. The helicase activity of PriA could then open the duplex to create the DnaB binding site. In a tightly coupled reaction on synthetic forked substrates, PriA promoted both the unwinding of the lagging strand arm and preprimosome assembly to load DnaB onto the lagging strand template. PriA apparently translocated 3' to 5' along the lagging strand template until sufficient single-stranded DNA was exposed for binding of DnaB, which then translocated 5' to 3' in the opposite direction. Mutant PriA lacking helicase activity was unable to promote this process, and loss of PriA helicase impaired Mu DNA replication in vivo and in vitro. This suggests that the opening of the duplex by PriA helicase is a critical step in the initiation of Mu DNA replication. Concerted helicase and primosome assembly functions would allow PriA to act as initiator on recombination intermediates and stalled replication forks. As part of the replisome, PriA may act as a mobile initiator that minimizes interruptions in chromosomal replication.

Bacterial Proteins↗