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Biomedical subjects

J Hammond

Publications and source records attributed to J Hammond.

At least 37 records · Page 2Linked to original sources

Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease.

Neuronal cell death, neurofibrillary tangles, and amyloid beta peptide (Abeta) deposition depict Alzheimer's disease (AD) pathology, but neuronal loss correlates best with dementia. We have shown that increased production of Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing. Here, we investigate key effectors of cell death, caspases, in human neuronal apoptosis and APP processing. We find that caspase-6 is activated and responsible for neuronal apoptosis by serum deprivation. Caspase-6 activity precedes the time of commitment to neuronal apoptosis by 10 h, indicating possible activity without subsequent apoptosis. Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Abeta. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Abeta-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons. A pulse-chase experiment reveals a precursor-product relationship between Capp6.5, intracellular Abeta, and secreted Abeta, indicating a potential alternate amyloidogenic pathway. Caspase-6 proenzyme is present in adult human brain tissue, and the p10 active caspase-6 fragment is detected in AD brain tissue. These results indicate a possible alternate pathway for APP amyloidogenic processing in human neurons and a potential implication for this pathway in the neuronal demise of AD.

Adult↗

The Pediatric Risk of Mortality (PRISM) Score and Injury Severity Score (ISS) for predicting resource utilization and outcome of intensive care in pediatric trauma.

OBJECTIVE: Mortality prediction in trauma is assessed using the Injury Severity Score (ISS) and Revised Trauma Score using Trauma Injury Severity Score (TRISS) methodology. The Pediatric Risk of Mortality (PRISM) score assesses mortality risk in critically ill children. We compared the ability of PRISM and ISS (using TRISS methodology) to predict resource utilization and outcome in pediatric trauma. DESIGN: Retrospective chart and database review. SETTING: Pediatric intensive care unit (PICU). PATIENTS: Consecutive admissions to a PICU over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: Demographic data including PICU resource utilization and outcome were recorded. Data were recorded on 1,052 admissions (31 deaths), including 125 pediatric trauma patients (11 deaths). Patients were stratified into low- and high-risk categories based on PRISM and ISS scores. Patients with PRISM scores <6 and ISS scores <10 were classified as low risk. While both low-risk PRISM and ISS scores readily identified survivors, PRISM was the more sensitive indicator of resource utilization. PRISM, however, performed less well in determining risk-adjusted mortality as compared with ISS. CONCLUSION: PRISM readily stratifies pediatric trauma patients for resource utilization. PRISM appears to underestimate mortality in pediatric trauma as compared with ISS using TRISS methodology.

Bias↗

Nucleotide sequence of the putative replicase gene of the sour cherry strain of plum pox potyvirus.

The complete nucleotide sequence of the NIb coding region of the sour cherry strain of plum pox potyvirus (PPV-SoC) has been determined. It consists of 1554 nucleotides and encodes a putative replicase protein of 518 amino acids. Sequence identity scores between NIb of PPV-SoC and other isolates of PPV are significantly low (c. 78%). Many of the nucleotide substitutions, however, are silent. PPV-SoC differs from isolates of PPV-D, PPV-M and PPV-E1 Amar at multiple amino acid positions that are conserved between the other isolates. The NIb sequence extends the PPV-SoC sequence presently available to 2781 nt from the 3' end (approximately 28% of the genome).

Amino Acid Sequence↗

Mitochondrial electron transport chain defect presenting as hypoglycemia.

A profoundly deaf female infant was found to have hypoglycemia and lactic acidemia after an episode of decreased oral intake and vomiting. Electron transport chain (ETC) enzyme studies revealed a combination defect of complexes I, III, and IV in liver but not in skeletal muscle. This case highlights the fact that defects of the ETC are clinically highly heterogeneous and should be considered with hypoglycemia and lactic acidosis in the absence of a glycogen storage disorder. Moreover, ETC defects can occur with a biochemical profile suggestive of a fatty acid oxidation disorder.

Acidosis, Lactic↗

Encapsidation of potyviral RNA in various forms of transgene coat protein is not correlated with resistance in transgenic plants.

Transgenic plants expressing either bean yellow mosaic potyvirus or chimeric potyvirus coat protein (CP) were inoculated with various potyviruses. Antigen-coated plate, indirect enzyme-linked immunosorbent assay and immunoelectron microscopy of virus purified from transgenic plants showed that progeny virions contained from < 1% to as much as 25% transgenic CP. Different levels of transcapsidation may reflect the extent of compatibility between transgene CP and the viral CP.

Amino Acid Sequence↗

Destabilization of potato spindle tuber viroid by mutations in the left terminal loop.

Infectivity studies with highly infectious RNA inocula generated by ribozyme cleavage were used to compare the biological properties of three apparently nonviable mutants of potato spindle tuber viroid (PSTVd). One of these mutants (PSTVd-P) contains three nucleotide substitutions in the left terminal loop, and mechanical inoculation of tomato seedlings with RNA transcripts at levels equivalent to 10(3)-10(5) times the ID50 for PSTVd-Intermediate failed to result in systemic infection. Viable progeny containing a spontaneous C-->G change at position 4 could, however, be recovered from transgenic Nicotiana benthamiana plants that constitutively expressed PSTVd-P RNA. The initial mutations in PSTVd-P led to an overall weakening of its native structure in vitro, and the precisely-full-length molecule released by ribozyme cleavage in vivo was also unstable. Even RT-PCR analysis failed to reveal detectable amounts of circularized PSTVd-P among the RNAs isolated from uninfected plants. Predicted stabilizing effects of a spontaneous mutation at position 4 suggest that the appearance of viable progeny was dependent on a combination of events: errors by host RNA polymerase II during transcription of the mutant transgene coupled with a strong selective pressure against alterations in the native structure of PSTVd.

Mutation↗

Respite-care needs--met and unmet: assessment of needs for children with disability.

The study aimed to ascertain the current use of respite-care services by families with children with a learning and/or a physical disability in a South London, UK, health authority, to estimate the type and extent of the unmet need, and to set standards for the provision of such services. Over 1200 families were sent an 11-page questionnaire. The results indicated that the child's level of dependency and the presence of behaviour and communication problems led to significantly higher levels of experienced stress among carers. This was also associated with a significantly greater use of respite care except by families of children with behavioural problems. The results showed that respite care was generally perceived as an inadequate service, though 88% of respondents had no knowledge of the existence of respite-care services. Recommendations are made in relation to information provision, choice, and flexibility for carers and for quality standards in general.

Adolescent↗

First prenatal diagnosis of the carnitine transporter defect.

We report the first attempt at prenatal diagnosis of the carnitine transporter defect in a fetus at high risk of having the disorder. Analysis of cultured CVS after prolonged culture predicted that the fetus was not affected but might be heterozygous for the carnitine transporter defect, but chromosome 15 satellite DNA markers showed no paternal contribution, suggesting that the CVS cells assayed were of predominantly maternal origin. Subsequent assay of cultured amniocytes predicted that the fetus would be affected, and this was confirmed in the newborn period. We conclude that prenatal diagnosis of the carnitine transporter defect is possible, but where results depend on extended culture of CVS, molecular studies should be performed to confirm genetic contributions from both parents.

Carnitine↗

Effects of dietary gamma-linolenic acid and prenatal ethanol on mouse brain and behavior.

Pregnant B6D2F mice were treated with ethanol (25% Kcal) from days 5-17 of gestation. The diet was supplemented with either 18 : 2n-6 [linoleic acid (LA)] or 18 : 3n-6 [gamma-linolenic acid (GLA)] throughout the study. Ethanol reduced 20 and 22 carbon n-6 and n-3 fatty acids in the brains of adult offspring. Feeding of GLA, compared with LA, increased levels of 20 : 3n-6 and 22 : 4n-6, but reduced 22 : 6n-3, particularly in the offspring of dams administered ethanol during gestation; adult brain weight was also lower in this group. Ethanol reduced the number of viable litters and adult body weight, and GLA reduced birth weight. Neither prenatal ethanol nor GLA affected open-field activity in adult males, nor did either treatment have an effect on the duration of immobility in the forced swimming test. However, GLA did affect circadian activity by increasing running wheel activity during the dark cycle, and decreasing it slightly during the light cycle. These results do not support a beneficial effect of GLA in preventing the developmental effects of ethanol; we suggest caution in the administration of high doses of GLA with ethanol during pregnancy.

Adrenergic Uptake Inhibitors↗

The air gun: toy or weapon?

Originally used in warfare, air guns are commonly used in target shooting, as toys, and as "beginner" guns for children. The projectile force of these weapons can rival that of many conventional handguns. Pneumatic weapons pose a serious threat to the pediatric population, and their potential for serious injury must be recognized.

Brain Injuries↗

Transmission of pressure within the abdomen.

The extent to which transmission of pressure within the abdomen is accomplished in accordance with the laws of fluid mechanics, i.e., homogeneous transmission to all portions of the abdomen, is controversial. To examine the cranial-to-caudal as well as side-to-side transmission of pressure within the abdomen in humans, we measured intra-abdominal pressure at four sites in five subjects undergoing colonoscopy. Liquid-filled catheters were inserted into the colon, and intracolonic pressure was measured in the rectum and in transverse, descending, and sigmoid colon. Differences in intracolonic pressure were recorded during breaths to total lung capacity and brief expulsive maneuvers. Measurements were taken in the supine, right lateral, and seated position. Comparison of pressure swings at all sites showed that the pressure changes were nearly equal during both inspiratory and expulsive maneuvers. The changes in pressure were uniform in the cephalocaudal axis as from side to side. We conclude that transmission of abdominal pressure in humans is nearly homogeneous. Our findings provide support for the hydraulic model of abdominal mechanics.

Abdomen↗

Barriers to sexual history taking in general practice.

OBJECTIVE: The aim of this pilot study was to identify barriers to the taking of a sexual history in general practice. METHOD: In order to canvass the widest range of opinion on this sensitive issue, focus groups of 4-8 general practitioners (GPs) were conducted using a GP facilitator. Groups shared one of the following common interests - considerable experience in sexual history taking, an interest in sexuality, large numbers of patients from a non-English speaking background, rural practice, Family Medicine Program trainee-ship or employment in a 24 hour clinic. RESULTS: GPs identified a range of barriers including lack of time, fear of intrusion, age and sex of both GP and patient, fear of inadequacy, patient's offending behaviours, cultural differences (ethnic, gay and youth) and the presence of a third party. CONCLUSION: To improve sexual history taking GPs may need assistance in the following areas: education about the range of sexual practices; initiation of a sexual history with both old and new patients; understanding how to deal with their own discomfort and in the use of appropriate and non-judgmental language. GPs need knowledge of resources for further information and referral. Recommendations regarding the minimum strategy for inclusion of a sexual history as part of a standard consultation are made.

Family Practice↗

Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with confusing biochemical features.

A female neonate was seen because of shock, ketosis, and undetectable blood glucose. Initial urinary findings indicated the possibility of a defect of fatty acid beta-oxidation; subsequent studies showed that she had medium-chain acyl-coenzyme. A dehydrogenase deficiency. This case highlights the fact that the initial symptoms may occur in the first few days of life, and that the presence of ketosis does not exclude the possibility of a fatty acid oxidation defect; the profiles of urinary organic acids and acylglycines may not be characteristic at that time.

Acyl-CoA Dehydrogenase↗