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Biomedical subjects

J Jenkins

Publications and source records attributed to J Jenkins.

At least 19 recordsLinked to original sources
PubMed2003

Monte Carlo simulations on marker grouping and ordering.

Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

Algorithms↗
PubMed2003

Making information available for quality improvement and service planning in neonatal care.

We describe a prospective two year study aimed at assessing information collected throughout a geographically defined region as a basis for clinical governance, quality improvement and service planning in neonatal intensive and special care. All 13 Northern Ireland units returned a range of socio-demographic, obstetric and neonatal data for all admissions or readmissions within 28 days of life. 8.2% of all live births required neonatal intensive or special care, with a requirement of 374 and 645 days per 1,000 births for intensive and special care respectively. In total there were 4,205 episodes of care provided for 3,946 infants (18,072 days of intensive and 31,141 days of special care). Complications arising during intensive care episodes included the following: septicaemia/bacteraemia (7.6%), necrotising enterocolitis (2.8%), pneumothorax (4.6%), patent ductus arteriosus (6.5%) and seizures (6.9%). Opportunities for quality improvement exist in a number of areas with potential for further reduction in morbidity. Comparisons with published criteria demonstrate the value of this type of information for local, regional and national quality improvement initiatives and service planning.

Health Planning↗
PubMed2002

Plant protein families and their relationships to food allergy.

The analysis of plant proteins has a long and distinguished history, with work dating back over 250 years. Much of the work has focused on seed proteins, which are important in animal nutrition and food processing. Early studies classified plant proteins into groups based on solubility ('Osborne fractions') or protein function. More recently, families have been defined based on stuctural and evolutionary relationships. One of the most widespread groups of plant proteins is the prolaminin superfamily, which comprises cereal seed storage proteins, a range of low-molecular-mass sulphur-rich proteins (many of which are located in seeds) and some cell wall glycoproteins. This superfamily includes several major types of plant allergen: non-specific lipid transfer proteins, cereal seed inhibitors of alpha-amylase and/or trypsin, and 2 S albumin storage proteins of dicotyledonous seeds.

Animals↗
PubMed2002

Allergens of the cupin superfamily.

The cupin family comprises a family of proteins possessing a common beta-barrel structure that is thought to have originated in a prokaryotic ancestor. This structural motif is found as a single domain in fungal spherulins, fern sporulins and the germins/oxalate oxidase proteins of plants, while the globular storage proteins of plants, called legumins (11 S) and euvicilins (7 S), are two-domain cupins. The 11 S globulins are hexameric heteroligomeric proteins of M (r) approximately 360000, with each subunit comprising an acidic 30000-40000- M (r) polypeptide that is disulphide-linked to a 20000- M (r) basic polypeptide. A number of cupins have been identified as major plant food allergens, including the 7 S globulins of soybean (beta-conglycinin), peanut (conarachin; Ara h 1), walnut (Jug r 2) and lentil, and the 11 S globulins of peanut (arachin; Ara h 3), soybean (glycinin) and possibly also coconut and walnut. Other members of the cupin superfamily have not been identified as allergens, with the exception of one germin (germination-specific protein) from pepper. Cupins are generally very stable proteins. A summary of our current knowledge of allergenic seed storage globulins will be presented, together with an overview of cupin structure and stability properties, as illustrated by the allergenic soya globulins, glycinin and beta-conglycinin.

Allergens↗
PubMed2002

Ambulatory paediatrics: does it work?

To determine whether a paediatric ambulatory assessment service is an effective and acceptable replacement for an inpatient unit. Analysis of hospital paediatric medical admissions. Postal questionnaire survey of local general practitioners. Telephone survey of parents of children who had attended the ambulatory service. Rural General Hospital in Northern Ireland. General practitioners. Parents of children referred to assessment service. Number of paediatric medical hospital admissions from the local area before and after the introduction of an ambulatory assessment service. General practitioner satisfaction levels. Parental satisfaction levels. Since the introduction of the new service in April 1996 there has been a marked progressive reduction in paediatric medical hospital admissions from the local area. By the third year of operation of the ambulatory service (1998/99), a 47% reduction in admissions was recorded, compared to the 1995/96 baseline year. The response rate to the general practitioner questionnaire was 65% (37 of 57) of whom most (31, 84%) found the service beneficial. Of the 37 respondents, 31 had referred patients to the service. The majority of these general practitioners (30, 97%) reported that the service was easy to access, and the same proportion felt that requests for consultation were met promptly. Most felt that feedback was appropriate (29, 94%). A telephone survey of 50 parents showed that most were either very satisfied (38, 76%), or satisfied (11, 22%) with the service. Most parents (41, 82%) felt their child had benefited by not being admitted to hospital. Most (46, 92%) felt they had received adequate information regarding their child's illness. A paediatric ambulatory assessment unit can reduce the number of children admitted to hospital and meet the needs of children, their families and general practitioners.

Ambulatory Care↗
PubMed2001

Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation.

PURPOSE: To evaluate the efficacy, toxicity, and optimal dose rate of gemcitabine in adult patients with advanced soft tissue sarcomas (STS) by comparing levels of gemcitabine triphosphate (GTP) in peripheral-blood mononuclear cells (PBMCs) of patients receiving two different dose rates. PATIENTS AND METHODS: Fifty-six assessable patients with STS (17 gastrointestinal [GI] leiomyosarcomas and 39 other histologies) were treated on a two-arm phase II study. Gemcitabine was given at 1 g/m2 as a 30-minute infusion weekly for up to 7 weeks followed by 1 week of rest and reassessment of tumor. Subsequent cycles were given at 1 g/m2 weekly for 3 weeks followed by 1 week of rest. Nine patients underwent cellular pharmacologic studies at two different dose rates (1 g/m2 over a standard 30-minute infusion on week 1 and over pharmacologically based infusion of 150 minutes on week 2) to evaluate GTP levels in PBMCs. RESULTS: Seven partial responses were noted among 39 patients, for an overall response rate of 18% (95% confidence interval, 7% to 29%). Median duration of response was 3.5 months (range, 2 to 13 months). Four of 10 patients with non-GI leiomyosarcomas achieved a partial response. No objective responses were noted in 17 patients with GI leiomyosarcomas. One patient had a mixed response. Median time to progression for all patients (both arms) was 3 months; median survival was 13.9 months. Treatment was generally well tolerated. Comparison of cellular pharmacology demonstrated a significant 1.4-fold increase in the concentration of GTP with the 150-minute infusion. CONCLUSION: Given the limited therapeutic armamentarium for STS, the activity of gemcitabine is encouraging. Its potential for combination therapy in the salvage setting should be studied with pharmacologically guided fixed dose-rate infusion.

Adult↗
PubMed2001

Alteration of lipase chain length specificity in the hydrolysis of esters by random mutagenesis.

The feasibility of altering the chain length specificity of industrially important Rhizomucor miehei lipase was investigated by randomly mutating Phe94 in the protein groove which is responsible for accommodating the acyl chain of the substrate. The recombinant lipase was initially expressed in E. coli. Individual colonies were selected, grown, and the DNA sequence of the lipase gene determined. Fourteen of the 19 possible mutants were identified and each of these was transformed into Pichia pastoris which expresses the enzyme extracellularly. The yeast was grown and the supernatants assessed in several assays with long and short chain substrates. Based on this preliminary screen, one mutant, Phe94Gly, was selected and purified to homogeneity for further analysis. It was found that the substitution of phenylalanine 94 with glycine led to an enzyme which was about six times less active against resorufin ester but displayed 3-4 times higher activity with short chain substrates such as butyric acid esters. The observed alteration to the enzyme specificity was rationalised using the available 3D structure of the lipase.

Amino Acid Substitution↗
PubMed2001

Probable locally acquired mosquito-transmitted malaria in Georgia, 1999.

In July 1999, the Centers for Disease Control and Prevention received notification of a case of malaria in a 32-year-old female native of Colquitt County, Georgia, who had no history of travel into an area where malaria transmission is endemic. An epidemiological investigation confirmed the absence of risk factors, such as blood transfusion, organ transplantation, malariotherapy, needle sharing, or past malaria infection. Active case finding revealed no other infected persons in Colquitt County. Light trapping and larvae-dipping failed to identify adult or larval anophelines; however, Colquitt County is known to be inhabited by Anopheles quadrimaculatus, a competent malaria vector. The patient's home was located near housing used by seasonal migrant workers from regions of southern Mexico and Central America where malaria is endemic, one of whom may have been the infection source. The occurrence of malaria in this patient with no risk factors, except for proximity to potentially gametocytemic hosts, suggests that this illness probably was acquired through the bite of an Anopheles species mosquito.

Adult↗
PubMed2001

Three-dimensional structure of Erwinia chrysanthemi pectin methylesterase reveals a novel esterase active site.

Most structures of neutral lipases and esterases have been found to adopt the common alpha/beta hydrolase fold and contain a catalytic Ser-His-Asp triad. Some variation occurs in both the overall protein fold and in the location of the catalytic triad, and in some enzymes the role of the aspartate residue is replaced by a main-chain carbonyl oxygen atom. Here, we report the crystal structure of pectin methylesterase that has neither the common alpha/beta hydrolase fold nor the common catalytic triad. The structure of the Erwinia chrysanthemi enzyme was solved by multiple isomorphous replacement and refined at 2.4 A to a conventional crystallographic R-factor of 17.9 % (R(free) 21.1 %). This is the first structure of a pectin methylesterase and reveals the enzyme to comprise a right-handed parallel beta-helix as seen in the pectinolytic enzymes pectate lyase, pectin lyase, polygalacturonase and rhamnogalacturonase, and unlike the alpha/beta hydrolase fold of rhamnogalacturonan acetylesterase with which it shares esterase activity. Pectin methylesterase has no significant sequence similarity with any protein of known structure. Sequence conservation among the pectin methylesterases has been mapped onto the structure and reveals that the active site comprises two aspartate residues and an arginine residue. These proposed catalytic residues, located on the solvent-accessible surface of the parallel beta-helix and in a cleft formed by external loops, are at a location similar to that of the active site and substrate-binding cleft of pectate lyase. The structure of pectin methylesterase is an example of a new family of esterases.

Amino Acid Sequence↗
PubMed2001

Genomic medicine: who will practice it? A call to open arms.

The Human Genome Project and other recent developments will broaden and increase the importance of genetics in health care. "Clinical genetics" will become "genomic medicine" and will no longer be almost the sole purview of genetic specialists-medical geneticists, genetic counselors, and genetic advanced practice nurses. The changing use of genetics in health care will require the acquisition of new knowledge, skills, and attitudes by many health care professionals who are not genetic specialists. Such health care professionals will not only be necessary to the widespread integration of genetics into clinical care, but they will make unique contributions to this integration that will add to the quality of genomic medicine. This new use of genetics in health care will also allow, even require, new ways of working for genetic specialists, who will continue to occupy unique and vital roles.

Delivery of Health Care↗
PubMed2001

The architecture of parallel beta-helices and related folds.

Three-dimensional structures have been determined of a large number of proteins characterized by a repetitive fold where each of the repeats (coils) supplies a strand to one or more parallel beta-sheets. Some of these proteins form superfamilies of proteins, which have probably arisen by divergent evolution from a common ancestor. The classical example is the family including four families of pectinases without obviously related primary sequences, the phage P22 tailspike endorhamnosidase, chrondroitinase B and possibly pertactin from Bordetella pertusis. These show extensive stacking of similar residues to give aliphatic, aromatic and polar stacks such as the asparagine ladder. This suggests that coils can be added or removed by duplication or deletion of the DNA corresponding to one or more coils and explains how homologous proteins can have different numbers of coils. This process can also account for the evolution of other families of proteins such as the beta-rolls, the leucine-rich repeat proteins, the hexapeptide repeat family, two separate families of beta-helical antifreeze proteins and the spiral folds. These families need not be related to each other but will share features such as relative untwisted beta-sheets, stacking of similar residues and turns between beta-strands of approximately 90 degrees often stabilized by hydrogen bonding along the direction of the parallel beta-helix.Repetitive folds present special problems in the comparison of structures but offer attractive targets for structure prediction. The stacking of similar residues on a flat parallel beta-sheet may account for the formation of amyloid with beta-strands at right-angles to the fibril axis from many unrelated peptides.

Amino Acid Sequence↗
PubMed2001

Using postoperative cardiac Troponin-I (cTi) levels to detect myocardial ischaemia in patients undergoing vascular surgery.

BACKGROUND: Cardiac complications occur commonly in vascular surgery patients. Diagnosis of cardiac complications is difficult because of the inaccuracies associated with traditional cardiac enzyme measurements. CTi, a highly sensitive and specific marker of myocardial injury, may be able to detect cardiac complications with greater ease and accuracy. METHODS: The study prospectively examined 100 consecutive patients who underwent major vascular surgery between 6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi, creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and haemoglobin were taken for three postoperative days. One postoperative electrocardiograph (ECG) was taken. An extensive cardiac history was taken. Intraoperative and postoperative events were recorded. FINDINGS: There were 100 patients. 18 patients (18%) had a cTi elevation. On the basis of classical diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication (either myocardial infarction, congestive cardiac failure, unstable angina or atrial fibrillation). One patient (1%) who had a cTi elevation died. CTi elevation occurred in five patients (5%) who were not diagnosed with cardiac complications based on traditional criteria. Despite not meeting specific diagnostic criteria for cardiac complications, all patients showed signs and symptoms that could be attributed to myocardial ischaemia. Every patient who developed congestive cardiac failure or atrial fibrillation had a cTi elevation. A Chi-square analysis revealed a significant association between cTi elevation and postoperative cardiac complications. Four variables contributed small but significant amounts of unique variance to the prediction of peak cTi on linear regression analysis. These were peak CKMB index, postoperative congestive cardiac failure, postoperative chest pain and postoperative cardiac complications. CONCLUSIONS: Routine cTi monitoring of postoperative vascular patients would be an effective and inexpensive way to detect patients with cardiac complications. The relationship between postoperative cTi elevation and significant coronary artery disease remains to be shown.

Adult↗
PubMed2001

Cell culture conditions affect LPS inducibility of the inflammatory mediators in J774A.1 murine macrophages.

Peripheral blood monocytes and tissue macrophages contribute significantly to the inflammatory response. Bacterial lipopolysaccharide (LPS) has profound effects on these cells including, but not limited, to differentiation into macrophages, production of reactive nitrogen and oxygen species and secretion of pro-inflammatory cytokines. Herein, we describe a variant of the J774A.1 murine macrophage line that is reversibly resistant to multiple effects of LPS when cultured in different types of media. J774A.1 cells are adherent and spread out when cultured in DMEM/F12; however, when cultured in RPMI 1640, the cells are rounded and relatively non-adherent. Different types of tissue culture plates, sera, and media supplements were not responsible for these changes. We examined LPS-induced reactive nitrogen species using the Greiss reagent. J774A.1 cells cultured in RPMI exhibit a 5-fold increase in nitrites in culture supernatants after LPS stimulation whereas those in DMEM/F12 do not. Zinc staining of total cellular protein of cells in COHLY ET AL. RPMI and DMEM/F12 electrophoresed on a SDS-PAGE showed noticeable banding differences. LPS-induced cytokine gene expression was studied by RT-PCR. LPS induced TNF-alpha, IL-1alpha, IL-1beta, and sIL-1Ra in cells cultured in RPMI but not those cultured in DMEM/F12 with the exception of TNFalpha. This report shows that environmental factors contained in the culture medium alone can reversibly alter the biochemical nature of monocytes and macrophages.

Animals↗
PubMed2001

Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection.

To describe the clinical features, histologic characteristics, and management of patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13 children who had histologically confirmed PXA and were referred to the neuro-oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI documented the anatomic location, tumor extent, and degree of resection. There were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years). The most frequent presentations included seizures (n = 8) and headache (n = 5). Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1), frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1) lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6 patients, with cyst wall enhancement in 3 patients. The solid component was uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients, and calcification was noted in 4 patients. Histopathologic findings included meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2. Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total resection was achieved in 8 patients, near total resection in 1, and subtotal resection in 4. Ten patients were alive with a median follow-up of 41 months at this writing. Two patients died of progressive disease, and 1 died of an unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm in childhood, commonly presenting with seizures. Gross total resection without adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients (85%) in our series.

Adolescent↗
PubMed2001

Ovarian hyperstimulation syndrome: an endocrinopathy?

Ovarian hyperstimulation syndrome remains a significant but incompletely understood complication of ovarian stimulation. Evidence has accumulated regarding a role for various cytokines, in particular vascular endothelial growth factor, in its occurrence. However, the pathogenesis of ovarian hyperstimulation syndrome is likely to be complex and may involve a network of interacting cytokines and endocrine factors. Recent studies suggest links between specific cytokines and specific functional abnormalities in severe ovarian hyperstimulation syndrome. Two clinical forms of ovarian hyperstimulation syndrome may be distinguished, based on time of onset, with implications for the prediction and prevention of ovarian hyperstimulation syndrome in clinical practice.

Female↗