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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 271 records · Page 15Linked to original sources

The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed during hematopoiesis and spermatogenesis.

Ship is a recently identified SH2-containing inositol polyphosphate 5-phosphatase that has been implicated as an important signaling molecule in cell-culture systems. To understand the physiologic function of Ship in vivo, we performed expression studies of Ship during mouse development. Results of this study demonstrate the expression of ship to be in late primitive-streak stage embryos (7.5 days postcoitus [dpc]), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in mouse embryo. In adult mice, Ship expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes, and lymphocytes, and is also found in the spermatids of the testis. Furthermore, the level of Ship expression is developmentally regulated during T-cell maturation. These results suggest a possible role for Ship in the differentiation and maintenance of the hematopoietic lineages and in spermatogenesis.

Animals↗

Cloning and expression of an immunoglobulin superfamily gene (IGSF1) in Xq25.

We have isolated a novel full-length cDNA for a gene (IGSF1) located in distal Xq25. This transcript is highly expressed in adult testis and fetal liver but is undetectable in adult liver. A smaller alternate form is highly expressed in adult heart. The gene encodes a protein of 1327 amino acids with several recognizable functional domains. The protein has a putative signal peptide and transmembrane region, 15 potential sites for N-linked glycosylation, and 12 C2-type immunoglobulin (Ig)-like domains. All of the Ig-like domains contain the two conserved cysteine residues that form intradomain disulfide bonds typical of this superfamily. These features are consistent with a possible role for this molecule in cell surface recognition or cell-cell interaction.

Amino Acid Sequence↗

Identification of an astrocyte cell population from human brain that expresses perforin, a cytotoxic protein implicated in immune defense.

The brain is an immunoprivileged organ isolated from the peripheral immune system. However, it has been shown that resident cells, notably astrocytes and microglia, can express numerous innate immune molecules, providing the capacity to generate a local antipathogen system. Perforin is a cytolytic protein present in the granules of cytotoxic T lymphocytes and natural killer cells. Expression in cells other than those of the hemopoetic lineage has not been described. We report here that fetal astrocytes in culture (passages 2 to 15), astrocytoma, and adult astrocytes expressed perforin. Reverse transcriptase polymerase chain reaction followed by Southern blot was carried out using multiple specific primers and all cDNAs were cloned and sequenced. Human fetal astrocyte perforin cDNA sequence was approximately 100% identical to the reported perforin cDNA cloned from T cells. Western blot analysis using monoclonal and polyclonal antiperforin peptide antibodies revealed a protein of 65 kD in both human fetal astrocyte and rat natural killer cell lysates (n = 4). Immunostaining followed by FACS(R) and confocal and electron microscopy analysis revealed that perforin was expressed by 40-50% of glial fibrillary acidic protein positive cells present in the fetal brain culture (n = 11). Perforin was not localized to granules in astrocytes but was present throughout the cytoplasm, probably in association with the endoplasmic reticulum. Perforin was not detected in normal adult brain tissue but was present in and around areas of inflammation (white and grey matter) in multiple sclerosis and neurodegenerative brains. Perforin-positive cells were identified as reactive astrocytes. These findings demonstrate that perforin expression is not unique to lymphoid cells and suggest that perforin produced by a subpopulation of astrocytes plays a role in inflammation in the brain.

Adult↗

Laminin-5 coating enhances epithelial cell attachment, spreading, and hemidesmosome assembly on Ti-6A1-4V implant material in vitro.

Enhancement of epithelial cell attachment to laminin-5-coated titanium alloy (Ti-6Al-4V) implant material was evaluated in vitro. Protein analysis showed that Ti-6Al-4V has a high affinity for laminin-5 and adsorbed significantly more laminin-5 than laminin-1. DNA analysis showed that laminin-5 enhanced attachment of normal human epidermal keratinocytes (NHEK) to Ti-6Al-4V significantly more than did laminin-1 or uncoated controls. The effect of passivation on laminin-5 adsorption and activity on Ti-6Al-4V also was evaluated. Passivation had no significant effect on the amount of protein adsorbed; however, AFM, ESCA, and ToF-SIMS analyses suggested that passivation affects the conformation of adsorbed laminin-5. Although laminin-5 coating significantly enhanced rapid attachment of epithelial cells to both passivated and unpassivated Ti-6Al-4V, surface area measurements showed that cells spread on laminin-5-coated passivated Ti-6Al-4V covered a significantly larger surface area than cells spread on laminin-5-coated unpassivated samples. TEM analysis showed that cells formed significantly more hemidesmosomes on the surface of laminin-5 coated passivated than on the surface of laminin-5 coated unpassivated titanium alloy. The enhancement of rapid cell attachment, spreading, and hemidesmosome assembly on laminin-5-coated passivated samples may reflect better integration between epithelial cells and titanium alloy and thus may be predictive of long-term implant stability.

Cell Adhesion↗

Use of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) for routine identification of enzymatically digested proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Automated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis of >100 tryptic digests carried out on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separated, Coomassie Blue-stained proteins that were prepared by >50 different laboratories demonstrates that a commercial electrospray/quadrupole ion trap mass spectrometer and the tandem mass correlation algorithm developed by Eng et al. (Am. Soc. Mass Spectrom. 1994, 5, 976-989) provide an extremely robust and facile approach to routine protein identification. By requiring a minimum of two significant matches to peptides that would be predicted to be produced by the protease that was used, low pmol levels of proteins can be identified with high confidence while minimizing the probability of identifying the protease itself and/or the ubiquitous contaminant, keratin. Hence, in only 7% of the digests analyzed was keratin identified and in only 5% of the digests analyzed was the protease itself identified. In contrast, 58% of the analyzed samples were identified and, in many instances, multiple proteins were identified in the same sample. Although the median amount of digest analyzed was 6.1 pmol, the limit of sensitivity (as the instrument is configured with a flow rate of 4 microL/min) appears to be at the 500 fmol level. Since one of the primary reasons for not identifying a sample is that its sequence is not yet in the database searched, the utility of an LC MS/MS approach to protein identification will certainly increase in the future as the sequences of more genomes are completed.

Chromatography, High Pressure Liquid↗

Overtaking road-accidents: differences in manoeuvre as a function of driver age.

Nine-hundred and seventy-three police road-accident files describing overtaking accidents were sampled from the headquarters of Nottinghamshire Constabulary, England, for the years 1989-1993. Salient facts were extracted from each case, including the exact manoeuvre involved, the principle explanatory factors, the driver(s) most at fault, and the drivers' ages. Two kinds of reliability measure for case interpretations. indicated high levels of consistency. Two induced exposure measures were used, comparing driver involvement in a given type of overtaking accident with involvement in overtaking accidents in general, and comparing the age profiles of the drivers most at fault with those of the other drivers involved. Ten types of overtaking accident were distinguished, and three are discussed in detail: collision with a right-turning vehicle (the most common injury-accident for overtakers), which tends to occur either because a young driver makes a faulty overtaking decision, or an older driver makes a faulty right turn; head-on collision, which affects all age groups roughly in proportion to exposure; and the 'return-and-lose-control' accident, which is associated particularly with young drivers. The study illustrates the 'structured judgement method' of accident causation research, in which human interpreters are used to ascribe causes and processes to individual cases, but orthodox research techniques are used to standardise procedures, and to assess and ensure reliability.

Accidents, Traffic↗

Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study.

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.

Acute Disease↗

Can shocks timed to action potentials in low-gradient regions improve both internal and out-of-hospital defibrillation?

During the first minute of fibrillation, circulating wavefronts excite new fibrillation action potentials almost immediately following termination of the preceding action potential. The extension of refractoriness hypothesis states that a successful defibrillating shock must produce a uniform postshock refractoriness of a specific optimal duration throughout the ventricle, which blocks these wavefronts and terminates fibrillation. We hypothesized that, if shocks are appropriately timed early in the fibrillation action potential in low-voltage-gradient regions, postshock refractoriness will already be long and the shock need not be strong enough to further extend it. This will result in a lower defibrillation threshold (DFT). This hypothesis was tested in the isolated rabbit heart model. Shocks were synchronized to monophasic action potentials recorded from a low-intensity region. An up/down protocol was used. I50 for early shocks was 17% lower than that for late shocks (31% decrease in E50). Standard deviation of I50 was reduced from 32% for late shocks to 18% for early shocks. Therefore, shock synchronization improves both DFT and intersubject variability during early fibrillation. As fibrillation duration increases, action potential frequency decreases and periods of diastole occur. Because of these ischemic changes, it is uncertain whether shock timing can produce similar improvements in defibrillation under out-of-hospital conditions.

Action Potentials↗

Penetration of household insecticides through different types of textile fabrics.

Six different types of fabrics were compared for their ability to protect against human exposure to three different commercial household aerosol insecticides. Fabrics used in this investigation were, 100% cotton, cotton-polyester thermal underwear, cotton-polyester blend (twill), 100% acrylic, 100% wool and artificial silk (rayon). The household insecticides were, Black Flag (Ant and Roach Killer), Raid (Ant and Roach Killer) and Hot Shot (Wasp and Hornet Killer) containing propoxur, permethrin/pyrethrins and chlorpyrifos/allethrins as their active ingredients respectively. A fluorescent tracer, 4-methyl-7-diethyl amino coumarin was mixed with the aerosol (or equivalent aliquot) and sprayed onto cloth squares fitted on Whatman paper patches. The percentage of penetration through the cloth was quantified by the intensity of the fluorescence spectrum of each patch extract and the amount of the tracer recovered was calculated. The extract was concentrated to 1/10th of the volume to measure the content of each of the insecticides by supercritical fluid chromatography (SFC) using electron capture (ECD) and diode array detectors. Scanning electron microscope (SEM) images of the fabrics showed the geometry of the yarn. The results obtained from the fluorescence spectra, SFC and SEM showed that cotton-polyester (twill), cotton, wool and cotton thermal underwear were the least penetrable materials for the aerosols. On the other hand, acrylic and artificial silk (rayon) were the most penetrable cloth types.

Aerosols↗

The motion path of the digits.

This study investigates whether the path taken by the fingertips of the human hand during unrestricted flexion and extension follows a precise mathematical pattern: an equiangular spiral. Eight normal subjects participated in the study. Subjects performed numerous flexion and extension trials at a random speed. Motion was recorded by a 6-camera, 3-dimensional motion analysis system with 24 retroreflective markers affixed to the dominant hand at predetermined locations. Four hundred eighty flexion-extension arcs were analyzed. We used the coefficient of multiple determination to compare the flexion and extension motion arc of each finger to an equiangular spiral curve derived mathematically. Our results indicate that the path of the hand during flexion and extension closely follows the path of an equiangular spiral with the coefficient of multiple determination values consistently above 0.95.

Adult↗

Maternal and fetal plasma levels of markers of bone metabolism in gestational diabetic pregnancies.

The aim of this study is to determine whether gestational diabetes has any effect on maternal and fetal bone metabolism. We collected maternal and umbilical cord blood samples from 19 women with gestational diabetes and 19 controls at the time of delivery. The plasma levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were used to monitor the rate of bone formation and degradation respectively. There is a significant correlation between the 1 hour postprandial blood glucose and the maternal levels of ICTP (r = 0.560, P = 0.004), but there was no significant difference in maternal or fetal levels of PICP and ICTP between the study and control groups (P = 0.411 maternal PICP, P = 0.241 maternal ICTP, P = 0.365 fetal PICP and P = 0.781 fetal ICTP). In the gestational diabetes group, there was a significant correlation between maternal and fetal ICTP (r = 0.694, P = 0.001), but there was no correlation between maternal and fetal levels of PICP (r = 0.334, P = 0.175). Although the maternal levels of ICTP is related to the 1 hour postprandial blood glucose level, gestational diabetes does not affect the maternal or umbilical cord levels of the serum markers of bone metabolism.

Biomarkers↗

Critical care provided in an urban emergency department.

The emergency department (ED) provides a substantial amount of critical care. The purpose of this study was to quantitate the critical care provided in an urban ED. The study was performed at a large urban hospital with an annual ED volume of 70,000 patients. All patients requiring critical care in the ED or hospital were prospectively observed between September 1 and November 30, 1993. Patients requiring recovery room care or neonatal intensive care were excluded. Data collected included age, disposition, length of stay, triage acuity assignment in the ED, primary diagnosis, and critical care procedures. During the study, 11,989 patients were examined in the ED with 500 (5%) requiring admission, 340 (3%) requiring a critical care intervention, and 96 (1%) being admitted to an intensive care unit (ICU). Ten percent of patients receiving critical care in the ED were admitted to the floor for lack of bed space. Triage assignment of emergent life-threatening or urgent potentially life-threatening condition predicted critical care need and waiting time to examination. The spectrum of critical care procedures performed in the ED and ICU were similar except for advanced life support intervention, which was more common in the ED (17 versus 3), and arterial line placement, which was more common in the ICU (14 versus 1). The spectrum of diagnoses reflected the age of patients with cardiovascular illnesses (33%), metabolic illnesses (18%), and trauma (16%) common in adults (age > or = 17) and infectious illnesses (46%) or metabolic illnesses (21%) more common in pediatric patients. Overall, 14% of adult critical care, 23% of pediatric critical care, and 15% of all critical care provided in the areas studied occurred in the ED. A significant proportion of critical care is provided in the ED, and triage acuity assignment reflects this need. A significant proportion of critically ill patients was admitted to the floor for lack of bed space, which highlights the financial constraints in urban hospitals such as the one studied.

Adult↗

Perceptions of body size in Pacific Islanders.

OBJECTIVE: To assess attitudes to body size and obesity in Samoans, a Pacific island group characterised by very high levels of obesity and traditionally strong positive cultural views of large bodies. DESIGN: Cross sectional study of Samoan adults in Samoa and New Zealand. SUBJECTS: 84 female and 77 male Samoans in Samoa and 41 female and 24 male Samoans in Auckland, New Zealand, aged 25-55 y. MEASUREMENT: Body mass index (BMI), standardised survey questionnaires of perceptions of bodyweight and health, diet and exercise, and perception of body sizes on a continuous scale. RESULTS: Although Samoans in both countries display high population levels of obesity, ideal body sizes are slim and body dissatisfaction and attempted weight losses were apparent. However, women and men above normal weight did not characteristically perceive themselves as obese, were as positive about their body size, weight and health, and obese women were no more likely to be attempting to lose weight than their slimmer peers. CONCLUSIONS: The traditional Samoan veneration of large bodies is not apparent as ideal body sizes are slim. An important difference in values with Western industrialised societies is the absence of a strongly negative view of obesity.

Adult↗

The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein.

The molecular basis of the three major alleles (Fy(a)/Fy(b)/Fy) of the Duffy (FY) blood group system has recently been established but the Fy(x) phenotype associated with weak expression of the Fy(b) and other FY antigens is poorly understood. In the Fy(x) genes of five unrelated British and Swedish donors with the Fy(a+b+weak) phenotype we found two missense mutations predicting amino acid changes Arg89Cys and Ala100Thr in the FY glycoprotein. The same mutations were found in two Fy(a-b+weak) samples from individuals of Swedish and Algerian origin. Their red blood cells showed a marked decrease in Fy(b), Fy3 and Fy6 expression measured by routine serology and flow cytometry. The rare FY genotypes Fy(x)Fy(x) and Fy(x)Fy were confirmed by family studies and DNA sequencing. Screening by allele-specific primer PCR (ASP-PCR) for these mutations among 100 Caucasian and 100 Black random blood donors indicated allele frequencies of 2.5% and 0% respectively. Ala100Thr alone was present in 33% of the Caucasians (but none of the Blacks) with no weakening of FY expression. A novel allele at the FY locus associated with the Fy(x) phenotype was studied. Mistyping of this weak Fy(b) antigen in clinical transfusion medicine may lead to delayed haemolytic transfusion reactions in immunized patients. A potential role for genomic typing is proposed.

Alleles↗

The diagnosis of severe growth hormone deficiency in elderly patients with hypothalamic-pituitary disease.

OBJECTIVE: Adults over the age of 60 years with organic disease of the hypothalamic-pituitary axis may be deficient in growth hormone (GH) to a degree that is distinct from the age-related decline in GH secretion and sufficient to cause perturbations of body composition, serum lipid profile and bone metabolism. In order to determine the best method for detecting GH deficiency in this age group we have compared spontaneous GH secretion, a provocative test of GH secretion, the arginine stimulation test (AST), and basal estimates of circulating insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP). DESIGN: Twenty-four patients (16 male) with organic hypothalamic-pituitary disease and 24 controls (17 male) were studied. The groups were matched for BMI but the patients were slightly younger than the controls, 66.0 (61.0-85.7) vs. 70.6 (60.8-87.5) years (P = 0.04). All subjects underwent a 24-h GH profile (20-minute sampling), measurement of serum IGF-I, IGF-II, IGFBP3, IGFBP2 and growth hormone binding protein (GHBP) and, after an overnight fast, an AST (intravenous arginine 20 g/m2 over 30 minutes). GH concentrations were measured using an ultrasensitive chemiluminescence assay (sensitivity 0.002 microgram/l). Normative data for serum IGF-I, IGF-II, IGFBP3 and IGFBP2 were obtained from 125 subjects aged 60-87 years. RESULTS: None of the parameters studied was able to distinguish between all the GH deficient patients and the healthy controls. The median (range) area under the GH profile (AUCGH) and peak GH response to arginine were lower in the patients than in the controls, 310.05 (18.90-2193.36) vs. 2518.20 (526.76-12024.97) min mU/l (P < 0.00001), 1.07 (0.08-17.90) vs. 23.06 (4.60-109.98) mU/l (P < 0.00001), respectively. There was a significant relationship between AUCGH and peak GH response to arginine in the patients (r = 0.89, P < 0.0001) and in the controls (r = 0.56, P = 0.005). Serum IGF-I, IGFBP2, and IGFBP3 levels were significantly lower in the patients compared with the normal range, 102 (14-162) vs. 142 (59-298) micrograms/l (P < 0.0001), 415 (122-1868) vs. 640 (140-2585) micrograms/l (P = 0.0007) and 2.29 (0.81-3.75) vs. 2.59 (1.00-3.52) mg/l (P = 0.009), respectively. The degree of overlap between the two groups, however, was too great to make these measurements useful diagnostically. Serum IGF-II and GHBP concentrations in the patients were not significantly different from the normal range. The patients were divided into groups determined by the number of anterior pituitary hormone deficits present. There was a significant downward trend in the peak GH response to arginine with increasing severity of hypopituitarism (J = -3.04, P = 0.0012). Ninety per cent of patients with two or three additional pituitary deficiencies had a peak GH response less than 2.0 mU/l. CONCLUSIONS: Of the indices studied the arginine stimulation test is more effective than GH markers, such as IGF-I or IGFBP3, or measurement of spontaneous GH secretion for diagnosing GH deficiency in adults over the age of 60 years. By relating the peak GH response to the degree of hypopituitarism, a GH response less than 2.0 mU/l is suggestive of severe GH deficiency in this age group under the appropriate clinical circumstances.

Aged↗

Unwanted sexual experiences reported by nursing students: implications for nurse education and training.

This study examined the nature and frequency of unwanted sexual experiences in childhood and adulthood reported by nursing students, using a questionnaire developed from the Sexual Events Questionnaire (Calam & Slade). The questionnaire was distributed to 109 second-year nursing students (90 female and 19 male) for anonymous completion. At the same time a further short questionnaire asked students about their perceptions of the first questionnaire, and how far their course had, up to the present, included consideration of issues related to sexuality. A high level of unwanted sexual experiences was reported. For example: 49 (45.0%) reported having witnessed indecent exposure; 27 (24.8%) reported someone having 'tried unsuccessfully to have sexual intercourse with you against your will'; 14 (12.8%) reported someone having 'succeeded in having sexual intercourse with you against your will'. In the second questionnaire, 74.1% thought that consideration of human sexuality had so far been included in their course either 'not at all' or 'a little', with 19.4% responding 'quite a lot' or 'very much'. It is argued that there is a particular need, for personal and professional reasons, for nursing students to have opportunities to address any unresolved effects of unwanted sexual experiences, and that within the formal curriculum there should be greater consideration of issues related to human sexuality.

Adult↗