Search PubMed⌕ Search

Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 271 records · Page 15Linked to original sources
PubMed1999

Density dependence of forced expiratory flows in healthy infants and toddlers.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22-1.54) and 1.23 (1.02-1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.

Aging↗
PubMed1999

Rate constant for forced expiration decreases with lung growth during infancy.

Airway caliber and lung volume (VL) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow-volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV(0.5)/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their VL and that VL increases more rapidly than airway caliber early in life.

Cross-Sectional Studies↗
PubMed1999

Domestic aeroallergen exposures among infants in an English town.

A multicentre, prospective cohort study of childhood asthma was established in three European countries; the purpose of the project is the examination of factors which modify the relationship between allergen exposure in infant life and subsequent atopy and asthma. Dust samples were collected from the homes of 643 infants in a single town in the UK (the first cohort) and assayed for house dust mites (Der p 1) and cat allergen (Fel d 1) concentrations by enzyme-linked immunosorbent assay. A questionnaire with potential relevance to the development of atopy and asthma was completed. A wide variation in exposure to both allergens was observed. Carpeted, double-glazed or damp living rooms, and those sampled in the winter months, had higher levels of Der p 1, but these features did not predict Fel d 1 concentrations. Measures of high home occupancy were positively related to Der p 1 concentrations; and inversely with levels of Fel d 1, a finding which could not be explained by cat ownership. Homes in which one or more persons smoked had significantly lower concentrations of Der p 1, but not Fel d 1. There were no consistent differences in allergen levels between homes where one or more parent or sibling was either atopic or asthmatic. These findings indicate complex interactions among domestic, behavioural and seasonal factors and early allergen exposure in British children.

Air Pollution, Indoor↗
PubMed1999

Local estrogen biosynthesis in males and females.

It is now apparent that in men and in postmenopausal women, estrogens have important physiological and pathophysiological roles. However, importantly, these actions are at a local level, namely paracrine, autocrine, and even 'intracrine' rather than endocrine in the classical sense. Thus for example local estrogen biosynthesis in the bones of men plays a hitherto unsuspected role in the maintenance of bone mineralization and in epiphyseal fusion; and in the testes, estrogen is essential for male germ cell development. On the other hand, in postmenopausal women, the mesenchymal cells of the breast are the major source of estrogen responsible for breast cancer development. This realization points to the importance of circulating C19 precursors in the maintenance of adequate estrogen biosynthesis in extragonadal sites and suggests the possibility of new therapies to block estrogen synthesis in a tissue-specific fashion.

Adipose Tissue↗
PubMed1999

Field immobilization and euthanasia of American opossum.

Seventeen recently trapped opossum, Didelphis virginiana, (median weight 2.45 kg; range = 1.6-5.0 kg; quartiles = 1.8-3.3 kg) were immobilized with either telazol (15 or 30 mg/kg) or a mixture of medetomidine (100 micrograms/kg), butorphanol (0.2 mg/kg), and ketamine HCl (10 mg/kg) based on estimated weights. Anesthetized animals were subjected to cardiac puncture for blood withdrawal and toe pinch. Euthanasia was accomplished by intracardiac administration of 1 ml of concentrated pentobarbital sodium/phenytoin solution. Weights were underestimated for 14 of 17 animals, but were within 0.5 kg of the actual weight. Both drug combinations provided rapid and calm immobilization. Median time to recumbency for the medetomidine-butorphanol-ketamine group (n = 5) was 6 min (range = 4-10 min; quartiles = 6 and 8 min). The median time to recumbency was not statistically different for the low (n = 6) and high dose (n = 6) telazol groups, 3 and 3.5 min respectively (quartiles 3; 3.5 and 4; 5.5 min). The stronger heart beat with telazol immobilization facilitated cardiac puncture. All five animals administered the medetomidine-butorphanol-ketamine mixture and three of six animals given the low telazol dose reacted to cardiac puncture. Only one of six animals given the estimated 30 mg/kg dose of telazol reacted slightly to cardiac puncture. We conclude that 30 mg/kg telazol provides sufficient immobilization and analgesia to allow accurate cardiac puncture of the opossum if the procedure is performed within 5 to 10 min of recumbency. Intracardiac administration of concentrated pentobarbital sodium/phenytoin solution followed by bilateral thoracotomy provides appropriate euthanasia suitable for field situations.

Analgesics↗
PubMed1999

Characterization of a transformed ovine lymphatic endothelial cell line.

OBJECTIVE: To develop a non-tumor-derived stable lymphatic endothelial cell line that exhibits rapid growth rate without serum and exogenous growth factors, while still maintaining key features characteristics of the non-transformed lymphatic endothelium. METHODS: Lymphatic endothelial cells were isolated from ovine mesenteric lymphatic vessels, grown to confluence and transfected with SV40 DNA using the calcium phosphate method. The resulting cell line was characterized using morphological, immunocytochemical, flow cytometric analysis, and immunoprecipatitation and Western blotting methods. RESULTS: The resulting cell line (sheep lymphatic endothelial transformed cell line, SLET-1) underwent rapid proliferation in the absence of growth factors and reduced concentrations of serum. In addition, key morphological and functional properties of the non-transformed lymphatic endothelium were retained. These include the ability to form confluent monolayer cultures, the expression of the lymphatic endothelial-specific VEGFR-3, FLT-4) tyrosine kinase receptor, the biosynthesis and secretion of von Willebrand factor and plasminogen activators. In addition, SLET-1 cells express cell surface antigens found on LEC that may act as antibody targets in various immune reactions. Monolayer cultures of the SLET-1 cells incubated with endothelial cell-growth factor formed tubular structures, indicating the retention of the capacity to differentiate. CONCLUSION: The SLET-1 cell line retained key morphological and functional properties characteristic of the non-transformed lymphatic endothelium. The ability to form capillary-like tubular structures provides an important cell line for defining the role of specific proteins that are involved in the lymphagiogenic (formation of new lymphatic vessels) process. Thus, this transformed lymphatic endothelial cell line provides an in citro model that may have widespread utility in studying regulatory mechanisms of lymphatic endothelial cell function and differentiation.

Animals↗
PubMed1999

Mortality in the Portuguese thorotrast study.

The Portuguese Thorotrast study cohort consists of a group of patients who received Thorotrast for diagnostic reasons between 1929 and 1956, and a group of similar patients who were given nonradioactive contrast agents. The cohort members were identified from medical records that contained information on reasons for the radiological investigation, type of procedure employed, and name and dose of the contrast medium used. This cohort was assembled in 1961, but its follow-up was interrupted in 1976. We have now reactivated this cohort and extended its follow-up through the end of 1996. Similar methods were used to follow up and ascertain cause of death for the Thorotrast-exposed and unexposed subjects. A total of 1931 patients who received Thorotrast systemically and 2258 unexposed subjects were initially identified from medical records. We were able to successfully follow up 58.6% (1131) of the Thorotrast patients and 45.7% (1032) of the unexposed patients. By the end of 1996, 92.2% of the Thorotrast patients and 75.2% of the unexposed patients were dead. Mortality from all causes was increased in the Thorotrast patients compared to those who were not exposed. This excess in mortality increased with time since exposure, peaking 30 years after administration of Thorotrast. The rise in overall mortality was essentially due to neoplasms [relative risk (RR) adjusted for sex, age and period = 6.04, 95% CI = 4.42-8.26], nonmalignant liver disorders (RR = 5.67, 95% CI 3.13-10.3) and nonmalignant hematological conditions (RR = 14.2, 95% CI = 2.54-79.3). The increase in mortality from neoplasms was explained mainly by increases in the risk of liver cancer (RR = 70.8, 95% CI = 19.9-251.3) and, to a much lesser extent, leukemia (RR = 15.2, 95% CI = 1. 28-181.7).

Adolescent↗
PubMed1999

Audit of condom issuing in eastbourne sexual health clinic.

A perennial question at meetings of family planning practitioners concerns the numbers of condoms to give to patients. If the condom is to act as an effective contraceptive method, then there must be a condom available for every occasion of sexual intercourse. In recent years, the condom has been promoted as a means of protecting against sexually transmitted infections, including HIV. The 'Double Dutch' approach whereby the condom is used alongside other methods of contraception such as the Pill, has been advocated, particularly for younger people. The condom has consequently become a more commonly used method of contraception, particularly amongst the young and single. The family planning clinic in Eastbourne is now part of an integrated Sexual Health Clinic incorporating family planning (FPC), genito-urinary medicine (GUM), HIV and AIDS clinics. At the time of this audit, steps towards integration were already well advanced. We were keen to develop standards for issuing condoms which took account of identified need in target populations. At the same time clinicians were anxious to avoid waste given that the budget for condoms is finite. Often the idea of using a condom is introduced by clinicians rather than by clients, and this may lead to the issuing of condoms which the client is not motivated to use. We were also keen to eliminate any judgements about frequency of requests for supplies of condoms, and to this end the local Health Promotion Department ran training on sexual history taking which included approaches to asking about frequency of sexual intercourse.

Adult↗
PubMed1999

Do people attending a same day testing clinic discuss their need for a HIV test with their GP?

In the United Kingdom, people with HIV infection present with advanced disease and general practitioners (GPs) are currently an underused resource for HIV testing. We describe the reasons for using an open-access clinic rather than primary care for testing for HIV. People attending the clinic were asked to complete a questionnaire asking about GP registration, access, and whether HIV testing was discussed in primary care. Despite access to GPs, HIV testing in primary care was rarely discussed. If HIV testing is to move to a general practice setting, GPs could address the issues, such as the recording of sensitive information in notes, future life insurance, and confidentiality, which this report identifies as the main barriers for using primary care.

Family Practice↗
PubMed1998

Epstein-Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions.

The Epstein-Barr virus (EBV) encoded Latent Membrane Protein-1 (LMP1) mimics a constitutively active receptor molecule, and has been shown to activate NF-kappaB and the MAPK and JNK pathways. Two regions within the cytosolic domain of LMP1 have been found to effect cell signalling. One of these, the carboxy-terminal activation region-1 (CTAR1), binds members of the TRAF family of proteins, and the other (CTAR2) binds TRADD, suggesting that LMP1 transduces signals similarly to the Tumour Necrosis Factor Receptor family of receptors. The ability to bind TRAFs, to activate NF-kappaB and the JNK pathway, to upregulate cellular genes such as CD54 (ICAM-1 adhesion molecule), and to affect cell growth and apoptosis has led to the suggestion that LMP1 signalling is similar to, or even identical to CD40. However, we now show that while ligand-induced CD40 signalling is impaired in the Jurkat T cell line, LMP1 was fully functional; therefore demonstrating that LMP1 and CD40 signalling differ. Mutated LMP1 genes, in which one or other of the CTAR1 and CTAR2 domains was non-functional, behaved more like CD40 in being unable to upregulate the CD54 cell surface marker in Jurkat cells. However, the CTAR1 domain of LMP1, which shared a TRAF-binding sequence motif with CD40, differed from CD40 in being unable to activate NF-kappaB in Jurkat. Cotransfection experiments with LMP1 mutants demonstrated that CTAR1 can cooperative with CTAR2 on separate LMP1 molecules, provided that they exist within the same oligomeric complex.

CD40 Antigens↗
PubMed1998

Randomised trial of management of hypertensive pregnancies by Korotkoff phase IV or phase V.

BACKGROUND: There is debate about whether diastolic blood pressure should be recorded as the fourth (muffling, K4) or fifth (disappearance, K5) Korotkoff sound in pregnancy. We compared maternal and fetal outcomes and the likelihood that episodes of severe hypertension would be recorded when hypertensive pregnancies were managed according to either K4 or K5. METHODS: 220 pregnant women with diastolic hypertension (K4 > or =90 mm Hg) after the 20th week of gestation were enrolled in a prospective randomised study at two obstetric units in Australia; they were randomly assigned management with K4 (n=103) or K5 (n=117) for the remainder of the pregnancy. Clinical management was according to a uniform department protocol. Analysis was by intention to treat. All the women completed the trial. FINDINGS: An episode of severe hypertension (systolic > or =170 mm Hg, diastolic > or =110 mm Hg, or both) was more likely to be recorded with use of K4 than with use of K5 (39 [38%] vs 30 [26%] women, p=0.051), mainly because of a greater likelihood that severe diastolic hypertension would be recorded (34 [33%] vs 20 [17%], p=0.006). The frequency of severe systolic hypertension and simultaneous severe systolic and diastolic hypertension did not differ between groups. Pregnancy was prolonged by an average of 2 weeks in both groups, and there were no significant differences between the groups in laboratory data, requirements for antihypertensive treatment, birthweight, fetal growth retardation, or perinatal mortality. There was no eclampsia or significant maternal morbidity in either group. INTERPRETATION: A change from use of K4 to K5 would mean that one fewer case of severe diastolic hypertension would be recorded for every six hypertensive pregnancies, but all other episodes of severe hypertension would be recorded with similar frequency. Since the K4/K5 difference is smaller in hypertensive than in normotensive pregnant women and since K5 is closer to the actual intra-arterial pressure and more reliably detected, universal adoption of K5 to record diastolic blood pressure in hypertensive pregnancy should be considered.

Blood Pressure Determination↗
PubMed1998

The amino terminus of human CCR5 is required for its function as a receptor for diverse human and simian immunodeficiency virus envelope glycoproteins.

The chemokine receptor CCR5 plays a key role in the CD4-dependent entry of human and simian immunodeficiency viruses into target cells. We have mapped the interaction sites on CCR5 for a number of novel anti-CCR5 monoclonal antibodies and have used these to study the role of the CCR5 N-terminal ectodomain in viral entry and to demonstrate differential CCR5 epitope expression on different cell types. Deletions of the CCR5 amino terminal domain or substitution with equivalent regions from other chemokine receptors did not affect cell surface expression or reactivity with loop-specific antibodies, suggesting that the loop regions remained conformationally intact. Exchanges of the amino terminal segment of CCR5 with the equivalent domains of CCR1, CCR2, and CXCR4 did not significantly affect infection with virus pseudotyped with envelope glycoproteins (Envs) from HIV-2 and SIV, but substitution with the CXCR4 sequence abrogated entry mediated by Env from HIV-1. In contrast, deletion of the amino terminus abrogated CCR5 receptor activity for all viral Envs examined. These data indicate that the amino terminus of CCR5 has an essential role in entry mediated by diverse viral Envs but that the sequence requirements are more relaxed for the HIV-2 and SIV Envs compared to the HIV-1 Env examined. This suggests that different viral Envs make distinct and specific interactions with the amino terminus of CCR5. Viral Env utilization of CCR5 expressed on 293-T cells does not always correlate with the cellular tropism of the virus, and one possible explanation is that Env-accessible interaction sites on CCR5 differ on different cell types. We therefore analyzed binding of several anti-CCR5 monoclonal antibodies to cell lines and primary cells that express this chemokine receptor and found that whereas all antibodies bound to CCR5-transfected 293T cells, several did not bind to PBMC. The results suggest that CCR5 undergoes cell type specific structural modifications which may affect interaction with different HIV and SIV envelope glycoproteins.

Amino Acid Sequence↗
PubMed1998

Dyspepsia in the community is linked to smoking and aspirin use but not to Helicobacter pylori infection.

BACKGROUND: The relationship between Helicobacter pylori infection and symptoms remains controversial. We aimed to determine if an association exists between unexplained dyspepsia (pain or discomfort centered in the upper part of the abdomen) and H pylori. METHODS: A validated questionnaire was completed by 592 healthy blood donors. Helicobacter pylori serologic values (via enzyme-linked immunosorbent assay), blood group status, and Rh status were measured; 4.9% of subjects who had a history of peptic ulcer disease were excluded from the analyses. RESULTS: The prevalence of dyspepsia and no ulcer history was 11% (95% confidence interval [CI], 8.6%-13.8%); 15.4% of subjects with dyspepsia had H pylori while 14.6% of subjects without dyspepsia were infected (P=.90). The mean dyspepsia impact scores (combining frequency and severity) in those with and without H pylori were 4.7 and 5.4, respectively (P=.20). The median H pylori optical density values in dyspepsia vs no dyspepsia were not significantly different (P=.30). Independent risk factors for dyspepsia were the use of aspirin (odds ratio [OR], 2.2; 95% CI, 1.3-3.7) and smoking (OR, 2.1; 95% CI, 1.3-3.6) but not age, sex, marital status, educational level, income, or the use of alcohol, coffee, or nonsteroidal anti-inflammatory drugs. Independent risk factors for H pylori were increasing age (OR, 1.8 per decade; 95% CI, 1.5-2.3), male sex (OR, 2.1; 95% CI, 1.3-3.4), and net family income (OR, 1.8; 95% CI, 1.2-3.3). CONCLUSION: Dyspepsia in the community is linked to smoking and aspirin use, but not to H pylori infection.

Adult↗