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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 397 records · Page 22Linked to original sources
PubMed1996

Combining inhibin A with existing second-trimester markers in maternal serum screening for Down's syndrome.

To assess the value of inhibin A as an additional second-trimester maternal serum marker of Down's syndrome we studied 56 affected and 280 unaffected pregnancies matched for gestational age. The median level in the cases was 1.62 multiples of the gestation-specific median (MOM) in the controls, with 95 per cent confidence limits of 1.34-1.96. The distribution of inhibin levels in affected and unaffected pregnancies was approximately log Gaussian, with means about 1 standard deviation apart. This degree of separation was similar to that for human chorionic gonadotropin (hCG), free beta-hCG, and unconjugated oestriol (uE3), but about double that of alpha-fetoprotein (AFP) measured in the same samples. Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation coefficient with hCG was 0.29 (P = 0.19) for Down's syndrome and 0.41 (P < 0.0001) for unaffected pregnancies; with free beta-hCG, it was 0.18 (P = 0.38) and 0.38 (P < 0.0001), respectively. On the basis of these results and other published studies, we estimate that measuring inhibin A in addition to AFP and hCG or free beta-hCG (with or without uE3) will increase the detection rate for a fixed 5 per cent false-positive rate by about 7 per cent.

Biomarkers↗
PubMed1996

Molecular cloning and characterization of rat sperm surface antigen 2B1, a glycoprotein implicated in sperm-zona binding.

The rat sperm surface antigen, 2B1, that has been proposed to play a key role in sperm adhesion to the zona pellucida, has been cloned and its entire cDNA sequenced. Northern blot analysis indicates that 2B1 is encoded by a 2.2-kb RNA transcript that is abundantly expressed in the testis. The deduced protein sequence contains 512 amino-acid residues with a strong candidate signal sequence and C-terminal transmembrane domain. Data base searches reveal a high degree of sequence similarity to guinea pig, rabbit, monkey, and human PH20 sperm surface antigens, and a lower degree of similarity to honey bee and whiteface hornet venom hyaluronidases. Rat 2B1 antigen also possesses hyaluronidase activity, suggesting that it is a bifunctional protein with putative roles in the dispersion of cumulus oophorus cells as well as zona adhesion. However, while it would appear that 2B1 is the rat homologue of the guinea pig PH20 antigen, they differ in a number of important biochemical respects (including their mode of attachment to the sperm membrane and distribution between soluble and membrane-bound fractions), as well as in their localization on the sperm membrane. Expression of regions of the 2B1 protein in recombinant bacterial cells has allowed a preliminary mapping of the 2B1 epitope, and has provided more definitive information on the endoproteolytic processing of 2B1 during epididymal transit.

Amino Acid Sequence↗
PubMed1996

Boar sperm proacrosin infrared investigation: secondary structure analysis after autoactivation and suramin binding.

Fourier transform infrared spectroscopy was used to investigate the secondary structure of boar sperm proacrosin at p2H 5.5, to determine the structural changes following protein autoactivation to beta-acrosin at p2H 8.0 and to study the effect of suramin binding on the protein secondary structure. At p2H 5.5, proacrosin contents of alpha-helix, beta-sheet, turns, and unordered structures were estimated to be 9, 49-51, 16-18, and 24%, respectively. At p2H 8.0, the protein was partially insoluble; spectral analysis of the soluble fraction, which contained beta-acrosin, showed an overall secondary structure quite similar to that of proacrosin at p2H 5.5. However, p2H 8.0 spectra of the soluble protein (beta-acrosin), together with the thermal denaturation experiments, indicated that, compared to proacrosin, beta-acrosin showed an increased content of beta-sheets exposed to the solvent as well as a different tertiary structure. Proacrosin/suramin interaction at p2H 5.5 resulted in the formation of soluble and insoluble complexes and the relevant infrared spectra showed only minor differences with respect to the native proacrosin. However, the thermal denaturation curves revealed that suramin induced a destabilization of proacrosin structure. The data also indicated that suramin could modify the interaction characteristics of proacrosin aspartyl and glutamyl residues, thus suggesting competition of suramin with these two residues for ionic interactions.

Acrosin↗
PubMed1996

Lung microvessel injury from peritoneal abscesses and gram-negative bacteremia.

To analyze the effect of an extrathoracic focus of infection on lung vessel wall structure, we produced peritoneal abscesses in the rat, over a period of 3 to 7 weeks, by implanting capsules containing live gram-negative bacteria (3.0 x 10(7) Escherichia coli and 5.0 x 10(7) Bactercides fragilis) with an adjutant. We document here by arteriography, morphometric analysis, and high resolution microscopy, microvessel cell injury, and wall remodeling. In the sepsis-injured lung, both dilated and thick-walled microvessels are present. The walls of dilated vessels are disrupted by extensive endothelial and precursor smooth muscle cell injury. In thick-walled vessels these cells are hypertrophied, and the precursor smooth muscle cells express filaments, demonstrating a shift toward a contractile phenotype. Infiltrating monocytic cells focally consolidate alveolar regions. In the residual nonconsolidated regions, alveolar-capillary membrane cells are attenuated and the capillaries dilated. Vessel changes after 7 weeks are similar to those after 3 weeks but alveolar-capillary membrane injury is more extensive. These structural changes, including the development of precursor smooth muscle cells, may contribute to the known increase in reactivity of these lung vessels to challenge by vasoactive agents.

Abdominal Abscess↗
PubMed1996

Cuff bulk of tracheal tubes in adolescence.

PURPOSE: To investigate cuff types for potential use in late childhood and early adolescence for appropriate fit. METHOD: Formulae suggest the use of a tracheal tube having a 6.5 mm internal diameter at ages 8 to 10 years, so a model system was used to test the passage of cuffed and uncuffed tracheal tubes of 6.5 mm internal diameter through calibrated holes 8.1-16.6 mm diameter, in plastic plates. RESULTS: Uncuffed tracheal tubes passed through 9.0 mm diameter holes. "High pressure" cuffed tubes passed through 10.5 to 11.3 mm holes. "Low pressure" cuffed tubes passed through 12.3 to 16.4 mm. CONCLUSION: Patients aged 8 to 10 yr have a limiting internal diameter at the cricoid of 8 to 10 mm. Their unstretched tracheal diameter below the cricoid is only about 11 mm. The actual outside diameters of "low pressure" cuffs chosen by commonly used formulae considerably exceed the limiting diameters of eight to ten year old patients, even considering recommended compensation factors. Analysis of background data indicates that these problems are especially aggravated at this age by non-linear growth of the cricoid.

Child↗
PubMed1996

The effect of refractive lenses on perceived direction.

The accuracy of directional localization with refractive lenses was determined by open-loop pointing for four myopic habitual contact lens wearers. The target was a single point of light at random locations (dark), or was embedded in a horizontal array of lights (light). In the dark, the regression slope of indicated vs actual target position was significantly less for spectacles than for contact lenses, as predicted from the prismatic effects of the spectacles. In the light, slopes for spectacles and contacts were not significantly different. These results suggest that spectacle wearers do not utilize eye position information in making direction judgments in the light.

Adaptation, Ocular↗
PubMed1996

Endothelin antagonist bosentan blocks neurogenic inflammation, but is not effective in aborting migraine attacks.

Bosentan, a specific mixed antagonist of endothelin receptors with no vasoconstrictor activity, inhibits neurogenic plasma extravasation (NPE) within rat dura mater. This would predict efficacy in aborting migraine attacks, without causing cardiovascular side-effects. We investigated the efficacy of 250 mg i.v. bosentan in a randomized, double-blind, placebo-controlled, clinical trial. Improvement from moderate/severe to mild/no headache at 2 h (primary efficacy measure) occurred in 5/23 (22%) of bosentan-treated and in 9/25 (36%) of placebo-treated patients (effect difference -14%; 95% CI -52%, 24%). Thus, inhibition of NPE may not predict clinical efficacy of experimental antimigraine drugs. Vasoconstrictor action may be needed.

Adult↗
PubMed1996

Dementia and 'borderline dementia' in Britain: 8-year incidence and post-screening outcomes.

Survivors from a nationally representative sample of elderly people originally screened in 1985 were reassessed in 1989 and again in 1993. On each occasion respondents were rated as cognitively impaired, borderline impaired or unimpaired (using a brief information/orientation scale), with the validity of these ratings assessed in subsequent clinical interviews. Where follow-up screening was not possible, information was derived from death certificates and hospital case-notes. Over 8 years (1985-93) the overall incidence rate per person-year at risk was 1.58%, giving age-specific rates of 0.72, 1.32, 1.63, 3.46, 2.55 and 1.41% for the age groups 65-69, 70-74, 75-79, 80-84, 85-89 and > or = 90 respectively. Of 43 individuals classified at screening as borderline impaired in 1985 and 1989, 19 were diagnosed as demented at clinical interviews conducted within 16 weeks of screening. Four-year follow-ups among the remaining 24 showed that 15 had died, while 6 showed a worsened cognitive status. Controlling for both age and sex, aggregated 4-year mortality was significantly higher among those defined at screening in 1985 and 1989 as either impaired or borderline, when compared with the unimpaired.

Aged↗
PubMed1996

Childhood vulvovaginitis and vaginal discharge in general practice.

OBJECTIVE: This study aims to examine the aetiology, clinical features and response to treatment of childhood vulvovaginitis in general practice. METHOD: A longitudinal survey of consecutive premenarchal patients presenting with vulvovaginitis and/or vaginal discharge in the course of normal consultations with a general practitioner was conducted in a semi-rural, group general practice with 11,000 patients in Plymouth, UK. Forty-two premenarchal girls with vaginal inflammation or discharge were surveyed, with main outcome measures being clinical evaluation, microbiological assessment of urine and vaginal swabs, and patients' and parents' assessments of resolution and relapse of symptoms. RESULTS: Non-specific vulvovaginitis with mixed bacterial flora, associated with poor hygiene and atrophic vaginal mucosa, was the commonest cause; specific bacteria were found in 10 out of 42 cases, including six of Streptococcus pyogenes. No candida was isolated. Treatment with topical oestrogen cream was effective only with mixed infection, oral antibiotics were effective in both mixed and single organisms. No evidence of sexual abuse nor foreign body was found. CONCLUSION: Childhood vulvovaginitis is not uncommon in general practice, is usually associated with mixed growth of faecal organisms, and is seldom due to serious causes such as sexual abuse or foreign body.

Case Management↗
PubMed1996

Inhibition of sperm-zona binding by suramin, a potential 'lead' compound for design of new anti-fertility agents.

Progress in developing new contraceptive agents, particularly for the male, is extremely slow. Here, we report on a novel property of the anti-trypanosomal drug suramin: the ability to act at the sperm-egg interface and prevent fertilization. Suramin is a polysulphonated compound that inhibits binding of capacitated mouse spermatozoa to the zona pellucida in vitro with an IC50 of 12.4 microM. The drug is only effective at the time of fertilization and is not inhibitory if gametes are pre-treated separately. Autoradiographic localization of suramin binding sites on mouse, boar and human spermatozoa shows that they are intracellular, principally in the head region. The sperm protein recognized by suramin has been identified as proacrosin which is known to interact with sulphate groups on zona glycoproteins. Zona pellucida glycoproteins do not bind suramin, suggesting that the drug blocks the ability of proacrosin/acrosin, exposed during the acrosome reaction, to mediate the secondary binding phase of spermatozoa to the zona during fertilization. Structure-based design studies have the potential to generate safe suramin mimetics that would form the basis for a new generation of non-steroidal contraceptive agents.

Acrosin↗
PubMed1996

Arterial thrombosis enhanced by an acute phase response.

Induction of an acute phase response causes changes in the levels of specific plasma proteins. Fibrinogen is elevated to approximately twice its normal concentration by trauma, inflammation, or infection. In this study, an acute phase response was induced by subcutaneous turpentine injection in rats. Twenty-four hours later, an arterial model of thrombosis was created bilaterally in the femoral arteries. Patency at 1 and 7 days postoperatively was 24% (9/38) in comparison to 56% (20/36) in control (saline-injected) rats undergoing the same thrombosis model. Fibrinogen levels were elevated in the turpentine group to 5.3 +/- 0.8 mg/ml at the time of the surgery and 7.2 +/- 0.3 mg/ml 24 hours after surgery. In contrast, the control group had plasma fibrinogen levels of 2.5 +/- 0.2 mg/ml at the time of surgery and 5.4 +/- 0.5 mg/ml 24 hours postoperatively. These findings suggest that when an acute phase reaction has been induced several hours prior to a microvascular procedure, there may be an increased risk for development of arterial thrombosis.

Acute-Phase Reaction↗
PubMed1996

Analogues of diverse structure are unable to differentiate native melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

1. The pineal hormone melatonin exerts its biological effects through specific, high affinity G-protein coupled receptors. Recently, three melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) have been cloned. Neither the cloned subtypes, nor the native receptors have yet been compared in a detailed pharmacological analysis. 2. The present study examined the structure-activity relationships of a series of 21 melatonin analogues, by comparing their potency on the pigment aggregation response in Xenopus laevis melanophores with their affinity in radioligand binding competition studies in chicken retina and sheep pars tuberalis (PT), two tissues in which melatonin is known to mediate a biological response. 3. All but four of the analogues were full melatonin receptor agonists producing a concentration-related redistribution of pigment granules in cultured Xenopus melanophores. The remaining analogues produced little pigment aggregation at 10 microM. 4. Saturation studies with 2-[125I]-iodomelatonin identified a single binding site in the chicken retina and sheep PT membranes, with a KD of 36.6 +/- 2.8 and 37.3 +/- 4.3 pM, and a maximal number of binding sites (Bmax) of 16.6 +/- 0.5, and 40.1 +/- 1.7 fmol mg-1 protein, respectively. 5. Comparison of the potency/affinity of the analogues for the binding sites gave a highly significant correlation in each case, retina/melanophore, r = 0.97 (P < 0.001, n = 17), PT/melanophore, r = 0.97 (P < 0.001, n = 17) and PT/retina, r = 0.98 (P < 0.001, n = 21). 6. Despite their large range in affinity and structural diversity these melatonin agonists were unable to distinguish between melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

Animals↗