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Biomedical subjects

J Wild

Publications and source records attributed to J Wild.

At least 37 records · Page 2Linked to original sources
PubMed1998

The hepatitis B virus e antigen cannot pass the murine placenta efficiently and does not induce CTL immune tolerance in H-2b mice in utero.

The function of the secretory core gene product (HBeAg) of the human hepatitis B virus is unclear. It has been discussed that this protein may be passed from the mother to the fetus, where it might induce immunologic tolerance. Here we have examined this possibility with transgenic mice expressing high levels of HBeAg. Analysis of serum samples obtained from nontransgenic fetuses which developed in HBeAg-positive mothers showed no evidence that the HBeAg can pass the placenta. Moreover, direct examination of the HBeAg- and HBcAg-specific cytotoxic T-cell immune response of H-2b mice which developed in either transgenic or nontransgenic mothers revealed no indication that mice which could have been exposed to the HBeAg in utero become tolerant to HBV core gene products. From these data we conclude that the placenta represents an efficient barrier for HBeAg transfer and that the HBeAg does not tolerize cytotoxic T cells, at least in mice of the H-2b haplotype.

Animals↗
PubMed1998

Similar as well as distinct MHC class I-binding peptides are generated by exogenous and endogenous processing of hepatitis B virus surface antigen.

Murine MHC class I-restricted cytotoxic T lymphocyte (CTL) responses can be primed by exogenous as well as endogenous hepatitis B surface antigen (HBsAg). Immunodominant CTL-defined epitopes of this viral envelope protein are the Ld-binding 12-mer S28-39 peptide IPQSLDSWWTSL in H-2d mice, and the Kb-binding 8-mer S208-215 peptide ILSPFLPL in H-2b mice. We tested if CTL recognizing these epitopes can be primed in vivo by HBsAg delivered as either an exogenous antigen (native HBsAg lipoprotein particles), or an endogenous antigen (plasmid DNA encoding HBsAg). Primed T cells were restimulated in vitro prior to the cytotoxicity assay with cells presenting the H-2 class I-binding epitopes generated by either exogenous or endogenous processing of HBsAg. The data indicate that the Ld-binding peptide S28-39 is generated during exogenous as well as endogenous processing of HBsAg. In contrast, the Kb-binding peptide S208-215 is generated during exogenous but not endogenous processing of HBsAg. Hence, some but not all MHC class I-binding, immunogenic peptides are generated during endogenous and exogenous processing of HBsAg but there also exists a repertoire of immunogenic peptides of viral origin that is only revealed after exogenous processing of viral proteins.

Animals↗
PubMed1998

A systematic study of the lactate lineshape in PRESS-localized proton spectroscopy.

J-coupled resonances such as lactate exhibit complex behavior in PRESS-localized spectroscopy. Polarization transfer effects due to nonideal slice profiles can lead to substantial errors in quantification unless recognized. In this work, it is shown how these effects can be predicted in a systematic way given the sequence timing and the RF pulse envelopes. Experimental results are presented to highlight the problems of working at the popular echo time of 2/J.

Humans↗
PubMed1998

[Interdisciplinary group therapy for fibromyalgia].

Fibromyalgia is present in 2% of the general population and leads to impairment by chronic pain and fatigue. It does not improve without therapy directed at the symptoms of fibromyalgia. We describe our interdisciplinary group treatment for patients with fibromyalgia. They received a physical examination, ergometry and psychometric tests both at admission and before discharge, and they were questioned to the degree and localization of their pain, to fatigue, sleeping disorders and functional symptoms. Therapy included information about fibromyalgia, learning of coping strategies, relaxation and endurance training. Our results show that our interdisciplinary group treatment is effective for fibromyalgia and improves anxiety, depression and well being after a period of 5 weeks of in-patient rehabilitation.

Adaptation, Psychological↗
PubMed1998

Polyvalent vaccination against hepatitis B surface and core antigen using a dicistronic expression plasmid.

Genes encoding the small (S) surface antigen (HBsAg) or the core (C) antigen (HBcAg) of hepatitis B virus (HBV) were cloned into the monocistronic expression vectors pCMV-1 or pCMV-2 under HCMV-IE promoter control. Coding fragments of these vectors were fused to generate a dicistronic expression construct pCMV/C-S in which the antigens HBcAg and HBsAg are coexpressed. Transient in vitro transfection studies demonstrated that HBcAg and HBsAg are coexpressed from this construct. Vaccination of mice of different H-2 haplotypes with mono- or dicistronic expression plasmids induced humoral and cellular immune responses to HBsAg and the HBcAg. In particular, intramuscular injection of 'naked' dicistronic plasmid DNA into mice elicited polyvalent humoral and cytotoxic T lymphocyte responses to HBsAg and HBcAg. The studies demonstrate that dicistronic expression plasmids are a novel way to construct a polyvalent vaccine against HBV that comprises HBsAg and HBcAg as immunogens.

Animals↗
PubMed1998

Cerebral circulation in sleep: vasodilatory response to cerebral hypotension.

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.

Animals↗
PubMed1998

Randomised double blind trial of morphine versus diamorphine for sedation of preterm neonates.

AIMS: To compare the safety and effectiveness of morphine and diamorphine for the sedation of ventilated preterm neonates in a double blind, randomised trial. METHODS: Eighty eight babies were allocated to receive either morphine (n = 44) or diamorphine (n = 44) by bolus infusion (200 or 120 mcg/kg, respectively, over two hours), followed by maintenance infusion (25 or 15 mcg/kg/h, respectively) during the initial phase of their respiratory disease. Serial monitoring of physiological, behavioural, and biochemical variables over the first 24 hours of the infusions was performed. Longer term outcomes were also monitored. RESULTS: Morphine, but not diamorphine, was associated with a mean (SEM) decrease in mean arterial blood pressure of 2.2 (1.0) mm Hg (p = 0.05) over the initial loading infusion. Physiological (blood pressure variability) and behavioural measures of sedation (clinical assessment and sedation scoring) indicated that the two drug regimens were equally effective after 24 hours, but the sedative effects of diamorphine were evident more quickly than those of morphine. Both regimens significantly reduced plasma adrenaline concentrations over the first 24 hours of the infusions. No significant differences in mortality, ventilator days, chronic lung disease or intracranial lesions were noted. CONCLUSIONS: Both drug regimens reduce the stress response to ventilation in preterm neonates. However, diamorphine's more rapid onset of sedation and morphine's hypotensive tendency suggest that diamorphine is preferable for the sedation of mechanically ventilated preterm neonates.

Anesthesia↗
PubMed1998

Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: relation between time from onset, neurological deficit, metabolite abnormalities in the infarct, blood flow, and clinical outcome.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy (MRS) can be used to study metabolite abnormalities in the brains of stroke patients. We have used it to examine the relations between the metabolites in the infarct (N-acetylaspartate [NAA] and lactate) and the time lapse from stroke to MRS, the presenting neurological deficit, infarct size and swelling (on MRI), blood flow to the infarct (estimated by transcranial Doppler ultrasound), and clinical outcome. METHODS: Patients with symptoms of a moderate to large cortical infarct underwent serial proton MRS (Siemens 1.5 Magnetom) within 4 days, from 5 to 10, and from 11 to 35 days after the stroke. A long echo time PRESS single voxel or chemical shift imaging acquisition was used. Transcranial Doppler ultrasound was performed daily in the first week and twice per week thereafter until the final MRS. Clinical features and baseline demographic data were collected independently by a stroke physician and 6-month outcome by postal questionnaire. RESULTS: Fifty patients underwent at least 1 MRS examination. Reduced NAA in the infarct within the first 4 days was related to the clinical stroke syndrome, more extensive infarction, more severely reduced blood supply to the infarct, and the presence of lactate. The presence of lactate was related to large infarcts and reduced NAA. Swelling in the infarct was most closely associated with large infarcts and reduced blood supply but not reduced NAA or the presence of lactate. Clinical outcome was most closely related to the extent of the infarct (more than to the clinical syndrome)--the larger the infarct the worse the outcome--but not to the metabolite concentrations alone. CONCLUSIONS: The reduction in NAA (but not the presence of lactate) in a visible infarct was related to the reduction in blood flow to the infarct, which in turn was related to infarct extent and clinical outcome.

Acute Disease↗
PubMed1998

Major vasodilator role for nitric oxide in the gastrointestinal circulation of the mid-gestation fetal lamb.

As nitric oxide (NO) may be a particularly important vasodilator in early life, we investigated its role in the regulation of the gastrointestinal (GI) circulation at mid-gestation. Cardiac output and GI blood flow were measured by the radioactive microsphere technique in eight chronically instrumented and unanesthetized mid-gestation fetal sheep. Mean arterial pressure (MAP), heart rate, blood flow, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, Nomega-nitro-L-arginine (L-NNA) at doses of 10 and 25 mg/kg. In response to L-NNA infusion, MAP increased (p < 0.01) and combined ventricular output decreased (p < 0.001). GI blood flow and oxygen delivery decreased and vascular resistance increased in the stomach and all segments of the small and large intestine (all p < 0.001). The greatest reduction in blood flow was in the small intestine (p < 0.01) and the basal differential pattern of small intestinal blood flow exceeding large intestinal flow was completely abolished. These changes were much greater than those previously described in late-gestation fetuses. Our results suggest that, at mid-gestation, NO plays a major role in the regulation of blood flow and vascular tone across all segments of the fetal GI tract, with its effects being more pronounced than later in development.

Animals↗
PubMed1997

Risk of neural tube defect-affected pregnancy is associated with a block in maternal one-carbon metabolism at the level of N-5-methyltetrahydrofolate:homocysteine methyltransferase.

The disposition of whole blood mono-to hexaglutamyl methylfolate and plasma homocysteine (HCY) was used to evaluate potential lesion sites in one-carbon metabolism which could be responsible for neural tube defect(NTD)-affected pregnancies. An isocratic high-performance liquid chromatographic system (HPLC) with photodiode array detection was used to quantify and speciate whole-blood methylfolate into mono-, di-, tri-, tetra-, penta-, and hexaglutamate forms. This technique was also used with off-line radioassay to identify nonmethyl whole-blood folates. Isocratic HPLC with fluorescence detection was used to quantify SBDF derivatized homocysteine in plasma. The study investigated blood from 11 women who had experienced a previous NTD-affected pregnancy and 11 controls of similar age and social class. No subjects were pregnant. HCY levels were significantly higher in NTD subjects (P = 0.0486, 95% CI-2.799,0.001 using the Mann-Whitney test), as was the ratio of known intracellular (tri-to hexaglutamyl) methylfolate compared to extracellular (mono- and diglutamyl) methylfolate (P = 0.0062 95% CI-0.543, 3.862 using the Mann-Whitney test). Vitamin B12, red cell folate, circulating total methylfolate, and circulating mono-to hexaglutamyl methylfolates showed no difference between population groups. The disposition between individual and cumulative glutamate chain lengths of methylfolate showed significant trends which differed between population groups: (i) total blood methylfolate (Glu1-6) appears to be utilized by N-5-methyltetrahydrofolate:homocysteine methyltransferase (MS) in control blood but not NTD blood, where it appears to accumulate following a 45-min incubation; (ii) whole-blood hexaglutamyl methylfolate (5CH3-H4PteGlus) becomes a larger proportion of the total blood methylfolate in NTD than in control populations; and (iii) the intermediate glutamate chains of methylfolate (Glu1-5) remain relatively constant as 5CH3-H4PteGlu6 accumulates in NTD but appear to increase linearly with 5CH3-H4PteGlu6 in controls. The significant elevation of HCY in the NTD population is associated with the increasing proportion of 5CH3-H4PteGlu6 relative to the total methylfolate, since, when corrected for HCY level, the proportion of 5CH3-H4PteGlus to total methylfolate is similar in NTD and control populations. These trends are consistent with a defect at the level of vitamin B12 dependent MS which "traps" folate at the 5CH3-H4PteGlus level.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

[Bolus tracking and NaCl bolus in biphasic spiral CT of the abdomen].

PURPOSE: To optimise injection parameters in helical CT of the abdomen with individual bolus tracking and subsequent NaCl bolus injection. To investigate the effect of bolus tracking on image quality in the abdomen. METHODS: Patients were randomised into three examination protocols and underwent biphasic helical CT (Hi-Speed Advantage, GE). The effect of NaCl bolus on duration of aortic enhancement was investigated. Contrast enhancement in parenchyma and vessels was examined. The influence of body mass index, injection flow and contrast material volume on enhancement was evaluated. RESULTS: Subsequent injection of NaCl provided significant extension of contrast enhancement in the aorta. Optimal image quality for pancreas and abdominal arteries was achieved in the arterial phase and for liver, spleen, kidneys and abdominal veins in the portal venous phase. Body mass index, injection flow and contrast material volume showed a significant influence on the time intervals resulting from bolus tracking. CONCLUSION: Individual bolus tracking with subsequent injection of 20 ml NaCl bolus optimises intravenous contrast application.

Aorta, Abdominal↗
PubMed1997

Vaginal delivery is associated with occult disruption of the anal sphincter mechanism.

Childbirth is thought to be an important cause of pelvic floor dysfunction. Heretofore, this has been thought due to pudendal denervation. Endovaginal sonography allows thorough assessment of the anorectum and in this study was used to assess nulliparous women and women before and after delivery. Two groups were studied. Thirty-two nulliparous subjects without complaints of incontinence were studied once. Thirty-four pregnant women were studied before and after delivery. Endovaginal sonography was used to assess integrity of internal and external anal sphincters, thickness of the levator bundle, internal and external sphincters, anal length, and the angle between the levator bundles. Delivery was associated with disruption of the internal and external sphincters. No nulliparous women (nonpregnant or pregnant) had sphincter disruption demonstrated. Episiotomy in the index delivery was associated with increased thickness in the external sphincter and a smaller angle between the levator bundles. Vaginal delivery is associated with occult disruption of the anal sphincters.

Adult↗
PubMed1997

DNA vaccination with plasmids encoding the intracellular (HBcAg) or secreted (HBeAg) form of the core protein of hepatitis B virus primes T cell responses to two overlapping Kb- and Kd-restricted epitopes.

Plasmid DNA encoding either the intracellular form HBcAg or the secreted form HBeAg of the core protein of hepatitis B virus (HBV) was injected into the muscle of H-2b, H-2d or F1b x d mice. Serum antibody responses and class I-restricted cytotoxic T lymphocyte (CTL) responses to HBcAg/ HBeAg were detected in all mice tested. Stable murine H-2b and H-2d transfectants that express either intracellular HBcAg were secreted HBeAg were constructed. With these cell lines we restimulated in vitro T cells primed in vivo and detected their specific cytolytic reactivity against naturally processed peptides. CD8+ CTL responses elicited by DNA vaccination with plasmids encoding HBcAg or HBeAg were specific for the (previously described) Kd-binding HBcAg93-100 peptide MGLKFRQL in H-2b mice or the (newly defined) Kd-binding HBcAg87-96 peptide SYVNTNMGL in H-2d mice. The overlapping epitopes span residues 87-100 of HBcAg, and are present on HBcAg and HBeAg. CTL responses were equally well elicited in vivo by injecting HBcAg- or HBeAg-expressing plasmid DNA, and CTL efficiently recognize in vitro HBcAg- and HBeAg-expressing transfectants. DNA vaccination of F1b x d mice with HBcAg- or HBeAg-expressing plasmid DNA primed CTL populations that recognized the Kb- or the Kd-restricted epitope. Both Kb- and Kd-binding peptides are thus generated from cytoplasmic/nuclear HBcAg and secreted HBeAg. These data make it unlikely that the appearance of HBeAg-negative variants during chronic HBV infection results from CTL-driven selection. DNA vaccination is an efficient technique to prime CTL responses against overlapping epitopes present on intracellular or secreted viral protein antigens.

Animals↗
PubMed1997

Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity.

Little is known about the prevalence of cerebral palsy (CP) within ethnic subgroups born in Britain. The Yorkshire Regional Cerebral Palsy Register has ascertained all cases of CP in children born within the Regional Health Authority boundary in 1985 to 1987 inclusive and diagnosed by 5 years of age. Birth registrations recorded by ethnic subgroups allowed us to determine the prevalence of CP within the Bradford District Health Authority (BDHA) boundaries by Asian and non-Asian ethnic subgroups. All the children with CP in BDHA were examined by one individual and careful family pedigrees recorded. We noted that BDHA had a high prevalence of CP; 3.87 to 4.16 per 1000. The prevalences in the non-Asian and Asian populations were 3.18, and between 5.48 and 6.42, per 1000, respectively. This difference was statistically significant (P = 0.03). First cousin marriages occurred in 15 of the 39 Asian families (51.7%) and nine of these families had another first or second degree family member with a similar type of CP to the index child. There was no consanguinity in the non-Asian families. These data highlight the increased need for services in some ethnic populations living in Britain and the likely genetic aetiology of a significant proportion of cases of CP in Asian families.

Cerebral Palsy↗
PubMed1997

A new Diamentor for measuring kerma-area product and air-kerma simultaneously.

The new M4KDK Diamentor (PTW-Freiburg) for measuring the air-kerma-area product (KAP) and air kerma (AK) simultaneously was evaluated. The special design of the Diamentor chamber influences the variation of the calibration factor with respect to the field size somewhat differently to what is the case with the classic Diamentor. It is therefore recommended that calibration be performed for a larger field size. If the M4KDK Diamentor is calibrated for a field size of 3.8 cm x 3.8 cm (at the chamber), an uncertainty in the AK value of better than 15% for a field size larger than the calibration field, can be expected. The influence of backscattered radiation on the calibration factor is equivalent to that for the classic Diamentor chamber. The variation in response in accordance with tube potential, is also comparable with that of the classic Diamentor. Dramatic changes in response have to be expected if additional filters are introduced in close proximity to the Diamentor chamber.

Biophysical Phenomena↗
PubMed1997

[Clinical use of software-controlled x-ray tube modulation with "Smart-Scan" in spiral CT].

PURPOSE: The modulation of tube current during 360 degree-rotation for equalization of local differences in absorption is able to reduce patient exposure in spiral-CT. The impact on CT investigations of thorax, abdomen and pelvis and the influence of patient geometry within the slice on the decrease of tube current are evaluated. METHODS: 300 spiral-CT's were performed on a HiSpeed Advantage scanner (GE) using a software-triggered modulation of tube current ("Smart-Scan"). The local absorption was measured in the 100 central channels of 2 scoutiviews (lateral and a.p.) and used for anatomical adapted modulation. The reduction of exposure as well as the height and width of the body cross-section were measured in reference slices of 100 thorax, 100 abdomen and 100 pelvis examinations. RESULTS: The use of "Smart-Scar" enables a decrease of tube current of 7% in thorax, 6% in abdomen and 11% pelvis. There is a significant correlation between the height and width of body cross-section and the reduction of exposure for examinations of thorax and abdomen, but not of the pelvis. CONCLUSION: Independent of patient geometry the clinical use of "Smart-Scan" achieves the pelvis. Anatomical regions with an oval body cross-section show a decrease of x-ray tube current, too.

Adult↗