Epilepsy of the human supplementary motor area: positron emission tomography.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
S Arnold
Publications and source records attributed to S Arnold.
[Analysis of microsatellite polymorphisms in Bernese mountain dogs and Newfoundlands].
As the number of detected inherited diseases in dogs is increasing, linkage mapping offers an opportunity for the localisation of the responsible genes. In humans microsatellites are ideal markers for constructing high-resolution genetic maps. Twenty-five dog specific microsatellites which are highly polymorphic in mixed dog breeds, were tested by PCR in a group of unrelated Newfoundlands and Bernese Mountain dogs. The polymorphisms found in this two breeds were clearly lower than in the mixed breeds suggesting that only 40% of the markers tested would be useful for linkage analysis. In addition the allele frequencies and distributions differed among this two purebred but related breeds. Our data suggest that a selection for useful markers for each specific breed has to be performed prior to linkage analysis.
Animals↗
Changes in coagulation and permeability properties of human endothelial cells in vitro induced by TNF-alpha or 5,6 MeXAA.
5,6 dimethyl xanthenone acetic acid (5,6 MeXAA), an analogue of flavone acetic acid (FAA), has been shown to be more active against murine tumours than FAA. As both drugs have a vascular component in their mechanism of action similar to that observed for TNF-alpha, we have studied the effects of 5,6 MeXAA alone and in combination with TNF-alpha on endothelial function in vitro. The changes induced by the drugs on procoagulant activity and permeability were determined under tumour-simulated conditions of low oxygen tension and the presence of tumour-secreted factors. Procoagulant activity was assayed by measuring the time taken for human umbilical vein endothelial cells (HUVECs) to clot normal human plasma, increased activity resulting in reduced clotting times. HUVECs incubated under aerobic conditions were more sensitive to TNF-alpha than cells incubated at < or = 0.2% oxygen. Culture medium conditioned by the human breast adenocarcinoma cell line MDA-MB-231 strongly upregulated procoagulant activity under both aerobic and hypoxic conditions; clotting times were further reduced by TNF-alpha. Both 5,6 MeXAA and FAA potentiated the effect of TNF-alpha on normal hypoxic endothelial cells; however, under all other conditions, neither drug in combination with TNF-alpha upregulated clotting activity. The presence of tumour-secreted factors had a far greater effect on upregulating procoagulant activity than did oxygen tension. In contrast to procoagulant activity, permeability was insensitive to TNF-alpha and low concentrations of 5,6 MeXAA also caused no change in permeability.
Antineoplastic Agents↗
Effect of nitro-L-arginine on blood flow, oxygenation and the activity of hypoxic cell cytotoxins in murine tumours.
This study was an investigation into the ability of nitro-L-arginine to change blood flow, oxygenation status and the activity of hypoxic cell cytotoxic agents in two different transplanted murine tumours. The tumour models were the C3H mammary carcinoma grown in the feet of female CDF1 mice and the SaF grown on the backs of CBA mice. Treatments were carried out in restrained non-anaesthetised animals when tumours were about 100 to 200 mm3 in size. Blood flow was monitored using laser Doppler flowmetry; oxygen partial pressure (pO2) distributions were obtained with an Eppendorf oxygen electrode; and response to treatment with hyperthermia (43.5 degrees C; 30 min) and RB6145 (250 mg kg-1;i.p.) assessed using a tumour growth delay assay. Nitro-L-arginine (10 mg kg-1; i.v.) significantly reduced blood flow by around 40-60% within 15 min after injection in C3H tumour and by 30 min in the SaF. However, nitro-L-arginine had absolutely no effect on tumour pO2 measured at the time of maximal blood flow reduction in both tumour types. It also failed to enhance the response of the C3H tumour to heat, but did produce a small yet significant increase in the response of the SaF tumour to RB6145.
Animals↗
Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes.
A multichannel laser Doppler system has been used to measure microregional fluctuations in perfusion in the HT29 human tumour xenograft and in patients with advanced malignant disease. A comparison is made with previously obtained data for the SaF, a transplantable murine tumour. The 300 microns diameter probes recorded fluctuations in erythrocyte flux in tumour microregions with an estimated volume of 10(-2) mm3. Of the 66 human tumour microregions sampled, 26% showed a change in erythrocyte flux by a factor of 2 or more over the 60 min measurement period, compared with 37% of HT29 and 48% of SaF microregions. In each of the studies more than 50% of changes were completed within 20 min, although slower changes were more common in the human tumours than in the experimental systems. Within the 1 h monitoring period at least 30% of the changes were reversed (human tumours 30%, HT29 45%, SaF 31%). These findings demonstrate that microregional changes in erythrocyte flux, consistent with transient, perfusion-driven changes in oxygenation, are a feature of human malignancies as well as experimental transplanted tumours.
Aged↗
Sexual health education interventions for young people: a methodological review.
OBJECTIVES: To locate reports of sexual health education interventions for young people, assess the methodological quality of evaluations, identify the subgroup with a methodologically sound design, and assess the evidence with respect to the effectiveness of different approaches to promoting young people's sexual health. DESIGN: Survey of reports in English by means of electronic databases and hand searches for relevant studies conducted in the developed world since 1982. Papers were reviewed for eight methodological qualities. The evidence on effectiveness generated by studies meeting four core criteria was assessed. Judgments on effectiveness by reviewers and authors were compared. PAPERS: 270 papers reporting sexual health interventions. MAIN OUTCOME MEASURE: The methodological quality of evaluations. RESULTS: 73 reports of evaluations of sexual health interventions examining the effectiveness of these interventions in changing knowledge, attitudes, or behavioural outcomes were identified, of which 65 were separate outcome evaluations. Of these studies, 45 (69%) lacked random control groups, 44 (68%) failed to present preintervention and 38 (59%) postintervention data, and 26 (40%) omitted to discuss the relevance of loss of data caused by drop outs. Only 12 (18%) of the 65 outcome evaluations were judged to be methodologically sound. Academic reviewers were more likely than authors to judge studies as unclear because of design faults. Only two of the sound evaluations recorded interventions which were effective in showing an impact on young people's sexual behaviour. CONCLUSIONS: The design of evaluations in sexual health intervention needs to be improved so that reliable evidence of the effectiveness of different approaches to promoting young people's sexual health may be generated.
Adolescent↗
Microparticle driven by parametric and random forces: Theory and experiment.
Explore the source record for details and available documents.
Journal Article↗
Changes in cognitive performance in children with spastic diplegic cerebral palsy following selective dorsal rhizotomy.
Children with cerebral palsy who receive selective dorsal rhizotomy (SDR) for treatment of spasticity may show suprasegmental changes in upper limb function and control of speech musculature. Anecdotal reports suggest that supra-segmental effects may extend to cognitive functions such as attention and language. This study examined the performance of 16 children with spastic diplegic cerebral palsy on tests of visual attention and other cognitive functions 1 day prior to and 6 months following SDR. Children undergoing SDR were compared with 9 children with spastic diplegia, matched for severity of cerebral palsy and amount of therapy, who did not receive SDR, and 24 age- and sex-matched normal children tested at initial and 6-month follow-up sessions. Children with cerebral palsy treated with SDR showed disproportionately greater improvement in specific attentional and cognitive operations than either of the other groups. These results document cognitive changes following SDR which heretofore were reportedly anecdotally. This improvement may be due to improved mood, reduced physical discomfort, increased therapeutic intervention, or possible cortical effects of SDR.
Attention↗
Structural relationship between the primary crystal formations and the matrix macromolecules in different hard tissues. Discussion of a general principle.
For many years we have investigated the earliest crystal formations of different developing hard tissues (matrix vesicle, bone, dentine, enamel, etc.) by different electron microscopic measurements. It was observed that primarily Ca-phosphate (apatite) "chains," composed of nanometer sized particles (dots, islands), exist, which coalesce rapidly to needles. For the mineralization of collagen (e.g., bone, dentine) the center to center distances between the dots in the mineral chains represent the distances between nucleating sites, so-called "active sites" of collagen which bind primarily Ca for a subsequent nucleation. For the mineralization of noncollagen macromolecules (e.g., enamel) the same principle of mineral nucleation at such "active sites" exists being represented indirectly by corresponding center to center distances between the dots in the mineral chains.
Apatites↗
Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4.
Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.
Amino Acid Sequence↗
Investigation of the early mineralisation on collagen in dentine of rat incisors by quantitative electron spectroscopic diffraction (ESD).
The earliest crystallites in dentine appear as chains of "dots" in ultra-thin sections viewed by transmission electron microscopy. These dots rapidly coalesce along the longitudinal directions of the collagen microfibrils to form needle-like structures that coalesce preferentially in lateral directions to form ribbon-like or plate-like crystallites. This morphological interpretation is supported by line-scans of the corresponding zero-loss filtered electron spectroscopic diffraction patterns, which demonstrate the crystalline structure of the dentine mineral (apatite). The intensity ratio of the Debye-Scherrer rings of the characteristic Bragg-reflections (002 to 300, together with 1 or 2 unresolved reflections) shows a maximum in the region of early chain-like and needle-like crystallites, decreasing with maturation of the dentine mineral to the ribbon-plate-like crystallites. Detailed investigations using line-scans of the zero-loss filtered electron spectroscopic diffraction patterns through the dentine zone show that the intensity ratio found near the mineralisation front is repeated 3-5 times at distances of about 10-20 microns. This may represent a circadian pattern of mineralisation corresponding to light microscopically visible incremental lines in dentine.
Animals↗
Substance use among the mentally ill: prevalence, reasons for use, and effects on illness.
Substance use among a random sample of mentally ill, community-based patients was examined. Current use was found to have declined substantially from a high lifetime prevalence, and a family history of substance abuse was associated with moderate to heavy use. No association was found between heavy substance use and elevated psychopathology, hospitalization, or medication noncompliance. Hospital admissions and some symptoms were less prevalent among users preferring marijuana.
Adolescent↗
Parametrically driven microparticle in the presence of a stationary zero-mean stochastic source: Model for thermal equilibrium in the Paul trap.
Explore the source record for details and available documents.
Journal Article↗
Skin cancer: helping those who need it most.
Explore the source record for details and available documents.
Humans↗
Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation.
Interleukin 4 (IL-4) exerts a decisive role in the coordination of protective immune responses against parasites, particularly helminths. A disregulation of IL-4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human IL-4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the IL-4 receptor (IL-4R(ex)). In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T-cell proliferation and B-cell CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type). IL-4 variants affected at site 2 exhibited partial agonist activity during T-cell proliferation; however, they still bound with high affinity to IL-4R(ex). [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO J., 11, 3237-3244)]. These findings indicate that IL-4 functions by binding IL-4R(ex) via site 1 which is constituted by residues on helices A and C.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Mechanisms of ventricular arrhythmia during amitriptyline toxicity.
The ventricular tachycardia (VT) caused by high-dose tricyclic antidepressants has been hypothesized to be due to a quinidinelike effect with generation of repolarization abnormalities and afterdepolarizations. To test this hypothesis further, we infused amitriptyline in a graded fashion (0.5-1 mg/kg/min) in 23 chloralose-anesthetized dogs during endocardial monophasic action potential (AP) recording and continuous hemodynamic monitoring. Three groups of dogs were studied: group A (n = 5), crushed sinus node and fixed atrial pacing at 100 beats/min; group B (n = 12), crushed sinus node and fixed atrial pace plus intermittent accelerated pacing to mimic group C; and group C (n = 6) intact sinus node and unimpeded sinus tachycardia. Amitriptyline infusion induced VT in no (0 of 5) group A dogs, all (12 of 12) group B dogs during accelerated pacing, and 83% (5 of 6) of group C dogs. Dogs with VT had significantly higher heart rates (HR 184.8 +/- 39.3 beats/min) as compared with dogs without VT (115.2 +/- 12.5 beats/min, p = 0.0015). There was a strong positive correlation between the last RR coupling interval to the first VT interval (r = 0.85; p = 0.0033). Amitriptyline infusion caused rate-dependent QRS prolongation in each group, especially group C (p < 0.001). Action potential duration at 50% and 90% of repolarization (APD50, APD90) showed a biphasic response with progressive shortening followed by prolongation as amitriptyline serum concentrations increased. Afterdepolarizations were not detected from any monophasic AP recording, even in dogs with VT.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Morphology and stereology of the female canine urethra correlated with the urethral pressure profile.
Perfusion-fixed urethrae of five sexually intact nulliparous female beagles in anestrus, between 2 and 3 years of age, were morphologically and morphometrically investigated. Absolute and relative volumes of different tissue components were stereologically estimated per urethral quarter. A discrete smooth muscle sphincter could neither be identified in the bladder neck nor in the urethra. However, the circularly arranged smooth muscle fibers in the proximal half of the urethra were regarded as being capable of sphincteric function. The connective tissue, composed of collagenous and longitudinally orientated numerous elastic fibers, accounted for the most predominant constituent. It comprised 77.3 to 78.2% of the total volume in the proximal three urethral quarters. The vascular plexus was most prominently developed in the proximal two urethral quarters, and its relative and absolute volumes significantly exceeded those of the third quarter. The discovered direct connections between small arteries and the sinusoids of the vascular plexus emphasize its importance as a major contributory component to urinary continence. The striated musculus urethralis was essentially confined to the distal half of the urethra and most strongly developed in the fourth quarter, where it surrounded the urethra transversely at its ventral and lateral aspects. The caudal muscle fibers continued dorsally to the vagina. A transitional epithelium bounded the urethral lumen. Its superficial cell layer progressively flattened towards the external urethral orifice, changing into a stratified squamous lining as also seen in the vestibulum. Recorded pressures, or pressure changes, could neither be correlated with volumes nor with morphology of particular tissue elements in the different urethral quarters.
Animals↗
Reproducibility of urethral pressure profiles in clinically normal sexually intact female dogs by use of microtransducer catheters.
Urethral pressures profiles (UPP) obtained by use of microtransducer catheters were determined in 8 anestrous sexually intact female Beagles during general anesthesia. A UPP study consisted of 3 consecutive recordings, and 4 UPP studies were repeated at an interval of 5 days in each dog. Maximal urethral pressure (cm of H2O), bladder pressure (cm of H2O), and anatomic urethral length (cm) were recorded. Maximal urethral closure pressure (cm of H2O) was calculated. Mean +/- SD (for all measurements) maximal urethral closure pressure was 12.8 +/- 5.6 cm of H2O (range, 2.4 to 25.2 cm of H2O). Maximal urethral closure pressure was significantly (P < 0.05) decreased during the first recording period (11.4 +/- 5.8 cm of H2O), compared with the second (13.0 +/- 5.2 cm of H2O) or third (14.1 +/- 5.7 cm of H2O) recording periods within a UPP study (3 consecutive recordings). Mean maximal difference in urethral closure pressure during a single UPP study was 4.8 +/- 2.4 cm of H2O. Significant difference in maximal urethral closure pressure was not observed between studies. Mean (for all measurements) anatomic urethral length was 6.2 +/- 0.9 cm (4.1 to 7.8 cm). Anatomic urethral length was significantly (P < 0.05) less during the first recording period (6.1 +/- 0.9 cm), compared with values for the second and third periods (6.3 +/- 0.9 cm, 6.4 +/- 0.9 cm respectively). Anatomic urethral length for time 3 was significantly (P < 0.05) less than the value for time 1 (5.8 +/- 0.7 cm vs 6.6 +/- 0.8 cm).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗