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Biomedical subjects

J A Wilson

Publications and source records attributed to J A Wilson.

At least 145 records · Page 8Linked to original sources

Localization of O6-alkylguanine transferase in cancer susceptible cells of human female breast.

The cell type specific distribution of O6-alkylguanine-DNA-alkyltransferase (AGT) protein was assessed using immunohistochemical localization in human female breast tissue sections and biochemical quantitation of fractionated cell extracts. The results demonstrated that the AGT protein is predominantly localized in luminal epithelial and myoepithelial cells of the intralobular mammary ducts. Western blot analysis revealed that the AGT level in epithelial cell rich organoid fraction was substantially higher than the whole tissue and fibro-collagenous stromal cell fraction of the normal breast. The quantitative activity measurements confirmed the occurrence of a statistically significant 2.7-fold (P = 0.05) and 4.0-fold (P = 0.04) enriched AGT activity in extracts prepared from the organoids compared to the whole tissue homogenate and fractionated stromal cells, respectively. The results suggest that the invariably high AGT level in malignant compared to the normal breast tissue could be due to AGT accumulation in luminal epithelial and myoepithelial cell mass, increasing as a consequence of the uncontrolled proliferation and differentiation of ductal cells in invasive carcinoma.

Breast↗

Enantioseparation of 3-phenylacetylamino-2,6-piperidinedione and related chiral compounds.

This paper reports HPLC methodology for the first successful enantiomeric separations of 3-phenylacetylamino-2,6-piperidinedione (PAP), a naturally occurring peptide derivative used for inhibiting the growth of cancer tissues. The chiral separation of four related hydrolysates is also described. A commercially available tris-4-methylbenzoate cellulose (Chiralcel OJ) column was used as the chiral stationary phase, operated in the normal-phase, mode. The results demonstrated that hydrolyzed products of PAP, each of which has a carboxylic acid functionality present in its structure, eluted in a reasonable time and are enantiomerically resolved only when a trace amount of organic acid is present in the mobile phase. Different alcohols (ethanol and isopropanol) and acid additives (trifluoroacetic acid, trichloroacetic acid and acetic acid) were evaluated. In general, for the separation of the acidic enantiomers, ethanol is superior to isopropanol and stronger acids enhance the resolution more effectively. However, chiral separation of PAP could only be accomplished with isopropanol in the mobile phase and no acidic additive was needed.

Benzeneacetamides↗

Distribution of calretinin-immunoreactive septal axons in the normal and deafferented medial habenula of adult rats.

To characterize the neural circuitry and plasticity of the septohabenular pathway, the present study analyzes the distribution of calretinin-immunoreactive fibers within the normal and deafferented medial habenula (MHb) at the light and ultrastructural levels. In the adult rat, a dense plexus of calretinin-positive fibers was found throughout the entire MHb neuropil; these immunoreactive terminals formed asymmetric synaptic contacts with unstained dendritic profiles. Calretinin-positive axons that innervate the MHb originated from neurons of the ipsilateral posterior septum, specifically those of the nucleus septofimbrialis and the nucleus triangularis. Unilateral deafferentation of the MHb resulted in the complete loss of calretinin-immunostained fibers within the ipsilateral MHb after 7 days; no reduction was apparent on the contralateral side. Four weeks after unilateral MHb deafferentation, new calretinin-immunoreactive fibers were found confined to the caudal regions of the MHb, these axons again formed asymmetrical contacts with unstained dendritic profiles. No calretinin-positive axons, however, were found within the MHb at 4 weeks following bilateral deafferentation, thus suggesting that the source of these new fibers within the long-term deafferented MHb arises from the contralateral septal neurons. Supporting this idea, injections of biotinylated dextran amine into the 4-week deafferented MHb resulted in retrogradely labeled somata observed in the contralateral posterior septum. These data reveal that septal projections to the MHb, which are normally ipsilateral, respond to a unilateral deafferentation by extending contralateral fibers that cross the midline at the habenular commissure and reinnervate the caudal regions of the nucleus.

Animals↗

Evaluation of investigations to diagnose the cause of dizziness in elderly people: a community based controlled study.

OBJECTIVE: To compare the findings in dizzy elderly people with those in controls of a similar age to identify which investigations differentiate dizzy from non-dizzy patients and to design an investigational algorithm. DESIGN: Community based study of clinical and laboratory findings in dizzy and control elderly people. SETTING: Research outpatient clinic at a teaching hospital. SUBJECTS: 149 dizzy and 97 control subjects aged over 65 years recruited from a community survey and articles in the local press. MAIN OUTCOME MEASURES: Findings on physical examination, blood testing, electrocardiography (at rest and over 24 hours), electronystagmography, posturography, and magnetic resonance imaging of head and neck (125 (84%) dizzy subjects and 86 (89%) controls); hospital anxiety and depression score; responses to hyperventilation, carotid sinus massage, and the Hallpike manoeuvre. RESULTS: Blood profile, electrocardiography, electronystagmography, and magnetic resonance imaging failed to distinguish dizzy from control subjects because of the frequency of asymptomatic abnormalities in controls. Posturography and clinical assessment (physical examination, dizziness provocation, and psychological assessment) showed significant differences between the groups. A cause of the dizziness was identified from clinical diagnostic criteria based on accepted definitions in 143 subjects, with 126 having more than one cause. The most common diagnoses were central vascular disease (105) and cervical spondylosis (98), often accompanied by poor vision and anxiety. CONCLUSION: Expensive investigations are rarely helpful in dizzy elderly people. The cause of the dizziness can be diagnosed in most cases on the basis of a thorough clinical examination without recourse to hospital referral.

Aged↗

An evaluation of the effects of susceptibility changes on the water chemical shift method of temperature measurement in human peripheral muscle.

Divergencies between chemical shift measurements of temperature and directly measured values using optical sensors have been studied in vivo in human peripheral muscle with the assistance of a variety of experimental and theoretical techniques. These include the modelling of both thermal and susceptibility changes using two- and three-dimensional finite element methods, as well as the use of multi-wavelength near-infrared observations. The conclusion of these studies is that a simple temperature calibration is not accessible, with results affected by the complex response of the tissue itself.

Humans↗

Life events and difficulties in relation to the onset of globus pharyngis.

Fifty patients with a diagnosis of globus pharyngis and 33 control patients attending the same ENT clinic were interviewed using the (Royal Holloway &) Bedford College Life Events and Difficulties Schedule (LEDS). Information was elicited concerning life events and difficulties over the 12 months before globus onset, and this was compared with the experiences of the control patients for the year before symptom onset or, where appropriate, before the interview. Globus patients had significantly more severe events than the control patients throughout the year. Moreover, globus patients had significantly fewer close confiding relationships with their partners than did controls. There is evidence, therefore, for both psychological diathesis and social stress factors in the etiology of globus pharyngis.

Adult↗

The neutron therapy clinical programme at the National Accelerator Centre (NAC).

A total of 721 patients were treated in the neutron therapy programme at NAC from February 1989-March 1995 with a p(66)/Be isocentric unit. The preliminary results showed: 3-year local control and survival probabilities of 57 and 79% respectively for advanced salivary gland tumours; increased local control for twice-daily neutron therapy for advanced head and neck cancer compared with photon therapy; local control rates of 68 and 83% for locally advanced breast cancer treated with 17 and 19 Gy respectively; complete response rates of 67% for macroscopic residual soft tissue sarcomas and those with irresectable disease of less than 10 cm; complete response rate of 56% for macroscopic residual uterine sarcoma with a median follow up of 38 months; 2-year local control rate and survival of 44 and 38% respectively for advanced squamous carcinoma of the maxillary antrum; complete response rate of 38% for advanced osteosarcomas and chondrosarcomas.

Breast Neoplasms↗

3-[(Phenylacetyl)amino]-2,6-piperidinedione hydrolysis studies with improved synthesis and characterization of hydrolysates.

In an attempt to clarify ambiguities in earlier reports on the preclinical chemistry of Antineoplaston A10 (3-[(phenylacetyl)amino]-2, 6-piperidinedione; PAP), we detail herein hydrolysis studies with improved synthesis and characterization of PAP hydrolysis products, (phenylacetyl)-glutamine (PAG), (phenylacetyl)isoglutamine (PAIG), and (phenylacetyl)-glutamic acid (PAGA). Flash chromatography proved superior to extraction in the isolation of synthetic standards and hydrolysates. Synthesis of PAIG directly from commercial isoglutamine showed consistently better yields than the previously reported method. The 1H and 13C NMR and HPLC-MS data from the synthesized standards matched the data from the isolated PAP hydrolysates formed under acid and alkaline degradation conditions. Multiple quantum coherence NMR methods (HMQC and HMBC) and HPLC-MS-MS methods were applied to provide unambiguous structural assignments for key isomers PAG and PAIG. Previous PAP hydrolysis studies are shown to be reproducible, and the structures of hydrolysis products are elucidated in detail.

Antineoplastic Agents↗

Relative efficacy of organophosphorus insecticides against susceptible and resistant strains of the strike blowfly Lucilia cuprina (Calliphoridae) in New Zealand sheep.

Four groups of five Romney lambs were treated by plunge dipping with one of four registered organophosphorus flystrike preventatives. Untreated lambs acted as controls. The sheep were challenged at weekly intervals with larval implants of organophosphate-susceptible and -resistant strains of Lucilia cuprina. All four treatments provided 19-21 weeks protection against susceptible larvae but chlorfenvinphos provided the longest protection (16-17 weeks), followed by propetamphos (15-16 weeks), dichlofenthion (10-13 weeks) and diazinon (9-13 weeks), against the resistant strain.

Journal Article↗

An increase in infant cranial deformity with supine sleeping position.

Abnormalities of the occipital cranial suture in infancy can cause significant posterior cranial asymmetry, malposition of the ears, distortion of the cranial base, deformation of the forehead, and facial asymmetry. Over the past 2 years, we have noted a dramatic increase in the incidence of deformation of the occipital skull in our tertiary referral center. Our patient referral base has not changed appreciably over the past 5 years and patients have been referred from the same primary practitioner base. The timing of this increase correlates closely with the acceptance in our area of recommended changes in sleeping position to supine or side positioning for infants because of the fear of sudden infant death syndrome (SIDS). A total of 51 infants with occipital cranial deformity, with a mean age of 5.5 months at presentation, have been evaluated and treated by a single craniofacial surgeon in the 16-month period from September 1993 to December 1994. Older infants were treated with continuous positioning by the parent keeping the infant off the involved side. Younger infants and those with poor head control were treated with a soft-shell helmet. Mean timing of initial diagnosis and start of treatment was 5.5 months. Mean duration of helmet for positional treatment was 3.8 months. To date, only 3 of 51 patients have required surgical intervention, and other patients demonstrated spontaneous improvement of all measured parameters. Follow up has ranged from 8 to 24 months. We believe that most occipital plagiocephaly deformities are deformations rather than true cranio-synostoses. Despite varying amounts of suture abnormality evidenced on computed tomographic scans, most deformities can be corrected without surgery. In cases where progression of the cranial deformity occurs, despite conservative therapy, surgical intervention should be undertaken at approximately 1 year of age. The almost universal acceptance in the State of North Carolina of positioning neonates on their backs to avoid SIDS, may well increase the incidence of these deformities in the future.

Cranial Sutures↗

Cerebral perfusion defects secondary to simple craniosynostosis.

Premature fusion of multiple cranial sutures has been associated with increased intracranial pressure and the potential for mental impairment. Isolated craniosynostosis, however, has been thought to be a benign condition primarily reconstructed for aesthetic purposes. On the basis of subjective developmental improvement postoperatively, an objective radiographic analysis (single positron emission computed tomography [SPECT] was used to assess differences in cerebral perfusion in the areas compressed secondary to the fused cranial suture both before and after cranial reconstructive surgery in patients with simple craniosynostosis. Seven children with craniosynostosis, six boys and one girl (age age, 3-28 months), were enrolled in this prospective study. Six of the seven had cranial asymmetry on preoperative cranial computed tomographic scans, and one had a symmetric defect and was used as a control. Each subject had a preoperative SPECT scan approximately 3 to 5 days before the cranial reconstruction procedure and a follow-up scan 6 to 10 weeks postoperatively. Preoperative asymmetries in cerebral perfusion ranged from 0 to 30% (mean, 13%) the areas compressed secondary to the premature suture fusion. In five patients cerebral blood flow, which was asymmetric before surgery, became symmetric after craniofacial reconstruction, and no new perfusion defects were documented. The control patient and one another patient had symmetric perfusion both pre- and postoperatively. Craniosynostosis may be associated with decreased cerebral blood flow as a result of the constriction of the brain from the prematurely fused suture. The correction of asymmetric cranial single-suture synostosis is more than a cosmetic procedure in that it allows for normalization of cerebral blood flow. This difference in blood flow supports early surgical intervention to prevent any potential central nervous system compromise secondary to abnormal blood flow.

Brain↗

Stereokinetic interaction effects involving static and slowly moving identical figures.

Here a new depth effect evoked by the spatial and temporal interaction in 2-D of a slowly moving circle (optimally at 0.6 rads/sec) with an identical static circle is reported. Typically, respondents report that with increasing adjacency, commencing with separations of a few diameters, the moving circle appears in a different plane of depth to the static circle, it then usually appears to "dip" onto the static circle and after complete coincidence with it to rise away from it. This effect, together with a number of associated descriptions are commented upon, in addition to observations when viewing overlapped static circles and overlapped circles in motion, this latter stimulus condition evoking the stereokinetic effect. The authors have previously suggested that contour "sliding," which simulates motion parallax, is the key to understanding stereokinesis. The stimulus conditions giving rise to this new effect directly simulate the motion parallax information present in a retinal image.

Adolescent↗

Arteriovenous fistula as a complication of C1-2 transarticular screw fixation. Case report and review of the literature.

A case is reported of a vertebral artery-to-epidural venous plexus fistula as a complication of posterior atlantoaxial facet screw fixation. The use of transarticular screws to stabilize the C1-2 joint has become an increasingly popular fixation technique, most notably for atlantoaxial instability due to trauma or rheumatoid disease. Despite the fact that this approach is technically challenging, there have been few reports of complications associated with C1-2 transarticular fixation. Although damage to the vertebral artery is a documented hazard of transarticular fixation at this level, a symptomatic arteriovenous fistula resulting from the procedure has not been described previously. The etiology, presentation, and treatment of this unusual complication are discussed.

Arteriovenous Fistula↗