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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 199 records · Page 11Linked to original sources

Optical sensor arrays for odor recognition.

Optical sensor arrays containing fluorescent solvatochromatic dyes immobilized in a plurality of polymers generate information-rich responses upon exposure to organic vapors. The response profiles are used to train a variety of computational networks such that subsequent exposure of the array to the vapors enables them to be classified and/or quantified. A number of strategies can be taken to enhance sensitivity and to increase sensor diversity.

Animals↗

Mutagenesis of human Mel1a melatonin receptor expressed in yeast reveals domains important for receptor function.

A yeast functional colorimetric assay was employed to test the effects of site-directed point mutations on the function of the human Mel1a melatonin receptor. Seven mutants were created in transmembrane domains III, V, and VII of the receptor to test the rhodopsin-based model of melatonin recognition. Two mutants in transmembrane domains III and VI were created to investigate the mechanisms of G protein activation in the melatonin receptor. Mutations in transmembrane domain V either potentiated agonist efficiencies (H195A) or totally abolished all responses to tested compounds (V192T+H195A). Mutation N124A in the conserved NRY motif in the end of transmembrane domain III seriously impaired receptor activation. Several mutants were found to have decreased ability to activate functional responses, reflecting the importance of these residues for receptor function. These data also suggest that activation of the receptor involves interaction of the 5-methoxy group of melatonin with the conserved histidine H195 in transmembrane domain V.

Binding Sites↗

The variation of position of the conus medullaris in an adult population. A magnetic resonance imaging study.

STUDY DESIGN: Sequential study of magnetic resonance images of the lumbar spine. OBJECTIVES: To determine the variation in position of the conus medullaris in a living adult population without spinal deformity. SUMMARY OF BACKGROUND DATA: Cadaveric studies have shown that the position of the conus medullaris in the adult most commonly is located at L1-L2. There have been several studies documenting the changing level of the conus throughout infancy and childhood, but there is no detailed study that documents the range of conus positions in a living adult population without spinal deformity. METHODS: The T1-weighted, midline, sagittal, spin-echo magnetic resonance imaging studies of 504 patients were assessed to identify the tip of the conus medullaris. This location was recorded in relation to the upper, middle, or lower third of the adjacent vertebral body or the adjacent intervertebral disc. RESULTS: The study group consisted of 231 men and 273 women with a mean age 46 years (range, 16-85 years). Most patients were being examined for low back pain. Patients with spinal deformity were excluded. The mean conus position was the lower third of L1 (range, middle third of T12 to upper third of L3). The variation in conus positions followed a normal distribution. No significant difference in conus position was seen between male and female patients or with increasing age. CONCLUSIONS: The distribution of conus location in a large adult population was shown to range from the middle third of T12 to the upper third of L3.

Adolescent↗

The value of lumbar spine magnetic resonance imaging in the demonstration of anular tears.

STUDY DESIGN: Retrospective review of magnetic resonance imaging and discography in patients investigated for low back pain before spinal fusion. OBJECTIVE: To determine the sensitivity of magnetic resonance imaging in the detection of painful anular tears manifested by the high-intensity zone. SUMMARY OF BACKGROUND DATA: Two studies have produced results showing that magnetic resonance imaging has a high specificity for the detection of painful anular tears manifested by a high-intensity zone. However, in a recent study, results showed no significant correlation between the high-intensity zone and pain reproduction. The sensitivity of magnetic resonance imaging in identifying anular tears in a symptomatic population has not been determined. METHODS: Anular tears were identified in magnetic resonance images by the presence of a high-intensity zone in the posterior anulus. The results were compared with the demonstration of painful anular tears on discogram, which has been considered the gold standard. RESULTS: The study group comprised 58 patients (31 men, 27 women; mean age 42, range 21-63 years). One hundred and fifty-two discs were injected and examined by discography, and 108 were considered degenerate. Of these, 86 had anular tears (54 posterior, 6 anterior, 26 both). Seventy anular tears were associated with concordant pain provocation. Twenty-seven high-intensity zones were identified in magnetic resonance imaging, of which 24 were associated with pain reproduction by discography. The sensitivity, specificity, positive predictive value, and negative predictive value of magnetic resonance imaging in the diagnosis of concordantly painful posterior anular tears are therefore 26.7%, 95.2%, 88.9%, and 47%, respectively. CONCLUSION: These results confirm that the high-intensity zone is a marker of a painful posterior anular tear. However, the usefulness of this sign is limited by low sensitivity.

Adult↗

Severe tiger snake envenomation in a wilderness environment.

A 44-year old bushwalker was envenomed in an isolated area late in the afternoon, and a succession of difficulties with his rescue resulted in his not reaching hospital until nearly 24 hours later. This case highlights the problems of prolonged delays before treatment for envenomation, and points to the advantages of physician-staffed emergency helicopter services carrying snake antivenoms into the field.

Adult↗

Osteoid osteoma and osteoblastoma of the spine. Factors associated with the presence of scoliosis.

STUDY DESIGN: A retrospective study of 44 museum cases of spinal osteoid osteoma or osteoblastoma and a meta-analysis using 421 additional cases from a review of the literature. OBJECTIVES: To identify the factors that are associated with the development of scoliosis in these patients. SUMMARY OF BACKGROUND DATA: Painful scoliosis is a well recognized presentation of spinal osteoid osteoma and osteoblastoma and is considered to be secondary to pain-provoked muscle spasm on the side of the lesion. Previous studies have been based on small numbers of patients that did not permit statistical validation of the reported observations. METHODS: Eight factors were assessed including: age, gender, duration of symptoms, site of lesion in the spine, vertebral level of lesion, site of lesion in the individual vertebra, type of lesion, and Cobb angle at presentation. Reports were reviewed only if the presence or absence of scoliosis could be determined. Statistical analyses initially were performed on the museum cases and then on a combination of museum cases and cases from the literature. RESULTS: Overall, 63% of subjects had scoliosis. The lesions were typically present on the concave aspect of the curve. Three cases of scoliosis from the literature involved lesions that were reported to be on the convexity. Scoliosis is significantly more common in cases of osteoid osteoma than in cases of osteoblastoma (P < 0.0001); lesions are more common in the thoracic and lumbar regions than in the cervical region (P < 0.0001), in lower cervical region than in the upper cervical region (P value = 0.0027), and they are more commonly located to one side of the midline (P < 0.0001). Age, gender, and duration of symptoms were of no significance. CONCLUSIONS: The findings support the concept that scoliosis is secondary to asymmetric muscle spasm in patients with spinal osteoid osteoma or osteoblastoma.

Adolescent↗

Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.

Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial AD kindreds were screened for mutations in PS-1, and seven different mutations were identified. Three of these were new mutations (G209V, A426P, and E120D), two were previously reported mutations in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date.

Adult↗

Expression of HIV-1 nef in yeast causes membrane perturbation and release of the myristylated Nef protein.

The human immunodeficiency virus type 1 (HIV-1) Nef protein is essential for AIDS pathogenesis, but its function remains highly controversial. During stresses such as growth in the presence of copper or at elevated temperature, myristylated Nef is released from yeast cells and, after extended culture in stationary phase, it accumulates in the supernatant as a dense membranous material that can be centrifuged into a discrete layer above the cell pellet. This material is unique to Nef-producing cells and represents a convenient source of Nef that may have application in further biological studies. Within the yeast cell, electron microscopic examination shows that Nef localises in novel, membrane-bound bodies. These data support the evidence for a role of Nef in membrane perturbation and suggest that there may be a similar localisation for myristylated Nef in HIV-1 infected cells.

Cell Membrane↗

An olfactory neuronal network for vapor recognition in an artificial nose.

Odorant sensitivity and discrimination in the olfactory system appear to involve extensive neural processing of the primary sensory inputs from the olfactory epithelium. To test formally the functional consequences of such processing, we implemented in an artificial chemosensing system a new analytical approach that is based directly on neural circuits of the vertebrate olfactory system. An array of fiber-optic chemosensors, constructed with response properties similar to those of olfactory sensory neurons, provide time-varying inputs to a computer simulation of the olfactory bulb (OB). The OB simulation produces spatiotemporal patterns of neuronal firing that vary with vapor type. These patterns are then recognized by a delay line neural network (DLNN). In the final output of these two processing steps, vapor identity is encoded by the spatial patterning of activity across units in the DLNN, and vapor intensity is encoded by response latency. The OB-DLNN combination thus separates identity and intensity information into two distinct codes carried by the same output units, enabling discrimination among organic vapors over a range of input signal intensities. In addition to providing a well-defined system for investigating olfactory information processing, this biologically based neuronal network performs better than standard feed-forward neural networks in discriminating vapors when small amounts of training data are used.

Animals↗

An analysis of radiating pain at lumbar discography.

This study aimed to identify the morphological abnormalities of the intervertebral disc, as demonstrated by lumbar discography, that are associated with pain radiation to the hip, groin, buttock or lower limb. We carried out a retrospective review of 99 consecutive lumbar discogram reports. The association of disc degeneration, annular tears (partial or full thickness) and the level of disc injected was determined with respect to the presence and pattern of radiating pain. A total of 260 discs were injected, of which 179 were considered abnormal. Posterior annular tears were demonstrated in 84 discs, anterior annular tears in 15 discs and 45 discs had both anterior and posterior tears. A significant association was identified between isolated posterior tears and the production of concordant radiating pain (P = 0.0041). No difference was identified between partial thickness posterior tears and full thickness posterior tears associated with leak of contrast medium, with regard to radiating pain. Similarly, there was no significant association between disc level injected and the pattern of pain radiation. The results indicate that pain experienced in the buttock, hip, groin or lower limb can arise from the posterior annulus of the intervertebral disc without direct involvement of the nerve root.

Adult↗

Vertebral end-plate (Modic) changes on lumbar spine MRI: correlation with pain reproduction at lumbar discography.

The vertebral end-plate has been identified as a possible source of discogenic low back pain. MRI demonstrates end-plate (Modic) changes in 20-50% of patients with low back pain. The aim of this study was to investigate the association between Modic changes on MRI and discogenic back pain on lumbar discography. The MRI studies and discograms of 58 patients with a clinical diagnosis of discogenic back pain were reviewed and the presence of a Modic change was correlated with pain reproduction at 152 disc levels. Twenty-three discs with adjacent Modic changes were injected, 21 of which were associated with pain reproduction. However, pain was also reproduced at 69 levels where no Modic change was seen. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for a Modic change as a marker of a painful disc were 23.3%, 96.8%, 91.3% and 46.5% respectively. Modic changes, therefore, appear to be a relatively specific but insensitive sign of a painful lumbar disc in patients with discogenic low back pain.

Adult↗

Envenoming and antivenom use in Australia.

Australia has a diverse and rich venomous fauna, both terrestrial and marine, including some of the most venomous species in each class. Antivenom is the principal therapy for the majority of medically significant envenomings and is currently supplied through a single source, CSL, Melbourne. Cases of envenoming reported to Australian poisons information centers (PICs) are dominated by spiderbite and insect stings, respectively accounting for 53.7% and 39.3% of all bite/sting calls. Marine animal bites/stings/poisonings account for only 4% of PIC calls in this category, while snakebites account for a mere 3% (still at least 400 calls/yr). Because most PIC calls are from the public, not doctors/hospitals, snakebite in particular is under-represented. The author has recently reviewed antivenom usage in Australia. Snakebite affects between 1,000 to 3,000 people per year, with an average annual mortality of about 2 cases. Brown snakes (genus Pseudonaja) cause the majority of deaths (and bites), with tiger snakes (genus Notechis) and taipans (genus Oxyuranus) accounting for nearly all other fatalities. Up to 500 cases require snake antivenoms each year, the majority of cases coming from rural areas of Queensland, Western Australia, New South Wales and Victoria, these being the most populated states. The wide availability of snake venom detection kits has allowed specific antivenom to be used more often, rather than polyvalent antivenom, but the latter is still used in nearly 30% of cases, suggesting underutilization of venom detection. The issue of premedication prior to antivenom remains unresolved. Antivenom usage and complication data for 1995 and 1996 will be presented. Red back spider antivenom is the most commonly used antivenom, with reports of usage being greater than for all other antivenoms combined. It is reported as being therapeutically efficacious in 94% of cases, with a single ampoule being used in 76% of cases, 2 ampoules in 18% of cases, and 3 or more ampoules in 6% of cases. Clinical experience suggests only 20% of red back spider bites require antivenom therapy. It is likely that between 5-10,000 bites occur annually.

Animals↗

Current trends in 'artificial-nose' technology.

Basic principles derived from biological olfaction, such as combining semiselective sensor arrays with pattern recognition, have been used to develop instrumentation capable of broad-band chemical detection and quantification. Commercially available instruments are useful in areas including quality control in the food, beverage and fragrance industries, environmental monitoring, chemical-purity and -mixture analysis, and medical diagnostics. Ongoing research is aimed at the development of more-advanced instruments that are smaller, cheaper, faster and more stable and reliable. These second-generation instruments are likely to find an increasing number of applications, including the on-line monitoring of fermentation and other bioprocesses.

Electronic Data Processing↗

Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes.

Multimeric soluble MHC class II molecules stably occupied with covalently attached peptides bind with appropriate specificity to T cell hybridomas and T cells from T cell receptor transgenic mice. There is a direct correlation between soluble T cell receptor affinity for monomeric MHC/peptide and level of binding of multimeric MHC/peptide to T cells. While binding of the multimeric MHC/peptide complex is proportional to T cell receptor affinity and expression level, there is little influence of T cell CD4.

Amino Acid Sequence↗

A crystallographic and molecular modeling study of butyrophenones.

The X-ray crystal structures of four butyrophenone analogues have been completed and are reported herein. These include spiperone hydrochloride (I), N-methylspiperone hydrochloride (II), pimozide (III), and fluspirilene (IV). These structures were compared to other structurally similar molecules with similar pharmacological activity. In addition, a molecular modeling study was done in order to determine the low energy conformations of these molecules. It was found that calculations of parameters that describe the molecular conformations showed that all four molecules were structurally similar. Crystallographic data: [see text]

Butyrophenones↗

Immunocytochemical staining of ovarian cyst aspirates with monoclonal antibody against inhibin.

Inhibin is a peptide hormone which is produced by ovarian granulosa cells during normal follicular development. It is important that granulosa cells are recognized in fine needle aspirates (FNAs) of ovarian cystic lesions, as this allows definite recognition of a functional cyst and exclusion of a potentially neoplastic epithelial lined cyst. Occasionally the distinction between granulosa and epithelial cells may be difficult, especially when aspirates from functional cysts are unusually cellular. In the present study, FNAs from 33 ovarian cystic lesions were immunostained with a monoclonal antibody against inhibin. Nine cases of peritoneal fluid containing malignant cells in patients subsequently confirmed to have ovarian adenocarcinoma were also stained. Where possible the cytological and immunocytochemical findings were correlated with subsequent biopsy. In most cases in which cytology suggested a functional cyst there was a strong positive staining with anti-inhibin, although occasional cases were negative. One case originally thought to contain epithelial cells stained strongly positive with anti-inhibin and on review was felt to represent a cellular functional cyst. In all other cases where cells were considered to be epithelial there was no staining with anti-inhibin. The study shows that immunocytochemical staining with anti-inhibin may be of value in confirming the presence of granulosa cells, thus establishing a diagnosis of functional cyst. Although negative staining does not exclude a functional cyst, positive staining with anti-inhibin allows exclusion of an epithelial lined cyst and may avoid unnecessary surgical intervention.

Adenocarcinoma↗