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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 235 records · Page 13Linked to original sources

Three year follow-up of a case of giant cell arteritis presenting with a chronic cough and upper limb ischaemic symptoms.

A case of giant cell arteritis presenting in an atypical fashion with respiratory and upper limb ischaemic symptoms is described. The subclavian and axillary arterial involvement is demonstrated in this case, and followed up with repeated angiographic examinations over the next 3 yr. Despite resolution of all symptoms and return of pulses and a recordable blood pressure in the ischaemic upper limb, there was no angiographic evidence of resolution of the axillary artery stenoses.

Arm↗

Biochemical characteristics of clinical and environmental isolates of Burkholderia pseudomallei.

The biochemical characteristics of 213 isolates of Burkholderia pseudomallei from patients with melioidosis and 140 isolates from the soil in central and northeastern Thailand were compared. Whereas the biochemical profiles of all the clinical isolates were similar, all soil isolates from the central area and 25% of isolates from northeastern Thailand comprised a different phenotype. This was characterised by the ability to assimilate L-arabinose (100%), adonitol (100%), 5-keto-gluconate (90%) and D-xylose (84%), but failure to assimilate dulcitol (0%), erythritol (0%) and trehalose (10%). Compared with clinical isolates, these organisms had similar antibiotic susceptibility profiles and were also recognised by a specific polyclonal antibody against B. pseudomallei. As melioidosis is rare in central Thailand, but common in the northeast, this raises the possibility that this biochemical phenotype may be less virulent, or may even represent a different species.

Anti-Bacterial Agents↗

Bioelectric response of human nasal epithelial cells to polycationic protein.

Polycationic proteins alter electrolyte transport by epithelium and endothelium, and in asthma are thought to disrupt the airway epithelium and contribute to hyperresponsiveness and airway plugging. In the present study, we used primary cultures of human nasal epithelial cells to investigate the response of respiratory tract epithelium to luminal presentation of a polycationic protein, protamine. Protamine (100 micrograms/ml) in the apical bathing solution had no significant effect on basal transepithelial resistance (Rt) but decreased short-circuit current (Isc) and hyperpolarized the apical membrane, indicating that Na+ absorption had been inhibited. Pretreating with amiloride inverted the response to protamine, resulting in an increase in Isc, depolarization of the apical membrane, and decrease in the fractional resistance of the apical membrane (fRa). The increase in Isc was inhibited by pretreatment with bumetanide. These results indicated that protamine augmented amiloride-induced Cl- secretion. Induction of Cl- secretion by bathing the apical surface in 3 mM Cl(-)-Ringer solution similarly resulted in protamine-induced depolarization of the apical membrane. Heparin precipitated protamine from solution and reversed the Isc responses. In summary, low concentrations of polycationic protein can alter electrolyte transport by human airway epithelium without desquamation, and the response is dependent on the secretory state of the tissue.

Bumetanide↗

A biomechanical study of torque and accuracy of halo pin insertional devices.

The purpose of the present study was to assess the accuracy and repeatability of the torque achieved with a variety of devices used for the insertion of halo pins. We found that equivalent devices from the same manufacturer did not reliably achieve the same torque, that the same device used by different surgeons did not reliably achieve the same torque, and that the devices achieved varying levels of accuracy and repeatability. The proportion of trials in which the achieved torque was within +/- 10 per cent of the intended torque averaged 64 per cent (range, less than 1 to 100 per cent). Our data suggest that the insertion of halo pins with use of most currently available torque-setting devices is an inherently inaccurate process.

Biomechanical Phenomena↗

Techniques for measurement of oxygen consumption rates of hepatocytes during attachment and post-attachment.

Three techniques for measuring oxygen consumption rate (OCR) of cultured cells relevant to the development of bioartificial liver devices are reported. In an oxystat apparatus, HepG2 cells immobilised on Cytodex 3 microcarriers at a concentration of 10(6) cells ml-1 had a mean OCR of 0.7 nmol s-1/10(6) cells. The OCR decreased with increasing cell density, a characteristic previously reported for other cell lines. Rat hepatocytes immobilised on single collagen layers in a flow cell and challenged with ammonia had a mean OCR of 0.59 nmol s-1/10(6) cells. A novel two-compartment oxystat system was used to determine the OCR of rat hepatocytes during the attachment phase. OCR declined from 1.0 nmol s-1/10(6) immediately after seeding to 0.7 nmol s-1/10(6) cells at nine hours. The low OCR for HepG2 reflects loss of certain oxygen dependent metabolic pathways. The OCR measured for rat hepatocytes during and post-attachment are significantly higher than those reported elsewhere and have major implications for the development of bioartificial liver devices.

Animals↗

Evidence for dissociation of histone mRNA expression from cellular proliferation in cutaneous human papillomavirus infection.

Replication of human papillomavirus (HPV) is thought to require the expression of components of the host cell DNA replication apparatus. The expression of the mRNA encoding the DNA replication-dependent histones H2B, H3, and H4 was investigated in a series of verrucae using an FITC-labelled oligonucleotide cocktail for in situ hybridization, to explore the possibility of HPV inducing the transcription of host cell histones. In contrast to normal epidermis, in which the majority of histone mRNA labelling was confined to basal cells, a bimodal distribution of histone positivity was observed in all verrucae. In addition to basal hyperproliferation-associated labelling, numerous positive suprabasal cells were found within the stratum spinosum. By contrast, in another hyperproliferative lesion, psoriasis, the labelling pattern was similar to that found in the normal controls, with characteristic basal hyperproliferation but no evidence of suprabasal labelling. The presence of HPV replication in every verruca and its absence from all controls of normal and psoriatic skin were demonstrated immunohistochemically, using a polyclonal antibody to the viral capsid proteins. It is proposed that the presence of histone mRNAs in differentiated suprabasal keratinocytes of verrucae is due to the virus turning on parts of the cellular apparatus in order for it to replicate in the absence of cellular proliferation. The results also emphasize that when assessing proliferation with in situ hybridization for histone mRNA, the possibility of HPV causing the labelling of non-proliferating cells should be considered.

Adolescent↗

Effects of benzodiazepine agonist exposure on corticotropin-releasing factor content and hormonal stress responses: divergent responses in male and ovariectomized female rats.

Benzodiazepine agonists affect endocrine responses of the hypothalamic-pituitary-adrenal axis and can antagonize many of the actions of corticotropin-releasing factor (CRF). Gender and gonad-related factors can influence both the development of tolerance to the benzodiazepines in rats and the concomitant neural adaptations associated with chronic benzodiazepine agonist exposure. This study compared changes in CRF content, corticosterone release and ACTH levels after diazepam exposure in ovariectomized female (OVX) and male rats. After treatment with diazepam for 3 days (acute) or 3 weeks (chronic), content of CRF immunoreactivity in eight brain areas and serum corticosterone were determined by radioimmunoassay in handling-habituated rats. The effects of acute and chronic benzodiazepine exposure on swim stress-induced corticosterone and ACTH release were also examined. Chronic diazepam exposure reduced stress-induced corticosterone and ACTH release in OVX, but not male, rats. Acute diazepam exposure similarly attenuated stress-induced corticosterone release in OVX rats, but did not affect ACTH release. OVX control groups had greater levels of CRF than males in several brain regions. Gender-specific alterations in CRF content after chronic diazepam exposure were observed in amygdala, locus ceruleus and median eminence. Chronic benzodiazepine agonist exposure increased CRF levels in the amygdala of OVX rats, but not males. Both chronic and acute diazepam exposure increased CRF content in the locus ceruleus of male, but not OVX, rats. These results indicate that the effects of benzodiazepine exposure on neural CRF systems are region specific and influenced by gender-related factors.

Adrenocorticotropic Hormone↗