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Biomedical subjects

T J Hall

Publications and source records attributed to T J Hall.

At least 73 records · Page 4Linked to original sources
PubMed1991

A comparison of the effects of inhibitors of carbonic anhydrase on osteoclastic bone resorption and purified carbonic anhydrase isozyme II.

We have assessed the effects of five sulfonamides with widely varying inhibitory activity for carbonic anhydrase (CA) in the bone slice assay using disaggregated rat osteoclasts (OCs), and in the Maren assay where the catalytic activity of purified CA isozyme II (CA II) was measured. There was an excellent correlation between the relative potencies of the compounds in the two assays: ethoxzolamide (ETH) greater than acetazolamide (AZ) greater than M&B 21659 greater than M&B 9811 greater than M&B 7973. In the bone slice assay, ETH and AZ were found to be the most potent inhibitors of OC bone resorption, with IC50 values of 0.09 and 0.8 microM, respectively (from plan surface area of bone resorbed). These results support previous observations showing that OCs use CA II to generate protons during bone resorption and that CA II activity is essential for OCs to be able to resorb bone.

Acetazolamide↗
PubMed1991

Identifying acoustic scattering sources in normal renal parenchyma from the anisotropy in acoustic properties.

Acoustical and histological properties of dog kidney parenchyma are examined in vitro to determine sources of acoustic scattering in the normal kidney. The speed of sound, attenuation, backscatter, effective scatterer size and scattering strength were measured within the frequency range 1-15 MHz and at eight angles of incidence with respect to the predominant nephron orientation. Significant angular dependence, or anisotropy, was observed in backscatter coefficient and scattering strength estimates; attenuation was found to be weakly anisotropic. All three parameters, each measured at 19 degrees C, exhibited values that were maximum for perpendicular incidence and minimum for parallel incidence. Speed of sound and scatterer size estimates were observed to be independent of scanning angle. Comparisons between these data for renal cortex and histological observations suggest that the glomerulus is the principal scatterer at low frequencies, and renal tubules and blood vessels at high frequencies.

Animals↗
PubMed1991

Assessment of the relative skin sensitizing potency of 3 biocides using the murine local lymph node assay.

The relative skin-sensitizing potency of 3 biocides, 5-chloro-2-methyl-4-isothiazolin-3-one (the major active ingredient in Kathon CG), 1,2-benzisothiazolin-3-one and 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, was assessed using the murine local lymph node assay. Potency was ranked according to the lowest dose of material which, following epicutaneous exposure, induced a significant proliferation of T lymphocytes in the draining lymph nodes. The results showed that 5-chloro-2-methyl-4-isothiazolin-3-one was able to induce proliferative activity at significantly lower dose levels than the other 2 biocides and that it may therefore be a more potent skin sensitizer.

Animals↗
PubMed1991

Improved resolution backscatter coefficient imaging.

This paper reports the extension of a method for imaging acoustic backscatter coefficients that allows for greater spatial resolution in the resulting images. This is done by using a broad-band excitation pulse and short-duration time gates in the analysis. The images produced had better spatial resolution than the previously reported technique [Ultrasonic Imaging 10, 121-138]. Furthermore, the pixel values were based upon quantitatively accurate backscatter coefficients at given spatial locations. The paper also discusses the additional computational requirements of greater spatial resolution and proposes a least-squares fit to a smoothly varying set of sparse data to generate the data points in between.

Ultrasonics↗
PubMed1991

Development of a co-culture system with induced HepG2 cells and K562 cells for examining drug metabolism in vitro. Studies with cyclophosphamide, ondansetron and cisplatin.

We have established a cell co-culture system for assessing potential cytotoxic effects of drugs and their metabolites in vitro. Human hepatoma cells (HepG2) were cultured for 7 days in modified Earle's medium in order to induce their drug metabolising (primarily mixed function oxidase) enzymes. K562 human erythroleukemic cells in Transwells, were used as indicator cells for the cytotoxic effects of cyclophosphamide (CYP) and Ondansetron (OND) and/or their metabolites, produced by induced HepG2 cells in the co-cultures. CYP was found to be approximately 1000 times more toxic to K562 cells when cultured in the presence of induced HepG2 cells. OND, a selective 5-HT3 receptor antagonist which is used as an anti-emetic during chemotherapy, was not found to be cytotoxic in the co-cultures at concentrations as high as 100 microM. Since OND has been particularly useful in relieving vomiting induced by cisplatin (cisPt) chemotherapy, we also examined the effect of cisPt on K562 cells in the presence and absence of OND, and found no evidence that OND significantly enhances the cytotoxic effect of cisPt on these cells alone or in co-cultures with induced HepG2 cells. The induced HepG2 co-culture system uses cells of human origin and clearly has considerable potential for examining the effects of drugs and their metabolites on indicator cells derived from a tissue of choice. This system may be particularly useful in the assessment of metabolism and toxicity of new drugs intended for human use.

Antiemetics↗
PubMed1991

Interleukin-2 nephrotoxicity assessed in vitro.

Immunotherapy with interleukin-2 (IL-2) is complicated by many side effects of which nephrotoxicity is the most limiting. We have examined IL-2 nephrotoxicity in vitro using the pig kidney cell line LLC-PK.1 model system. Human recombinant IL-2 (HrIL-2) was toxic to LLC-PK.1 cells at concentrations comparable to those seen in the serum of patients undergoing cancer immunotherapy. Many of the side effects of IL-2 immunotherapy are due to IL-2-induced synthesis of tumour necrosis factor-alpha (TNF-a) and can be alleviated by co-administration of steroids. However, HrIL-2 nephrotoxicity in vitro was unaffected by addition of dexamethasone to cultures and LLC-PK.1 cells were found to be resistant to the anti-proliferative effects of TNF-a. These results suggest that the nephrotoxic effect of HrIL-2 is due to a direct toxic effect on kidney cells.

Animals↗
PubMed1990

Na+/H+ antiporter is the primary proton transport system used by osteoclasts during bone resorption.

We have examined the effects of inhibitors of proton transport systems on osteoclastic bone resorption using an in vitro bone slice assay, where osteoclasts (OCs) are free from the influence of other bone cells. Amiloride (AM) and dimethylamiloride (DMA), inhibitors of the Na+/H+ antiporter, were potent inhibitors of bone resorption (IC50 approximately 9 and 0.7 microM for AM and DMA, respectively). Omeprazole (OM), a potent inhibitor of parietal cell K+/H+(-)ATPase, was a poor inhibitor of OC bone resorption (IC50 approximately 100 microM). These results strongly suggest that the Na+/H+ antiporter is the primary proton system used by OCs during bone resorption.

Adenosine Triphosphatases↗
PubMed1990

Lithium counteracts histamine suppression of human T cell mitogenesis.

Human T cell proliferative responses to concanavalin A (conA) were suppressed by approximately 50% by histamine (100 microM). In contrast, LiCl (1 or 3 mM) potentiated T cell responses by about 50%, but 10 mM LiCl had no significant effect on T cell proliferation. Histamine suppression was not significantly affected by the presence of potentiating concentrations of LiCl, whereas 10 mM LiCl completely abrogated histamine suppression.

Adult↗
PubMed1990

Gallium inhibits bone resorption by a direct effect on osteoclasts.

Gallium nitrate has been used clinically to treat cancer-related hypercalcemia. It has been suggested that gallium may reduce calcium release from bone by inhibiting bone resorption, but the mechanism(s) involved remain to be elucidated. Therefore, we have examined the effect of gallium on bone resorption in vitro using osteoclasts isolated from neonatal rat long bones cultured on slices of cortical bone. Gallium nitrate (0.01-100 micrograms/ml) produced a concentration-dependent inhibition of bone resorption. Morphological studies showed that even (100 micrograms/ml) gallium nitrate induced no light microscopical change in osteoclast morphology and did not affect their survival on bone slices. Pretreatment of bone slices with gallium nitrate (100 micrograms/ml for 18 h), followed by extensive washing also inhibited subsequent osteoclastic bone resorption. These results suggest that gallium can be adsorbed onto the calcified surface of bone and inhibit osteoclastic bone resorption.

Animals↗
PubMed1990

Characterising the microstructure of random media using ultrasound.

This paper describes a technique of forming images of the average size and scattering strength of scatterers in a random medium using ultrasound. Quantitative ultrasound images provide a more direct interpretation of the underlying structure of the medium, e.g. size, shape, number and elastic properties of scatterers, and increased detectability for regions of varying structure. A signal-to-noise analysis was used to show quantitatively how properties of the imaging system influence low-contrast detectability in quantitative ultrasound images. In one experiment, signal-to-noise measurements using phantoms were compared with B-mode imaging for several transducer bandwidths to observe variations in image contrast and speckle noise. The findings are being used to optimise the design of quantitative imaging systems for specific diagnostic tasks.

Agar↗
PubMed1990

Describing small-scale structure in random media using pulse-echo ultrasound.

A method for estimating structural properties of random media is described. The size, number density, and scattering strength of particles are estimated from an analysis of the radio frequency (rf) echo signal power spectrum. Simple correlation functions and the accurate scattering theory of Faran [J.J. Faran, J. Acoust. Soc. Am. 23, 405-418 (1951)], which includes the effects of shear waves, were used separately to model backscatter from spherical particles and thereby describe the structures of the medium. These methods were tested using both glass sphere-in-agar and polystyrene sphere-in-agar scattering media. With the appropriate correlation function, it was possible to measure glass sphere diameters with an accuracy of 20%. It was not possible to accurately estimate the size of polystyrene spheres with the simple spherical and Gaussian correlation models examined because of a significant shear wave contribution. Using the Faran scattering theory for spheres, however, the accuracy for estimating diameters was improved to 10% for both glass and polystyrene scattering media. It was possible to estimate the product of the average scattering particle number density and the average scattering strength per particle, but with lower accuracy than the size estimates. The dependence of the measurement accuracy on the inclusion of shear waves, the wavelength of sound, and medium attenuation are considered, and the implications for describing the structure of biological soft tissues are discussed.

Models, Theoretical↗
PubMed1990

Parametric ultrasound imaging from backscatter coefficient measurements: image formation and interpretation.

A broadband method for measuring backscatter coefficients sigma b and other acoustic parameters is described. From the sigma b measurements, using a commercially-available imaging system, four high-resolution parametric ultrasound images are formed in a C-scan image plane. Scatterer size images are computed from the frequency dependence of sigma b and a correlation model function that describes the structure and elastic properties of the medium. Scattering strength images are computed from the absolute magnitude of sigma b. Chi-square images are generated to display how well the correlation model represents the interrogated medium. Integrated backscatter coefficient images are formed over the transducer bandwidth. All four images are generated simultaneously and compared with the corresponding B-mode image. Test samples with known physical properties were used to demonstrate experimentally that accurate parametric images are possible if an accurate correlation model is used. Local variations in attenuation, the center frequency and bandwidth of the transducer, and the distribution of scatterer sizes greatly influence the accuracy of estimates and the appearance of the image, thus demonstrating the importance of these factors in parametric image interpretation.

Agar↗
PubMed1990

Lack of effect of verapamil and MDL 646, a cytoprotective PGE1 analogue on cyclosporin A nephrotoxicity in vitro.

Nephrotoxicity is the most troublesome side effect of cyclosporin A (CSA) therapy. In vitro studies have shown that verapamil and PGE analogues can protect human and rat kidney allografts and murine pancreatic B cells from CSA cytotoxicity. The LLC-PK.1 pig kidney cell line has recently been shown to be a use-ful in vitro model system for studying CSA nephrotoxicity. We have adopted the MTT assay to assess the effects of CSA on LCC-PK.1 cell growth and have examined the effects of verapamil and MDL 646, a cyto-protective PGE1 analogue, on CSA nephrotoxicity. The results show that neither compound prevents the cytotoxic effects of CSA on kidney cells.

Alprostadil↗
PubMed1989

Optimal bone resorption by isolated rat osteoclasts requires chloride/bicarbonate exchange.

We have examined the effect of DIDS (4,4'-diisothiocyanatostilbene sulfonic acid) a potent, specific and irreversible inhibitor of chloride/bicarbonate exchange on bone resorption by disaggregated rat osteoclasts, using an in vitro bone slice assay. DIDS inhibited bone resorption in concentration dependent fashion, without affecting osteoclast viability or survival on bone slices. The role of anion exchange in the resorptive process is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗