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Biomedical subjects

T J Hall

Publications and source records attributed to T J Hall.

At least 19 recordsLinked to original sources
PubMed1992

Na+/H(+)-antiporter activity is essential for the induction, but not the maintenance of osteoclastic bone resorption and cytoplasmic spreading.

We have examined the kinetics of the effects of inhibitors of the Na+/H(+)-antiporter (dimethylamiloride) and the vacuolar H(+)-ATPase (bafilomycin A1) on bone resorption by disaggregated rat osteoclasts in the bone slice assay. Bafilomycin A1 (100 nM) inhibited resorption by approximately 95%, 75%, 80% and 60% respectively, when added at t = 0, 1, 3 or 6 hr after osteoclast adherence to bone slices, during a 24 hr culture period. The incomplete inhibition by bafilomycin A1 when added after the start of incubation was presumably accounted for by resorption that had occurred prior to addition of the compound. Dimethylamiloride (100 microM) inhibited bone resorption by 80% and 65% when added at t = 0 or 1 hr after osteoclast adherence, but was without effect when added at t = 3 or 6 hr. In addition, dimethylamiloride but not bafilomycin A1 strongly inhibited osteoclast cytoplasmic spreading. The results indicate that Na+/H(+)-antiporter activity is essential for controlling intracellular pH during early activation events stimulated by the adherence of osteoclasts to mineralized bone surfaces, which lead to cytoskeletal activation, cell spreading and bone resorption.

Amiloride↗
PubMed1992

Computers in ultrasonic imaging.

This article describes the role of computers and digital electronics in state-of-the-art diagnostic ultrasound scanners. An overview of the computational requirements is provided, and limits on color flow image frame rates are discussed. The new scanner architectures emerging may be used to extend current limitations of ultrasonography, making features such as automatic phase aberration correction, speckle reduction, and tissue characterization available.

Humans↗
PubMed1992

Identifying acoustic scattering sources in normal renal parenchyma in vivo by varying arterial and ureteral pressures.

Ultrasonic backscatter properties of normal dog kidney parenchyma are examined in vivo to determine sources of acoustic scattering. We systematically varied the renal perfusion and ureteral pressures to obtain detailed information about scattering sources that could not be seen under in vitro conditions. These data suggest that in normal parenchyma the principal sources of backscatter are Bowman's capsule at low frequencies (2.5-5.0 MHz) and glomerular arterioles at high frequencies (5.0-15.0 MHz). We found that the integrated backscatter coefficient (IBC) in normally perfused kidney cortex is approximately half that measured in the ischemic organ at all frequencies. Ischemia was found to reduce scatterer size estimates (D) by 10% at low frequencies and increase D54% at high frequencies. Acute obstruction of the kidney, under diuresis, produced an 11% increase in D at low frequencies, and no significant change in D at high frequencies. These variations in backscatter measurements are explained in terms of changes in the microscopic anatomy of the kidney.

Animals↗
PubMed1992

Laparoscopic appendectomy. Initial experience in a teaching program.

From February 1990 to December 1991, 16 laparoscopic procedures were performed for right lower quadrant pain. There were nine men and seven women, aged 16 to 47 years (mean, 27.2 years). All procedures were performed by surgical chief residents with prior experience in laparoscopic cholecystectomy, first-assisted by an attending surgeon. The appendix was visualized and a definitive diagnosis was made in all patients. One patient with acute salpingitis underwent diagnostic laparoscopy only; two patients underwent laparotomy (perforated appendicitis, perforated diverticulitis). A fourth patient had an acute torsion of an ovarian cyst managed laparoscopically. Laparoscopic appendectomy was successfully performed in 12 patients (acute appendicitis, 9; fibrosis or chronic inflammation, 2; normal appendix, 1). Mean operative time for laparoscopic appendectomy was 95.7 minutes, and mean postoperative stay was 2.5 days. The authors conclude that operative time, diagnostic accuracy, and complication rates for laparoscopic appendectomy are acceptable. Within the context of a training program, laparoscopic appendectomy provides an opportunity for surgical residents to expand laparoscopic skills.

Adolescent↗
PubMed1992

Specific inhibition of IgE antibody production by an antisense oligodeoxynucleotide oligomer (Oligostick).

We have investigated the ability of an antisense oligonucleotide (ASE-1) to specifically inhibit IgE synthesis by a human myeloma cell line, U266. ASE-1 inhibited IgE production in a concentration-dependent manner, as assessed by isotype-specific ELISA measurement of immunoglobulin in myeloma cell supernatants. Inhibition of IgE production was specific and not due to cytotoxicity since IgG1 and IgM production by human myeloma cell lines ARH-77 and RPMI-1788 respectively, was not significantly affected by up to 20 microM ASE-1 whereas IgE production was inhibited by approximately 70% at this concentration. These results indicate that antisense oligonucleotides represent a potential therapeutic approach to the treatment of IgE-mediated allergic diseases.

Antibodies, Neoplasm↗
PubMed1991

Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators.

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E2 and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
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↗