Biomedical subjects

A K Ho

Publications and source records attributed to A K Ho.

At least 73 records · Page 4Linked to original sources

PubMed1995

Inhibition of serine/threonine protein phosphatases enhances agonist-stimulated cAMP accumulation in UMR 106 osteoblast-like cells.

Protein phosphatases regulate the activity of signal transduction mechanisms by dephosphorylating activated components. By utilizing selective inhibitors of these phosphatases, we investigated their role in regulating cAMP accumulation in the UMR 106 osteoblast-like tumor cell line. PTHrP, PTH and PGE2 stimulated cAMP accumulation up to 100-fold. Calyculin A, a potent inhibitor of protein phosphatase type 1 (PP1) and type 2A (PP2A), did not affect basal levels of cAMP, but concentrations of 10(-11) M to 10(-8) M increased PTHrP-, PTH-, and PGE2-stimulated cAMP accumulation up to 1.7-fold, and this increase was concentration-dependent. Similar results were obtained with tautomycin, another potent inhibitor of PP1 and PP2A. In contrast, okadaic acid, a potent inhibitor of PP2A which inhibited PP1 less potently, did not enhance PTHrP-, PTH-, or PGE2-stimulated cAMP accumulation. The effect of calyculin A on agonist-stimulated cAMP accumulation persisted in cells treated with isobutyl methylxanthine, a phosphodiesterase inhibitor. When the effect of calyculin A was compared with that of 4 beta-phorbol 12-myristate 13-acetate (PMA), it was found that while PMA enhanced both the receptor and forskolin-stimulated cAMP accumulation, calyculin A had no effect on the forskolin-stimulated cAMP accumulation. The effect of calyculin A on PTHrP- and PTH-stimulated cAMP accumulation persisted in cells treated with PMA. These results suggest that protein phosphatases play an important role in agonist-stimulated cAMP accumulation in osteoblast-like cells, and that PP1 but not PP2A may be the major phosphatase involved. In contrast to activation by protein kinase C, the site of action for the phosphatase appears to be predominantly at a step prior to the activation of adenylyl cyclase in the cAMP signal transduction pathway.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Tyrosine kinase inhibitors enhance cGMP production in rat pinealocytes.

The role of tyrosine kinase(s) in the regulation of cGMP accumulation in rat pinealocytes was investigated using three tyrosine kinase inhibitors. Treatment with genistein, erbstatin or the active analogues of tyrphostin selectively increased basal cGMP accumulation in a dose-dependent manner without a concomitant increase in cAMP. In contrast to the norepinephrine- and vasoactive intestinal peptide-stimulated cGMP responses, the stimulatory effect of genistein was not blocked by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Furthermore, in the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor, neither genistein nor erbstatin had an effect on cGMP accumulation. These results indicate that tyrosine kinase inhibitors increase pineal cGMP accumulation through inhibition of the metabolism of cGMP.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Evaluation of a well-type ionization chamber for calibration of HDL and LDR brachytherapy sources.

The Atomlab 44D well-type ionization chamber is being evaluated for calibration of high dose rate (HDR) Ir-192 and low dose rate (LDR) Cs-137 sources. The chamber has a flat response (sweet spot) of +/- 0.5% along approximately 3.5 cm for an Ir-192 HDR linear source and 3 cm for a Cs-137 LDR spherical source. The short-term stability of the chamber was determined using a cylindrical Cs-137 source positioned in the sweet spot region. The chamber response over a range of 17.4 mCi (644 MBq, Cs-137) and 8.82 Ci (326 GBq, Ir-192) is evaluated. The chamber may be used for calibrating the activities of both HDR Ir-192 and LDR brachytherapy sources.

Brachytherapy↗

PubMed1995

A simple device for prostate and rectal localization in radiation therapy.

A simple device for prostate and rectum localization in radiation therapy may be constructed as follows: first, dental wax is used to make up a shape of the rectal probe. Second, dental stone is used to make a two-piece mold by molding the dental wax probe. Third, using the mold, the rectal probe is made from a mixture of silicone and barium. The final step involves the attachment of the "plug," which is made of aluminum. From the simulation films for the prostate setup, the location of the anterior wall of the rectum, anal sphincter, and anal verge can easily be identified, such that the appropriate regions are shielded accordingly. A CT scan with the probe in the rectum did not give too much artifacts from the barium/silicone mixture. The rectal probe with the plug is useful for localizing the prostate more accurately, compared with using the other rectal localization techniques such as barium injection or some rectal markers.

Aluminum↗

PubMed1995

Application of the "bioeffects" algorithm of a treatment planning system.

In this study, both a four-field box and two-field AP/PA treatment plan are combined with two insertions of Cs-137 in a tandem and ovoids setup, to evaluate the bioeffects program of a treatment planning system. External beam energies studied are 18 and 6 MV. It is shown that there is a slight difference in the 50-70 time dose fractionation (TDF) isolines when comparing 6 MV and 18 MV, for the AP/PA setup. There is practically no difference for TDF isoline values larger than 80 for both energies with either the four-field or the two-field setup. This is because the brachytherapy contributed the majority of the dose to the regions near the applicator and the TDF values reflect the higher dose delivered by the brachytherapy relative to the external beams in that region. For this simple evaluation of the bioeffects program, the combination of the external beam plan and the brachytherapy plan does not give us enhanced information on the effectiveness of the plan.

Algorithms↗

PubMed1995

Accuracy of the point source approximation to high dose-rate Ir-192 sources.

The accuracy of the point source approximation used in dose calculations for an implant comprised of multiple high dose rate (HDR) Ir-192 source dwell positions is investigated. First, a single dwell position implant is modeled. The exposure rate about the source is calculated using both the point source approximation and the more rigorous line source formalism. A comparison of these calculated exposure rates is made. It is found that for each HDR Ir-192 source dwell position, the point source approximation results in a dose overestimation of 1% at a distance of 1 cm on the source transverse axis, while dose underestimations of more than 2% can be found at a distance of 1 cm on the source longitudinal axis. Even larger errors occur closer to the source. The results of this academic study are then extended to two clinical cases--an endobronchial treatment and a tandem and ovoids setup, both involving multiple source dwell positions. Since clinical HDR Ir-192 implants are comprised of many individual source dwell positions, there will be inaccuracy in the calculated overall dose distribution leading to dose delivery errors. For example, the dose delivered to a prescription point located 0.5 cm from an endobronchial applicator will be 3% lower than prescribed. Similar errors are produced in gynecologic implants. To decrease below 0.5% the dose delivery error resulting from the point source approximation, prescription points should be at a distance of at least 1 cm from any applicator. Since the dosimetry error is a direct result of the choice of model used to describe the source, the use of anisotropy factors accounting for the variation of photon fluence around the HDR Ir-192 source will not completely correct the calculation.

Brachytherapy↗

PubMed1995

Evaluation of dose delivery based on a comparison of dosimetry calculations using open beam and wedged beam depth dose data.

The purpose of this study is to evaluate the magnitude of the error in dose delivery caused by the use of open beam depth dose data in dosimetry calculations for wedged photon beams. Isodose plans were calculated for treatments given in a 3-field isocentric prostate or rectal setup using an open AP beam with two lateral wedged beams. The dose distributions were first calculated using open beam depth dose data for all three fields. Next, the open beam data was used only for the AP field and true wedged beam depth dose data was substituted for the two lateral wedged fields. The magnitude of the depth dose variations for wedged vs open beams depends on the nominal beam energy, the wedge angle, and the depth of measurement. Consequently, isodose distributions calculated for wedged fields were found to be different when true wedged beam depth dose data was used instead of open beam data as is commonly done. Monitor unit calculations using a field size specific wedge factor show that dose delivery errors up to 4% can result from the use of open beam depth dose data in wedged beam dose distribution calculations for a 6-MV photon beam. Accurate treatment planning for wedged fields requires the use of wedged beam depth dose data specific to each wedge. Simply using open beam depth dose data in dose calculations for wedged beams will result in dose delivery errors, the magnitude of which depends on the combination of wedge angle, field size, and nominal beam energy.

Evaluation Studies as Topic↗

PubMed1995

Pituitary adenylate cyclase-activating polypeptide: control of rat pineal cyclic AMP and melatonin but not cyclic GMP.

In this study, the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic nucleotide accumulation and melatonin (MT) production in dispersed rat pinealocytes were measured. Treatment with PACAP (10(-7) M) increased MT production 2.5-fold. PACAP (10(-7) M) also increased cyclic AMP accumulation four- to fivefold; this effect was potentiated two- to three-fold by alpha 1-adrenergic activation. This potentiation appears to involve protein kinase C (PKC) because alpha 1-adrenergic activation is known to translocate PKC and the PACAP-stimulated cyclic AMP accumulation was potentiated ninefold by a PKC activator, 4 beta-phorbol 12-myristate 13-acetate (PMA). Phenylephrine and PMA also potentiated the PACAP-stimulated MT accumulation. These results indicate that cyclic AMP is one second messenger of PACAP in the pineal gland and that the effects of PACAP on cyclic AMP and MT production can be potentiated by an alpha 1-adrenergic-->PKC mechanism. In addition to these findings, it was observed that PACAP treatment with or without phenylephrine or PMA did not alter cyclic GMP accumulation. This indicates that PACAP is the first ligand identified that increases cyclic AMP accumulation in the pineal gland without increasing cyclic GMP accumulation. That PACAP fails to activate the vasoactive intestinal peptide/cyclic GMP pathway suggests that the vasoactive intestinal peptide receptors present in the pineal may be distinct from the type II PACAP receptors.

Animals↗

PubMed1995

Potentiation of agonist-stimulated cyclic AMP accumulation by tyrosine kinase inhibitors in rat pinealocytes.

To study cross-talk mechanisms in rat pinealocytes, the role of tyrosine kinase or kinases in the regulation of adrenergic-stimulated cyclic AMP production was investigated. Both norepinephrine- and isoproterenol-stimulated cyclic AMP accumulation were increased by two distinct tyrosine kinase inhibitors, genistein or erbstatin, in a concentration-dependent manner. A similar increase was observed with two other inhibitors, tyrphostin B44 and herbimycin. In contrast, daidzein, an inactive analogue of genistein, was ineffective; whereas vanadate, a phosphotyrosine phosphatase inhibitor, reduced the adrenergic-stimulated cyclic AMP accumulation. The tyrosine kinase inhibitors were effective in potentiating the cholera toxin-or forskolin-stimulated cyclic AMP accumulation, indicating that their sites of action are at the postreceptor level. Neither an activator nor inhibitors of protein kinase C influenced the potentiation of the cyclic AMP responses by genistein, suggesting that the potentiation effect by tyrosine kinase inhibitors does not involve the phospholipase C/protein kinase C pathway. However, when the phosphodiesterase was inhibited by isobutylmethylxanthine, genistein failed to potentiate and vanadate did not inhibit the adrenergic-stimulated cyclic AMP accumulation, indicating that the phosphodiesterase is a probable site of action for these inhibitors. These results suggest that cyclic AMP metabolism in the pinealocytes is tonically inhibited by tyrosine kinase acting on the cyclic AMP phosphodiesterase.

Animals↗

PubMed1995

Phosphatase inhibitors potentiate adrenergic-stimulated cAMP and cGMP production in rat pinealocytes.

The role of phosphoprotein phosphatase in the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rat pinealocytes was investigated using the three phosphatase inhibitors calyculin A, tautomycin, and okadaic acid. Calyculin A (0.1 microM) was found to enhance the isoproterenol- and norepinephrine-stimulated cAMP accumulation six- and threefold, respectively, whereas tautomycin and okadaic acid were less effective. The effect of calyculin A was rapid (within 5 min) and persisted in the presence of phosphodiesterase inhibition. However, in contrast to protein kinase C activation or intracellular calcium elevation, the phosphatase inhibitors were less effective in potentiating the cAMP response stimulated by forskolin or cholera toxin, and their effects were not blocked by calphostin C or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. The adrenergic-stimulated cGMP response was also less sensitive to the phosphatase inhibition. Therefore, our results suggest that 1) the adrenergic-stimulated cAMP signal is subjected to the tonic inhibition by phosphoprotein phosphatase; 2) phosphatase inhibitors enhance cAMP synthesis through their actions at the receptor level; and 3) the cAMP signal is more sensitive to the regulation by phosphorylation than cGMP in rat pinealocytes.

1-Methyl-3-isobutylxanthine↗

PubMed1995

cGMP inhibits L-type Ca2+ channel currents through protein phosphorylation in rat pinealocytes.

In this study, the effect of cGMP on the dihydropyridine-sensitive (L-type) Ca2+ current was investigated using the whole cell version of the patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 x 10(-4) M) induced a pronounced inhibition of the L-type Ca2+ channel current. The dibutyryl-cGMP effect was concentration dependent. Elevation of cGMP by nitroprusside had a similar inhibitory action on the L-type Ca2+ channel current. Norepinephrine, which increased cGMP in rat pinealocytes, also inhibited this current. The action of cGMP was independent of cAMP elevation since the cAMP antagonist, Rp-cAMPs, had no effect on the inhibitory action of dibutyryl-cGMP. The involvement of cyclic GMP-dependent protein kinase was suggested by the blocking action of two protein kinase inhibitors, (1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), on the dibutyryl-cGMP effect on the L-type Ca2+ channel current. Taken together, these results suggest that (1) cGMP modulates L-type Ca2+ channel currents in rat pinealocytes, causing inhibition of this current; (2) the action of cGMP appears to be independent of cAMP elevation; and (3) phosphorylation by cGMP-dependent protein kinase may be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1995

Scrub typhus pneumonitis with delayed resolution.

A 35-year-old lady was admitted to hospital with fever and dry cough. Chest radiograph showed bilateral basal infiltrate. Her Weil-Felix test was strongly positive (OX-K > 1:160) and her fever came down with intravenous tetracycline. There was no improvement in the lung shadow and spirometry showed a severe restrictive defect. Open lung biopsy confirmed the diagnosis of interstitial pneumonitis. CT of thorax 6 months after presentation showed partial resolution of the interstitial shadow.

Adult↗

PubMed1995

Multiple drug classes and hyperosmolarity alter binding of muscarinic drugs to mesothelial cells in vitro.

Mesothelial cells in vitro exhibited binding sites for L-quinuclidinyl[phenyl-4-3H]-benzilate ([3H]-QNB), but not [3H]-N-methylscopolamine (NMS), a cell-impermeable ligand. [3H]-QNB binding demonstrated a biphasic pattern of binding in living cells: a maximum after 15 min at 37 degrees C was followed by a decrease out to 90 min. [3H]-QNB binding was blocked by increasing concentrations of atropine; WIN35428 and GBR12909, dopamine transport inhibitors also decreased binding. Pretreatment of cells for 18 hours with atropine, QNB, or WIN35428 resulted in enhanced [3H]-QNB binding, but coexposure to cycloheximide blocked this increase. Hyperosmolarity caused by NaCl or mannitol decreased binding of [3H]-QNB to living cells. Thus rabbit peritoneal mesothelial cells possess binding sites for [3H]-QNB that are influenced by other drugs and osmolarity.

Animals↗

PubMed1994

Acute elevation of intracellular pH translocates protein kinase C activities in rat pinealocytes.

The relationship between elevation of intracellular pH and activation of protein kinase C in rat pinealocytes was investigated in rat pinealocytes. It was found that direct elevation of intracellular pH alone by ammonium chloride or methylamine translocated protein kinase C activities in a dose-dependent manner. This translocation was blocked by EGTA, suggesting a requirement of Ca2+ for the process. However, elevation of intracellular pH by methylamine had no significant effect on intracellular Ca2+ or diacylglycerol content, suggesting the translocation was not due to increased intracellular Ca2+ or diacylglycerol contents. These data suggest that elevation of intracellular pH alone can trigger activation of protein kinase C through a mechanism distinct from increases in diacylglycerol or intracellular Ca2+.

Ammonium Chloride↗

PubMed1994

Vasoactive intestinal polypeptide stimulates cyclic AMP production in mouse N1E-115 neuroblastoma cells: modulation by a protein kinase C activator and ionomycin.

In this study, we investigated the vasoactive intestinal polypeptide (VIP)-stimulated cAMP production and its interaction with protein kinase C activation and elevation of intracellular Ca2+ in N1E-115 neuroblastoma cells. VIP treatment caused a 55-fold increase in cAMP accumulation. Addition of 4 beta-phorbol 12-myristate 13-acetate reduced VIP- but not forskolin-stimulated cAMP response. In comparison, ionomycin potentiated both VIP- and forskolin-induced cAMP accumulation. Our results indicate that VIP stimulates cAMP accumulation in N1E-115 cells, and that although activation of protein kinase C inhibits the VIP-stimulated cAMP response, elevation of intracellular Ca2+ potentiates this signaling pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Comparison of Nucletron and ROCS brachytherapy treatment planning systems for LDR and HDR applications.

The Nucletron Plato system is being used in our Institute for both high dose rate (HDR) and low dose rate (LDR) treatment planning, while the radiation oncology computer system (ROCS) is used for external beam planning. This paper compares both systems, using a gynecological application for the LDR case and an esophageal application for the HDR. It is shown that ROCS may be used as a backup to the Nucletron treatment planning system for LDR and simple HDR cases. The Nucletron planning system is a better system than ROCS for both LDR and HDR applications.

Brachytherapy↗

PubMed1994

Electron energy constancy check using a five-chamber detector array.

Two methods are shown here to determine the 50% depth ionization (d50) using buildup materials of different thickness placed on top of a five-chamber detector array. In the first method, two sets of different thickness buildup material are required to perform the check, one set for checking 6 and 9 MeV, while another set is used for 12, 16, and 20 MeV electron beam from a Varian Clinac 2100C. The second method only requires two data points to determine the d50 depth for each energy. The d50 depths determined were compared with the d50 depth obtained using a water phantom with ionization chamber measurements. The method is simple to use especially for departments that use a similar detector to perform quality assurance tests such as output/symmetry/flatness check.

Electrons↗

PubMed1994

Uncertainty in delivered dose resulting from the distribution of source activities in a Selectron LDR afterloader.

The uncertainty in the delivered dose resulting from the distribution of 137Cs source activity in a clinical Selectron LDR unit has been studied. A comparison is made of the dose delivered to a point 'A' in an implant with sources of equal activity to the actual dose delivered in the same implant with source activities randomly chosen from the population in the afterloader.

Cesium Radioisotopes↗