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Biomedical subjects

A Garner

Publications and source records attributed to A Garner.

At least 181 records · Page 10Linked to original sources

Measurements of daunorubicin uptake of Yoshida sarcoma cells in culture using flow cytofluorimetry.

A comparative measurement of the transport and localisation of daunorubicin into Yoshida sarcoma cells, was undertaken by a biochemical extraction process and a flow cytometric method. An advantage of this latter procedure would be to identify subpopulation of cells which have enhanced or impaired daunorubicin incorporation as well as the ability to exclude any non-specific incorporation into cell debris, which would otherwise interfere with the overall estimation. It has been possible to use the Biophysics argon ion laser at a wavelength of 488 nm which coincides with the visible absorption bands of daunorubicin and doxorubicin (adriamycin) and the cytofluorimetric estimations of daunorubicin incorporation have now been compared with biochemically determined uptake in Yoshida cells. A high lethal dose of 10 microM was required to achieve the direct measurement by cytofluorimetry procedures on the Biophysics instrument. From cell fractionation and CHCl3/amyl alcohol extraction, it was possible to show that during a 5-h exposure period to daunorubicin (10 microM), the uptake into the nucleus was at first rapid and that into the cytoplasm was much slower. After about 3-h incubation, the level in the cytoplasm decreased, followed by a decrease from the nucleus 1 h later. This could be equated when observed microscopically to the gain in fluorescent cell debris. If all nuclear binding is to DNA, then at the level of (10 microM) concentration in the medium, the number of base pairs to daunorubicin would be 9 : 1, respectively. Cytofluorimetry showed a broad spread of intracellular daunorubicin fluorescence which increases with cell size. Increasing external concentration caused a more rapid incorporation as well as a quicker release from the cells.

Animals↗

Influence of luminal acidification on bicarbonate transport by gastric and duodenal isolated mucosae.

Transport of HCO3- was measured by pH-stat titration in pairs of amphibian fundic or proximal duodenal mucosa using a modified Ussing chamber. Separate unbuffered solutions bathed the luminal sides of two tissues while their serosal surfaces were in contact with a common buffered solution. Lowering luminal pH bathing one fundic mucosa from 7.40 to 1.85 significantly increased HCO3- transport by another fundus. However, acidification of fundic mucosa did not affect duodenal HCO3- transport. In duodenal mucosal pairs, lowering pH from 7.40 to 5.46 caused an increase in HCO3- transport by the other tissue. Luminal H+ ion concentration may therefore regulate HCO3- transport via a humoral mechanism.

Animals↗

Effect of parathyroid hormone on bicarbonate secretion in the guinea-pig stomach and the amphibian isolated gastric mucosa.

1. The effect of parathyroid hormone on gastric bicarbonate secretion was determined in the anaesthetized guinea pig. Subcutaneous injections of bovine parathyroid hormone (75 U.S.P units day-1 kg-1) for 7 days caused a significant increase in HCO3- output. There was also a rise in K+ output and a slight elevation of H+ secretion. A similar increase in HCO3- output occurred after acute intravenous injection of the hormones (75 U.S.P. units/kg). 2. Both chronic and acute administration of parathyroid hormone caused a significant increase in serum calcium concentration and it is likely that the changes in gastric ion outputs reflect raised calcium levels. Given alone intravenous calcium (1.5 mg/kg body wt.) stimulated gastric secretion of both HCO3- and H+. 3. To determine whether parathyroid hormone had a direct action on gastric ion transport experiments were performed in the amphibian isolate mucosa. Antrum transports HCO3- spontaneously while HCO3- transport in fundus was studied after inhibition of the greater H+ secretion by the histamine H2-receptor antagonist metiamide. Parathyroid hormone at a concentration of 0.2 United States Pharmacopea (U.S.P.) unit/ml in the nutrient-side bathing solution inhibited both antral and fundic HCO3- transport. A higher concentration (2.0 units/ml) had no effect on fundic H+ secretion. 4. The inhibitory effect in vitro was greater in the antrum and parathyroid hormone may almost abolish the active component of HCO3- transport in this tissue. It is likely that any similar inhibition of gastric HCO3- secretion by parathyroid hormone in vivo is masked by the stimulatory effects of released calcium.

Animals↗

Effect of carbenoxolone on alkaline secretion by isolated amphibian gastric and duodenal mucosa.

The influence of carbenoxolone sodium on HCO-3 transport has been examined in spontaneously alkalinizing amphibian antral (Necturus and Rana catesbeiana) and proximal duodenal (Rana catesbeiana) mucosa and in cimetidine-treated fundic mucosa (Rana temporaria) in vivo. Low concentrations of carbenoxolone (10(-6)-10(-4) mol/l, serosal side and 10(-5) mol/l, luminal side) did not affect the secretory rate or electrical properties of these tissues. In the stomach a higher concentration of carbenoxolone (10(-3) mol/l, serosal side) caused an immediate fall in transmucosal potential difference (PD) and electrical resistance. There was an initial decrease in the rate of HCO-3 transport followed by an increase in titratable alkalinization due to passive permeation of base from the serosal bathing solution. The non-steroidal anti-inflammatory agent ibuprofen (3 x 10(-3) mol/l, serosal side) inhibited alkaline secretion while the bile salt sodium taurocholate (10(-4) mol/l, luminal side) converted net alkaline secretion to a titratable acidity in cimetidine-treated fundus. Pretreatment of the mucosa with carbenoxolone (10(-4) mol/l) did not influence the response to taurocholate but when added with ibuprofen it potentiated the inhibitory effect of this drug on fundic alkaline secretion. In contrast, prostaglandin E2 (10(-6) mol/l) markedly reduced the inhibition of fundic alkaline secretion caused by ibuprofen. The anti-ulcer properties of carbenoxolone do not appear to be related to effects on gastroduodenal HCO-3 transport.

Animals↗

Local recurrence of choroidal malignant melanoma following enucleation.

542 cases of choroidal malignant melanoma were reviewed. Local recurrence occurred in only 6 patients (1.11%). Five of the 6 patients had distant metastases when the local recurrence was diagnosed, and the remaining patient also developed metastases after a passage of time. These figures do not support the concept of withholding a primary implant at the time of enucleation.

Aged↗

Effect of sodium taurocholate on secretion by amphibian gastric mucosa in vitro.

Effects of sodium taurocholate on the electrical and secretory activity of amphibian gastric mucosa have been studied in vitro. Exposure of the luminal surface of fundic mucosa to high concentrations (5 X 10(-2) M) at low pH (2.0 and 3.0) produced a marked fall in potential difference and electrical resistance. At lower concentrations (10(-3) to 10(-4) M) and higher pH (7.4), taurocholate did not alter the electrical properties but significantly increased net acidification from 1.39 +/- 0.27 to 2.01 +/- 0.18 mueq . cm-2 . h-1 (means +/- SE; P less than 0.01). Pretreatment of fundic mucosa with cimetidine resulted in net alkaline secretion (0.27 +/- 0.07 mueq . cm-2 . h-1), and addition of taurocholate (10(-4) M) to the luminal surface at pH 7.4 converted net alkalinization to net acidification (0.94 +/- 0.28 mueq . cm-2 . h-1). This response was not inhibited by atropine (10(-5) M) or somatostatin (10(-6) M) but exhibited marked tachyphylaxis. Taurocholate (10(-4) M) inhibited alkaline secretion in thiocyanate-treated fundic mucosa (0.63 +/- 0.04 to 0.14 +/- 0.09 mueq . cm-2 . h-1; P less than 0.001) and in spontaneously alkaline-secreting antral mucosa (0.36 +/- 0.12 to 0.09 +/- 0.06 mueq . cm-2 . h-1; P less than 0.05), but acidification did not occur. Apparent stimulation of acid secretion and simultaneous inhibition of alkaline secretion of sodium taurocholate may play a role in the pathogenesis of mucosal damage by bile.

Action Potentials↗

The masquerade syndrome.

Malignant lesions of the lid and ocular adnexae may present with striking inflammatory signs and this has most often been described with meibomian gland carcinoma and given the name of the masquerade syndrome. This paper presents examples of lid malignancies which have not only masqueraded as predominantly inflammatory lesions but whose origin was further obscured by the nature of the spread of the tumour in lid and conjunctiva. Recognition of the true nature of the malignancy only follows biopsy of the centre of the lesion which is fully justified in an older patient presenting with unilateral chronic, unresponsive inflammation especially involving the canthus and bulbar conjunctiva as well as the lid. Histological confirmation of the nature of the peripheral spread of the tumour is also of importance since pagetoid spread has been shown to be associated with more aggressive neoplasia and increased mortality.

Aged↗

Macromelanosomes in X-linked ocular albinism.

Examination of clinically normal skin from four patients with X-linked ocular albinism of the Nettleship-Falls type by light and electron microscopy revealed the presence of macromelanosomes in some melanocytes and keratinocytes. Measuring up to 5 micron many of the abnormal melanosomes showed a concentrically laminated structure suggestive of a phasic growth pattern. Epidermis from three female carriers contained similar but fewer macromelanosomes. These findings indicate that skin biopsy could be of value not only in confirming the diagnosis of ocular albinism in affected males, but also to establish carrier status in asymptomatic females.

Albinism↗

Stimulation of gastric acid and bicarbonate secretions by calcium in guinea pig stomach and amphibian isolated mucosa.

Administration of Ca++ (1.5 mg/kg i.v.) increased the output of both H+ and HCO-3 from the stomach of the anesthetized guinea pig as determined by measurement of gastric intraluminal pH and pCO2. The rise in HC-3 secretion was slightly greater than that in H+, resulting in a decrease in net acidity. Fundic mucosa isolated from frogs was used to study the mechanisms of the stimulatory actions. An increase in Ca++ concentration in the nutrient (serosal) bathing solution from 1.8 to 7.2 mM stimulated H+ transport in this preparation. The effect of raising Ca++ concentration was inhibited by the histamine H2 receptor antagonist Metiamide and by increasing nutrient Mg++. Stimulation of H+ transport, sensitive to Metiamide, was also observed with the calcium ionophore A23187 (4 micrograms/ml, nutrient side). The results indicate that at the mucosal level, Ca++ stimulates H+ transport by release of histamine from mucosal stores with properties similar to those of mast cells. Transport of HCO-3 in isolated mucosae was studied after inhibition of H+ transport my metiamide. An increase in nutrient Ca++ concentration stimulated the HCO-3 transport but the calcium ionophore had no effect. This action of Ca++ was abolished by atropine (10(-6) M) and by raising nutrient Mg++, suggesting that it reflects release of acetylcholine from intramucosal nervous tissue. Thus Ca++ stimulated gastric transport of both H+ and HCO-3 in vivo and in vitro but evidence for a direct action on the transporting (parietal and epithelial) cells was not obtained.

Animals↗