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H Cable

Publications and source records attributed to H Cable.

8 recordsLinked to original sources

Cellular uptake and release of two contrasting iron chelators.

Desferrioxamine and CP94 (1,2-diethyl-3-hydroxypyridin-4-one) are metal chelators used or proposed for use in the clinical treatment of iron overload. Recent data on their capacity to deplete intracellular iron led to the conjecture that the differences observed arose from the different membrane-penetration properties of the two compounds. The time-course of accumulation and subsequent release of [14C]CP94 by the rat visceral yolk sac in-vitro was compared with that of [14C]desferrioxamine and for 125I-labelled poly(vinylpyrrolidone), a marker for fluid-phase endocytosis. The results indicate that [14C]CP94 crosses the plasma and lysosome membranes rapidly whereas [14C]desferrioxamine and 125I-labelled poly(vinylpyrrolidone) are effectively incapable of crossing these membranes, entering cells only by endocytosis. It is concluded that although CP94 readily enters and leaves cells, desferrioxamine has the potential to accumulate to high concentration in the lysosomes and complex with intralysosomal iron. The results support and extend the proposed correlation between pharmacological activity and capacity for membrane penetration.

Animals↗

Glycogen metabolism in the rat visceral yolk sac. 2. Activity of glycogen-degrading enzymes.

In an attempt to explain the previous observation of the rise and subsequent fall in glycogen content of the rat visceral yolk sac during the latter half of gestation, the activities of glycogen phosphorylase, glucose-6-phosphatase and lysosomal alpha-glucosidase were measured. Glycogen phosphorylase was found to be present in the yolk sac and, as in adult rat liver, was predominantly in the 'a' (active) form. The specific activity of the enzyme was lower than in adult rat liver, when expressed per mg tissue protein or per mg tissue wet weight, but similar when expressed per mg tissue glycogen. Phosphorylase activity in yolk sac was similar at 16.5 and 18.5 days of gestation. Glucose-6-phosphatase activity was not detectable in the yolk sac at either 15.5 or 18.5 days of gestation. Two lysosomal enzymes, acid alpha-glucosidase and N-acetyl-beta-hexosaminidase, were shown to be present in the yolk sac at higher specific activity than in adult liver. Alpha-Glucosidase activity in yolk sac was similar at 15.5 and 18.5 days of gestation. It is concluded that the net degradation of yolk sac glycogen initiated around 18.5 days of gestation does not serve to provide glucose for the fetus, and may indicate an increased demand for metabolic energy within the yolk sac itself.

Animals↗

Evidence that desferrioxamine cannot enter cells by passive diffusion.

Accumulation of [14C]desferrioxamine by rat visceral yolk sac in vitro has been compared with that of [14C]sucrose, a probe for fluid-phase pinocytosis. Kinetic parameters for both substrates are closely similar, as are the effects of inhibitors. It is concluded from these data, and from theoretical considerations, that desferrioxamine cannot enter cells other than by pinocytosis and that, once internalized, it will remain in the lysosomes. The results indicate the need for a re-evaluation of the pharmacokinetic mechanisms traditionally accepted for the drug's ability to deplete iron from cells and tissues.

Animals↗

Gallium-67 scintigraphy in well-differentiated lymphocytic lymphoma of the skin.

Skin lymphomas are now divided into "T" or thymic cell lymphomas (mycosis fungoides being the principal type) and "B" cell lymphomas after the bursa of Fabricius. The "T" cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed "B" cell lymphomas. A large percentage of these non "T" cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.

Gallium Radioisotopes↗

Thoracic CT scanning in the staging of bronchogenic carcinoma.

The use of thoracic CT scans in the staging of bronchogenic carcinoma has been controversial. Previous studies have resulted in conflicting conclusions concerning the incidence of false positive and false negative scans. We attempted to determine if thoracic CT scans were of value in staging bronchogenic carcinoma using objective criteria and in a clinical situation applicable to most modern medical centers. Forty-eight patients who had a staging mediastinoscopy and/or thoracotomy and a CT scan prior to surgery were studied. Twenty-eight had evidence of mediastinal node enlargement on CT scan, and 19 of those patients had metastatic disease confirmed. One of 20 patients without evidence of mediastinal lymph node enlargement on CT scan had lymph node metastases at surgery. The CT scan was 68.0 percent specific, 95.0 percent sensitive, and 79.2 percent accurate in predicting mediastinal neoplastic involvement. No difference was noted between left upper lobe tumors and tumors arising in other areas of the lung. We conclude that the third generation chest CT scan is extremely sensitive in identifying enlarged mediastinal lymph nodes, but this is not specific for metastatic disease. Patients with a positive chest CT scan should have pathologic confirmation of metastatic disease with a surgical staging procedure. Patients with a negative chest CT scan, however, can be taken directly to thoracotomy.

Carcinoma, Bronchogenic↗

Oak (Quercus rubor)poisoning in cattle.

Two outbreaks of oak poisoning in cattle in the Republic of South Africa are described. In the first outbreak 22 out of 80 head of cattle were severely affected while 40 out of a herd of 135 cattle were affected in the second outbreak. Of these 40, only one survived after 9 months despite vigorous treatment. Only young cattle under 2 years were affected during both outbreaks in spite of an average herd age of approximately 6 years in the second group of cattle. Clinical signs included severe weakness with a swaying gait, diarrhoea and dehydration. Some were pot bellied while others were emaciated and remained stunted. The most prominent macroscopic and microscopic lesion present in 3 animals autopsied, was a non-suppurative interstitial nephritis which was accompanied by oedema and ulceration of the caecum and colon. Histochemical studies were carried out on pigment granules observed in kidney sections.

Animals↗