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Biomedical subjects

D R Richardson

Publications and source records attributed to D R Richardson.

At least 19 recordsLinked to original sources
PubMed1992

Intermediate steps in cellular iron uptake from transferrin. Detection of a cytoplasmic pool of iron, free of transferrin.

The uptake of transferrin-bound iron by receptor-mediated endocytosis has been the subject of extensive experimental investigation. However, the path followed by iron (Fe) after release from transferrin (Tf) remains obscure. Once Fe is released from Tf within the endosome, it must be transported across the endosomal membrane into the cell. The present investigation describes the presence of a cytoplasmic Tf-free Fe pool which is detectable only when cells are detached from their culture dishes at low temperature, after initial incorporation of diferric transferrin at 37 degrees C. This cellular iron pool was greatly reduced if incubation temperatures were maintained at 37 degrees C or if cells were treated with pronase. Human melanoma cells (SK-MEL-28) in culture were prelabeled by incubation with human 125I-59Fe-transferrin for 2 h, washed, and reincubated at 4 degrees C or 37 degrees C in balanced salt solution in the presence or absence of pronase. The cells were then mechanically detached from the plates and separated into "internalized" and supernatant fractions by centrifugation. Approximately 90% of cellular 59Fe and 20% of 125I-Tf remained internalized when this reincubation procedure was carried out in balanced salt solution at 37 degrees C. However, at 4 degrees C, cellular internalized iron was reduced to approximately 50% of the initial value. The release of this component of cellular 59Fe (approximately 40% of total cell 59Fe) at 4 degrees C was completely inhibited in the presence of pronase and other general proteinases at 4 degrees C and at 37 degrees C, without affecting internalized transferrin levels. Similar results were obtained in fibroblasts and hepatoma cells, indicating that this phenomenon is not unique to melanoma cells. The characterization of this Tf-free cellular Fe pool which is detectable at low temperature may yield valuable insights into the metabolic fate of iron following its transport across the membrane of the endocytotic vesicle.

Cytoplasm↗
PubMed1992

A low-spin iron complex in human melanoma and rat hepatoma cells and a high-spin iron(II) complex in rat hepatoma cells.

Human melanoma and rat hepatoma cells cultured in the presence of low concentrations (2.5 microM) of low-molecular-weight iron (Fe) chelates and Fe-transferrin complexes have been studied with 57Fe Mössbauer spectroscopy. The spectra show that holoferritin is only a minor fraction of the total iron present in the cells. The major form of Fe was in a low-spin state unlike the high-spin Fe(III) found in ferritin. Only about 10% of the Fe could be attributed to ferritin. In addition, the hepatoma cells had a high-spin Fe(II) spectral component which made up about 20% of the Fe present.

Animals↗
PubMed1992

The effect of desferrioxamine and ferric ammonium citrate on the uptake of iron by the membrane iron-binding component of human melanoma cells.

The effect of ferric ammonium citrate (FAC) and desferrioxamine (DFO) on membrane iron and transferrin uptake have been investigated using SK-MEL-28 human melanoma cells which express the membrane-bound transferrin homologue, melanotransferrin, at high concentrations. Exposure of melanoma cells to DFO increased membrane non-Tf-bound Fe uptake (putative melanotransferrin Fe-binding sites), suggesting upregulation of the membrane Fe-binding component. However, exposure to FAC did not result in down-regulation. Indeed, an increase in non-Tf-bound membrane Fe was apparent. Results suggested that non-Tf-bound membrane Fe uptake occurred by two processes corresponding to the specific and non-specific mechanisms of Fe uptake from Tf described previously (Richardson, D.R. and Baker, E. (1990) Biochim. Biophys. Acta 1053, 1-12).

Cell Membrane↗
PubMed1991

The release of iron and transferrin from the human melanoma cell.

The role of the transferrin homologue, melanotransferrin (p97), in iron metabolism has been studied using the human melanoma cell line, SK-MEL-28, which expresses this antigen in high concentrations. The release of iron and transferrin were studied after prelabelling cells with human transferrin doubly labelled with iron-59 and iodine-125. Approx. 45% of internalised iron was in ferritin with little redistribution during reincubation. Iron release was linear with time, while transferrin release was biphasic, suggesting that iron was leaving the cell independently of transferrin. Unlabelled diferric transferrin increased transferrin release, implying a degree of coupling between cell surface binding, internalisation and release of transferrin. Increasing the preincubation time increased the amount of transferrin which remained internalised within the cell. A membrane-bound, iron-binding component with properties consistent with melanotransferrin was observed. Desferrioxamine or pyridoxal isonicotinoyl hydrazone could not remove iron from this compartment, suggesting a high affinity for iron. The number of membrane iron-binding molecules per cell was estimated to be 387,000 +/- 7000 . The non-transferrin-bound membrane Fe did not decrease during reincubation periods up to 5 h, suggesting that the cell was not utilising it. Hence, melanotransferrin may not have a role in internalising iron in melanoma cells.

Antigens, Neoplasm↗
PubMed1990

The uptake of iron and transferrin by the human malignant melanoma cell.

The role of the transferrin homologue, melanotransferrin (p97), in iron metabolism has been studied using the human melanoma cell line, SK-MEL-28, which expresses this antigen in high concentrations. The mechanisms of iron and transferrin uptake were investigated using human transferrin labelled with iodine-125 and iron-59. Internalised and membrane-bound iron and transferrin were separated using the proteinase, pronase. The uptake of iron from transferrin occurred by at least two processes. The first process was saturable and consistent with receptor-mediated endocytosis, involving internalisation of transferrin bound to specific binding sites. Uptake of iron also occurred by a second process which was non-saturable up to 0.06 mg/ml (0.75 microM) and was of higher efficiency than the saturable process. This process of iron uptake may be the dominant one at physiological serum transferrin concentrations. A membrane-bound, pronase-sensitive, temperature-dependent, iron-binding component was also identified. The number of binding sites was estimated to be approx. 340,000 per cell (assuming 2 atoms of iron per site) and it is suggested that this binding component may be melanotransferrin.

Antigens, Neoplasm↗
PubMed1990

Effects of atherosclerosis on the cutaneous regional and microcirculatory response to ischemia.

The cutaneous vascular response to gravity load is abnormal in atherosclerosis. In this study we compared the macrocirculatory and microcirculatory response to ischemia in atherosclerotic smokers, nonatherosclerotic smokers, and healthy nonsmokers. Using videodensitometry, the capillary blood velocity of hallux nail fold capillaries was measured at rest and following 1 minute of ankle cuff occlusion. Blood-flow velocity of the dorsal metatarsal artery was measured by ultrasound Doppler. Resting dorsal metatarsal artery velocity and capillary blood velocity of atherosclerotic subjects were lower than those of nonatherosclerotic smokers and nonsmokers. The dorsal metatarsal artery velocity and capillary blood velocity increased in each group following occlusion. Peak postocclusion dorsal metatarsal artery velocity was lower in the atherosclerotic subjects, but peak capillary blood velocity was not significantly different among groups. Atherosclerosis does not alter the mechanisms of reactive hyperemia in either the macrocirculation or the microcirculation. The magnitude of hyperemia is diminished at the macrocirculatory level.

Arteriosclerosis↗
PubMed1990

A case of military Munchausen's syndrome.

Since its initial description in 1951 many variants of Munchausen's Syndrome have been described. This present case report is of a patient who adopts military rank in order to gain admission to a service hospital: a case of Military Munchausen's Syndrome.

Adult↗
PubMed1990

A survey of students' notions of body function as teleologic or mechanistic.

The objectives of this study were to determine 1) the relative degrees to which students' notions of physiological functions are teleologic or mechanistic in nature, 2) whether these notions differ between students in elementary and advanced-level physiology courses, and 3) whether the degree of teleologic vs. mechanistic thinking can be modified by direct discussion of this topic. A questionnaire that determined whether students thought about body functions in a teleologic (why) or mechanistic (how) manner was administered to the following categories of students: 1) a class of high school biology students, 2) classes of students taking elementary college-level physiology courses, and 3) college students in advanced physiology courses. Overall, there was an average 61% teleologic response among the various classes, and differences between the classes were not statistically significant (P greater than 0.05). To address objective 3, one of the classes was presented the questionnaire after being given a lecture on teleology vs. mechanistic approaches to body function. The average teleological response of this class was only 12%, a value significantly lower in comparison, by a one-way analysis of variance, to any of the other groups (P less than 0.0001). These results indicate that the students have a strong tendency to think of body functions in teleological terms and that this tendency can be modified on a short-term basis by a direct discussion (by an instructor) of teleologic vs. mechanistic thinking.

Africa↗
PubMed1990

Time-dependent changes in cardiovascular regulation caused by chronic tobacco smoke exposure.

The purpose of this study was to determine whether chronic tobacco smoke exposure for less than 2 mo alters cardiovascular regulation. One group of male Sprague-Dawley rats was administered tobacco smoke from low-nicotine cigarettes (group A, 1 mg/cigarette) for 4-6 wk, while a second group (B) served as a sham control by receiving only puffs of room air. Reflex adjustments in mean arterial blood pressure (MAP) after bilateral common carotid occlusion (BCCO) were compared between the two groups. In the anesthetized control state, no significant difference existed for the cardiovascular parameters measured in the two groups. However, MAP increases after BCCO were significantly greater in the smoke-treated animals (P less than 0.05) compared with the sham-treated group. At 10, 20, 30, and 40 s after BCCO, MAP increases above preocclusion values were 66, 45, 42, and 38% for group A and 35, 26, 24, and 22% for group B, respectively. Additionally, the time required to reach maximum MAP after BCCO was significantly less (P less than 0.05) for the smoke-treated vs. sham-treated animals (8.5 +/- 0.2s for group A, 11.2 +/- 0.3s for group B). MAP changes during BCCO were significantly different (P less than 0.05) between the treatment groups after cervical vagotomy. It is concluded that chronic tobacco smoke exposure in experimental animals for periods as short as 4-6 wk alters the reflex regulation of the cardiovascular system.

Animals↗
PubMed1989

Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II).

Formation constants for the calcium(II), magnesium(II) and zinc(II) complexes of the orally effective iron chelator, pyridoxal isonicotinoyl hydrazone (PIH) and three analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone (PpMBH) and pyridoxal m-fluorobenzoyl hydrazone (PmFBH) have been determined by potentiometry at 25 degrees C and I = 0.1 M [KNO3]. The four ligands bind calcium(II) weakly and magnesium(II) only slightly more strongly, as a 1:1 complex which is formed at pH greater than 8. The chelation of zinc(II) for all the ligands studied was greater than that for calcium(II) and magnesium(II), with complexation generally becoming significant at about pH 5. Thus, chelation of zinc(II) but not calcium(II) or magnesium(II) at physiological pH, 7.4 may be expected. Calculated values of the concentration of uncomplexed metal ion indicate that the selectivity of these ligands towards Fe(III) is comparable to that of the clinically used chelator desferrioxamine.

Calcium↗
PubMed1985

Transurethral resection of the prostate and bladder neck incision: a review of 700 cases.

Transurethral resection (TUR) is regarded as the treatment of choice for relief of outflow tract obstruction in the male, but bladder neck incision (BNI) is an acceptable alternative when the gland is small. Seven hundred cases of TUR/BNI have been reviewed (TUR = 388; BNI = 312). BNI was performed when the gland was less than 35 g and where there was no clinical suspicion of malignancy. The operative details of our single incision technique are given. While the patients in the BNI group were younger, catheter stay was shorter, there was less infection, a significantly reduced need for blood transfusion and a satisfactory outcome in terms of control and need for further surgery. BNI is a technically simpler procedure than TUR and is easy to teach and learn. Results show it is safe and effective for patients in acute retention as well as those treated electively and it is the operation of choice for small benign prostates.

Adult↗