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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 343 records · Page 19Linked to original sources
PubMed1977

The origin of androgen and estrogen in a virilized postmenopausal woman with bilateral benign cystic teratomas.

Clitoromegaly was observed in a 73-year-old woman who had bilateral ovarian benign cystic teratomas that contained only epithelial derivatives. Scattered in the stroma of these ovaries were clusters of hyperplastic cells. The plasma testosterone production rate was 2.4 mg/day, a value that is ten times greater than that of normal postmenopausal women. The elevated plasma concentrations of testosterone and androstenedione decreased to normal by the second day after bilateral oophorectomy. Ovarian venous concentrations of testosterone and androstenedione were also increased and were considerably greater than those in peripheral blood. Estrone production was 68 microng/day, most of which could be accounted fo by the extraglandular formation from androstenedione. Estradiol production was 71 microng/day, of which 75% was computed to arise from extraglandular formation and the remainder likely arose by ovarian secretion. The modest increase in estrogen production was associated with slight cystic hyperplasia of the endometrium. From this study we conclude that the hyperplastic ovarian stroma was the source of the excessive androgen production.

Aged↗
PubMed1977

Radioiron and erythropoiesis: methods, interpretation and clinical application.

Ferrokinetic studies have fallen somewhat out of fashion and this is probably because T 1/2, PIT and percentage utilization give a poor reflection of the state of erythropoiesis. Recent advances have, however, enabled total, effective and ineffective erythropoiesis to be measured. The technique is simple but time-consuming, and analysis of the data requires access to computing facilities. Nevertheless, when bone marrow erythroid activity must be assessed these radioiron methods offer a rational approach.

Anemia, Aplastic↗
PubMed1976

The purification and properties of ferritin from human serum.

1. Ferritin has been isolated from the serum of four patients with iron overload by using two methods. 2. In method A, the serum was adjusted to pH 4.8 and heated to 70 degrees C. After removal of denatured protein, ferritin was concentrated and further purified by ion-exchange chromatography and gel filtration. In most cases, only a partial purification was achieved. 3. In method B, ferritin was extracted from the serum with a column of immuno-adsorbent [anti-(human ferritin)] and released from the column with 3M-KSCN. Further purification was achieved by anion-exchange chromatography followed by the removal of remaining contaminating serum proteins by means of a second immunoadsorbent. Purifications of up to 31 000-fold were achieved, and the homogeneity of the final preparations was demonstrated by polyacrylamide-gel electrophoresis. 4. Serum ferritin purified by either method has the same elution volume as human spleen ferritin on gel filtration on Sephadex G-200. Serum ferritin has a relatively low iron content and iron/protein ratios of 0.023 and 0.067 (mug of Fe/mug of protein) were found in two pure preparations. On anion-exchange chromatography serum ferritin has a low affinity for the column when compared with various tissue ferritins. Isoelectric focusing has demonstrated the presence of a high proportion of isoferritins of relatively high pI. 5. Possible mechanisms for the release of ferritin into the circulation are briefly discussed.

Chromatography, Ion Exchange↗
PubMed1976

Serum ferritin concentration in untreated Hodgkin's disease.

Serum ferritin has been estimated in 125 untreated patients with Hodgkin's disease. Increasing concentrations are found at each advancing stage of the disease and high concentrations are found in patients with systemic symptoms. In all cases this is associated with a low serum Fe concentration and reduced transferrin saturation. There is no relationship between serum ferritin concentration and histological type of disease. The findings are compatible with a non-specific response of the reticuloendothelial system to malignancy, producing a secondary disorder of Fe metabolism.

Ferritins↗
PubMed1976

Serum ferritin concentration in early breast cancer.

The concentration of circulating ferritin was measured in 250 normal adult women and 229 women presenting with early breast cancer. Ferritin concentrations are higher in cancer patients than in normal women. Patients with an intial circulating ferritin concentration above 200 mug/1 have a higher tumour recurrence rate during the subsequent 4 years.

Adolescent↗
PubMed1976

The effect of chelating agents on cellular iron metabolism.

1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects.

Binding Sites↗
PubMed1976

Iron uptake and ferritin synthesis by peripheral blood leucocytes from normal subjects and patients with iron deficiency and the anaemia of chronic disease.

The ferritin content of monocytes, lymphocytes and polymorphs is reduced in patients with iron deficiency anaemia. In patients with the anaemia of chronic disease a reduced serum iron concentration is associated with an increase in the ferritin content of all peripheral blood leucocytes. Iron uptake by all cell types is related to transferrin saturation. In iron deficiency anaemia lymphocyte iron uptake is greatly increased, possibly relfecting intracellular iron depletion. In patients with active rheumatoid arthritis and carcinomatosis there is no alteration in leucocyte iron uptake or ferritin synthesis.

Anemia, Hypochromic↗
PubMed1976

The use of chang cells cultured in vitro to evaluate potential iron chelating drugs.

A number of iron chelating agents, consisting largely of hydroxamic acid and benzoic acid derivatives, have been studied in an in vitro Chang cell culture system to determine their effect on cellular iron uptake, ferritin synthesis and the incorporation of iron into ferritin. The results have been compared with those of a previous study in which iron balance was determined in hypertransfused rats. Both techniques appear to be of value in screening new iron chelating agents for potential therapeutic use in patients with iron overload.

Benzoates↗
PubMed1976

The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.

We have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7 and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-deficient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a3, c1, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport.

Anemia, Hypochromic↗
PubMed1976

The effect of chelating agents on iron mobilization in Chang cell cultures.

The investigation of chelating agents with potential therapeutic value in patients with transfusional iron overload has been facilitated by the use of Chang cell cultures. These cells have been incubated with [59Fe]transferrin for 22 hr, following which most of the intracellular radioiron is found in the cytosol, distributed between a ferritin and a nonferritin form. Iron release from the cells depends on transferrin saturation in the medium, but when transferrin is 100% saturated, which normally does not allow iron release, desferrioxamine, 2,3-dihydroxybenzoic acid, rhodotorulic acid, cholythydroxamic acid, and tropolone all promote the mobilization of ferritin iron and its release from cells. They are effective to an approximately equal degree. The incubation of [59Fe]transferrin with tropolone in vitro at a molar ratio of 1:500 results in the transfer of most of the labeled iron to the chelator, reflecting the exceptionally high binding constant of this compound. How far these phenomena relate to therapeutic potentially remains to be seen.

Anemia, Hypochromic↗
PubMed1976

Serum ferritin.

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Adult↗