The transferrin receptor system is not involved in the pathogenesis of hematological disorders with 3q inversion.

To clarify the idea that an alteration of the transferrin receptor (TF-R) gene, localized to 3q26, may be of pathogenetic significance in hematological disorders with 3q anomaly, we studied the TF-R systems of erythroblasts from both functional and genetic aspects. The patient described here had refractory anemia with an excess of blasts (RAEB), with paracentric inversion, inv(3)(q21q26). The patient had the characteristic findings of micromegakaryocytosis and thrombocytosis, with giant platelets.

Mechanism of Decrease in Transferrin Receptor Synthesis by Interferon-α Treated Human Lymphoblastoid Cells.

To clarify the mechanism of antiproliferative action of interferon-α (IFN-α) in hematological malignancy, we examined the transferrin receptor system in the lymphoblastoid cell line, Daudi cells treated with IFN-α. When cells were cultured with 10(4)U/ml of IFN-α, the number of surface transferrin receptors was decreased to 60% of that seen in the control culture. This decrease was not neutralized by co-incubation with the iron chelator, desferrioxamine (10-200 μM), suggesting that the change in the level of chelatable iron did not account for the decrease in transferrin receptor numbers.

Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: effect of vehicle and percutaneous penetration enhancer.

The effects of vehicle and percutaneous penetration enhancer on the penetration of acyclovir through excised hairless mouse and rat skin were investigated. Four solvents, propylene glycol (PG), ethanol (ET), isopropanol (IPA), and isopropyl myristate (IPM), were employed as vehicles, in combination with four enhancers, 1-farnesylazacycloheptan-2-one (7FU), 1-geranylazacycloheptan-2-one (7GU), 1-geranylazacyclopentan-2-one (5GU), and 1-dodecylazacycloheptan-2-one (Azone). Acyclovir was suspended in vehicles to avoid the effect of the thermodynamic activity of acyclovir in the vehicle.

Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis.

Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease.

Mechanisms involved in the development of adriamycin resistance in human leukemic cells.

We have developed three adriamycin (ADR)-resistant K562 sublines with different degrees of resistance. These sublines show a decreased accumulation and an increased efflux of ADR in proportion to the degree of resistance. Two membrane proteins (mol.

Possible mechanism of ineffective erythropoiesis by an altered transferrin receptor cycle in erythroleukemia.

Involvement of the transferrin receptor cycle was noted in erythroblasts from a patient with erythroleukemia (FAB classification M6). The kinetics of transferrin receptor cycle in bone marrow erythroblasts was obtained by pulse-chase experiments before the initiation of therapy. Internalization of transferrin was impaired and resulted in a delayed peak of internalized transferrin, as compared with the kinetics pattern seen in healthy subjects.

Regulation of biosynthesis and phosphorylation of P210bcr/abl protein during differentiation induction of K 562 cells.

The changes of P210bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with 32PO4 and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210bcr/abl protein and other phosphoproteins.

Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias.

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects (p less than 0.

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia.

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor.

[The age-related changes in serum 17-hydroxyprogesterone secretion in men].

In order to clarify the age-related changes in serum 17-hydroxyprogesterone (17-OHP) secretion in men, serum basal 17-OHP levels were determined in 203 healthy male subjects from 10 months to 116 years of age, and serum 17-OHP responses to dexamethasone (Dex), fluoxymesterone (FM), HCG and ACTH were compared between the young and elderly groups. The mean basal 17-OHP level remarkably increased from pubescence to the third decade and gradually decreased with advance in age after fifty. Basal serum 17-OHP level was correlated more closely with serum testosterone (T) than cortisol (F), and was suppressed more remarkably after the administration of FM than Dex in both groups.

Effect of vitamin E on function of pituitary-gonadal axis in male rats and human subjects.

The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma.

Intestinal tumors of rats by gastric or intestinal administration of cycad extract and cycasin.

Sprague-Dawley rats were given gastric intubation of cycad extract (group 1), rectal infusion of cycasin (group 2), or rectal indusion of cycad extract after external colostomy at 1/3 proximal portion of the large intestine (group 3). In group 1, intestinal tumors developed in any portion of the intestinal tract ranging from the duodenum to the rectum. In group 2, tumors developed in mucosa of the large intestine.

Hepatic tumors of rabbits induced by cycad extract.

Fifteen rabbits were administered cycad extract by gastric intubation, 1 ml/rabbit, once a week for 27 or 33 weeks. The extract contained 16.6 mg of cycasin/ml.