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Biomedical subjects

D C Aron

Publications and source records attributed to D C Aron.

At least 19 recordsLinked to original sources
PubMed1992

The Cleveland Veterans Affairs Medical Center firm system.

Hospital-based "firms" provide a means for combatting the fragmentation experienced by both patients and caregivers in the modern teaching hospital environment. A "firm" is an academic group practice that includes attending physicians, physician trainees, nurses, other staff, and patients. Each person's relationship with a firm lasts throughout his or her association with a particular institution. This article describes the firm system that was recently implemented on the Medical Service of the Cleveland VAMC. This system incorporates both inpatient and outpatient general medical services and provides for unbiased assignment of patients, physicians, and nurses.

Adult↗
PubMed1992

Somatostatin-producing neuroendocrine tumor of the ampulla (ampullary somatostatinoma). Evidence of prosomatostatin production.

Two cases of somatostatin-producing ampullary neuroendocrine tumors (somatostatinoma) are reported. The authors have characterized their immunoreactivity using antibodies specific for the amino- and carboxyl-terminal portions of prosomatostatin, the precursor of somatostatin in the normal synthetic pathway. Cytoplasmic staining was found using each of these two antibodies in the tumor cells of both ampullary somatostatinomas as well as in the cytoplasm of cells in the hypothalamus, crypt cells of the duodenal mucosa, mucosal cells of the biliary tract, D cells of the pancreatic islets, and parafollicular cells of fetal thyroid. These studies suggest that the synthesis of somatostatin in ampullary somatostatinomas occurs through the normal pathway from the precursor prosomatostatin.

Ampulla of Vater↗
PubMed1992

Cushing's syndrome with cranial and pulmonary lesions: necessity for tissue diagnosis.

This report describes two cases of Cushing's syndrome associated with radiologic abnormalities in the lung and brain. In both cases, the pathologic diagnosis of the intracranial lesion was unsuspected and prompted changes in management. These cases illustrate that the etiology of pulmonary and central nervous system mass lesions in patients with Cushing's syndrome may not be predicted on clinical grounds or by conventional radiologic methods. A tissue diagnosis is essential as a guide to appropriate management, and biopsies of such lesions are indicated.

Aged↗
PubMed1992

Insulin-like growth factor I and erythropoiesis.

The bone marrow, the primary site of hematopoiesis, is a self-renewing system consisting of a unique micro-environment that promotes the differentiation and proliferation of the various hematopoietic cell lines. While many critical factors necessary for red cell production have been identified, the regulation of erythropoiesis has not been completely elucidated. In addition to multi-lineage growth factors (e.g. interleukin 3 or 4) and lineage-specific hematopoietic growth factors (e.g. erythropoietin), several lines of evidence suggest a key role for insulin-like growth factor I (IGF-I). First, growth hormone stimulates erythropoiesis and IGF-I is known to mediate many of growth hormone's actions (somatomedin hypothesis). Second, factors in bovine serum and in serum from an anephric human with erythropoietic activity distinct from erythropoietin have been identified as IGFs. Third, IGF receptors are found on both erythrocyte precursors as well as mature erythrocytes. Fourth, in vitro IGF-I stimulates erythropoiesis in bone marrow cultures. Fifth, IGF-I administration to neonatal or hypophysectomized animals results in increased erythropoiesis in vivo. Recent studies indicate that IGF-I at physiologic concentrations stimulates erythropoiesis and that growth hormone's action is indirect, occurring via IGF-I. The physiologic source of IGF-I for the bone marrow may be delivery from the serum (an endocrine mechanism) or synthesis within the bone marrow by stromal or other cells (a paracrine mechanism). Our recent studies have shown that mouse bone marrow stromal cells secrete both IGF-I and IGF binding proteins (IGFBPs). The role of IGFBPs in erythropoiesis is not known, but they might modulate the local concentration of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Secretion of insulin-like growth factor I and its binding proteins by collecting duct cells.

Insulin-like growth factor I (IGF-I) has been found in the kidney, particularly in the collecting duct in the rat. Since cultured rabbit collecting duct cells constitute a convenient system for in vitro studies, we have examined whether these cells secrete IGF-I. Culture medium conditioned by collecting duct cells was concentrated by reverse phase chromatography and applied to a Sephadex G100 column equilibrated in a denaturing buffer. Two major species with apparent molecular weights of 7.5 and greater than 25 kilodaltons (kD) were identified by IGF-I RIA. A smaller amount of 10 kD species was also observed. Further characterization of 7.5 kD IGF-I immunoreactive species by reverse phase HPLC showed that it eluted in a single peak. To determine whether the higher molecular weight species possessed IGF-I binding activity, appropriate fractions were desalted, incubated with [125I]IGF-I (thr59) for two hours at 30 degrees C and applied to a Sephadex G100 column equilibrated in a non-dissociating buffer. The major peak of radioactivity was confined to a high molecular weight region; there was no radioactivity in the fractions corresponding to 7.5 kD. Western ligand analysis of unreduced conditioned medium identified two IGF-I binding species of 25 and 30 kD, similar in size to species observed in normal rabbit serum. 125I-IGF-I binding as assessed in a charcoal adsorption assay could be displaced by IGF-I and IGF-II but not by insulin. Further characterization of the 10 kD peak of IGF-I immunoreactivity indicated that it did not possess IGF-I binding activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Secretion of insulinlike growth factor I and insulinlike growth factor-binding proteins by murine bone marrow stromal cells.

Insulin-like growth factor I (IGF-I) stimulates hematopoiesis. We examined whether bone marrow stromal cells synthesize IGF-I. Secretion of IGF-I immunoreactivity by cells from TC-1 murine bone marrow stromal cells was time-dependent and inhibited by cycloheximide. Gel filtration chromatography under denaturing conditions of TC-1 conditioned medium demonstrated two major peaks of apparent IGF-I immunoreactivity with molecular weights of approximately 7.5-8.0 kD, the size of native IGF-I, and greater than 25 kD. Expression of IGF-I mRNA was identified by both RNase protection assay and reverse transcription/polymerase chain reaction. To determine whether the greater than 25-kD species identified by RIA possessed IGF-binding activity, a potential cause of artifactual IGF-I immunoreactivity, charcoal adsorption assay of these gel filtration fractions was performed. The peak of IGF-binding activity coeluted with apparent IGF-I immunoreactivity suggesting that TC-1 cells secrete IGF-binding protein(s). Unfractionated conditioned medium exhibited linear dose-dependent increase in specific binding of [125I]-IGF-I with a pattern of displacement (IGF-I and IGF-II much greater than insulin) characteristic of IGF-binding proteins. Western ligand analysis of conditioned medium showed three IGF-I binding species of approximately 31, 38, and 40 kD. These data indicate that TC-1 bone marrow stromal cells synthesize and secrete IGF-I and IGF-binding proteins and constitute a useful model system to study their regulation and role in hematopoiesis.

Amino Acid Sequence↗
PubMed1990

Spontaneous resolution of Cushing's syndrome after pregnancy.

Pregnancy is a rare occurrence in women with Cushing's syndrome. Even more uncommon is the exacerbation of Cushing's syndrome during pregnancy and spontaneous resolution post partum. We report one such case in which biochemical and radiologic findings suggested adrenocorticotropic hormone-dependent disease.

Adult↗
PubMed1990

Cushing's syndrome and pregnancy.

Pregnancy is a rare occurrence in women with Cushing's syndrome. Amenorrhea or oligomenorrhea occurs in about 75% of premenopausal women with Cushing's syndrome as a result of suppression of gonadotrophin secretion primarily by excess glucocorticoids. We have reviewed pregnancies in women with Cushing's syndrome (63 cases from the literature and four cases of our own). Since pregnant women without Cushing's syndrome develop some features of Cushing's syndrome, such as hypertension, hyperglycemia, and striae, a high index of clinical suspicion must be maintained to prevent delay in diagnosis. The physiologic changes in adrenocorticosteroid metabolism during pregnancy further complicate the diagnosis. Maternal and fetal risks increase markedly when pregnancy does occur in women with hypercortisolism. However, the wide spectrum of severity of the disease mandates an individualized approach to the therapy in each case.

Adrenalectomy↗
PubMed1990

Secretion of insulin-like growth factor-I and binding proteins by rat liver fat-storing cells: regulatory role of platelet-derived growth factor.

Insulin-like growth factor (IGF-I) is synthesized in multiple organs, including the liver, and may play a role in tissue growth and repair. We report that liver fat-storing cells (FSC) secrete IGF-I immunoreactivity in the culture medium. Secretion of IGF-I immunoreactivity was blocked in the presence of cycloheximide, suggesting de novo synthesis. Culture medium conditioned by FSC was concentrated and applied to a Sephadex G100 column equilibrated in a denaturing buffer. Two major species with apparent mol wts of 7.5 and greater than 25 k were identified by IGF-I RIA. Reverse phase HPLC of the 7.5 kilodalton species (the size of IGF-I) showed that it eluted in a single peak. To determine whether the higher mol wt species possessed IGF-I binding activity, appropriate fractions were desalted, incubated with [125I]IGF-I for 2 h at 30 C and applied to a Sephadex G100 column equilibrated in a nondissociating buffer. The major peak of radioactivity was confined to a high mol wt region. Western blot ligand analysis revealed the presence of two insulin-like growth factor binding proteins of approximately 28 and 31 kilodaltons. Platelet-derived growth factor, a potent mitogen for FSC, resulted in a 230% increase in release of IGF-I immunoreactivity that could be accounted for by an increase in IGF-I binding activity. In addition IGF-I increased DNA synthesis in FSC and this effect was additive to that of platelet-derived growth factor. IGF-I treatment also resulted in an increase in cell number. IGF-I and insulin-like growth factor binding proteins secreted by FSC may play a role in the hepatic tissue response to injury via autocrine and/or paracrine mechanisms.

Animals↗
PubMed1990

Feminizing adrenocortical tumor: steroid hormone response to ketoconazole.

A 58-yr-old man presented with gynecomastia and elevated serum estrogens. The diagnosis of an estrogen-secreting adrenal tumor was made based upon the finding of a 4-cm left adrenal mass, elevated levels of estradiol in peripheral and left adrenal venous blood, and increased urinary 17-ketosteroids. In addition to marked elevations in estradiol and 17-ketosteroids there was an increased baseline level of 11-deoxycorticosterone and a slightly decreased level of 18-hydroxycorticosterone, suggesting the possibility of impaired P450c11 activity. The effect of ketoconazole administration (600 mg/day) for 4 weeks was studied. Urinary free cortisol and 17-ketosteroid excretion and serum testosterone levels fell acutely (1 week). Serum estradiol levels decreased gradually over the 4-week course. Plasma aldosterone levels were essentially unaltered and 18-hydroxcorticosterone levels fell gradually, but there were marked increases in 11-deoxycorticosterone and corticosterone. Coincident with the increase in 11-deoxycorticosterone there was an increase in blood pressure and a transient fall in serum potassium. We conclude that ketoconazole administration may result in a hypermineralocorticoid state. Therefore, the usefulness of ketoconazole therapy for steroid hormone-producing neoplasms will depend upon the individual tumor's steroidogenic profile.

17-Ketosteroids↗
PubMed1989

Synthesis and binding of insulin-like growth factor I by human glomerular mesangial cells.

Insulin-like growth factor I (IGF-I) has been found in the kidney, but its precise cellular localization is not known. Since there is evidence that IGF-I is an autocrine factor in many tissues and since murine mesangial cells have IGF-I receptors, we examined whether human mesangial cells produce IGF-I. Culture medium conditioned by mesangial cells was concentrated by reverse phase chromatography and applied to a Sephadex G-100 column equilibrated in a denaturing buffer. Two major species with apparent mol wt (MW) of 7,500 and 25,000 daltons were identified by IGF-I RIA. To determine whether the high MW species possessed IGF-I binding activity, appropriate fractions were desalted, incubated with [125I]Thr59-IGF-I for 2 h at 30 C, and applied to a Sephadex G-100 column equilibrated in a nondissociating buffer. The major peak of radioactivity was confined to a high MW region; there was no radioactivity in the fractions corresponding to 7,500 daltons. Further characterization of 7,500 dalton IGF-I immunoreactive species by reverse phase high performance liquid chromatography showed that it coeluted with synthetic human IGF-I. Isoelectric focusing revealed it to have a pI between 8.1 and 8.5, corresponding to the pI of human IGF-I of 8.25. Northern blot analyses of poly(A)+ RNA from human mesangial cells and human liver using a cDNA probe for human IGF-I showed that a 2.0-kilobase transcript predominated in the mesangial cells, whereas the liver contained 1.1- and 2.0-kilobase species. Specific binding of IGF-I to mesangial cells was demonstrated, and competition curves indicated a rank order of potency (IGF-I greater than IGF-II greater than insulin) consistent with type I IGF receptors. We conclude that human mesangial cells 1) express IGF-I mRNA transcripts, 2) secrete IGF-I and IGF-I-binding activity, and 3) possess specific IGF-I receptors. These data suggest that IGF-I may act as an autocrine or paracrine factor that regulates glomerular cell functions.

Animals↗
PubMed1989

Endocrine complications of the acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a multisystem disorder characterized by defects in the immune system that result in opportunistic infections and neoplasms. While endocrine dysfunction has not been a prominent clinical feature of AIDS, all endocrine glands may be affected by the opportunistic infections and neoplasms or by agents used in their treatment. Adrenal cortical insufficiency related to cytomegalovirus and ketoconazole therapy, hypoglycemia related to pentamidine therapy, and hyponatremia secondary to diverse causes are the most serious endocrine abnormalities that commonly occur. As the numbers of patients with AIDS increase, the development of these and other endocrine complications will occur more often. Because the clinical manifestations of endocrine dysfunction may be nonspecific or subtle, they may be overlooked, particularly in the setting of chronically and severely ill patients. Recognition and prompt therapy for endocrine dysfunction is essential for optimal treatment of these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cushing's disease.

Cushing's disease is a form of Cushing's syndrome, persistent inappropriate hypercortisolism, that results from pituitary ACTH hypersecretion. It currently accounts for 70 per cent of adult cases of Cushing's syndrome and affects mainly women of childbearing age. The pathology, cause, and clinical and laboratory features of the disease are discussed. The initial step in diagnosis is documentation of endogenous hypercortisolism, which is followed by identification of the cause. Selective transsphenoidal resection of ACTH-producing pituitary adenomas is the initial treatment of choice. The roles of radiotherapy and medical therapy are discussed.

Adrenalectomy↗