Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chromophobic pituitary adenoma induced on BD IX-rats has been grafted on animals of the same strain. The transplanted tumour takes in 90-100%; it grows at a slow rate (in 7 months after grafting a weight of 7-20 g is attained). Tumour-bearing animals display gigantism and hypertrophy of adrenals; moreover, in 33% of cases, diabetes is observed. With non-diabetic animals, splenomegaly and marked leukocytosis are observed; immature white and red cells are present in the peripheral blood. Spontaneous regression of the tumour never occurs. After surgical removal, tumour regrowth and the formation of metastases are observed. Diabetes is characterised by pronounced hyperglycaemia, glucosuria, polyphagia and polydipsia. Histochemically, insulin cannot be detected in pancreas. Splenomegaly is never observed in diabetic animals. Transplanted adenoma frequently tends to stop growing. No recurrence is observable after extirpation. Spontaneous regression of the tumour sometimes occurs. Gigantism, hypertrophy of adrenals and diabetes are considered as consequences of growth hormone- and ACTH-secretion of the transplanted adenoma. At present the tumour is running in the 8th passage. It did not change its characteristics over a period of 5 years.
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PMID:Transplantable, STH-producing and diabetogenic pituitary adenoma of the BD IX-strain of rats. 17 13

Castrate yearling male sheep were treated for 8 weeks with either 50 micrograms/kg body wt/8 hourly sc insulin-like growth factor-I (IGF-I) (n = 10) or with saline (n = 9). IGF-I treatment increased plasma IGF-I from 235 +/- 17 to 347 +/- 16 ng/ml (P less than 0.001). There was a gradual divergence in body wt (P less than 0.10) between treatment groups. Food intake did not change significantly. The weight of the spleen corrected for body wt increased by 40% (P less than 0.001) and there was a marginal increase in adjusted kidney wt (P less than 0.1). There was no effect of IGF-I on carcass weight or dimensions, or on long bone length, although the weight per unit length of the tibia (P less than 0.05) and femur (P less than 0.10) were increased. There was no effect on wool growth. Plasma IGF binding proteins (IGFBPs) were quantified by ligand blot analysis. In the IGF-I treated group, IGFBP-1 showed a transient increase (P less than 0.05) at day 3 but was similar in both groups at day 55 of treatment. IGFBP-2 was suppressed (P less than 0.05) by day 55 and IGFBP-3 and 4 did not change. Plasma glucose was elevated (P less than 0.05) and plasma insulin was suppressed (P less than 0.01) from 280 +/- 32 pg/ml to 124 +/- 30.4 pg/ml, plasma urea (P less than 0.01) and creatinine (P less than 0.05) were reduced in the IGF-I treated group. The somatogenic effect of IGF-I in this study was minimal suggesting that in the well fed animal with an intact somatotropic axis IGF-I treatment at doses which double plasma IGF-I does not enhance somatic growth performance. However, the marked splenomegaly shows the sensitivity of splenic growth to systemic IGF-I. The suppression of insulin with chronic IGF-I treatment was accompanied by hyperglycaemia--this may explain in part the lack of a significant anabolic response and may limit the utility of IGF-I therapy unless higher doses with insulin-like effects are used.
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PMID:Body growth, carcass composition, and endocrine changes in lambs chronically treated with recombinantly derived insulin-like growth factor-I. 137 17

The non-obese diabetic mouse (NOD mouse) is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta cells mediated by T cells and culminating in insulin-dependent diabetes mellitus. Here, we report that the NOD mouse also develops Coombs'-positive hemolytic anemia, a B cell-mediated autoimmune disease. Aged NOD mice were found to have splenomegaly and jaundice predominantly due to raised unconjugated serum bilirubin. Their hematocrits were markedly lowered, and there was a reciprocal increase in the reticulocyte count. Red blood cells (RBC) from anemic mice showed a normal lytic response to hypotonicity. RBC from non-anemic mice had normal half lives in non-anemic, non-diabetic NOD mice by 51Cr labeling but, dramatically shortened half lives in anemic mice. Similar results were obtained with RBC from anemic mice. Hemolysis could be transferred with serum from anemic mice resulting in reticulocytosis. The antibody-mediated nature of the anemia was confirmed with the direct Coombs' test. Anemia was found only in mice aged greater than 200 days and was more common in diabetic (4/8) than non-diabetic (1/16) mice at 300 days. However, by 550 days, 14/17 non-diabetic mice were affected.
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PMID:Hemolytic anemia in non-obese diabetic mice. 188 56

We previously reported that streptococcal preparation (OK-432), which is a TNF inducer, inhibits insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and Bio-Breeding (BB) rats, as animal models of insulin-dependent diabetes mellitus. We have recently shown that recombinant human (h)TNF-alpha also suppresses development of diabetes in NOD mice. In this study we have extended our observation on TNF to BB rats in order to see whether TNF generally inhibits autoimmune diabetes. A total of 5 x 10(4) U of rhTNF-alpha was administered i.p., twice a week to male and female BB rats from 4 to 27 wk of age. The cumulative incidence of diabetes by 27 wk of age in nontreated rats was 36.4% (8/22), whereas that in hTNF-alpha-treated rats was 0% (0/21) (p less than 0.001). The hTNF-alpha-treated rats did not lose body weight and maintained normal blood glucose concentrations. Immunologic and histologic examinations were performed at the end of the experiment. Spleen cell cytotoxicities for NK-sensitive YAC-1 and rat insulinoma (RINm5F) cells in hTNF-alpha-treated rats significantly decreased in comparison with nontreated and nondiabetic BB rats. Intensity of insulitis was also inhibited in hTNF-alpha-treated rats. Interestingly, a huge hepatomegaly and splenomegaly was found in two of the 21 hTNF-alpha-treated rats. The latter consisted of W3/13dull+ and W3/25dull+ cells, which did not exhibit cytotoxicity for either YAC-1 or RINm5F cells. These results indicate that the chronic and systemic administration of TNF has a regulatory role in autoimmune diabetes in BB rats as well as in NOD mice, and that these animals may have a defect in TNF-mediated immunoregulation.
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PMID:Inhibition of type 1 diabetes in BB rats with recombinant human tumor necrosis factor-alpha. 238 63

Because growth failure is a frequent complication of chronic liver disease in childhood, we examined the growth hormone/insulin-like growth factor type I axis and its relationship to growth disturbances, nutritional status, and carbohydrate metabolism in nine children (2.1 to 18.6 years of age) with chronic cholestatic liver disease. Seven had cholestasis associated with splenomegaly and histologic findings of cirrhosis; two patients had Alagille syndrome. Stature was less than or equal to 15th percentile in all except the youngest subject and less than 5th percentile in five subjects. Ten-hour, nocturnal, integrated serum concentrations of growth hormone were considerably higher in patients with cholestasis than in control subjects (mean +/- SD) 9.7 +/- 3.8 vs 4.7 +/- 1.9 ng/ml; p less than 0.02). Serum concentrations of insulin-like growth hormone type I were less than 95th percentile confidence intervals for age- and sex-matched norms in five patients and at the lower limits of normal in the remaining four patients. Insulin sensitivity, determined with the minimal model intravenous glucose tolerance test, was not decreased in five patients despite elevated levels of circulating growth hormone. The estimated mean caloric and protein intake exceeded the recommended dietary allowance and the weight-for-height index was greater than 90% for six of nine patients. Triceps and subscapular skin-fold thicknesses, indicators of body fat stores, were greater than 25th percentile for five of nine and eight of nine patients, respectively, suggesting deficient lipolytic action of GH. We conclude that children with cholestatic liver disease have a resistance to the growth-promoting, diabetogenic, and lipolytic properties of growth hormone.
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PMID:Resistance to the growth-promoting and metabolic effects of growth hormone in children with chronic liver disease. 239 94

Oral medium-chain triglycerides were given to 10 normal volunteers, 12 cirrhotics (group I) without and 28 cirrhotics (group II) with abnormal portal systemic communications (ascites, splenomegaly, oesophageal varices, or surgically-created portacaval shunts). After 30 ml of medium-chain triglyceride oil there was no appreciable change in serum glucose levels in any of the three groups nor in serum insulin levels in the normals and in cirrhotics in group I. However, there was a significant increase in serum insulin levels in the cirrhotic patients in group II. It is suggested that the rise in serum insulin levels after medium-chain triglycerides noted in the cirrhotics with shunts is due to shunting of insulin-containing portal blood around the liver (anatomical shunts) and to a diminished hepatic cell mass capable of extracting insulin (functional shunt). This differential response of serum insulin levels to medium-chain triglycerides may prove to be of value in detecting the presence of abnormal portal systemic communications in cirrhotic patients.
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PMID:Stimulation of insulin secretion by medium-chain triglycerides in patients with cirrhosis. 554 59

One of the hallmarks of the hyperglycemic-hyperinsulinemic infant of the diabetic mother (IDM) is macrosomia and selective organomegaly. Primary hyperinsulinemia, with insulin levels similar to those observed in human IDMs at delivery, was produced in the fetal rhesus monkey during the last third of gestation. The effects of this physiologically relevant hyperinsulinemia, in the absence of hyperglycemia, on fetal growth were studied. Fetal macrosomia, with a 23% increase in total body weight, was observed in physiologically hyperinsulinemic fetuses. A similar 27% increase in weight was produced by fetal insulin levels that were 10 times higher. A logarithmic correlation was observed between fetal birth weight ratio and fetal plasma insulin concentration. In contrast to this increase in weight, skeletal growth, as measured by crown-heel length and head circumference, was not affected by hyperinsulinemia. Only cardiomegaly was found in the low-dose hyperinsulinemic fetuses, whereas cardiomegaly, hepatomegaly, and splenomegaly were produced by hyperinsulinemia in which insulin levels were in the highest range. Compositional analysis of heart and skeletal muscle indicated no differences in the protein, RNA and DNA concentration, or in the protein-to-DNA ratio in hyperinsulinemic fetuses. We interpret these data as indicating that fetal insulin plays the predominant role in controlling the normal, as well as the augmented, fetal weight characteristic of the human infant of the diabetic mother.
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PMID:Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiologic hyperinsulinemia on fetal growth and composition. 637 21

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periarteritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and (3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.
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PMID:Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats. 884 18

We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m2 x 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1 1/2 years post transplant. He presented with microhematuria and proteinuria 4 1/2 years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulin-dependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation.
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PMID:Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child. 982 23

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20


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