Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a newly recognized autosomal recessive disorder of copper-iron metabolism due to mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical triad; diabetes mellitus, retinal degeneration and neurological disorder in her middle age. Laboratory findings were characteristic for no detectable serum ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive storage of iron in hepatocytes and magnetic resonance imaging of the brain was indicative of increased iron content in the basal ganglia, thalamus and dentate nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209-2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a premature termination codon at the amino acid position 388. Truncation of Cp, even if effectively translated, may cause loss of its normal function because of drastic change in its triangular structure.
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PMID:A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis. 955 83

Hepatocytes are rich in mitochondria, which play an important role in hepatic metabolism. In certain pathologic conditions (most often alcoholic liver disease) mitochondria became enlarged; nevertheless, even in these conditions they are hardly detectable on light microscopy. Recently an antimitochondrial antibody (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of the present study was to study immunoreactivity of this antibody in a series of liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an ultrastructural study was also done, and in 2 cases Western blot analysis was performed. Cases were divided as follows: alcoholic liver disease (ALD, 31); steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)-related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1); sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12). All the patients were investigated for alcohol or drug abuse, pharmacological treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse. Electron microscopic immunogold and Western blot analysis confirmed that in the conditions examined the protein recognized by the mAM showed greater expression. Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic insult even in cases in which the histological picture was blurred by viral infection.
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PMID:Identification of mitochondria in liver biopsies. A study by immunohistochemistry, immunogold and Western blot analysis. 976 31

We report a 49-year-old female with hereditary ceruloplasmin deficiency with hemosiderosis. There was a family history of the same symptoms; her brother showed hypoceruloplasminemia and decrease of the serum copper content. On physical examinations, dementia, dysarthria, downbeat nystagmus, sensorineural hearing disturbance, orthostatic hypotension, retinitis pigmentosa, diffuse goiter, and cerebellar ataxia were noted. Laboratory examinations disclosed leukopenia, diabetes mellitus, hypothyroidism, decrease of copper content in the serum and urine. Serum ferritin concentration was remarkably increased. Serum ceruloplasmin could not be detected. Biopsy of the liver showed that iron content in the liver was increased. On MRI study, dentate nucleus of the cerebellum, basal ganglia, and the liver showed low intensity in both T1 and T2 weighted images. A nonsense mutation in the ceruloplasmin gene was found in this patient. Systemic iron deposition and tissue damage were considered as caused by deficiency of function of ceruloplasmin as ferroxidase. To our knowledge, the characteristic combination of the clinical signs in this patient has not been reported.
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PMID:[A case of hereditary ceruloplasmin deficiency with hemosiderosis]. 1039 Oct 79

Increased echogenicity of the pancreas, due to hemosiderosis, is a frequent laboratory finding in children and adolescents with beta-thalassemia. The aim of this study was to investigate whether increased echogenicity of the pancreas is associated with dysfunction. The ultrasonic image of the pancreas was examined in 34 children aged 12+/-3.8 years old and was compared to the endocrine and exocrine functioning of the gland. Oral glucose tolerance test (OGTT) was performed with simultaneous measurement of insulin and serum trypsin. Twenty-six of the 34 patients (76.5%) presented increased echogenicity, while 8 (23.5%) had a normal ultrasonic pancreatic image. 77% of the patients with increased echogenicity had abnormal OGTT, 46%, with subnormal or increased insulin values, and 32.5% manifested low levels of trypsin. Among the patients with normal ultrasound, 25% had abnormal OGTT and 37.5% abnormal insulin values. Statistical analysis with Student's t-test revealed that patients with increased echogenicity had significantly higher glucose values on OGTT at 60: 7.6 +/- 1.8 mmol/l (137.3 +/- 33.7 mg/dl) as compared to the patients with normal ultrasound: 6.1 +/- 1.2 mmol/l (110.75 +/- 21.72 mg/dl) (p<0.05). Insulin values were significantly affected at 30, 60, and 90 min: 570+/-301, 332+/-156, 294+/-158 pmol/l (79.54 +/- 42, 46.4 +/- 21.8, 41.04 +/- 22 mU/l) respectively in patients with increased echogenicity in comparison to those with normal ultrasonographic image of the gland: 301 +/- 170, 192 +/- 52, 135 +/- 63 pmol/l (42 +/- 23.7, 26.85 +/- 7.36, 18.9 +/- 8.8 mU/l) (p<0.05). No statistical significance was observed between the two groups regarding trypsin levels, even though abnormal values were observed in more children with increased echogenicity than in patients with a normal ultrasound. The above findings confirm that increased echogenicity of the pancreas is associated with disturbance of its function. This simple imaging method could be used as a rough early index of detection of an increased risk for developing diabetes mellitus in patients with beta-thalassemia.
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PMID:Ultrasonography of the pancreas, as a function index, in children with beta-thalassemia. 1071 56

Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.
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PMID:Islet hyperplasia in callitrichids. 1214 99

We describe a case of a female who developed haemosiderosis, in the course of treatment for very severe unstable aplastic anaemia for fourteen years. She was 37 years old at the time of initial diagnosis. Her management consisted of regular blood transfusions aimed at haemoglobin above 8.5 g/dl, antimicrobials, oxymetholone, low dose prednisone and folate. She had received about seventy five units of blood at the start of 2 grams of desferrioxamine with every subsequent blood transfusion. Annual tests of serum ferritin showed progressive increase. She developed skin changes, diabetes mellitus, heart disease, recurrent infections, generalized joint and abdominal pains and liver failure. She died within six weeks of developing congestive heart failure coupled with liver failure due to haemosiderosis despite regular use of desferrioxamine.
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PMID:Transfusion haemosiderosis inspite of regular use of desferrioxamine: case report. 1616 82

Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide. Primary hemochromatosis is the most common genetic disorder with an allele frequency greater than 10% in individuals of European ancestry, while hemosiderosis is less common but associated with a much higher morbidity and mortality. Iron overload leads to iron deposition in many tissues especially the liver, brain, heart and endocrine tissues. Elevated cardiac iron leads to diastolic dysfunction, arrhythmias and dilated cardiomyopathy, and is the primary determinant of survival in patients with secondary iron overload as well as a leading cause of morbidity and mortality in primary hemochromatosis patients. In addition, iron-induced cardiac injury plays a role in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron overload also routinely suffer from a range of endocrinopathies, including diabetes mellitus and anterior pituitary dysfunction. Despite clear connections between elevated iron and clinical disease, iron transport remains poorly understood. While low-capacity divalent metal and transferrin-bound transporters are critical under normal physiological conditions, L-type Ca2+ channels (LTCC) are high-capacity pathways of ferrous iron (Fe2+) uptake into cardiomyocytes especially under iron overload conditions. Fe2+ uptake through L-type Ca2+ channels may also be crucial in other excitable cells such as pancreatic beta cells, anterior pituitary cells and neurons. Consequently, LTCC blockers represent a potential new therapy to reduce the toxic effects of excess iron.
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PMID:Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. 1660 32

Grossly apparent and microscopically intermediate trophoblast-lined subchorionic, septal, and cell island cysts are relatively common placental findings. To analyze the clinicopathologic correlations of histologically similar but grossly inapparent microscopic chorionic pseudocysts (lakes) arising in the chorion laeve of placental membranes (mccpm), selected placental and clinical parameters of all 172 consecutive placentas with mccpm (study group, sg) and all consecutive 3743 placentas without mccpm (comparative group, cg) from years 1994 through 2005 were statistically compared; mccpm were observed in 4.3% of all placentas and in 14.9% of placentas from preeclamptic mothers from 24- to 42-week pregnancies, their gestational weeks' distribution almost mirroring that of the distribution of preeclampsia, with a peak in the middle of the 3rd trimester. Microscopic chorionic pseudocysts (lakes) arising in the chorion laeve of placental membranes were statistically significantly more common in patients with preeclampsia and maternal diabetes mellitus. In placentas with mccpm, decidual arteriolopathy, homogeneous placental maturation, global hypoxic pattern of placental injury, chorangiosis, placental infarction, laminar necrosis of membranes, stem obliterative endarteritis, erythroblasts of fetal blood, and decidual hemosiderosis were statistically significantly more common, while acute chorioamnionitis, villous fibrosis, and villous edema were less common (P < or = 0.05). There were no statistically significant differences between sg and cg in meconium staining, retroplacental hematoma, perivillous fibrin deposition, intervillous thrombi, chronic villitis, chorangiomas, placenta accreta, amnion nodosum, and marginate/vallate placenta. Highly statistically significant associations of mccpm with preeclampsia and a cluster of placental lesions known to be linked to placental hypoxia indicate that the mccpm form in response to hypoxia, particularly in patients with preeclampsia; mccpm should therefore be regarded and reported as a hypoxia-associated placental lesion.
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PMID:Microscopic chorionic pseudocysts in placental membranes: a histologic lesion of in utero hypoxia. 1753 86

Diabetes mellitus was diagnosed in a 5-year-old male chestnut-fronted macaw (Ara severa) and an 8-year-old female Military macaw (Ara militaris) based on persistent hyperglycaemia and glucosuria. Hepatic biopsies showed marked hepatic haemosiderosis, while pancreatic biopsies showed no inflammatory lesions. Repeatable and titratable responses to bovine or porcine protamine zinc insulin were recorded in both patients, who were followed up for more than 2 years. In addition, iron-elimination therapy was initiated by chelation or phlebotomy, and the birds' diet was changed to low-iron content pellets. Both birds responded favourably to this therapy, showing a decreased demand for extrinsic insulin. Follow-up biopsies demonstrated marked reduction in hepatic haemosiderin. Plasma fructosamine and beta-hydroxybutyric acid levels were measured periodically in both birds and compared with euglycaemic psittacines. Both tests appeared useful for monitoring treatment success. The potential association between diabetes mellitus and excessive iron storage in birds should be further investigated.
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PMID:Diabetes mellitus concurrent with hepatic haemosiderosis in two macaws (Ara severa, Ara militaris). 1762 Jan 81

Deferoxamine mesylate (Desferal) is a chelating agent used in hemosiderosis and aluminium overload consecutive to renal dialysis. This drug is the most efficacious for treating iron overload but is associated with ocular toxicity: dose and duration related symptomatic optic neuropathy on the one hand, reversible if treatment stopped, and acute retinal involvement followed by irreversible paucisymptomatic pigmentary changes on the other hand. Toxic risk factors are intravenous mode of administration, high doses, small iron or aluminium overload, diabetes and young age. Hence, dosis should be adapted to the amount of overload and ophthalmological follow-up should be instaured. Indeed, if treatment is stopped at the beginning of the toxic effect, ocular involvement is reversible. The baseline ophthalmological examination should include visual acuity measurement, color vision, visual fields, slit lamp and fundus. In case of risk factors, electrophysiology and fluoangiography should be added.
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PMID:[Retinal pigment epithelium--desferal]. 1771 28


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