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

Associated visceral organ involvement evidence by systemic fibrosis has not been explored in oral submucous fibrosis (OSF). The investigations in this aspect were limited to loco-regional sites of naso/oropharynx and oesophagus. The study of whether the oral fibrosis is part of a systemic spectrum of disease involving multiple organs is an interesting pursuit. With this intention the patients diagnosed on clinical and histological grounds for OSF were concurrently tested by biophysical means for the presence of endomyocardial fibrosis (EMF), pancreatic (PF) and retroperitoneal fibrosis (RPF), which are endemic to the area studied. Twenty-five (n = 25) cases of OSF who visited the Department of Oral pathology & Microbiology. Govt. Dental College, Trivandrum, India for symptomatic relief of their illness comprised the study group. Ten (n = 10) age and sex matched healthy volunteers comprised the control. All the subjects have had undergone cardiologic and gastrointestinal investigations to rule out the possibility of concurrent EMF and PF. The patients were all of Indian ethnic extraction and mostly (> 90%) were from low socio economic classes. The mean age of the patients was 54.16 +/- 14.6 years, including 18 females and 7 males (F:M = 2.57:1). The severity of fibrosis was unrelated to the age of patients (P > 0.05). All the patients were chewers of areca quid (12%)/tobacco (88%). In addition to quid chewing 3/25 (12%) patients smoked 'bidi' and 6/25 (24%) consumed home brewed liquor (arrack/toddy) which contain about 40-50% ethanol. Statistically no relationship was observed between the clinical stages of OSF and severity of epithelial dysplasia in this study (P > 0.05). Out of the 25 patients, 5 (20%) showed sclerotic aortic value which may be an age related finding. Also 7 (28%) patients were found to be hypertensive and interstitial lung disease was present in 2 (8%). The possibility of EMF in one female patient who showed thickened RV apical endocardium was ruled out by cardiac catheterisation. Thus none of the patients showed evidence of endomyocardial fibrosis. The pancreas was found to be hyperchoic in 8(32 1/4) by ultra sonography. Liver was found to be hyperchoic in 6 (24%). Fat stain in stool samples was found to be positive in 13(58%). The hyperchogenecity of pancreas may be due to alcoholism or an underlying endocrine pancreatic insufficiency like diabetes and not due to pancreatic fibrosis. The positivity of fat stain could be due to fatty liver/alcoholism. Thus the study fails to reveal any evidence of pancreatic fibrosis in the group. The lack of any evidence of an associated visceral organ fibrosis in OSF made it prudent to believe that this is a loco-regional disease, initiated by local factors and propagated under their influence without systemic involvement.
 ...
PMID:Visceral organ involvement is infrequent in oral submucous fibrosis (OSF). 1144 4

A 56-year-old woman was hospitalized with a right hemiplegia and aphasia evoking a cerebral infarction. In fact the neurologic deficits were of post-ictal origin, secondary to a partial epilepsy which began a few weeks before, at the same time as a polyuria-polydipsia syndrome revealing diabetes mellitus. This case illustrates the possibility for a partial epilepsy to occur in relation with a nonketotic hyperglycemia. If in most of those cases there is no underlying cortical lesion, in some observations the hyperglycemia is associated with an infarction. In our case the MRI revealed another type of lesion: a cortical dysplasia in form of a unilateral micropolygyria with a perisylvian distribution centered around the insula. The discovery of a cortical dysplasia at such an age is very unusual.
 ...
PMID:[Epileptic seizures, hemiplegia and hyperglycemia: late discovery of a localized cortical dysplasia]. 1145 89

Understanding the pathology of familial pancreatic carcinoma may provide important insights into pancreatic tumorigenesis. We now describe in detail the pancreatic pathology of an autosomal dominant pancreatic carcinoma kindred with distinct clinical, genetic, and pathologic manifestations differing from all other reported forms of sporadic or familial pancreatic neoplasia. Affected individuals develop a prodrome of diabetes mellitus, pancreatic exocrine insufficiency, and characteristic pancreatic imaging abnormalities. Eleven family members have undergone total pancreatectomy, revealing a unique and characteristic fibrocystic, lobulocentric pancreatic atrophy. This was patchy to diffuse in distribution and was invariably associated with a nesidioblastosis-like endocrine cell hyperplasia. All but one resected pancreas demonstrated glandular epithelial dysplasia: 10 had low-grade dysplasia (pancreatic intraductal neoplasia grade II of III or PanIN II) and seven also had high-grade dysplasia (pancreatic intraductal neoplasia grade III of III or PanIN III). Dysplasia was multifocal in small-to medium-sized duct-like structures within areas of acinar atrophy, microcystic change, and mucinous hyperplasia. Two pancreata had carcinomas of multiple and unusual histologic subtypes, including small cell undifferentiated carcinoma and giant cell anaplastic carcinoma. The findings in this kindred yield important information on a distinctive and previously unrecognized pancreatic cancer precursor. Recognition of this entity may help identify additional kindreds and perhaps the underlying genetic defect. As is the case for other familial cancers, the as yet unknown specific genetic defect may have wider implications for pancreatic cancer in general.
 ...
PMID:Familial fibrocystic pancreatic atrophy with endocrine cell hyperplasia and pancreatic carcinoma. 1147 89

A 14 year old boy with proximal focal femoral deficiency (PFFD) on left side, contralateral hip dysplasia in association with ulnar hypoplasia and cleft hand was seen our clinic one year ago. From our research, despite it is atypical presentation, this case in a broad context conforms with the femoral-fibula-ulna complex (FFU). This boy was born to healthy and nonconsanguineous parents. Pregnancy and delivery were uncomplicated, and no history of prenatal teratogen exposure, any drug ingestion, infection, diabetes mellitus or other conditions that could be associated with malformation. The patient refused any sort of surgical treatment.
 ...
PMID:Proximal focal femoral deficiency, contralateral hip dysplasia in association with contralateral ulnar hypoplasia and clefthand: a case report and review of literatures of PFFD and/or FFU. 1173 9

Ischemic renal disease (IRD) is a frequent cause of end-stage renal disease. Its prevalence is mainly known from autopsy or retrospective arteriographic studies. This prospective study was conducted in 115 subjects selected from 732 patients with advanced chronic renal failure (CRF). Only patients with clinical features suggestive of IRD were selected for this study. In addition to detailed clinical and laboratory evaluation, captopril renal scintigraphy was performed in selected cases. All subjects underwent renal arteriography and all were followed up for 18.4 +/- 11.4 months. Renovascular disease was seen in 15 patients and significant bilateral renal artery disease leading to IRD was observed in 13 (11.3%). Hence the prevalence of IRD in the advanced CRF patients was 1.7%. The majority of patients with IRD (8 [61%]) were above 46 years of age and there were more men than women (10:3). Atherosclerotic renovascular disease was the most common (10 [77%]), even though arthritis (1 [7.6%]), and fibromuscular dysplasia (2 [15.3%]) were also observed. Serum creatinine at time of presentation was significantly higher in patients with IRD (784 +/- 292, p = 0.043) compared to those who did not have IRD (359 +/- 126). Corrective procedures were performed in 5 patients. After treatment the improvement in serum creatinine in patients with IRD at 3 and 6 months (166 +/- 32 and 173 +/- 47, respectively) was significantly different (p < or = 0.05) compared to those who were not treated (610 +/- 194 and 645 +/- 220, respectively). Hyperlipidemia, coronary artery disease and peripheral vascular disease were more prevalent in patients who had IRD compared to those with renal failure. The incidence of diabetes mellitus were similar in both groups. This study denotes a lower prevalence of IRD in the advanced CRF population; they had more severe renal failure at presentation but specific corrective treatment delayed progression of renal disease significantly.
 ...
PMID:Ischemic renal disease in Kuwait. 1186 39

Shwachman-Diamond syndrome (SDS), described just under 40 years ago, is a rare, autosomal-recessive disorder usually manifest in infancy and characterized by exocrine pancreatic insufficiency, short stature, and bone marrow dysfunction. Additional clinical features include metaphyseal dysostosis, epiphyseal dysplasia, immune dysfunction, liver disease, growth failure, renal tubular defects, insulin-dependent diabetes mellitus, and psychomotor retardation. Hematological manifestations other than neutropenia include anemia, raised fetal hemoglobin (HbF) levels, thrombocytopenia, impaired neutrophil chemotaxis, and aplastic anemia; as with other constitutional bone marrow failure syndromes, there is a predilection to malignant myeloid transformation. No unifying pathogenetic mechanism(s) has yet been shown to be responsible for SDS, although new insights into the molecular, genetic, and cellular basis of this rare disease have recently been described.
 ...
PMID:Shwachman-Diamond syndrome. 1195 91

Wolcott-Rallison syndrome (WRS) is an autosomal recessive disorder characterized by neonatal or early infancy type 1 diabetes, epiphyseal dysplasia, and growth retardation. Mutations in the EIF2AK3 gene, encoding the eukaryotic initiation factor 2alpha-kinase 3 (EIF2AK3), have been found in WRS patients. Here we describe a girl who came to our attention at 2 months of age with severe hypertonic dehydration and diabetic ketoacidosis. A diagnosis of type 1 diabetes was made and insulin treatment initiated. Growth retardation and microcephaly were also present. Anti-islet cell autoantibodies were negative, and mitochondrial diabetes was excluded. Imaging revealed a hypoplastic pancreas and typical signs of spondylo-epiphyseal dysplasia. The diagnosis of WRS was therefore made at age 5 years. Sequencing analysis of her EIF2AK3 gene revealed the presence of a homozygous T to C exchange in exon 13 leading to the missense serine 877 proline mutation. The mutated kinase, although it partly retains the ability of autophosphorylation, is unable to phosphorylate its natural substrate, eukaryotic initiation factor 2alpha (eIF2alpha). This is the first case in which the pathophysiological role of EIF2AK3 deficiency in WRS is confirmed at the molecular level. Our data demonstrate that EIF2AK3 kinase activity is essential for pancreas islet function and bone development in humans, and we suggest EIF2AK3 as a possible target for therapeutic intervention in diabetes.
Diabetes 2002 Jul
PMID:Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. 1208 64

Autonomic neuropathy is a significant complication of diabetes resulting in increased patient morbidity and mortality. A number of studies, which have shown correspondence between neuropathologic findings in experimental animals and human subjects, have demonstrated that axonal and dendritic pathology in sympathetic ganglia in the absence of significant neuron loss represents a neuropathologic hallmark of diabetic autonomic neuropathy. A recurring theme in sympathetic ganglia, as well as in the pot-ganglionic autonomic innervation of various end organs, is the involvement of distal portions of axons and nerve terminals by degenerative or dystrophic changes. In both animals and humans, there is a surprising selectivity of the diabetic process for subpopulations of autonomic ganglia, nerve terminals within sympathetic ganglia and end organs, from end organ to end organ, and between vascular and other targets within individual end organs. Although the involvement or autonomic axons in somatic nerves may reflect an ischemic pathogenesis, the selectivity of the diabetic process confounds simple global explanations of diabetic autonomic neuropathy as the result of diminished blood flow with resultant tissue hypoxia. A single unifying pathogenetic hypothesis has not yet emerged from clinical and experimental animal studies, and it is likely that diabetic autonomic neuropathy will be shown to have multiple causative mechanisms, which will interact to result in the variety of presentations of autonomic injury in diabetes. Some of these mechanisms will be shared with aging changes in the autonomic nervous system. The role of various neurotrophic substances and the polyol pathway in the pathogenesis and treatment of diabetic neuropathy likely represents a two-edged sword with both salutary and exacerbating effects. The basic neurobiologic process underlying the diabetes-induced development of neuroaxonal dystrophy, synaptic dysplasia, defective axonal regeneration, and alterations in neurotrophic substance may be mechanistically related.
 ...
PMID:Neuropathology and pathogenesis of diabetic autonomic neuropathy. 1219 13

Primary adrenal hyperplasia, which may occur as a familial disorder, is a rare cause of ACTH-independent Cushing's syndrome. In most of these cases the underlying pathology is primary adrenocortical micronodular dysplasia. Very few cases of familial Cushing's syndrome due to primary macronodular adrenal hyperplasia have been described. We report a family with seven affected family members. The pedigree indicates an autosomal dominantly inherited disorder. Interestingly only female family members developed the clinically apparent syndrome. The only available obligatory male gene carrier failed to adequately suppress his plasma cortisol level on overnight dexamethasone suppression test. His adrenal glands showed nodular enlargement on abdominal computed tomographic imaging. Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient. In conclusion, this family is the largest kindred reported in the literature with ACTH-independent Cushing's syndrome due to autosomal dominant inherited macronodular adrenocortical hyperplasia. Four currently alive and affected family members in two generations and further careful observation of the yet unaffected members of the third available generation might offer the opportunity to identify the still unknown gene defect in the future.
Exp Clin Endocrinol Diabetes 2002 Sep
PMID:Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members. 1237 31

A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive. We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient's cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations. This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.
 ...
PMID:A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. 1262 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>