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At least 145 records · Page 8Linked to original sources
PubMed2002

Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans.

Male embryonic mice with mutations in the X-linked aristaless-related homeobox gene (Arx) developed with small brains due to suppressed proliferation and regional deficiencies in the forebrain. These mice also showed aberrant migration and differentiation of interneurons containing gamma-aminobutyric acid (GABAergic interneurons) in the ganglionic eminence and neocortex as well as abnormal testicular differentiation. These characteristics recapitulate some of the clinical features of X-linked lissencephaly with abnormal genitalia (XLAG) in humans. We found multiple loss-of-function mutations in ARX in individuals affected with XLAG and in some female relatives, and conclude that mutation of ARX causes XLAG. The present report is, to our knowledge, the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation.

Alleles↗
PubMed1999

Structural abnormalities do not explain the early functional abnormalities in the peripheral nerves of the streptozotocin diabetic rat.

The streptozotocin (STZ)-diabetic rat, the most commonly employed model of experimental diabetic neuropathy, is characterised by a reduction in nerve conduction velocity, pain threshold and blood flow. Whether or not structural abnormalities underlie these functional abnormalities is unclear. 10 adult male Sprague-Dawley STZ-diabetic rats (diabetes duration 27 d) and 10 age-matched (23 wk) control animals were studied. Motor nerve conduction velocity (m s(-1)) was significantly reduced in diabetic (41.31 +/- 0.8) compared with control (46.15 +/- 1.5) animals (P < 0.001). The concentration of sciatic nerve glucose (P < 0.001), fructose (P < 0.001) and sorbitol (P < 0.001) was elevated, and myoinositol (P < 0.001) was reduced in diabetic compared with control animals. Detailed morphometric studies demonstrated no significant difference in fascicular area, myelinated fibre density, fibre and axon areas as well as unmyelinated fibre density and diameter. Endoneurial capillary density, basement membrane area and endothelial cell profile number did not differ between diabetic and control animals. However, luminal area (P < 0.03) was increased and endothelial cell area (P < 0.08) was decreased in the diabetic rats. We conclude there is no detectable structural basis for the reduction in nerve conduction velocity, pain threshold or blood flow, observed in the streptozotocin diabetic rat.

Animals↗
PubMed1981

Use of cultured lymphoblastoid cells for the study of abnormal enzymes: molecular abnormality of a phosphoglycerate kinase variant associated with hemolytic anemia.

A phosphoglycerate kinase (PGKase: ATP:3-phosphoglycerate 1-phosphotransferase, EC 2.7.2.3; X chromosome-linked) variant, PGKase-Tokyo, is associated with enzyme deficiency, nonspherocytic hemolytic anemia, and neurological disturbances. Because a sufficient amount of the patient's erythrocytes was not available, the variant enzyme was purified to homogeneity from the cultured lymphoblastoid cells of the patient. The enzyme activity of the variant lymphoblastoid cells was about 16% of that of the normal lymphoblastoid cells. PGKase-Tokyo, compared to the normal enzyme, had a lower specific activity (31% of normal in the backward reaction and 15% of normal in the forward reaction), higher than normal Michaelis constants for ATP and 3-phosphoglycerate, a more acidic pH optimum, and increased thermal instability. Microscale peptide mapping analysis revealed that the structural abnormality of PGKase-Tokyo is a single amino acid substitution from valine to methionine at position 266. Thus, the use of the cultured lymphoblastoid cells is proven to be useful for the study of structural and functional abnormalities of mutant enzymes.

Amino Acids↗
PubMed1997

Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau.

The microtubule-associated protein (MAP) tau is abnormally hyperphosphorylated in Alzheimer disease and accumulates in neurons undergoing neurofibrillary degeneration. In the present study, the associations of the Alzheimer-hyperphosphorylated tau (AD P-tau) with the high molecular weight MAPs (HMW-MAPs) MAP1 and MAP2 were investigated. The AD P-tau was found to aggregate with MAP1 and MAP2 in solution. The association of AD P-tau to the MAPs resulted in inhibition of MAP-promoted microtubule assembly. However, unlike the coaggregation of AD P-tau and normal tau, the association between AD P-tau and the HMW-MAPs did not result in the formation of filaments/tangles. The affinity of the tau-AD P-tau association was higher than that of HMW-MAPs-AD P-tau because normal tau inhibited the latter binding. The association between AD P-tau and the HMW-MAPs also appeared to occur in situ because these proteins cosedimented from the Alzheimer brain extracts, and, in the sediment, the levels of the HMW-MAPs correlated with the levels of AD P-tau. These studies suggested that the abnormally phosphorylated tau can sequester both normal tau and HMW-MAPs and disassemble microtubules but, under physiological conditions, can form tangles of filaments only from tau.

Alzheimer Disease↗
PubMed1988

Abnormalities of urine urobilinogen and urine bilirubin assays and their relation to abnormal results of serum liver function tests.

A prospective observational study of 324 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. High positive predictive values (88% for at least one abnormal LFT) make the evaluation of positive urine screens detected during routine health care maintenance examinations imperative. Because extraneous factors may influence both urine and serum test results, however, urine assays obtained as a screening parameter in clinical presentations (abdominal pain, jaundice, constitutional symptoms, etc) have only limited clinical utility. The high proportion of false-negative results for both urine assays renders their statistical properties unacceptable as screens in these clinical situations.

Adolescent↗
PubMed1995

Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain.

Genetic analysis of the development and evolution of the vertebrate head is at a primitive stage. Many homeo box genes, including the Distal-less family, are potential regulators of head development. To determine the function of Dlx-2, we generated a null mutation in mice using gene targeting. In homozygous mutants, differentiation within the forebrain is abnormal and the fate of a subset of cranial neural crest cells is respecified. The latter causes abnormal morphogenesis of the skeletal elements derived from the proximal parts of the first and second branchial arches. We hypothesize that the affected skull bones from the first arch have undergone a transformation into structures similar to those found in reptiles. These results show that Dlx-2 controls development of the branchial arches and the forebrain and suggests its role in craniofacial evolution.

Animals↗
PubMed1981

The effect of protamine on serum levels of placental protein 5 (PP5) in normal and abnormal pregnancy: a possible relation to coagulation abnormalities.

The levels of placental protein 5 (PP5) in pregnancy serum show an apparent increase after the addition of protamine sulphate. The difference of the apparent concentrations of serum PP5 in the presence and absence of protamine (delta PP5) was determined in 345 normal and abnormal pregnancies. A positive delta PP5 was less frequent in diabetic pregnancy (45 per cent) and pre-eclampsia (57 per cent) than in normal pregnancy (80 per cent). These findings provide further evidence that PP5 may be involved in the coagulation system, and in particular may relate to abnormal coagulation processes at the placental site.

Blood Coagulation↗
PubMed2001

A new meiotic abnormality in Zea mays: multiple spindles associated with abnormal cytokinesis in both divisions.

Abstract: We report here a new meiotic abnormality recorded in one plant of an inbred line of Zea mays. After an apparently normal prophase I, chromosomes did not congregate in a single metaphase plate. Bivalents remained scattered in the cytoplasm, giving rise to several spindles. Despite the occurrence of multiple spindles, meiosis I proceeded normally, forming a varied number of nuclei at telophase I. The presence of one or a few chromosomes in the nucleus was enough to induce local cytokinesis, which was evident from metaphase I. Each cell resulting from meiosis I expressed its own program and progressed through the cell cycle. Therefore, failure of chromosome congregation on a single plate also occurred at meiosis II, where further irregular cytokinesis was observed. As a consequence of the two abnormalities, polyads occurred, resulting in pollen grains of different sizes and in sterility at a frequency of up to 93.5%.

Brazil↗
PubMed1983

Abnormal responses of wasted ventilation fraction (VD/VT) during exercise in patients with pulmonary vascular abnormalities.

The finding of a rise in VD/VT or failure of VD/VT to fall during exercise has been proposed as a useful noninvasive indicator of pulmonary vaso-occlusive disease in patients with unexplained dyspnea. However, we previously reported a normal fall in VD/VT during exercise in patients with pulmonary hypertension at rest and/or during exercise due to collagen vascular disease. To investigate further the relationship between pulmonary vascular abnormalities and VD/VT responses to exercise, we studied 4 subjects with severe hypoxemia due to cirrhosis or diffuse telangiectasia. We found an abnormal VD/VT response to exercise in these subjects despite normal pulmonary hemodynamics which effectively excluded hemodynamically significant pulmonary vascular obstruction. These findings provide further support for the lack of utility of the VD/VT measurement at rest and during exercise as a screening method for detecting pulmonary vaso-occlusive disease, since the VD/VT cannot only fall appropriately during exercise in patients with pulmonary hypertension but can also remain unchanged or rise during exercise in patients with normal pulmonary hemodynamics.

Adolescent↗
PubMed1988

Abnormal blood pathways in left ventricular cavity in acute myocardial infarction. Experimental observations with special reference to regional wall motion abnormality and hemostasis.

To elucidate the mechanism of regional hemostasis in the left ventricular (LV) cavity during myocardial infarction, the blood pathway in LV cavity was examined with contrast echocardiography injected from the left atrium before and after coronary ligation in nine canines. Before coronary ligation, contrast echoes spread over LV cavity with one rush. After ligation, smokelike echoes indicating hemostasis were observed at the apical middle of the LV cavity in five dogs with apical akinesis and at the apical area in four dogs with apical dyskinesis. The contrast echoes did not reach the apex within one diastolic period but turned upward to the outflow tract in the middle of the cavity in all dogs. In the cardiac beats that followed, some contrast echoes spread slowly toward the apex, forming a thin layer along the posterior wall in cases with akinesis but not in cases with dyskinesis. The area separated from the blood pathway developed where the smokelike echoes had been developed. Tachycardia exaggerated the abnormality of blood pathway and widened the contrast echo-free area. The abnormal pathway of the blood in apical myocardial infarction develops hemostasis in the apex. This should be one of the mechanisms of thrombus formation in myocardial infarction.

Animals↗
PubMed1994

Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida.

The reproductive development of alligators from a contaminated and a control lake in central Florida was examined. Lake Apopka is adjacent to an EPA Superfund site, listed due to an extensive spill of dicofol and DDT or its metabolites. These compounds can act as estrogens. Contaminants in the lake also have been derived from extensive agricultural activities around the lake that continue today and a sewage treatment facility associated with the city of Winter Garden, Florida. We examined the hypothesis that an estrogenic contaminant has caused the current failure in recruitment of alligators on Lake Apopka. Supporting data include the following: At 6 months of age, female alligators from Lake Apopka had plasma estradiol-17 beta concentrations almost two times greater than normal females from the control lake, Lake Woodruff. The Apopka females exhibited abnormal ovarian morphology with large numbers of polyovular follicles and polynuclear oocytes. Male juvenile alligators had significantly depressed plasma testosterone concentrations comparable to levels observed in normal Lake Woodruff females but more than three times lower than normal Lake Woodruff males. Additionally, males from Lake Apopka had poorly organized testes and abnormally small phalli. The differences between lakes and sexes in plasma hormone concentrations of juvenile alligators remain even after stimulation with luteinizing hormone. Our data suggest that the gonads of juveniles from Lake Apopka have been permanently modified in ovo, so that normal steroidogenesis is not possible, and thus normal sexual maturation is unlikely.

Alligators and Crocodiles↗
PubMed1992

[A case of chronic toluene intoxication with abnormal MRI findings: abnormal intensity areas in cerebral white matter, basal ganglia, internal capsule, brain stem and middle cerebellar peduncle].

We reported a case of 21 years old man of chronic toluene intoxication with abnormal intensity areas on MRI in cerebral white matter, basal ganglia, internal capsule (especially posterior limb), brain stem and middle cerebellar peduncle. The patient developed various neurological abnormalities such as blurred vision, ataxic speech, gaze evoked horizontal nystagmus, bilateral pyramidal tract sign and limb ataxia after 8 years sniffing of thinner (mainly toluene). MRI examination revealed diffuse high intensity areas in cerebral white matter on T1 weighted image. On T2 weighted image, high intensity areas of deep cerebral white matter, internal capsule (especially posterior limb), cerebral peduncle, ventral pons and middle cerebellar peduncle were noted. Basal ganglia (caudate nucleus, lenticular nucleus and thalamus) were displayed as low intensity area on T2 weighted image. These high intensity areas of internal capsule, brain stem and middle cerebellar peduncle on T2 weighted image would be significant for understanding pyramidal tract sign and cerebellar sign of this case. On the basis of neuropathological descriptions of chronic toluene intoxication, these high intensity areas of T2 weighted image were presumed to be demyelinating lesions of the central nervous system.

Adult↗
PubMed1997

[Abnormal metabolism of fatty acids and ketone bodies in Duchenne muscular dystrophy, and the effect of biotin on these abnormalities].

It has been reported that serum levels of ketone bodies often elevate in patients with Duchenne muscular dystrophy (DMD). The cause of this abnormal metabolism, however, has not been elucidated. In this study, serum levels of ketone bodies were measured in the early morning in patients with DMD, congenital muscular dystrophy and cerebral palsy. Serum free fatty acids (FFA), glucose, and thickness of subcutaneous fat were also measured. Ketone bodies elevated in most DMD patients, but not elevated in patients with the other disorders. Hyperketonemia in the DMD patients was accompanied by elevation of the FFA level, but no correlation was seen between hyperketonemia and the creatine kinase level or the severity of muscle involvement. No differences were found between DMD patients and others in the levels of FFA, glucose and thickness of subcutaneous fat. These results indicate that DMD patients are more prone to ketosis than the others. The effect of biotin administration (2 mg/day) on hyperketonemia also was investigated in 11 patients with DMD. The levels of total ketone bodies decreased by biotin administration for 2 weeks. These data suggest that the utilization of FFA and ketone bodies may be impaired in DMD patients. Biotin treatment will be useful for improving the abnormal metabolism of ketone bodies in DMD patients.

Adolescent↗
PubMed1977

Multiple abnormalities of ectoglycosyltransferases in cultured fibroblasts from patients with mucolipidosis II: Possible indication for abnormal plasma membrane glycoproteins.

Ectoglycosyltransferase activities were measured in cultured normal and mucolipidosis II fibroblasts using endogenous glycoproteins and glycolipids and whole cells. Nucleotide pyrophosphatase, known to interfere with glycosyltransferases, was completely inhibited with 6 mM 5' AMP. Since preliminary experiments have shown multiple abnormalities of ectoglycosyltransferases in mucolipidosis II fibroblasts (Di Donato, unpublished results), galactosyl (Gal)-and N-acetylglucosaminyl (GluNac)-transferase were studied in further detail in confluent and nonconfluent cultures of normal and patient fibroblasts. Activities of both transferases on glycoproteins were higher in nonconfluent cultures. A 50% reduced activity of Gal-transferase was measured in confluent mucolipidosis II cultures and of GluNac-transferase in nonconfluent mucolipidosis II cultures towards incorporation of sugar precursors into glycoproteins. Substrate saturation kinetics of both transferases in mucolipidosis II fibroblasts revealed an abnormal Km for Gal incorporation into endogenous glycoproteins. Glycosylation of glycolipids in mucolipidosis fibroblasts was normal.

Acetylglucosamine↗
PubMed1997

[The relationship between insulin resistance and abnormalities of cellular calcium metabolism and cell membrane abnormalities in patients with essential hypertension].

OBJECTIVE: To investigate the relationship between the insulin resistance (IR) and the abnormalities of cellular calcium metabolism and cell membrane in patients with essential hypertension. METHODS: Plasma insulin and glucose before and during OGTT, membrane ATPase activity, cholesterol (C) and phospholipid (P), lipid peroxides (MDA), intracellular total calcium concentration [(Ca2+)i] and calcium binding capacity of inner surface of membranes were determined in 26 normotensive (NT) subjects, 17 hypertensives (HT), and 16 hypertensives associated with IR (HT + IR). RESULTS: The HT + IR group had higher levels of plasma glucose and insulin than that in the NT group and HT group with significant differences. The HT + IR group consistently demonstrated depressed activity of each Na(+)-K(+)-ATPase and Ca(2+)-ATPase studied with significant differences when compared with the NT group, but no difference was found if compared with the HT group. There was a higher [(Ca2+)i] in the HT + IR group than those in the NT group and even in the HT group with significant differences, respectively. Insulin sensitivity in the HT + IR group was significantly lower than that in both groups of HT and NT, respectively. The membrane C/P molar ratio and MDA content in the HT + IR group and HT group were significantly higher than those in the NT group, respectively. CONCLUSIONS: It is likely that there is a causal relation between IR and abnormalities of cellular calcium metabolism and membrane lipids in patients with essential hypertension.

Aged↗
PubMed2001

A new familial syndrome with facial abnormalities, abnormal EEG, and mental retardation.

Two sisters are reported with up-slanting palpebral fissures, hypertelorism, ptosis, a broad, bifid nasal tip, a high-arched palate, mental retardation, abnormal EEG and hand malformations in one of the patients. The girls' parents originate from the same village. Although the findings resemble the recently defined neurofaciodigitorenal syndrome, some findings suggest that this is a newly recognized syndrome.

Abnormalities, Multiple↗
PubMed2003

Unknown diagnosis in two male cousins with facial abnormalities, optic atrophy, abnormal EEG, and severe psychomotor retardation.

We report two male cousins with short stature, microcephaly, hypertelorism, optic atrophy, ptosis, absent ear lobes, high-arched palates, abnormal EEG, and severe mental retardation. Both cousins have consanguineous parents. Differential diagnoses are discussed and the possibility that we might be reporting on a new syndrome is raised.

Abnormalities, Multiple↗
PubMed2002

Genetics analysis of mouse mutations Abnormal feet and tail and rough coat, which cause developmental abnormalities and alopecia.

Mutations in the mouse Brachyury (T) gene are characterized by a dominant reduction of tail length and recessive lethality. Two quantitative trait loci, Brachyury-modifier 1 and 2 (Brm1 and Brm2) are defined by alleles that enhance the short-tail Brachyury phenotype. Here we report on a genetic analysis of a visible dominant mutation Abnormal feet and tail (Aft) located in the vicinity of Brm1. Affected animals display kinky tails and syndactyly in the hindlimbs, both likely resulting from a defect in apoptosis. We observed an unusual genetic incompatibility between Aft and certain genetic backgrounds. We show that Aft and T are likely to interact genetically, since some double heterozygotes are tailless. In addition to the tail and hindlimb phenotypes, Aft-bearing mutants display characteristic late-onset skin lesions. We therefore tested for allelism between Aft and a closely linked recessive mutation rough coat (rc) and found that these two mutations are likely nonallelic. Our results provide a valuable resource for the study of mammalian skin development and contribute to the genetic analysis of Brachyury function.

Abnormalities, Multiple↗