Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplacental exposure to the DNA alkylating agent N-methyl-N-nitrosourea on day 16 of gestation in CD-1 albino mice induces a degeneration of the retina, the severity of which depends upon the dosage level of the drug. A 1 mg kg-1 dose provokes a progressive retinal degeneration in the offspring which begins at about 4-6 weeks of age and is characterized by gradual thinning of the retinal layers. A 15 mg kg-1 dosage of MNU provokes severe retinal dysplasia characterized morphologically by rosettes in the outer nuclear layer and loss of rod outer segments (ROS). In the present biochemical experiments, retinal protein synthesis was examined in mice 2-, 4-, and 6 weeks of age exposed to 1 mg kg-1 MNU and 2- and 5 weeks of age exposed to 15 mg kg-1 MNU. Phospholipid synthesis was examined in mice 2-, 4-, 6- and 12 weeks of age exposed to 1 mg kg-1 MNU and at 2 weeks in mice exposed to 15 mg kg-1 MNU. Retinas were incubated for 2 hr at 37 degrees C in media supplemented with either [3H]leucine for protein synthesis studies or [3H]glycerol for phospholipid synthesis experiments. Aliquots of crude ROS and the retinal debris were taken for protein determination, scintillation counting, SDS-PAGE separation of labeled opsin, phosphorus determination and TLC separation of phospholipids. Results indicated that mice exposed to 1 mg kg-1 MNU did not differ significantly from age-matched controls in these measurements, whereas mice exposed to 15 mg kg-1 MNU were significantly different from controls. These results suggest that even as early as 2 weeks of age protein and lipid metabolism are adversely affected in mice exposed to the higher dose of the alkylating agent at a critical time in retinal development, but general protein and lipid synthesis is not affected in animals exposed to 1 mg kg-1 MNU at least up to 12 weeks of age. These studies suggest further investigation of more subtle derangement in the retinal function in animals exposed to low levels of MNU.
 ...
PMID:Biochemical characterization of retinal protein and phospholipid synthesis in mice exposed transplacentally to N-methyl-N-nitrosourea. 319 72

We have examined the collagens synthesized by cultures of normal human corneal stromal cells. Radioactively labeled products, accumulated in the culture medium during a 24-h labeling period, were treated with pepsin and analyzed by SDS-polyacrylamide gel electrophoresis. The cell layer collagen was characterized by 2.6 M and 4.4 M salt fractionation at neutral pH. CM-cellulose column chromatography, SDS-gel electrophoresis, and cyanogen bromide peptide mapping. Type I alpha 1 and alpha 2 chains were the predominant components in both the cell layer and the medium fractions of normal human stromal cultures; type III collagen was found mostly in the culture medium; and type V collagen was associated with the cell layer. Immunofluorescent techniques used to visualize collagen deposition in the cell layer confirmed the presence of these collagen types. Keratoconus is a disease characterized by thinning and scarring of the central cornea. Stromal cells grown from keratoconus corneas produced similar types of collagen (types I, III, and V) as normal human controls. Cells from keratoconus patients, however, contained more type V collagen in the cell layer than did normal cells. The difference was seen only in the 4.4 M salt precipitates. Since type V collagen is one component of cell surfaces, the primary defect in cultures from keratoconus corneas could involve cell membrane and cell surface components.
 ...
PMID:Identification of collagens synthesized by cultures of normal human corneal and keratoconus stromal cells. 633 47

In the normal myocardium matrix metalloproteinases (MMP) are present in the latent form. To examine whether MMP are activated following infarction or idiopathic dilated cardiomyopathy (DCM), we extracted and measured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP activity in infarcted left ventricle (LV), noninfarcted LV and right ventricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Accuracy of the zymographic technique was shown for tissue samples as small as 0.05 mg and was comparable to results obtained by a spectrophotometric method. After normalization for total protein concentration, we found 3 +/- 1% collagenase activity in normal atrial tissue which could be activated to 80-90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV, on the other hand, collagenase activity was 85-95% and 10-20%, respectively, while 5-10% and 3-5%, respectively, in noninfarcted LV. In DCM, collagenolytic activity in the endo and epimyocardium was 75 +/- 5 and 35 +/- 5% in the LV and 35 +/- 7 and 20 +/- 5% in the RV, respectively. Thus, in dilated failing human hearts secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and noninfarcted portions of either ventricle with MI and in both ventricles in DCM. This suggests that an activation of collagenase throughout the myocardium may contribute to its remodeling that includes ventricular dilatation and wall thinning.
 ...
PMID:Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts. 871 34

Rheograms of Alcaligenes eutrophus (NCIMB 40529) and Escherichia coli (C90 NCIMB 10616) cells lysed by sodium dodecyl sulphate were compared before and after a variety of heat shock regimes. It was found that unheated cells produced a very characteristic shear thickening rheogram which could be destroyed by DNase treatment. Cells which had been subjected to heat shock produced rheograms very similar to DNase digested material. We thus suggest that the rheogram is largely due to the presence of intact DNA molecules. The extent and nature of the heat shock affected the shape of the rheogram of the SDS lysed material. Heat shock of cells after SDS lysis did not appear to significantly damage the DNA. Storage of the cells at 10 degrees C before heat shock considerably reduced the shear thinning effect of subsequent heat shock at 90 degrees C. We attribute the shear thinning effect of the heat shock to the action of nucleases which are activated and then depolymerise the DNA molecules.
 ...
PMID:Effects of heat shock on gram negative bacteria: use of lysis by sodium dodecyl sulphate as a probe for the integrity of DNA. 881 67

Twenty-seven thalassaemic patients (13 F, 14 M, aged 8.1-14.9 yr), regularly transfused and chelated with desferrioxamine (30-40 mg/kg/day) were studied. Every patient was submitted to auxological evaluations, dual X-ray absorptiometry to measure bone mineral density (BMD), and to the determination of bone metabolic markers of osteoclastic activity (total urinary hydroxylysylpyridinoline crosslinks, carboxyterminal pyridinoline crosslinked telopeptide of type I collagen [ICTP]) and of osteoblastic activity (bone Gla protein [BGP] and carboxyterminal propeptide of type I procollagen [PIPC]). The evaluations were repeated after 1 year, during which 13 patients continued desferrioxamine chelation while 14 underwent deferiprone chelation (75 mg/kg/day in 3 doses). The data demonstrate widespread bone alterations consisting of osteoporosis, growth failure and bone age delay. Lumber spine (L2-L4) BMD areal values (Z score) inversely correlated with age, as did height SDS of both male and female patients, indicating osteoporosis progressing with age in parallel with growth insufficiency. No clear-cut alterations in bone mineral metabolism were found in basal state and after 1 year. Extensive MR imaging studies are needed to define the contribution of residual bone marrow hyperplasia to thalassaemic osteopathy suggested by subtle radiological signs as enlargement of bone marrow cavities with thinning of the cortical bone and abnormalities of the trabecules of spongy bone.
 ...
PMID:Bone density and metabolism in thalassaemia. 1009 Nov 47

Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with beta-amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to beta-amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.
 ...
PMID:Agrin in Alzheimer's disease: altered solubility and abnormal distribution within microvasculature and brain parenchyma. 1033 11

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
 ...
PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

The amastigogenesis primary of T. cruzi occurs naturally when metacyclic trypomastigotes transform into amastigotes within the cells of the mammalian host. The in vitro study of the macromolecular changes that occur over several days during the transformation process should provide significant indications of how the parasite adapts to the mammalian host environment. We show here that metacyclic trypomastigotes pre-incubated at 37 degrees C in a protein-rich medium reach a high degree of transformation to amastigotes when re-incubated in the fresh medium. Giemsa-stained smears show that during the pre-incubation phase, the metacyclic trypomastigotes undergo lengthening at the posterior end and a thinning out of the entire body. SDS-PAGE analysis of polypeptides and glycopeptides or Western blot with stage-specific antisera analyses indicate that the in vitro primary amastigogenesis is associated with abrupt changes in protein, glycoprotein, and stage-specific antigens that occur simultaneously during the first 24 hours of pre-incubation. Since the differentiating system consists of a rich media at 37 degrees C, temperature and medium constitution must trigger a macromolecular differentiation to amastigotes that precedes the morphological transformation by several days. This transformation is associated with the rearrangement of stage-specific antigens and takes place when the culture medium is changed.
 ...
PMID:Early and late molecular and morphologic changes that occur during the in vitro transformation of Trypanosoma cruzi metacyclic trypomastigotes to amastigotes. 1212 4

We have investigated the rate of water evaporation from concentrated oil-in-water (o/w) emulsions containing an involatile oil. Evaporation of the water continuous phase causes compression of the emulsion with progressive distortion of the oil drops and thinning of the water films separating them. Theoretically, the vapor pressure of water is sensitive to the interdroplet interactions, which are a function of the film thickness. Three main possible situations are considered. First, under conditions when the evaporation rate is controlled by mass transfer across the stagnant vapor phase, model calculations show that evaporation can, in principle, be slowed by repulsive interdroplet interactions. However, significant retardation requires very strong repulsive forces acting over large separations for typical emulsion drop sizes. Second, water evaporation may be limited by diffusion in the network of water films within the emulsion. In this situation, water loss by evaporation from the emulsion surface leads to a gradient in the water concentration (and in the water film thickness). Third, compression of the drops may lead to coalescence of the emulsion drops and the formation of a macroscopic oil film at the emulsion surface, which serves to prevent further water evaporation. Water mass-loss curves have been measured for silicone o/w emulsions stabilized by the anionic surfactant SDS as a function of the water content, the thickness of the stagnant vapor-phase layer, and the concentration of electrolyte in the aqueous phase, and the results are discussed in terms of the three possible scenarios just described. In systems with added salt, water evaporation virtually ceases before all the water present is lost, probably as a result of oil-drop coalescence resulting in the formation of a water-impermeable oil film at the emulsion surface.
 ...
PMID:Evaporation rates of water from concentrated oil-in-water emulsions. 1583 53

The rheological properties of the microemulsion region of the SDS, pentanol, and water micellar system have been studied experimentally. The W/O and O/W microemulsions behave as typical Newtonian fluids: viscosity remains constant independent of the shear rate. For the bicontinuous system the shear-thinning effect is observed. The addition of ascorbic acid to the system caused a microemulsion viscosity increase, which was the highest in the bicontinuous region and at the lowest temperature.
 ...
PMID:The influence of ascorbic acid on the rheological properties of the microemulsion region of the SDS/pentanol/water system. 1613 47


1 2 3 Next >>