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81.
The melanocortin 1 receptor (MC1R) gene is a major determinant of human pigmentation and specific allelic variants have been associated with red hair and sun sensitive skin types as well as increased skin cancer risk in Caucasian individuals. We screened for allelic variants the entire MC1R coding region of 100 unrelated individuals sampled from an Italian population who has darker pigmentary traits than populations analyzed to date. Twenty MC1R variants were identified, eighteen located at non-synonymous sites and two at synonymous sites. We report four novel MC1R allelic variants: C35Y (g.104G>A), V38M (g.112G>A), L44V (g.130C>G) and I120T (g.359T>C). 相似文献
82.
A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy 总被引:3,自引:4,他引:3
Milasin J; Muntoni F; Severini GM; Bartoloni L; Vatta M; Krajinovic M; Mateddu A; Angelini C; Camerini F; Falaschi A; Mestroni L; Giacca M 《Human molecular genetics》1996,5(1):73-79
X-linked dilated cardiomyopathy (XLDC) is a familial heart disease
presenting in young males as a rapidly progressive congestive heart
failure, without clinical signs of skeletal myopathy. This condition has
recently been linked to the dystrophin gene in some families and deletions
encompassing the genomic region coding for the first muscle exon have been
detected. In order to identify the defect responsible for this disease at
the molecular level and to understand the reasons for the selective heart
involvement, a family with a severe form of XLDC was studied. In the
affected members, no deletions of the dystrophin gene were observed.
Analysis of the muscle promoter, first exon and intron regions revealed the
presence of a single point mutation at the first exon-intron boundary,
inactivating the universally conserved 5' splice site consensus sequence of
the first intron. This mutation introduced a new restriction site for MseI,
which cosegregates with the disease in the analyzed family. Expression of
the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje
cell-promoters) was completely abolished in the myocardium, while the
brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in
the skeletal muscle. Immunocytochemical studies with anti- dystrophin
antibodies showed that the protein was reduced in quantity but normally
distributed in the skeletal muscle, while it was undetectable in the
cardiac muscle. These findings indicate that expression of the muscle
dystrophin isoform is critical for myocardial function and suggest that
selective heart involvement in dystrophin- linked dilated cardiomyopathy is
related to the absence, in the heart, of a compensatory expression of
dystrophin from alternative promoters.
相似文献
83.
Francesco Muntoni Anna Mateddu Maria Giovanna Marrosu Miiena Cau Rita Congiu Maria Antonietta Melis Antonio Cao Carlo Cianchetti 《Clinical genetics》1992,42(1):35-38
The majority of Duchenne muscular dystrophy (DMD) female carriers show dystrophin immunostaining abnormalities, although a significant proportion of clinically non-manifesting carriers are normal following this analysis. We had the opportunity to study dystrophin immunostaining in two different muscles, the vastus lateralis and the rectus abdominis of a possible DMD carrier. While the vastus showed normal dystrophin immunostaining, pathological staining was detected in her rectus abdominis. These findings seem to indicate that dystrophin expression can vary in different muscle groups of a DMD carrier. The implications of these findings in DMD carrier detection and possible dystrophin function are discussed. 相似文献
84.
Lauren E. Sergio David J. Ostry 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1995,105(1):123-137
The present study quantifies electromyographic (EMG) magnitude, timing, and duration in one and two degree of freedom elbow movements involving combinations of flexion-extension and pronation-supination. The aim is to understand the organization of commands subserving motion in individual and multiple degrees of freedom. The muscles tested in this study fell into two categories with respect to agonist burst magnitude: those whose burst magnitude varied with motion in a second degree of freedom at the elbow, and those whose burst magnitude depended on motion in one degree of freedom only. In multiarticular muscles contributing to motion in two degrees of freedom at the elbow, we found that the magnitude of the agonist burst was greatest for movements in which a muscle acted as agonist in both degrees of freedom. The burst magnitudes for one degree of freedom movements were, in turn, greater than for movements in which the muscle was agonist in one degree of freedom and antagonist in the other. It was also found that, for movements in which a muscle acted as agonist in two degrees of freedom, the burst magnitude was, in the majority of cases, not different from the sum of the burst magnitudes in the component movements. When differences occurred, the burst magnitude for the combined movement was greater than the sum of the components. Other measures of EMG activity such as burst onset time and duration were not found to vary in a systematic manner with motion in these two degrees of freedom. It was also seen that several muscles which produced motion in one degree of freedom at the elbow, including triceps brachii (long head), triceps brachii (lateral head), and pronator quadratus displayed first agonist bursts whose magnitude did not vary with motion in a second degree of freedom. However, for the monoarticular elbow flexors brachialis and brachioradialis, agonist burst magnitude was affected by pronation or supination. Lastly, it was observed that during elbow movements in which muscles acted as agonist in one degree of freedom and antagonist in the other, the muscle activity often displayed both agonist and antagonist components in the same movement. It was found that, for pronator teres and biceps brachii, the timing of the bursts was such that there was activity in these muscles concurrent with activity in both pure agonists and pure antagonists. The empirical summation of EMG burst magnitudes and the presence in a single muscle of both agonist and antagonist bursts within a movement suggest that central commands associated with motion in individual degrees of freedom at the elbow may be superimposed to produce elbow movements in two degrees of freedom. 相似文献
85.
L. E. Sergio Stephen H. Scott 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,122(2):157-164
This study examines whether the kinematics of pointing movements are altered by the sensory systems used to select spatial
targets and to guide movement. Hand and joint paths of visually guided reaching movements of human subjects were compared
with two non-visual conditions where only proprioception was available: (1) movements of the same subjects with blindfolds,
and (2) movements by congenitally blind subjects. While hand-path curvatures were overall quite small, sighted subjects wearing
a blindfold showed a statistical increase in hand-path curvature compared with their visually guided movements. Blindfolded
subjects also showed greater hand-path curvature than blind subjects. These increases in hand-path curvature for blindfolded
subjects did not always lead to a decrease in joint-path curvature. While there were differences between blind subjects and
sighted subjects using vision for some movement directions, there was no systematic difference between these two groups. The
magnitude of joint-path curvature showed much greater variation than hand-path curvature across the movement directions. We
found variation in joint-path curvature to be correlated to two factors, one spatial and one geometrical. For all subject
groups, joint-path curvature tended to be smaller for sagittal-plane movements than for transverse or diagonal movements.
As well, we found that the magnitude of joint-path curvature was also related to the relative motion at each joint. Joint-path
curvature tended to increase when movements predominantly involved changes in shoulder angle and was minimal when movements
predominantly involved elbow motion. The consistently small curvatures of hand trajectory across blind and sighted subjects
emphasize the powerful tendency of the motor system to generate goal-directed reaching movements with relatively straight
hand trajectories, even when deprived of visual feedback from very early in life.
Received: 16 July 1997 / Accepted: 20 May 1998 相似文献
86.
Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression 总被引:2,自引:1,他引:2
Manilal S; Recan D; Sewry CA; Hoeltzenbein M; Llense S; Leturcq F; Deburgrave N; Barbot J; Man N; Muntoni F; Wehnert M; Kaplan J; Morris GE 《Human molecular genetics》1998,7(5):855-864
Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been
studied both by DNA sequencing and by emerin protein expression. Fourteen
had mutations in the X-linked emerin gene, while three showed evidence of
autosomal inheritance. Twelve of the 14 emerin mutations caused early
termination of translation. An in-frame deletion of six amino acids from
the C-terminal transmembrane helix caused almost complete absence of emerin
from muscle with no localization to the nuclear membrane, although mRNA
levels were normal. This shows that mutant emerin proteins are unstable if
they are unable to integrate into a membrane. A 22 bp deletion in the
promoter region was expected to result in reduced emerin production, but
normal amounts of emerin of normal size were found in leucocytes and
lymphoblastoid cell lines. This shows that DNA analysis is necessary to
exclude emerin mutations in suspected X-linked EDMD. Emerin levels in
female carriers often deviated from the expected 50% and this was due, in
at least two families, to skewed emerin mRNA expression from the normal and
mutated alleles. In one family with a novel deletion of the last three
exons of the emerin gene, a carrier had a cardiomyopathy and very low
emerin levels (<5% of normal) due to skewed X-inactivation. In the three
autosomal cases of EDMD, emerin was normal on western blots of blood cells,
which suggests that autosomal EDMD is not caused by indirect reduction of
emerin levels.
相似文献
87.
88.
Domenico Lapenna Andrea Mezzetti Sergio de Gioia Agostino Consoli Davide Festi Carmine Di Ilio Franco Cuccurullo 《Pflügers Archiv : European journal of physiology》1994,427(5-6):432-436
The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, -glutamylcysteine synthetase and -glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H2O2-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocarium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury. 相似文献
89.
Francesca Grassi Aldo Giovannelli Sergio Fucile Elisabetta Mattei Fabrizio Eusebi 《Pflügers Archiv : European journal of physiology》1993,425(1-2):117-125
The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca2+ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca2+ ([Ca2+]i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca2+]i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca2+ channels. The stimulation of the nAChR induced transient whole-cell currents (I
ACh). Little or no current was detected in isotonic extracellular Ca2+, with Cs+ in the patch pipette. Cell pretreatment with muscarine reduced I
ACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/ RD cells, muscarinic stimulation increases [Ca2+]i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides. 相似文献
90.
Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors 总被引:2,自引:0,他引:2
Savarino A Lucia MB Rastrelli E Rutella S Golotta C Morra E Tamburrini E Perno CF Boelaert JR Sperber K Cauda R 《Journal of acquired immune deficiency syndromes (1999)》2004,35(3):223-232
OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function. 相似文献