共查询到20条相似文献,搜索用时 31 毫秒
1.
Amano H Ikeda W Kawano S Kajita M Tamaru Y Inoue N Minami Y Yamada A Takai Y 《Genes to cells : devoted to molecular & cellular mechanisms》2008,13(3):269-284
It was previously shown that platelet-derived growth factor (PDGF) receptor physically and functionally interacts with integrin αv β3 , effectively inducing cell movement. We previously showed that Necl-5, originally identified as a poliovirus receptor, interacts with integrin αv β3 and enhances its clustering and the formation of focal complexes at the leading edges of moving cells, resulting in an enhancement of cell movement. We showed here that Necl-5 additionally interacts with PDGF receptor in NIH3T3 cells and regulates the interaction between PDGF receptor and integrin αv β3 , effectively inducing directional cell movement. PDGF receptor co-localized with Necl-5 and integrin αv β3 at peripheral ruffles over lamellipodia, which were formed at the leading edges of moving cells in response to PDGF, but not at the focal complexes under these ruffles, whereas Necl-5 and integrin αv β3 co-localized at these focal complexes. The clustering of these three molecules at peripheral ruffles required the activation of integrin αv β3 by vitronectin and the PDGF-induced activation of the small G protein Rac and subsequent re-organization of the actin cytoskeleton. These results indicate a key role of Necl-5 in directional cell movement by physically and functionally interacting with both integrin αv β3 and PDGF receptor. 相似文献
2.
Julien Ochala Mingxin Li Homa Tajsharghi Eva Kimber Mar Tulinius ers Oldfors Lars Larsson 《The Journal of physiology》2007,581(3):1283-1292
A novel R133W β-tropomyosin (β-Tm) mutation, associated with muscle weakness and distal limb deformities, has recently been identified in a woman and her daughter. The muscle weakness was not accompanied by progressive muscle wasting or histopathological abnormalities in tibialis anterior muscle biopsy specimens. The aim of the present study was to explore the mechanisms underlying the impaired muscle function in patients with the β-Tm mutation. Maximum force normalized to fibre cross-sectional area (specific force, SF), maximum velocity of unloaded shortening ( V 0 ), apparent rate constant of force redevelopment ( k tr ) and force–pCa relationship were evaluated in single chemically skinned muscle fibres from the two patients carrying the β-Tm mutation and from healthy control subjects. Significant differences in regulation of muscle contraction were observed in the type I fibres: a lower SF ( P < 0.05) and k tr ( P < 0.01), and a faster V 0 ( P < 0.05). The force–pCa relationship did not differ between patient and control fibres, indicating an unaltered Ca2+ activation of contractile proteins. Collectively, these results indicate a slower cross-bridge attachment rate and a faster detachment rate caused by the R133W β-Tm mutation. It is suggested that the R133W β-Tm mutation induces alteration in myosin–actin kinetics causing a reduced number of myosin molecules in the strong actin-binding state, resulting in overall muscle weakness in the absence of muscle wasting. 相似文献
3.
David Fernandez Azad Ghanta Krista I. Kinard Michael C. Sanguinetti 《The Journal of physiology》2005,567(3):737-755
Cd2+ slows the rate of activation, accelerates the rate of deactivation and shifts the half-points of voltage-dependent activation ( V 0.5,act ) and inactivation ( V 0.5,inact ) of human ether-à-go-go -related gene (hERG) K+ channels. To identify specific Cd2+ -binding sites on the hERG channel, we mutated potential Cd2+ -coordination residues located in the transmembrane domains or extracellular loops linking these domains, including five Cys, three His, nine Asp and eight Glu residues. Each residue was individually substituted with Ala and the resulting mutant channels heterologously expressed in Xenopus oocytes and their biophysical properties determined with standard two-microelectrode voltage-clamp technique. Cd2+ at 0.5 m m caused a +36 mV shift of V 0.5,act and a +18 mV shift of V 0.5,inact in wild-type channels. Most mutant channels had a similar sensitivity to 0.5 m m Cd2+ . Mutation of single Asp residues located in the S2 (D456, D460) or S3 (D509) domains reduced the Cd2+ -induced shift in V 0.5,act , but not V 0.5,inact . Combined mutations of two or three of these key Asp residues nearly eliminated the shift induced by 0.5 m m Cd2+ . Mutation of D456, D460 and D509 also reduced the comparatively low-affinity effects of Ca2+ and Mg2+ on V 0.5,act . Extracellular Cd2+ modulates hERG channel activation by binding to a coordination site formed, at least in part, by three Asp residues. 相似文献
4.
Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles 总被引:13,自引:2,他引:13
M. A. Pellegrino M. Canepari R. Rossi G. D'Antona C. Reggiani R. Bottinelli 《The Journal of physiology》2003,546(3):677-689
Maximum shortening velocity ( V 0 ) was determined in single fibres dissected from hind limb skeletal muscles of rabbit and mouse and classified according to their myosin heavy chain (MHC) isoform composition. The values for rabbit and mouse V 0 were compared with the values previously obtained in man and rat under identical experimental conditions. Significant differences in V 0 were found between fibres containing corresponding myosin isoforms in different species: as a general rule for each isoform V 0 decreased with body mass. Myosin isoform distributions of soleus and tibialis anterior were analysed in mouse, rat, rabbit and man: the proportion of slow myosin generally increased with increasing body size. The diversity between V 0 of corresponding myosin isoforms and the different myosin isoform composition of corresponding muscles determine the scaling of shortening velocity of whole muscles with body size, which is essential for optimisation of locomotion. The speed of actin translocation ( V f ) in in vitro motility assay was determined with myosins extracted from single muscle fibres of all four species: significant differences were found between myosin isoforms in each species and between corresponding myosin isoforms in different species. The values of V 0 and V f determined for each myosin isoform were significantly correlated, strongly supporting the view that the myosin isoform expressed is the major determinant of maximum shortening velocity in muscle fibres. 相似文献
5.
The nature of the MHC class I peptide loading complex 总被引:14,自引:0,他引:14
Summary: Peptide binding to major histocompatibility complex (MHC) dass I molecules occurs in the endoplasmic reticulum (ER). Efficient peptide binding requires a number of components in addition co the MHC class I-β2 microglobulin dimer (β2 m). These include the two subunits of the transporter associated with antigen presentation (TAP1 and TAP2), which are essential for introducing peptides into the ER from the cytosol, and tapasin, an MHC-encoded membrane protein. Prior to peptide binding, MHC class I-β2 m dimers form part of a large multisubnnit ER complex which includes TAP and tapasin. In addition to these specialized components two soluble 'house-keeping' proteins, the chaperone calreticulin and the thiol oxidoreductase ERp57, are also components of this complex. Our current understanding of the nature and function of the MHC class I peptide loading complex is the topic of this review. 相似文献
6.
Oliver Schnell MD ; Bjarne Krebs MD ; Erika Wagner ; Alexander Romagna ; Ambros J. Beer MD ; Stefan J. Grau MD ; Niklas Thon MD ; Claudia Goetz MD ; Hans A. Kretzschmar MD ; Jörg-Christian Tonn MD ; Roland H. Goldbrunner MD 《Brain pathology (Zurich, Switzerland)》2008,18(3):378-386
In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of αv β3 integrin caused by malignancy. The aim of our study was to assess the extent and pattern of αv β3 integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of αv β3 integrin and quantified by an imaging software. The expression of αv β3 was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of αv β3 integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the β3 integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of αv β3 integrin in gliomas and are of relevance for the inhibition of αv β3 integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth. 相似文献
7.
ZHAN-GUO LI O. KEMP T. LONGHURST & N. MANOLIOS 《Scandinavian journal of immunology》1996,43(2):140-145
The clonotypic T-cell antigen receptor (TCR)-β chain contains two extracellular intrachain disulfide bonds. It belongs to the immunoglobulin gene superfamily and is subdivided into variable (V), joining (J), diversity (D) and constant (C) region. Monoclonal antibody (MoAb) KJ25 is believed to recognize an epitope in the V-domain of TCR-β (Vβ3 ) chain, but its epitope requirements are unknown. In this study of TCR-αβ chain interactions using chimeric recombinant TCR-β chains, the authors found that partial substitution of the Cβ-domain with that of interleukin-2 receptor α chain (Tac) sequences led to the loss of TCR-Vβ3 epitope recognition by KJ25. These results suggest that epitope recognition of the TCR-Vβ3 by KJ25 MoAb is dependent not only on the V-domain, but also on the close contact with the extracellular C-domain which influences the conformation and epitope recognition of the Vβ3 -region. This may not be unique to Vβ3 and may be a general feature of TCR-β protein folding. 相似文献
8.
Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans 总被引:1,自引:1,他引:1
James P. Fisher Shigehiko Ogoh Ellen A. Dawson Paul J. Fadel Niels H. Secher Peter B. Raven Michael J. White 《The Journal of physiology》2006,572(3):869-880
We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with β1 -adrenergic blockade (metoprolol, 0.15 ± 0.003 mg kg−1 ) or parasympathetic blockade (glycopyrrolate, 13.6 ± 1.5 μg kg−1 ). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to −80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise ( P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain ( G max ) of the CBR-HR function curve (−0.58 ± 0.10 to −0.06 ± 0.01 beats min−1 mmHg−1 , P < 0.05), but had no effect on the G max of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate ( P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G max . Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise. 相似文献
9.
A radioimmunoassay for pregnancy-specific-β1 -glycoprotein (Bohn. 1971) has been established with a limit of detection of 2 μMg/litre in serum. The assay has been used to measure serial levels of pregnancy-specific-β1 -glycoprotein (β1 SP1 ) in the serum of patients with choriocarcinoma and teratoma for comparison with measurements of the β-subunit of human chorionic gonadotrophin. The value of the assay for β1 SP1 , in the management of these patients is discussed. 相似文献
10.
Abstract: The monoclonal antibody W6/32 is one of the most commonly used pan-HLA-ABC antibodies in studying human MHC I structure and function. We have discovered that the reactivity of W6/32 is absolutely sensitive to the amino terminus of human β2 -microglobulin (hβ2 m). Bac-terially expressed recombinant forms of hβ2 m that have been extensively used in structural and biochemical studies of MHC I molecules often have an additional methionine at their amino terminus. Cell surface MHC I molecules reconstituted with allele-specific peptides and recombinant hβ2 m are reactive with various HLA-specific mAbs, but not W6/32. In contrast, cell surface HLA molecules reconstituted with peptide and native hβ2 m, which has no amino terminal methionine, are recognized by W6/32 as well as other HLA-specific mAbs. Thus, the specificity of W6/32 includes the amino terminus of hβ2 m. 相似文献
11.
Bento Arce-Gomez Elizabeth A. Jones Colin J. Barnstable Ellen Solomon Walter F. Bodmer 《Tissue antigens》1978,11(2):96-112
The lymphoblastoid cell line Daudi lacks both HLA—A and B antigens and β2 microglobulin. Somatic cell hybrids derived from a fusion between this line and D98/AH-2 were shown to express four HLA antigens not detectable on either parent cell, A1, A10(Aw26), Bw16(Bw38, Bw17. The initial definition by direct cytotoxicity assay was confirmed by absorption of reactions against target T lymphocytes, thus avoiding problems due to contaminating Ia antibodies, and by blocking the reactions by pretreatment with a chicken anti-human β2 microglobulin serum. That the new specificities were due to the Daudi HLA region was confirmed by the finding that interspecific hybrids between Daudi and A9L, containing a single human chromosome 6, expressed A10 and Bw17. This also defined the haplotypes of Daudi as A10(Aw26), Bw17 and A1, Bw16(Bw38).
The re-expression of the Daudi HLA—A and B antigens in two independent sets of hybrids indicates that it does not carry a mutation in the HLA region. It has previously been reported that somatic cell hybrids with Daudi, which contain chromosome 15, do not express human β2 microglobulin. These results suggest that the reason for the lack of HLA—A and B antigens on Daudi is a secondary effect due to the mutation(s) in the β2 microglobulin gene. 相似文献
The re-expression of the Daudi HLA—A and B antigens in two independent sets of hybrids indicates that it does not carry a mutation in the HLA region. It has previously been reported that somatic cell hybrids with Daudi, which contain chromosome 15, do not express human β
12.
S. CASPAR-BAUGUIL J. ARNAUD A. HUCHENQ W. R. HEIN C. GEISLER† B. RUBIN 《Scandinavian journal of immunology》1994,40(3):323-336
In the present study, we have investigated the importance of a phenylalanine (phe195 ) in the Tcr-Cα region on Tcr-α, β/CD3 membrane expression. An exchange of phe195 with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with aspartic acid, histidine or valine prohibit completely Tcr/CD3 membrane expression. This seems to be due to a lack of interaction between mutated Tcr-α, β/CD3-γɛ, δɛ complexes and ζ2 homodimers. The Tcr-Cα region around phe195 seems together with the same region in the Tcr-Cβ region to constitute an interaction site for ζ2 homodimers. The presence of phe195 on both Tcr-Cα and Tcr-Cβ causes high avidity interaction with ζ2 homodimers, whereas his195 in both Tcr-Cγ and Tcr-Cδ results in an apparently lower avidity interaction with ζ2 homodimers. It is suggested that the phe195 region (on β-strand F) and eventually adjacent aromatic amino acid residues on β-strand B region may play an important role in Tcr-α, β/CD3 membrane expression, in Tcr-α, β/CD3 competition with Tcr-γ, δ/CD3 complexes for ζ2 homodimers and in the control of formation of 'mixed' Tcr heterodimers. 相似文献
13.
Cardiac troponin T (cTnT) is an essential component of the thin filament regulatory unit (RU) that regulates Ca2+ activation of tension in the heart muscle. Because there is coupling between the RU and myosin crossbridges, the functional outcome of cardiomyopathy-related mutations in cTnT may be modified by the type of myosin heavy chain (MHC) isoform. Ca2+ activation of tension and ATPase activity were measured in muscle fibres from normal rat hearts containing α-MHC isoform and propylthiouracil (PTU)-treated rat hearts containing β-MHC isoform. Muscle fibres from normal and PTU-treated rat hearts were reconstituted with two different mutations in rat cTnT; the deletion of Glu162 (cTnTE162DEL ) and the deletion of Lys211 (cTnTK211DEL ). α-MHC and β-MHC isoforms had contrasting impact on tension-dependent ATP consumption (tension cost) in cTnTE162DEL and cTnTK211DEL reconstituted muscle fibres. Significant increases in tension cost in α-MHC-containing muscle fibres corresponded to 17% ( P < 0.01) and 23% ( P < 0.001) when reconstituted with cTnTE162DEL and cTnTK211DEL , respectively. In contrast, tension cost decreased when these two cTnT mutants were reconstituted in muscle fibres containing β-MHC; by approximately 24% ( P < 0.05) when reconstituted with cTnTE162DEL and by approximately 17% ( P = 0.09) when reconstituted with cTnTK211DEL . Such differences in tension cost were substantiated by the mechano-dynamic analysis of cTnT mutant reconstituted muscle fibres from normal and PTU-treated rat hearts. Our observation demonstrates that qualitative changes in MHC isoform alters the nature of cardiac myofilament dysfunction induced by mutations in cTnT. 相似文献
14.
Exogenously added β2 microglobulin (β2 m) binds to a variety or murine cell types. The 'receptor' for β2 m has been isolated. The purified 'receptor' comprised a 48,000-dalton chain and occasionally a 25,000-dalton component. Direct crosslinking of β2 m to the receptor on intact cells gave rise to a single 60,000-dalton β2 m-'receptor' complex. The molecular characteristics of the 'receptor' were considerably changed on binding β2 m. The size of the β2 m-'receptor' complex was increased partly due to enhanced binding of deoxycholate. The 'receptor' was less easily degraded by proteases when β2 m was bound then when free. The solubilized 'receptor' reacted with a heteroantiserum raised against H-2K and D antigens but did not exhibit any alloantigenic determinants shared with H-2 K, D or Ia antigens. 相似文献
15.
Intestinal lamina propria T cells are believed to be derived, via the systemic circulation, from gut-associated lymphoid tissue. After migration into the lamina propria, T cells are capable of luminally directed migration following the loss of surface epithelial cells. For adhesion and migration within the extracellular matrix, T cells are likely to utilize the integrin family of adhesion molecules. The aim of this study was to quantitatively and qualitatively investigate the expression of α5 and α6 integrin subunits on the surface of human T cells that: (a) migrated out of the lamina propria, (b) remained resident within the matrix and (c) were present in the circulation. In both subpopulations of CD4 and CD8-positive T cells, from both normal and inflamed (inflammatory bowel disease) colonic mucosa, there were significantly fewer α5 and α6 -positive cells than in the peripheral blood. In addition, there were significantly fewer α6 integrin molecules on the surface of CD4 and CD8-positive lamina propria T-cell subpopulations, compared with those in the circulation. Our studies suggest that, following migration into the lamina propria, there is down-regulation of α5 and α6 integrin-subunit expression on the surface of T cells. Molecules other than members of very late activation antigen-5 (VLA-5) (α5 β1 ) and VLA-6 (α6 β1 ) families of adhesion molecules are likely to be important in interactions with extracellular components in the lamina propria of normal and inflamed human colonic mucosa. 相似文献
16.
Non-selective β-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans 总被引:1,自引:1,他引:0
Thomas Seifert Larsen Peter Rasmussen Morten Overgaard Niels H. Secher Henning B. Nielsen 《The Journal of physiology》2008,586(11):2807-2815
Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O2 /(glucose +½lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 ± 4.2 m m (mean ± s.d. ) and the arterial–jugular venous (a–v) difference from −0.02 ± 0.03 m m at rest to 1.0 ± 0.5 m m ( P < 0.05). The a–v difference for glucose increased from 0.7 ± 0.3 to 0.9 ± 0.1 m m ( P < 0.05) at exhaustion and the cerebral metabolic ratio decreased from 5.5 ± 1.4 to 3.0 ± 0.3 ( P < 0.01). Administration of a non-selective β-adrenergic (β1 +β2 ) receptor antagonist (propranolol) reduced heart rate (69 ± 8 to 58 ± 6 beats min−1 ) and exercise capacity (239 ± 42 to 209 ± 31 W; P < 0.05) with arterial lactate reaching 9.4 ± 3.6 m m . During exercise with propranolol, the increase in a–v lactate difference (to 0.5 ± 0.5 m m ; P < 0.05) was attenuated and the a–v glucose difference and the cerebral metabolic ratio remained at levels similar to those at rest. Together with the previous finding that the cerebral metabolic ratio is unaffected during exercise with administration of the β1 -receptor antagonist metropolol, the present results suggest that the cerebral metabolic ratio decreases in response to a β2 -receptor mechanism. 相似文献
17.
Valerie B. Caraiscos S. John Mihic John F. MacDonald Beverley A. Orser 《The Journal of physiology》2002,539(2):495-502
Glycine receptors (GlyRs) are transmitter-gated channels that mediate fast inhibitory neurotransmission in the spinal cord and brain. The GlyR β subunit contains a putative tyrosine phosphorylation site whose functional role has not been determined. To examine if protein tyrosine kinases (PTKs) regulate the function of GlyRs, we analysed whole-cell currents activated by applications of glycine to CA1 hippocampal neurons and spinal neurons. The role of a putative site for tyrosine phosphorylation at position 413 of the β subunit was examined using site-directed mutagenesis and expression of recombinant (α1 βY413F ) receptors in human embryonic kidney (HEK 293) cells. Lavendustin A, an inhibitor of PTKs, depressed glycine-evoked currents ( I Gly ) in CA1 neurons and spinal neurons by 31 % and 40 %, respectively. In contrast, the intracellular application of the exogenous tyrosine kinase, cSrc, enhanced I Gly in CA1 neurons by 56 %. cSrc also accelerated GlyR desensitization and increased the potency of glycine 2-fold (control EC50 = 143 μ m ; cSrc EC50 = 74 μ m ). Exogenous cSrc, applied intracellularly, upregulated heteromeric α1 β receptors but not homomeric α1 receptors. Substitution mutation of the tyrosine to phenylalanine at position β-413 prevented this enhancement. Furthermore, a selective inhibitor of the Src family kinases, PP2, down-regulated wild-type α1 β but not α1 βY413F receptors. Together, these findings indicate that GlyR function is upregulated by PTKs and this modulation is dependent on the tyrosine-413 residue of the β subunit. 相似文献
18.
J. M. NTHALE J. SYFRIG T. W. PEARSON† J. NAESSENS 《Scandinavian journal of immunology》1995,42(5):524-528
A set of monoclonal antibodies (MoAbs) to leucocyte antigens is an essential tool to identify different cell types and functional membrane molecules involved in immune responses. Since no MoAbs existed to bovine integrins, except against the β2 subfamily, we generated MoAbs to β3 integrin after the immunization of mice with bovine platelets. Two MoAbs, IL-A164 (IgG2a ) and IL-A166 (IgG1 ), were selected that reacted specifically with bovine platelets and detected the same membrane molecule. The antigen was a heterodimer of two polypeptide chains of 122 kDa and 95 kDa as resolved by SDS-PAGE under reducing conditions. Although the Mr of the smaller subunit is identical to that of β2 integrin, pre-absorption with an antibody to β2 (or CD18) did not remove the bovine antigen. Comparing the molecular masses of the two subunits in reduced and non-reduced forms showed a pattern that was similar to that of human GPIIb/IIIa (also called αIIb β3 or CD41a). Reduction of the bovine molecule increased the apparent Mr of the light chain from 76 kDa to 95 kDa, while the heavy subunit changed from 136 kDa to 122 kDa. As with human GPIIb, the decrease in Mr of the α-subunit is probably a result of a small disulphide-linked polypeptide, although no additional evidence for this was detected for the bovine integrin. Sequencing of the N-terminal amino acids of both bovine polypeptides showed identity of the bovine integrin with human GPIIb/IIIa. 相似文献
19.
Shoichi Arai Rumiko Matsuoka Kenji Hirayama Hisanao Sakurai Masaharu Tamura Tenkou Ozawa Misa Kimura Shin-Ichiro Imamura Yoshiyuki Furutani Kunitaka Joh-o Masatoshi Kawana Atsuyoshi Takao Saichi Hosoda Kazuo Momma 《American journal of medical genetics. Part A》1995,58(3):267-276
Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. We describe a missense mutation of the β-cardiac myosin heavy chain (MHC) gene, a G to T transversion (741 Gly→Trp) identified by direct sequencing of exon 20 in four individuals affected with familial hypertrophic cardiomyopathy. Three individuals with sporadic hypertrophic cardiomyopathy, whose parents are clinically and genetically unaffected, had sequence variations of exon 34 of the α-cardiac MHC gene (a C to T transversion, 1658 Asp→Asp, resulting in FokI site polymorphism), of intron 33 of the α-cardiac MHC gene (a G to A and an A to T transversion), and also of intron 14 of the β-cardiac MHC gene (a C to T transversion in a patient with Noonan syndrome). Including our case, 30 missense mutations of the β-cardiac MHC gene in 49 families have been reported thus far worldwide. Almost all are located in the region of the gene coding for the globular head of the molecule, and only one mutation was found in both Caucasian and Japanese families. Missense mutations of the β-cardiac MHC gene in hypertrophic cardiomyopathy may therefore differ according to race. © 1995 Wiley-Liss, Inc. 相似文献
20.
Thomas S. Seifert Patrice Brassard Thomas B. Jørgensen Ahmad J. Hamada Peter Rasmussen Bjørn Quistorff Niels H. Secher Henning B. Nielsen 《The Journal of physiology》2009,587(1):285-293
During brain activation, the decrease in the ratio between cerebral oxygen and carbohydrate uptake (6 O2 /(glucose + 1 /2 lactate); the oxygen–carbohydrate index, OCI) is attenuated by the non-selective β-adrenergic receptor antagonist propranolol, whereas OCI remains unaffected by the β1 -adrenergic receptor antagonist metroprolol. These observations suggest involvement of a β2 -adrenergic mechanism in non-oxidative metabolism for the brain. Therefore, we evaluated the effect of adrenaline (0.08 μg kg−1 min−1 i.v. for 15 min) and noradrenaline (0.5, 0.1 and 0.15 μg kg−1 min−1 i.v. for 20 min) on the arterial to internal jugular venous concentration differences (a-v diff) of O2 , glucose and lactate in healthy humans. Adrenaline ( n = 10) increased the arterial concentrations of O2 , glucose and lactate ( P < 0.05) and also increased the a-v diff for glucose from 0.6 ± 0.1 to 0.8 ± 0.2 m m (mean ± s.d. ; P < 0.05). The a-v diff for lactate shifted from a net cerebral release to an uptake and OCI was lowered from 5.1 ± 1.5 to 3.6 ± 0.4 ( P < 0.05) indicating an 8-fold increase in the rate of non-oxidative carbohydrate uptake during adrenaline infusion ( P < 0.01). Conversely, noradrenaline ( n = 8) did not affect the OCI despite an increase in the a-v diff for glucose ( P < 0.05). These results support that non-oxidative carbohydrate consumption for the brain is driven by a β2 -adrenergic mechanism, giving neurons an abundant provision of energy when plasma adrenaline increases. 相似文献