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81.
V J?nsson H D Schr?der T Staehelin Jensen C Nols?e B Stigsby W Trojaborg A Svejgaard E Hippe 《Acta medica Scandinavica》1988,223(3):255-261
In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three of them, including two siblings with a demyelinating peripheral neuropathy, the IgM was bound to the myelin-associated glycoprotein (MAG) of peripheral nerves. One had axonal neuropathy with IgM activity against the peri- and endoneurium, while another case with post-infectious neuritis had IgM activity against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported. 相似文献
82.
Integrin-linked kinase (ILK) is required for polarizing the epiblast,cell adhesion,and controlling actin accumulation 总被引:15,自引:0,他引:15 下载免费PDF全文
Sakai T Li S Docheva D Grashoff C Sakai K Kostka G Braun A Pfeifer A Yurchenco PD Fässler R 《Genes & development》2003,17(7):926-940
Integrin-mediated cell-matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that link integrins to the actin cytoskeleton, and phosphorylates the serine/threonine kinases PKB/Akt and GSK-3beta. Here we show that mice lacking ILK expression die at the peri-implantation stage because they fail to polarize their epiblast and to cavitate. The impaired epiblast polarization is associated with abnormal F-actin accumulation at sites of integrin attachments to the basement membrane (BM) zone. Likewise, ILK-deficient fibroblasts showed abnormal F-actin aggregates associated with impaired cell spreading and delayed formation of stress fibers and FAs. Finally, ILK-deficient fibroblasts have diminished proliferation rates. However, insulin or PDGF treatment did not impair phosphorylation of PKB/Akt and GSK-3beta, indicating that the proliferation defect is not due to absent or reduced ILK-mediated phosphorylation of these substrates in vivo. Furthermore, expression of a mutant ILK lacking kinase activity and/or paxillin binding in ILK-deficient fibroblasts can rescue cell spreading, F-actin organization, FA formation, and proliferation. Altogether these data show that mammalian ILK modulates actin rearrangements at integrin-adhesion sites. 相似文献
83.
During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level. 总被引:1,自引:0,他引:1
Carsten Lundby Robert Boushel Paul Robach Kirsten M?ller Bengt Saltin José A L Calbet 《The Journal of physiology》2008,586(1):123-130
To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O(2) delivery with O(2) demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 mug (kg body mass)(-1) min(-1)) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 +/- 1.0 versus 7.9 +/- 1.0 l min(-1)) and femoral arterial oxygen delivery (1.2 +/- 0.2 versus 1.3 +/- 0.2 l min(-1); control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 +/- 14.2 versus 83.3 +/- 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 +/- 5.3 to 72.0 +/- 10.2% (P < 0.05), and the corresponding venous O(2) content was increased from 25.5 +/- 10.0 to 46.3 +/- 18.5 ml l(-1) (control and ATP, respectively, P < 0.05). With ATP, leg arterial-venous O(2) difference was decreased (P < 0.05) from 139.3 +/- 9.0 to 116.9 +/- 8.4(-1) and leg .VO(2max) was 20% lower compared to the control trial (1.1 +/- 0.2 versus 0.9 +/- 0.1 l min(-1)) (P = 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O(2) delivery with O(2) demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg .VO(2peak) is not limited by restricted vasodilatation in the altitude-acclimatized human. 相似文献
84.
There is evidence for an involvement of the hypothalamic paraventricular nuclei (PVN) in the regulation of pineal melatonin synthesis in rats. Since electrical stimulation of the PVN or the systemic administration of arginine-vasopressin (AVP) result in a depression of the nocturnal melatonin surge, this neuropeptide appears to be pivotal for the transduction of PVN-efferent, pinealopetal signals. We therefore used an AVP-deficient animal model, the Brattleboro rat, to further investigate the mechanisms responsible for pineal regulation. Anesthetized adult male animals received 2 min of bilateral electrical stimulation of the PVN either during the day or at night. Thirty min later, pineal glands were removed and pineal N-acetyltransferase (NAT) activities and melatonin contents were determined. Stimulation resulted neither during the day nor at night in any significant alterations of pineal NAT activity or melatonin content when compared to control or sham-stimulated animals. These data further support the proposed modulatory role of AVP for the regulation of melatonin synthesis in the Epiphysis cerebri of genetically intact rats. 相似文献
85.
Paternal behavior is associated with an increase in prolactin levels in fish, birds and mammals, including rodents. The striped mouse (Rhabdomys pumilio) from southern Africa shows highly developed paternal care. We investigated whether striped mouse fathers have higher prolactin levels than nonfathers, and whether there is a relationship between tactile stimulation with pups and prolactin secretion in fathers. We measured serum prolactin in 42 male striped mice assigned to one of four different experimental groups (single males, paired males, fathers housed with mother and pups, and fathers separated from their family by a wire-mesh partition). Our results revealed no increases in prolactin levels in fathers, and fathers with tactile contact with pups did not have higher prolactin levels than the fathers that were prevented from making tactile contact with pups. In contrast, experienced males had higher prolactin levels than inexperienced males. Male striped mice are polygynous in nature, living in groups, with three breeding females, and are permanently associated with pups during the breeding season. In a field study, males had higher prolactin levels during the breeding season than during the nonbreeding season. Thus, prolactin secretion in the polygynous striped mouse might be regulated by environmental stimuli, whereas social stimuli might be important for monogamous species. This is the first study to demonstrate seasonal changes in prolactin levels in a free-living male mammal. 相似文献
86.
Expression of calcium-binding proteins MRP8 and MRP14 in inflammatory muscle diseases 总被引:7,自引:0,他引:7 下载免费PDF全文
Seeliger S Vogl T Engels IH Schröder JM Sorg C Sunderkötter C Roth J 《The American journal of pathology》2003,163(3):947-956
The pathophysiological role of infiltrating macrophages and their subtypes in idiopathic inflammatory myopathies such as dermatomyositis, polymyositis, and inclusion body myositis is not fully clear. Monocytes exhibit various phenotypes with different functional properties such as release of pro- or anti-inflammatory mediators. Expression of myeloid-related proteins MRP8 and MRP14, two calcium-binding S100-proteins, characterizes a proinflammatory subtype of macrophages. We immunohistochemically investigated expression of MRP8 and MRP14 in muscle biopsies of 33 patients with dermatomyositis, polymyositis, and inclusion body myositis. We found a clear association of expression of MRP8 and MRP14 by infiltrating macrophages with degeneration of myofibers. Because MRP8 and MRP14 are secreted by activated macrophages we investigated if these proteins would have direct extracellular effects on myocytes. We found that the purified MRP8/MRP14 complex inhibited proliferation and differentiation of C2C12 myoblasts and that it induced apoptosis via activation of caspase-3 in a time- and dose-dependent manner. These results indicate that in the course of inflammatory myopathies, activated macrophages can promote destruction and impair regeneration of myocytes via secretion of MRP8/MRP14. 相似文献
87.
Immunohistochemical and molecular analysis of p53, RB,and PTEN in malignant peripheral nerve sheath tumors 总被引:3,自引:0,他引:3
Mawrin C Kirches E Boltze C Dietzmann K Roessner A Schneider-Stock R 《Virchows Archiv : an international journal of pathology》2002,440(6):610-615
The molecular basis of both sporadic and neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs) is yet largely undetermined. Therefore, we analyzed a series of 12 MPNSTs - including two cases which arose in the setting of NF1 - for molecular alterations in the p53, retinoblastoma ( Rb), and PTEN tumor suppressor genes. Furthermore, the immunohistochemical expression of p53, RB, and PTEN protein was examined in these tumors. One mutation (8%), an A to T transversion leading to an amino acid exchange, was found in exon 5 of the p53 gene in a sporadic MPNST. In two other sporadic tumors (20%), loss of heterozygosity (LOH) of the p53 gene occurred. Nuclear overexpression of p53 protein was observed in ten tumors (83%). Loss of RB protein expression was seen in two MPNSTs (17%), and LOH of the Rb gene was detected in four tumors (44%), including the two NF1-associated MPNSTs, one of them showing concomitant loss of RB protein expression. No mutation in the PTEN gene was detected, and cytoplasmic immunoreactivity for the PTEN protein was maintained in eight MPNSTs (67%). We suggest that alterations in the p53 and RB pathway, both are essential in controlling the cell-cycle progression, are critical points in the tumorigenesis of sporadic and NF1-associated MPNSTs, whereas the PTEN gene seems to play no significant role in this process. 相似文献
88.
Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene 总被引:3,自引:0,他引:3
Schröder NW Meister D Wolff V Christan C Kaner D Haban V Purucker P Hermann C Moter A Göbel UB Schumann RR 《Genes and immunity》2005,6(5):448-451
Periodontitis is an inflammatory disease affecting the connective tissue surrounding the teeth leading to tooth loss. Pathogens associated with periodontitis interact with Toll-like receptors (TLRs) to induce cytokines causing and aggravating disease. We screened 197 individuals suffering from generalized periodontitis for the presence of Asp299Gly and Thr399Ile of TLR-4 as well as Arg753Gln of TLR-2 in comparison to matched controls. Single-nucleotide polymorphisms (SNPs) of TLR-4 were elevated among patients (odd's ratio 3.650, 95% CI 1.573-8.467, P < or = 0.0001), while no difference was observed for TLR-2. TLR-4 SNPs were correlated with chronic periodontitis (odd's ratio 5.562, 95% CI 2.199-14.04, P < or = 0.0001), but not with aggressive periodontitis. This observation was confirmed employing a group of periodontally healthy probands over 60 years of age. These data demonstrate that genetic variants of TLR-4 may act as risk factors for the development of generalized chronic periodontitis in humans. 相似文献
89.
The effect of reduced umbilical blood flow rate on fetal core temperature was investigated in five chronically instrumented fetal sheep (gestational age 124 days). On average, fetal-maternal temperature difference increased 0.13±0.02 °C when blood flow rate was decreased to about 1/3 of normal (248±69 ml min–1) for 30 min. The small temperature rise is the consequence of predominant heat dissipation through the placenta, and of diminished oxygen consumption. 相似文献
90.
M. Vierbuchen S. Schröder G. Uhlenbruck A. Lavena R. Fischer 《Virchows Archiv : an international journal of pathology》1994,424(2):205-211
Forty-six medullary thyroid carcinomas (MTC) were subjected to a qualitative and quantitative characterization of native and sialic acid masked Lewisa (Lea) antigens. Immunohistochemical investigations included monoclonal antibodies (MABs) directed against alpha(2,3)-sialyl-Lea, i.e. CA19-9 (MAB 19-9), native Lea (MAB anti Lea) and alpha(2,3) sialyl type 1 structure, i.e. CA 50 (MAB C50). To detect sialic acid masked Lea reactivity, MAB anti-Lea was also applied to native and enzymatically desialylated tissue sections with and without masking of sialic acid residues by sialic acid and sequence specific lectins. Only 7 MTC (15%) displayed a weak expression of CA19-9, while 16 (33%) showed moderate positive staining for native Lea. Twenty-seven tumours exhibited a strong staining by the N'ase MAB anti Lea staining sequence. The latter could most effectively be inhibited by the simultaneous masking of alpha(2,3)-and alpha-(2,6)-linked sialic acid residues due to the comptetitive binding of sialic acid and sequence specific lectins: Maackia amurensis agglutinin (specific alpha(2,3)-linked sialic acid) and Sambucus nigra agglutinin (specific alpha(2,6)-linked sialic acid). Thus, in MTC the major portion of sialic acid masked Lea antigen reactivity is different from that detected by the MAB 19-9. The antigen reactivity is probably due to Lea structures containing both alpha(2,3) and alpha(2,6)-linked sialic acid residues. A highly significant correlation between the expression of CA50 and that detected by the N'ase MAB anti-Lea staining sequence indicates that the alpha(2,3)-sialyl type 1 chain represents a common intermediate structure within the pathway of the biosynthesis of sialylated Lea antigens, excluding the formation of CA19-9 via the formation of the disialyl type 1 structure. This is subsequently fucosylated to the corresponding sialic acid masked Lea. Preliminary clinicopathological studies indicate that the sialic acid masked Lea antigens detected by the N'ase MAB anti-Lea staining sequence are related to biologically aggressive MTC. 相似文献