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1.
On page 265, Table 3 should have appeared as : Table 3. Comparison of the electrophysiological properties of native bovine and sheep parotid Kir currents and bKir2.1 expressed in HEK293 cells 相似文献
2.
Taurine is a semiessential amino acid and naturally occurring antioxidant. One of its main roles is to protect tissues against attack by chlorinated oxidants particularly hypochlorous acid (HOCl). It is found in high concentrations in neutrophils and previous studies showed it possesses potent antimicrobial properties and attenuates high glucose induced endothelial cell apoptosis. In humans taurine has been shown to up-regulate constitutive nitric oxide synthase (cNOS), a known cytoprotector. No reported studies to date have looked at the possible therapeutic role of taurine in preventing diabetic endothelial dysfunction. We therefore hypothesised that taurine would attenuate the microvascular changes associated with hyperglycaemia in an animal model through alteration of leucocyte–endothelial interactions. Male Sprague Dawley rats were randomised into control, hyperglycaemia, and taurine + hyperglycaemia groups. Taurine was gavaged (200 mg/kg) for 5 d prior to the experiment. Hyperglycaemia was established by intravenous infusion of 50% glucose. Blood glucose reached a steady state of 3 times baseline at 30 min. Using intravital microscopy leukocyte rolling, adhesion and transendothelial migration was determined in mesenteric postcapillary venules for 3 h. Intracellular adhesion molecule-1 (ICAM-1) was immunohistochemically graded using a scoring system to determine the expression in mesenteric tissue. Taurine pretreatment significantly attenuates leukocyte-endothelial adhesion and transendothelial migration following acute hyperglycaemia but not leukocyte rolling velocity. The mechanism by which taurine protects against these effects is in part by inhibition of ICAM-1 expression .
3.
Differential mortality as a function of birth weight was studied up to the 4th week of life in all single births in Italy in 1974. - (i)
Both selection intensity and selective mortality are much higher with increasing immaturity. - (ii)
For babies born at term or after 8 months of pregnancy selection intensity tends io relax as early as one week after birth, while for those born after 7 months selection is at work for a longer period. - (iii)
Selective mortality, on the other hand, keeps increasing after birth but its relevance is relatively decreasing since average mortality after birth continues to decrease.
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4.
The chromatography of alpha-fetoprotein (AFP) containing sera on concanavalin A-Sepharose 4 B immunoadsorbant (Con A) yields two fractions, one which does and the other which does not bind the Con A. It is thus possible to calculate for various specimens the ratios
5.
Some new methods for demonstration and differentiation of acid mucopolysaccharides were described. - 1)
Cationic surfactive resin-azo dye method could be used for all kinds of acid mucopolysaccharide demonstration. - 2)
Neutral red method was found to differentiate sulfated and non-sulfated groups on one section. - 3)
Two principles to identify keratosulfate in mesenchymal tissues were studied;
- (1)
Hyaluronidase-methylation-saponification method can differentiate keratosulfate B which are both sensitive to testicular hyaluronidase. - (2)
Sugar reactions: Molisch reaction, carbazol-sulfuric acid reaction, etc. can demonstrate the presence of galactose-containing keratosulfate in the frozen sections.
By using these together with well established methods a differential table was made. The author is deeply grateful to Dr. SHIDA and Dr. KUSHIDA of the General Institute for Medical Biochemistry, Kyoto, Kowa Co., Kaken Yakukako Co., and Hodogaya Chemical Industry Co. for the supply of several kinds of samples. 相似文献
6.
We present the clinical findings and follow-up data of four female children with Cohen syndrome, two sisters and one pair of dizygotic female twins. The most characteristic findings from birth on were as follows: - 1.
Low-normal growth parameters at birth. - 2.
Mild hypotonia and evidence of progressive microcephaly with narrow forehead in the first year of life. - 3.
Neutropenia was present from the beginning, remained unchanged over the years and is not associated with higher susceptibility to infections. - 4.
Autistic behavior and severe psychomotor retardation up to the age of 2 years. At that age the ocular anomalies with high-grade myopia and chorioretinal dystrophy were diagnosed. Correction of the myopia resulted in a marked catch-up in psychomotor development. - 5.
After the age of 6 years facial stigmata became more evident with short philtrum of the upper lip and broad and large upper incisors. - 6.
Tendency to truncular obesity with rest hypotonia and poor muscle development after the ages of 6 to 8 years.
The clinical findings and follow-up data in the present four children with Cohen syndrome illustrate that the diagnosis of Cohen syndrome in infancy is very difficult. 相似文献
7.
Human lymphocytes were reacted with antisera against β-2-microglobulin (β-2-m) or HL-A antigens, and with xenogeneic anti-lymphocyte sera under conditions where redistribution and aggregation of the corresponding cell-membrane components were induced. The results demonstrate that: - 1)
Treatment with anti-β-2-m antisera aggregated and completely removed the HL-A anti-genic structures from the cell membrane, but not, however, the structures reactive with anti-lymphocyte sera. - 1)
Treatment with anti-HL-A antisera also aggregated some of the β-2-m carrying structures, but left others undisturbed. - 1)
Treatment with anti-lymphocyte sera did not disturb expression of HL-A antigens or β-2-m structures. - 1)
Anti-β-2-m and anti-HL-A antisera inhibited antigen activation of lymphocytes, but this was not so in the case of the anti-lymphocyte sera used. - 1)
The anti-β-2-m antiserum and the anti-lymphocyte sera were mitogenic for normal lymphocytes.
Taken together, our results strongly suggest that β-2-m is also part of native cell-membrane bound HL-A antigens, and that the antigenic structures which react with xenogeneic anti-lymphocyte sera may reside on molecules separate from those carrying HL-A and β-2-m activity. Furthermore, the results indicate that the two sub-unit molecules consisting of HL-A alloantigenic determinants and β-2-m are closely associated — structurally or functionally — with lymphocyte receptor structures. 相似文献
8.
The role of nitric oxide in gut inflammation was evaluated by comparing the effects of selective or nonselective inhibitors of nitric oxide synthase (NOS). Aminoguanidine, a selective inducible NOS (iNOS) inhibitor, or NG-nitro-l-arginine methyl ester (l-NAME) were administered via the drinking water to normal guinea pigs or following induction of ileitis with trinitrobenzene sulfonic acid (TNBS 30 mg/kg). Aminoguanidine had no detectable effect in normal animals. In contrast,l-NAME caused a time and dose-dependent increase in ileal myeloperoxidase activity and circulating leukocyte numbers. Only the ileum was inflamed withl-NAME treatment. In TNBS ileitis, both NOS inhibitors were protective, inhibiting in a dose-dependent manner granulocyte infiltration and submucosal fibrosis, with concurrent reductions in substance P immunoreactivity, epithelial protein leak and bowel wall thickening. Aminoguanidine was remarkably potent with an EC50 value of 100 ng/ml (drinking water concentration).l-NAME was approximately 100-fold less potent than aminoguanidine. We conclude from this pharmacological profile, that a lack of cNOS activity or an excess of iNOS activity can lead to gut inflammation. Aminoguanidine is the most potent inhibitor of experimental inflammatory bowel disease yet reported. 相似文献
9.
Objective To study the clinical significance of a nested polymerase chain reaction (PCR) method compared to immunofluorescence (IF) for detection of Pneumocystis carinii . Methods The medical records of 89 patients with 91 episodes of pneumonia were scrutinised retrospectively. The pneumonia episodes were divided into categories according to the likelihood that the patient had had clinical Pneumocystis carinii pneumonia (PCP). All respiratory tract samples from the 89 patients (34 broncho-alveolar lavage (BAL) and 57 sputa) were tested for Pneumocystis carinii by IF and nested PCR. Results Fifteen episodes, as diagnosed by IF, were classified as true PCP (combination of the groups with definite and probable PCP; sensitivity 60%, specificity 97%). Among the P. carinii DNA-positive episodes, detected with nested PCR, 24 were classified as true PCP (combination of the groups with definite and probable PCP; sensitivity 96%, specificity 59%), since all IF-positive samples were nested PCR positive. Only one pneumonia episode classified as a probable PCP, was negative with both methods, as applied to a BAL sample. Conclusions IF applied to BAL or sputum seems to be the most specific method for diagnosis of clinical PCP. Additional clinical cases can be found by nested PCR, although this then gives a high risk of detecting subclinical colonisation of P. carinii . 相似文献
10.
The literature concerning brain damage due to hydrocephalus, especially in children and animal models, is reviewed. The following conclusions are reached:
11.
Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families). - 1)
Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients. - 2)
Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3. - 3)
An excess of HLA-identical affected siblings was found. - 4)
An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased.
The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature. 相似文献
12.
Summary: Living systems operate under interactive selective pressures. Populations have the ability to anticipate the future by generating a repertoire of elements that cope with new selective pressures. If the repertoire of such elements were transcendental, natural selection could not operate because any one of them would be too rare. This is the problem that vertebrates faced in order to deal with a vast number of pathogens. The solution was to invent an immune system that underwent somatic evolution. This required a random repertoire that was generated somatically and divided the antigenic universe into combinatorials of determinants. As a result, it became virtually impossible for pathogens to escape recognition but the functioning of such a repertoire required two new regulatory mechanisms: 1) a somatic discriminator between Not-To-Be-Ridded ('Self') and To-Be-Ridded ('Non-self') antigens, and 2) a way to optimize the magnitude and choice of the class of the effector response. The principles governing this dual regulation are analyzed in the light of natural selection.
13.
Chromosomal investigations were performed on fibroblast cultures established from tumour tissue of six patients with multiple basal cell carcinoma, and from one patient with a solitary basal cell carcinoma. In four instances, fibroblast cultures from specimens of unaffected skin areas Were examined simultaneously. Metaphases of peripheral blood lymphocytes were analysed in all patients. Three individuals showed increased rates of chromosomal breakage and rearrangement; the possibility of a relationship between these findings and the Occurrence of multiple basal cell carcinoma is discussed: - 1).
The chromosomal aberrations noted in one patient with multiple arsenic-induced basal cell carcinoma probably reflect the long-term effect of exposure to arsenic. - 2).
In the second case, the aberrations found in cultures from unaffected skin and blood lymphocytes may be due to repeated X-ray therapy of multiple nevoid basal cell carcinoma - 3).
In the third patient, likewise affected by multiple nevoid basal cell carcinoma, the etiology of the increased frequency of chromosomally altered cells remains obscure. Taken together with two other observations (Happle et al. 1971, Happle & Kupferschmid 1972), the aberrations could indicate that in some patients with nevoid basal cell carcinoma syndrome the incidence of spontaneous chromosomal breakage tends to increase.
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14.
Changes of the proximal convoluted tubular epithelium of the rats which were sacrificed instantaneously at 5, 15, 30 minutes, 1, 3, 6, and 8 hours after intraperitoneal injections of 40 to 52 cc per kg of a 50 % aquenous solution of sucrose, were observed by electron microscopic and histochemical methods. The results obtained can be summarized as follows: - 1)
The vacuoles begin to appear 15 minutes after the injection in the apical portion of the tubular cytoplasm and become distinct in 30 minutes. After 6 hours, it is observed in the entire cytoplasm which is filled with large vacuoles. - 2)
The vacuoles originate from dilatation of simple pinocytotic vesicles which exist physiologically beneath the brush border microvilli. The small vacuoles of 1 to 1.5 microns in diameter reveal heavy acid phosphatase activity and have temporarily a character of so-called lysosome or cytosome. With the enlargement of vacuoles, the surrounding single limiting membrane reveals discontinuity or rupture at numerous sites. At this stage, the vacuoles aggregate and fuse with each other to form larger ones of 4 to 4.5 microns in diameter and lose their acid phosphatase activity. - 3)
Vacuolar alteration of the proximal convoluted tubules and the role of lysosome and FCD are discussed.
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15.
Aims : To determine the immunohistochemical localization of basement membrane components laminin and type IV collagen in premalignant and malignant lesions of the oral epithelium. Methods and resultsFormalin-fixed tissue sections of 12 epithelial hyperplasias with no dysplasia and 30 dysplasias, clinically diagnosed as leukoplakia and/or erythroplakia, as well as 50 invasive squamous cell carcinomas, were stained with mouse monoclonal antibodies to human laminin and type IV collagen. Statistical analysis showed that there was a linear trend for discontinuous distribution of laminin from epithelial hyperplasia to epithelial dysplasia and invasive squamous cell carcinoma ( P < 0.001). Laminin staining showed a linear trend for discontinuity with increasing grade of dysplasia ( P < 0.05) and was more frequently discontinuous in areas of deep tumour invasion than in central or superficial areas ( P < 0.05). Brush-shaped thickening and reduplication of the basement membrane were also identified. ConclusionsAlterations in the distribution of laminin and type IV collagen in oral premalignant and malignant lesions indicate that the loss of continuity of the subepithelial basement membrane parallels the progression of the neoplastic transformation process in oral epithelium. 相似文献
16.
Background It has been shown that a vacuum cleaner (VC) can increase airborne cat allergen levels. This study aimed to compare the degree of leakage of airborne Fel d 1 levels among five different VCs, both under laboratory conditions and in an apartment with cats. Methods Three of the VCs were marketed as antiallergic: a HEPA filter VC (VC A), a water impingement and HEPA filter VC (VC B), and a foam fabric filter VC (VC C). The other two were standard VCs: VC D and VC E. VCs were tested in a 20 m', airtight, experimental room and in a 53 m 2* living room in an apartment with three cats. Air was sampled with a glass-fiber filter and an impinger at 20 1/min for 30 min before, during, and after vacuuming. Airborne Fel d 1 was measured with a two-site monoclonal ELISA assay. Results In the experimental room, no airborne Fel d 1 level was measured before using the VCs. After introducing a dust sample containing Fel d 1 in the VCs. we found that VCs A, B, and E did not provoke any increase in airborne Fel d I. In contrast, VCs C and D significantly increased airborne Fel d 1 levels (GM: 4.9 and 5.3 ng/m, respectively). In the apartment, all VCs induced an increase in airborne Fel d 1, which was carried by particles greater than 5 nm. However, VCs C and D provoked significantly greater increases in airborne Fel d 1 than VCs A, B, and E (P=0.0001). Conclusions Our results suggest that: - 1)
The two VCs with leakage in the experimental room had greater leakages in the apartment. - 2)
In the apartment with cats, all VCs provoked increases in airborne Fel d 1, primarily carried by large particles. - 2)
Given the increased marketing of "antiallergic" VCs, further studies are needed to standardize methods for testing airborne allergen leakage by VCs.
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17.
Amino acids 17-35 of the thrombospondin1 (TSP1) N-terminal domain (NTD) bind cell surface calreticulin to signal focal adhesion disassembly, cell migration, and anoikis resistance in vitro. However, the in vivo relevance of this signaling pathway has not been previously determined. We engineered local in vivo expression of the TSP1 calreticulin-binding sequence to determine the role of TSP1 in tissue remodeling. Surgical sponges impregnated with a plasmid encoding the secreted calreticulin-binding sequence [NTD (1-35)-EGFP] or a control sequence [mod NTD (1-35)-EGFP] tagged with enhanced green fluorescent protein were implanted subcutaneously in mice. Sponges expressing NTD (1-35)-EFGP formed a highly organized capsule despite no differences in cellular composition, suggesting stimulation of collagen deposition by the calreticulin-binding sequence of TSP1. TSP1, recombinant NTD, or a peptide of the TSP1 calreticulin-binding sequence (hep I) increased both collagen expression and matrix deposition by fibroblasts in vitro. TSP1 stimulation of collagen was inhibited by a peptide that blocks TSP1 binding to calreticulin, demonstrating the requirement for cell surface calreticulin. Collagen stimulation was independent of TGF-β activity and Smad phosphorylation but was blocked by an Akt inhibitor, suggesting that signaling through the Akt pathway is important for regulation of collagen through TSP1 binding to calreticulin. These studies identify a novel function for the NTD of TSP1 as a mediator of collagen expression and deposition during tissue remodeling.Tissue remodeling is a highly orchestrated process that requires coordinated regulation of cell migration, proliferation, extracellular matrix deposition and remodeling, and eventual cell regression. The extracellular matrix provides both biochemical and mechanical cues to regulate these complex cellular responses to injury and repair. A family of extracellular matrix proteins, the matricellular proteins, has been shown to regulate cell behavior and extracellular matrix deposition during tissue remodeling and wound repair. 1–3Thrombospondin 1 (TSP1) is a multifunctional, matricellular protein that constitutes 25% of the protein released from the α-granules of activated platelets. 4,5 TSP1 is present in wounds and expressed by cells involved in wound healing, including macrophages, fibroblasts, endothelial cells, and vascular smooth muscle cells. 6–9 TSP1 knockout mice display compromised wound healing, characterized by reduced macrophage infiltration and a delay in capillary angiogenesis, but persistence of granulation tissue. 9 It induces focal adhesion disassembly, stimulates cell motility, activates latent transforming growth factor-β (TGF-β), and inhibits nitric oxide signaling. 10–12 Depending on whether the N- or C-terminal domain of TSP1 is engaged, it is either anti- or proangiogenic. 12–14 TSP1 can be proapoptotic to endothelial cells, but it also stimulates cell survival by signaling resistance to anoikis. 15 These diverse and sometimes paradoxical activities can be ascribed to its interactions with multiple receptors, including integrins, syndecans, 13,16 CD47, 17 CD36, 18 low-density lipoprotein receptor-related protein 1 (LRP1), 19 and calreticulin (CRT). 20To date, the role of TSP1 in tissue remodeling has largely been studied through injury models in TSP1-null mice. 9,21,22 These models have been useful for identifying many functions of TSP1 but are limited in their ability to mimic tissue remodeling in a normal organism, in which TSP1 expression, proteolysis, and interactions with multiple receptors will be modulated both temporally and spatially. The susceptibility of TSP1 to proteolytic cleavage by a wide spectrum of proteases suggests that cells are likely to be exposed to fragments of TSP1 during tissue remodeling. 23 Both the N- and C-terminal domains can be detected separately from the full-length TSP1 molecule in vivo. 23,24 Therefore, ongoing questions include whether TSP1 can signal simultaneously through multiple receptors and whether isolated domains elicit responses distinct from the intact molecule. For these reasons, in vivo models expressing isolated TSP1 domains on a wild-type genetic background are relevant to the physiological conditions of TSP1 in wound healing.Previously, we showed that amino acids 17-35 of the N-terminal domain (NTD) of TSP1 signal focal adhesion disassembly and increased cell migration in vitro. 25 Furthermore, signaling through this sequence prevents anoikis. 19 This sequence in the NTD binds to a cell surface cocomplex of CRT and LRP1 and stimulates signaling through focal adhesion kinase (FAK), extracellular signal related kinase (ERK), and phosphoinositide 3-kinase (PI3 kinase), which results in transient phosphorylation of Akt and down-regulation of Rho kinase. 26,27 Signaling downstream from TSP1 engagement of the CRT/LRP1 cocomplex induces an intermediate state of adhesion in endothelial cells, fibroblasts, and vascular smooth muscle cells. 25,26 Intermediate adhesion is characterized by a reduced number of focal adhesions and actin stress fibers without the loss of cell attachment or spreading. 28 This intermediate adhesive state precedes migration in response to the TSP1 CRT-binding sequence. 28,29 Induction of intermediate adhesion, cell migration, and anoikis resistance are similarly regulated by TSP1, a recombinant trimeric form of the NTD (NoC1), and by a synthetic peptide comprising the CRT-binding sequence (aa 17-35, hep I peptide). Furthermore, TSP1 binding to aa19-36 in the NTD of CRT is necessary for TSP-CRT binding and induction of signaling, and cells lacking this site in CRT do not respond to TSP1. 15,30,31The role of TSP1 binding to the CRT-LRP1 complex in vivo is unknown. Based on previous studies, we hypothesized that local expression of the secreted CRT-binding sequence of TSP1 at sites of injury in vivo would signal intermediate cell adhesion and migration of CRT-expressing cells to increase cellularity of wounds. To test this hypothesis, we used an in vivo mouse model of the foreign body response to drive local expression of a secreted enhanced green fluorescent protein (EGFP)-tagged fusion protein of the TSP1 CRT-binding sequence. Unexpectedly, our results showed that the CRT-binding sequence of TSP1 stimulates the formation of a highly organized collagen capsule, which reduced cellular infiltration into the sponges. In vitro studies confirmed that TSP1 stimulates fibrillar collagen expression by fibroblasts and increased incorporation of collagen into the extracellular matrix in a CRT-dependent manner. Although TSP1 can activate latent TGF-β, the recombinant TSP1 NTD protein NoC1 stimulated collagen independently of both TGF-β activity and Smad2 phosphorylation. Rather, the CRT-binding sequence requires Akt activity to stimulate collagen. These studies identify a previously unknown role for the NTD of TSP1 in tissue remodeling through a CRT-dependent TGF-β–independent stimulation of collagen matrix formation. 相似文献
19.
(1-3)-β- d-Glucan (BG) reactivity was tested in serum samples from 28 patients with human immunodeficiency virus infection or a hematological malignancy and Pneumocystis jirovecii pneumonia (PCP) and 28 control patients. The sensitivity and specificity of BG detection with the Fungitell assay for PCP were 100 and 96.4%, respectively, using a cutoff value of 100 pg/ml. Serum BG testing looks promising for the noninvasive diagnosis of PCP. Our data suggest that a higher cutoff value for the diagnosis of PCP than for the diagnosis of invasive aspergillosis or candidiasis could be used safely and will improve the specificity of the test. Pneumocystis jirovecii pneumonia (PCP) remains a serious cause of morbidity and mortality in immunocompromised patients. PCP may be difficult to diagnose owing to nonspecific signs and symptoms and possible coinfection with microorganisms other than P. jirovecii. Moreover, Pneumocystis cannot be propagated in culture. Diagnosis relies on the visualization of the fungus upon microscopic examination of induced sputum samples, bronchoalveolar lavage (BAL) fluids, or biopsy specimens. The sensitivity of microscopy varies according to the staining technique (it is highest with monoclonal antibodies) and the sample type ( 10). PCR detection of Pneumocystis nucleic acids has been shown to have higher sensitivity for the diagnosis of PCP than conventional staining techniques ( 1). However, PCR may also give positive results for patients with P. jirovecii colonization, and the clinical management of the disease in patients with positive PCR results but negative microscopy findings remains challenging. Furthermore, the diagnosis of PCP generally relies on invasive diagnostic tests, such as bronchoscopy, which is not always feasible for patients with severe respiratory distress.The measurement of serum (1-3)-β- d-glucan (BG), a cell wall component of most pathogenic fungi, including P. jirovecii, may be a useful aid for establishing the diagnosis of PCP. There are a number of diagnostic kits commercially available for detecting BG. The Fungitell BG assay (Associates of Cape Cod, East Falmouth, MA) is approved by the U.S. Food and Drug Administration as an adjunct for the diagnosis of invasive fungal disease, and the assay kit also carries the European CE mark. Up to now, data about the performance characteristics of the Fungitell BG test for the diagnosis of PCP have been scarce ( 2, 5, 8, 9). Few patients were included in the studies reported, and generally no relevant control patients were included. It is not known whether the cutoff value proposed by the manufacturer (80 pg/ml) can be used for the diagnosis of PCP. Elevated BG levels in PCP patients have been detected, but since many factors were reported to cause false-positive results, data for control groups are needed before the test can be used in routine practice.We retrospectively measured BG concentrations in sera from PCP patients and controls in two major risk groups, namely, patients with advanced human immunodeficiency virus (HIV) infection and patients with a hematological malignancy, with the aim of determining the diagnostic potential of BG testing for both groups. 相似文献
20.
Aims: Keloid is characterized by excessive deposition of collagen, resulting from aberrant extracellular matrix (ECM) production and degradation. The aim was to investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in pathological wound healing in keloids. Methods and results: Semiquantitative analysis of 60 keloid tissue samples and 25 mature scar tissue samples demonstrated significantly increased expression of MMP-2, TIMP-2 and TIMP-3 in keloids compared with mature scars. Within keloid regions, MMP-2 expression was significantly higher in collagen bundle regions than in non-collagen bundle regions. Double immunofluorescence revealed that keloid fibroblasts between collagen bundles exhibited MMP-2, TIMP-2 and membrane-type 1 MMP (MT1-MMP) co-expression, whereas only MMP-2 expression was evident on the edge of collagen bundles. Western blot analysis and gelatin zymography of 13 keloid-derived fibroblasts (KFbs) and six normal skin dermal-derived fibroblasts (NFbs) demonstrated that unstimulated KFbs exhibited significantly increased MMP-2 activity and expression compared with NFbs under the same conditions. Conclusions: These results together indicate that MMP-2 activity can be promoted in keloid fibroblasts between collagen bundles in cooperation with TIMP-2 and MT1-MMP. This could contribute to remodelling of collagen bundle regions and invasion of fibroblasts into peripheral normal regions through promoted degradation of ECM. 相似文献
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