BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) represents a common condition having a substantial impact on the patients' quality of life, as well as the health system. According to many studies, the BARX1 and ADAMTS17 genes have been suggested as genetic risk loci for the development of GERD and its complications. The purpose of this study is to investigate the potential association between GERD and BARX1 and ADAMTS17 polymorphisms. METHODS: The present is a prospective cohort study of 160 GERD patients and 180 healthy control subjects of Greek origin, examined for BARX1 and ADAMTS17 polymorphisms (rs11789015 and rs4965272) and a potential correlation to GERD. RESULTS: The rs11789015 AG and GG genotypes were found to be significantly associated with GERD (P = 0.032; OR, 1.65; 95% CI, 1.06–2.57 and P = 0.033; OR, 3.00; 95% CI, 1.15–7.82, respectively), as well as the G allele (P = 0.007; OR, 1.60; 95% CI, 1.14–2.24). Concerning the rs4965272, only the GG genotype was significantly associated with GERD (P = 0.035; OR, 3.42; 95% CI, 1.06–11.05). CONCLUSIONS: This is a study investigating the potential correlation between BARX1 and ADAMTS17 polymorphisms and the development of GERD, showing a considerable association between both polymorphisms and the disease. This finding suggests that esophageal differentiation or altered regulation on microfibrils in the cell environment could be implicated as possible mechanisms in the pathogenesis of GERD.
Alleles ; Cohort Studies ; Gastroesophageal Reflux ; Genotype ; Humans ; Microfibrils ; Polymorphism, Genetic ; Prospective Studies ; Quality of Life

Marfan syndrome (MFS) is an inherited connective tissue disorder with a mutation in the fibrillin-1 (FBN1) gene. Fibrillin is a major building block of microfibrils, which constitute the structural component of the connective tissues. A 10-year-old girl visited our hospital with the chief complaint of precocious puberty. According to her medical history, she had a pulmonary wedge resection for a pneumothorax at 9 years of age. There was no family history of MFS. Mid parental height was 161.5 cm. The patient's height was 162 cm (>97th percentile), and her weight was 40 kg (75th-90th percentile). At the time of initial presentation, her bone age was approximately 11 years. From the ophthalmologic examination, there were no abnormal findings except myopia. There was no wrist sign. At the age of 14 years, she revisited the hospital with the chief complaint of scoliosis. Her height and weight were 170 cm and 50 kg, respectively, and she had arachnodactyly and wrist sign. We performed an echocardiograph and a test for the FBN1 gene mutation with direct sequencing of 65 coding exons, suspecting MFS. There were no cardiac abnormalities including mitral valve prolapse. A cytosine residue deletion in exon 7 (c.660delC) was detected. This is a novel mutation causing a frameshift in protein synthesis and predicted to create a premature stop codon. We report the case of a patient with MFS with a novel FBN1 gene missense mutation and a history of pneumothorax at a young age without cardiac abnormalities during her teenage years.
Arachnodactyly ; Child ; Clinical Coding ; Codon, Nonsense ; Connective Tissue ; Cytosine ; Exons ; Female ; Humans ; Marfan Syndrome* ; Microfibrils ; Mitral Valve Prolapse ; Mutation, Missense ; Myopia ; Parents ; Pneumothorax* ; Puberty, Precocious ; Scoliosis ; Wrist

Formation of dermal collagen fiber is a complicated and sequential process with the progressive assembly of collagen. Collagen monomers form stepped and orderly protofibrils through longitudinal displacement. Subsequently, protofibrils or protofibrils and collagen are bonded by covalent bonds to form orderly lamellar structure of collagen fibers. Then collagen fibers are tightly wound into coarse collagen fiber bundles by covalent crosslinking. Decorin is a multifunctional small leucine-rich proteoglycan. It can prevent the aggregation of protofibrils by binding to the specific site of collagen with its core protein, and adjusting the spacing between the protofibrils with its glycosaminoglycan chain. Thus, by effecting the formation of collagen fibers with regulation of collagen assembly, decorin may help prevent scar formation and even promote regeneration.
Collagen ; Decorin ; metabolism ; Extracellular Matrix ; Extracellular Matrix Proteins ; metabolism ; pharmacology ; Fibrillar Collagens ; metabolism ; ultrastructure ; Fibrin ; metabolism ; Humans ; Microfibrils ; metabolism ; Proteoglycans ; metabolism ; pharmacology

BACKGROUND: The zebrafish, Danio rerio, is a small bony fish that has genetic information and organ systems similar to those seen in human beings. The zebrafish has many advantages as an experimental animal model. There have been studies of zebrafish skin, especially epidermis, but there have been no studies about the elastic fibers in zebrafish skin. OBJECTIVE: The purpose of this study was to investigate the age-related, ultrastructural changes seen in the elastic fibers in zebrafish skin using electron microscopy. METHODS: We examined zebrafish skin using elastic tissue stains, the results of which were confirmed with polymerase chain reaction. We observed the ultrastructural features and age-related degenerative changes using transmission electron microscopy. RESULTS: Elastic fibers existed as a band-like layer beneath the epidermal basement membrane in zebrafish skin, which consisted of electron-dense homogeneous core material and microfibrils surrounding it and scattered inside. Elastic fibers were prominent and compact at 30 days post-fertilization. However, with aging, they started to develop small cysts and lacunae, and finally became fragmented and cracked. CONCLUSION: In zebrafish skin, elastic fibers exist beneath the epidermal basement membrane and, similar to human elastic fibers, show morphologic changes with age. Therefore, this study suggests that zebrafish skin may be useful in elastic tissue research.
Aging ; Basement Membrane ; Coloring Agents ; Elastic Tissue ; Electrons ; Epidermis ; Humans ; Microfibrils ; Models, Animal ; Polymerase Chain Reaction ; Skin ; Zebrafish

A 72-year-old woman presented with generalized edema and proteinuria. Renal biopsy disclosed highly organized fibrillary deposits in subendothelial area by electron microscopy. The microfibrils were 14 nm in diameter and randomly arranged. They did not have a microtubular appearance. These materials were negative for Congo red staining. Cryoglobulinemia or paraproteinemia including light chains was not found. So we can diagnose her as fibrillary glomerulonephritis (GN). In fibrillary GN serum complement levels are usually normal except in rare cases with systemic disease. Here we present a rare case of fibrillary GN with unusual hypocomplementemia.
Aged ; Biopsy ; Complement C3 ; Complement System Proteins ; Congo Red ; Cryoglobulinemia ; Edema ; Female ; Glomerulonephritis ; Humans ; Light ; Microfibrils ; Microscopy, Electron ; Paraproteinemias ; Proteinuria

Allografts or autografts of bone-tendon unit has been used widely for ligament or tendon reconstruction of ligament injuries or ligament deficiencies after limb salvage operation to treat malignant bone tumors around joints. While the remodeling process of the ligament or tendon itself after allograft or autograft and the microscopic and biomechanical changes of tendon- bone graft interface have been widely investigated, little is known about the ultrastructural and biochemical changes of the transitional zone in tendon-bone junction. This study was performed to analyze the morphological changes by microscopic (part I), and ultrastructural, and biochemical remodeling of the transitional zone after tendon-bone auto- and allo-grafting (part II). Preliminary, a microscopic studies at bone to tendon insertion site was done as control (part I). And as an experimental work (part II), a total of twenty four rabbits were divided into two group. In 12 animals (allograft group), an Achilles tendon-bone unit was taken with tenotomy 3 cm proximal to calcaneal attachment and osteotomy 5mm distal to the attachment site. This unit was preserved below -70degrees C for 2 weeks and then it was transplanted to another rabbit. In the other 12 animals (autograft group), the Achilles tendon-bone unit was harvested with the same maneuver from one side and transplanted to the other side of the rabbit. After operation, their legs were immobilized with short leg cast for 4 weeks, and then mobilized freely. Four animals in each group were sacrificed at four, eight and sixteen-weeks after transplantation, and their grafted Achilles tendon-bone interfaces were used for analysis of the ultrastrucural and biochemical changes. The following results were obtained. Part I: We conducted an experiment (part I) to investigate the histologic chronologic changes of tendon to bone fixation using the Cole's method and the role of periosteum to the tenodesis. The periosteum around the tenodesis was excised in group I, but it was incised longitudinally and sutured to tendon in group II. As a result, the tendons in the marrow cavity of tibia were firmly fixed by fibrosseous metaplasia in group I at 8 weeks after experiment, but not formed the fibrocartilagenous layer in both groups as a transitional zone of internal stress transmission from tendon to bone in normal tendon, and the group II show the firm connection between sutured periosteum and transferred tendon by external calluses after 3 weeks. These mean the periosteum should be sutured over the inserted tendon to get the early rigid fixation by the induction of external callus around the edges of the tendon to bone insertion. Part II: Histologically in part II experiment, new cartilage cells were observed at postoperative 16 weeks with locally presence of faint tidemark in the autograft group but not in the allograft group. Complete histological remodeling of the transitional zone had not restored both groups.. Ultrastructural analysis revealed no definite differences, but showed time-related restoration of fibers and fibroblasts between both groups except the slightly rapid appearance of parallelism and cross-striation of microfibrils in the autograft group. From biochemical analysis, type I collagen was increased in its concentration, and an early rapid increase of type III collagen and glycosaminoglycan was also observed. In conclusion, these data suggested that type III collagen and glycosaminoglyan are important in stabilization of grafted tendon-bone unit, especially in the transitional zone. The histological and biochemical changes in allograft group were relatively similar to that of autograft group although the allograft group showed the delayed pattern of remodeling. And so the tendon-bone allograft could be used as a good but second substitute followed by autograft.
Allografts ; Animals ; Autografts ; Bone Marrow ; Bony Callus ; Cartilage ; Collagen Type I ; Collagen Type III ; Fibroblasts ; Joints ; Leg ; Ligaments ; Limb Salvage ; Metaplasia ; Microfibrils ; Osteotomy ; Periosteum ; Rabbits* ; Tendons ; Tenodesis ; Tenotomy ; Tibia ; Transplants*

The hallmark of exfoliation syndrome is the appearance of white granular deposits and dandruff-like flakes on the lens,iris and angle. The incidence of glaucoma is high,and due to zonular weakening, complications are likely to occur in cataract surgery. A histopathological study with electron microscopy was performed on the iris and conjunctival tissue in order to clarify the production process of exfoliation material in the eyes with exfoliation syndrome. The materials were obtained from 13 eyes with exfoliation syndrome during surgery for glaucoma or cataract. The clumps of microfibrils were observed in the extracellular matrix, and the exfoliation materials were closely related with microfibrils.It was found that the basic unit of the exfoliation materials was microfibril. The cellular degenerations were observed in the basement membrane of capillary endothelium, especially the cells near the iris vessels. The exfoliation materials were observed around the degenerated cells; the mature or immature exfoliation materials around the iris melanocyte which show the various degrees of degeneration. The more degeneration and melting of the cells, the larger amount of exfoliation materials. This study suggests that the exfoliation materials in the eyes with exfoliation syndrome are derived from the abnormal microfibril, abnormal basement membrane, and degenerated cell itself.
Basement Membrane ; Cataract ; Endothelium, Vascular ; Exfoliation Syndrome* ; Extracellular Matrix ; Freezing ; Glaucoma ; Incidence ; Iris ; Melanocytes ; Microfibrils ; Microscopy, Electron

Allografts or autografts of bone-tendon unit have been used for ligament injuries or deficiencies after limb salvage operation for malignant bone tumors around joints. While the remodeling process of the ligament or tendon of the allograftor autograft and the microscopic and biomechanical changes of tendon-bone graft interface have been widely investigated, little is known about the ultrastructural and biochemical changes of the transitionall zone in tendon-bone junction. This study was performed to analyzed the ultrastructural and biochemical changes of the transitional zone after tendon-bone auto-and allo-grafting. A total of twenty four rabbits were divided into two group. In 12 animals(allograft group), two Achilles ten-don-bone unit per each animal were taken and transplanted to another rabbit after preservation below -70degrees C for 2 weeks. In the other 12 animals(autograft group), the Achilles tendon-bone unit was harvested from one side and transplanted to the other side of the rabbit. After operation, their legs were immobilized with short leg cast for 4 weeks, and then mobilized freely. Four animals in each group were sacrificed at four, eight and sixteen-weeks after the transplantation, and their grafted Achilles tendon-bone interfaces were used for analysis of the ultrasturctural and biochemical changes. The following results were obtained. 1. Histologically new cartilage cells were observed at postoperative 16 weeks with local presence of faint tidemark in the autograft group but not in the allograft group. Complete remodeling of the transitional zone had not observed histologically in both groups. 2. Ultrasturctural analysis revealed no definite differences between both groups. However, the slightly rapid appearance of parallelism and cross-striation of microfibrils in the autograft group and time-related restoration of fibers and fibroblasts were observed. 3. From biochemical analysis, type I collagen concentratin was increased, and an early rapid increase of type III collagen and glycosaminoglycan were also observed. In conclusion, these data suggested that type III collagen and glycosaminoglycan are important in stabilization of grafted tendon-bone unit, especially in the transitional zone. The histological and biochemical changes in allograft group were relatively similar to that of autograft group although the allograft group showed the delayed pattern of remodeling. Therefore, the tendon- allograft could be used as a good substitute for the autograft for tendon or ligament reconstruction when no suitable autograft is available.
Allografts ; Animals ; Autografts ; Cartilage ; Collagen Type I ; Collagen Type III ; Fibroblasts ; Joints ; Leg ; Ligaments ; Limb Salvage ; Microfibrils ; Rabbits* ; Tendons ; Transplants*

This study was carried out to investigate the ultrastructural changes of lens fiber cells, length of gap junctions, and distribution of proteoplycans in cataractous lens. The cataract was induced by stabbing the posterior surface of the lens with 25 gauge needle. The lens were obseved by electron microscopy with estimation of the gap junction. Alcian blue stain was performed for examination of proteoglyscas. The results were as follows. Characteristic changes of the cataractous lens fiber cells were swelling and condensation of the cytoplasm, alterations of cytoplasmic granules including changes of density and size of cytoplasmic granules, and formation of microfibrills, high electron-dense amorphous substance, electron-dense particles, variably sized globular bodies, and multilamellar bodies. The lengths of gap junctions were 2.51+/-1.09um in control and 1.06+/-0.33um in cataractous lens fiber cells(P<0.001). Proteoglycans showing high electron-dense amophorous substance were distributed in the intercellular spaces along the cytoplasmic membrane in control group, but disapperaed in cataractous lens fiber cells. According to these results, it is conceivalble that the changes of the gap junctions and proteoglycans were closely related to the pathogenesis of cataract.
Alcian Blue ; Cataract* ; Cell Membrane ; Cytoplasm ; Cytoplasmic Granules ; Extracellular Space ; Gap Junctions ; Microfibrils ; Microscopy, Electron ; Needles ; Proteoglycans

Prenatal development of the thoracic aorta of the human during the period ranging from gestation weeks 7 (C-R length 20mm) to 30 (C-R length 260mm) was examined by transmission electron microscopy and the following results were obtained. The early form of cuboidal or columnar endothelial cells at 7-9 weeks of gestation changed gradually to typical flat endothelial cells at 12-14 weeks of gestation. At 9 weeks of gestation, the mesenchymal cells begin to differentiate to myoblasts, which have small clusters of myofilaments with dense bodies and rough endoplasmic reticulum. And from 14 weeks the differentiating cells begin to form a parallel concentric lamellar structure. At 12th week of gestation, elastic fibers were first seen in subendothelial connective tissue and the intercellular spaces between smooth muscle cells. Elastic fibers appeared as small globular shape which composed of a central core of elastic and peripheral microfibrils. From this period the amount of elastic fibers and their aggregation increases gradually in both the subendothelial space and the intercellular spaces between smooth muscle cells. At 30th week of gestation, subendothelial elastic fibers almost completed the internal elastic lamina and also well formed elastic laminae were seen between the smooth muscle cells adjacent to endothelial cells. However, in the space between the smooth muscle cells near the adventitia the elastic lamina formation is delayed. In the adventitia elastic fiber were scanty but collagen fibers are abundant.
Adventitia ; Aorta, Thoracic* ; Collagen ; Connective Tissue ; Elastic Tissue ; Endoplasmic Reticulum, Rough ; Endothelial Cells ; Extracellular Space ; Fetus* ; Humans* ; Microfibrils ; Microscopy, Electron, Transmission ; Myoblasts ; Myocytes, Smooth Muscle ; Myofibrils ; Pregnancy