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Biomedical subjects

A Yamakage

Publications and source records attributed to A Yamakage.

At least 19 recordsLinked to original sources
PubMed1997

Nailfold capillary abnormality and pulmonary hypertension in systemic sclerosis.

BACKGROUND: Patients with systemic sclerosis (SSC) show a capillary abnormality of nailfolds with controversial correlation with organ involvement. Our purpose was to study the correlation between this nailfold capillary abnormality and pulmonary hypertension in patients with SSC. METHODS: We studied the nailfold capillaries, using capillary microscopy, and the pulmonary arterial pressure, using right-heart catheterization, in 44 patients with SSC. Canonical discriminant analysis was used to define the capillary abnormality in patients with SSC, which was then compared with that of 40 normal controls. The correlations between the patterns of nailfold capillaries and the cardiopulmonary findings, including the pulmonary arterial pressure, were examined using Fisher's test. RESULTS: Thirty-two of 44 patients with SSC could be differentiated from normal controls by our definition of the SSC pattern. The SSC pattern correlated significantly with elevated pulmonary vascular resistance, as well as with pulmonary fibrosis, electrocardiographic abnormalities, decreased vital capacity, and decreased diffusing capacity for carbon monoxide. All SSC patients with pulmonary hypertension showed this SSC pattern. In patients with elevated pulmonary arterial pressure, capillary microscopy and diffusion capacity for carbon monoxide (DCCM) showed the highest rate of abnormalities. A limited-type SSC significantly correlated with DCCM and with anticentromere antibody, and the diffuse-type SSC with pulmonary fibrosis and anti-sci-70 antibody. CONCLUSION: Our data suggest that in patients with SSC, nailfold capillary abnormalities correlate with pulmonary arterial hypertension as well as with clinical and laboratory findings indicating pulmonary hypertension.

Adolescent↗
PubMed1997

Cutaneous localization of endothelin-1 in patients with systemic sclerosis: immunoelectron microscopic study.

BACKGROUND: Endothelin-1 (ET-1) has some relation to the pathogenesis of systemic sclerosis (SSc) and Raynaud's phenomenon. This study was performed to determine the localization of ET-1 in patients with SSc. METHODS: The localization of ET-1 on the specimen by skin biopsies from nine patients with SSc, was observed with immunoelectron microscopic techniques. RESULTS: High-density deposits existed on the ribosomes and on the rough endoplasmic reticulum in the endothelial cells of microvessels of the upper dermis. The same findings were also seen in the fibroblasts of the dermis, but not found in the skin of normal controls. The level of deposits in the endothelial cells and dermal fibroblasts seemed to have a positive correlation with the serum levels of ET-1 of patients with SSc. CONCLUSIONS: From these results, it can be seen that ET-1 is produced much more from the endothelial cells and fibroblasts of the dermis in the skin of SSc patients than from the normal controls. It is suspected that ET-1 is one of the pathogenetic factors of SSc.

Biopsy↗
PubMed1996

Electron-microscopic study of sclerodermatous chronic graft-versus-host disease.

BACKGROUND: Sclerodermatous chronic graft-versus-host disease (SC-GVHD) resembles systemic scleroderma (SSD) closely, both clinically and histologically. Our purpose was to try to define the morphologic differences of collagen fibers between SC-GVHD and SSD. MATERIALS AND METHODS: Using electron microscopy, we compared the morphology of collagen fibers in a 15-year old girl with SC-GVHD with those of three patients with SSD. RESULTS: In SC-GVHD, sclerosis is located in the superficial dermis and collagen fibers of irregular diameter are seen in the subepidermal area. In SSD, sclerosis is seen in the lower dermis and subcutaneous fatty tissue, and collagen fibers of irregular diameter are located in the deep dermis. Some of the collagen fibers were degenerative in the superficial dermis in SC-GVHD. We observed low-density, round structures in cross sections of collagen fibers. CONCLUSIONS: The difference in initial location and morphologic appearance of collagen fibers may indicate a different pathogenesis in SC-GVHD compared to SSD.

Adolescent↗
PubMed1995

Image analysis of nailfold capillaries in patients with undifferentiated connective tissue syndromes.

Several studies have reported patients that show nailfold capillary abnormality without fulfilling any of the criteria for rheumatic diseases. Our objective was to define how many patients with undifferentiated connective tissue syndrome (UCTS) have nailfold capillary abnormalities and to determine the correlation between capillary abnormality and clinical findings. We analyzed videograph images of nailfold capillaries in 75 patients with UCTS, comparing them with 22 normal controls (NL) and 55 patients with systemic sclerosis (SS), using standardized canonical discriminant analysis. Sixty patients with UCTS showed the SS type pattern and 15, the NL type pattern. The SS type pattern in patients with UCTS significantly correlated with Raynaud's phenomenon, telangiectasia, and anti-nuclear antibody. The UCTS patients with nailfold capillary abnormalities correlated with symptoms of SS have a possibility of progressing to SS. The follow up study of these patients will show whether progression to SS occurs.

Adolescent↗
PubMed1995

Image analysis of nail fold capillaries in patients with Raynaud's phenomenon.

Videograph images of nail fold capillaries in patients with Raynaud's phenomenon were analyzed, and capillary patterns were defined using standardized canonical discriminant analysis. Of sixty-eight patients with Raynaud's phenomenon, forty-nine (72 percent) showed a systemic sclerosis pattern and nineteen (28 percent) showed a normal pattern. The systemic sclerosis type capillary pattern significantly correlated not only with secondary Raynaud's syndrome but also with sclerodactyly, telangiectasia, and antinuclear antibody. This study confirms the value of nail fold capillary microscopy as a noninvasive technique for the examination of the cutaneous microcirculation in vivo. We should continue to evaluate the patients with Raynaud's phenomenon who showed systemic sclerosis pattern abnormality to determine if these patients would show a progression to systemic sclerosis or not.

Adolescent↗
PubMed1995

Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.

OBJECTIVE: Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease s poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc. METHODS: Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [3H]thymidine incorporation. RESULTS: SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF alpha receptor. CONCLUSION: Our studies support a role for PDGF and TGF-beta 1 in the pathogenesis of SSc lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Statistical definition of nailfold capillary pattern in patients with psoriasis.

BACKGROUND: The microvasculature plays an important role in the pathogenesis of psoriatic skin lesions. Our purpose was to try to define a psoriatic pattern in the nailfold capillary, to clarify the relationship between nailfold capillary microscopic changes and nail involvement and to note the general clinical features of psoriasis. METHODS: Image analysis of nailfold capillaries was performed in 62 patients with psoriasis. The capillary pattern was defined statistically comparing it with that of 51 healthy volunteers. We attempted to differentiate the psoriatic pattern from normal controls with "canonical discriminant analysis." RESULTS: Forty-nine of 62 patients with psoriasis could be differentiated from normal controls by our definition of psoriatic pattern that was significantly correlated with periungual psoriatic plaque, nail pitting, onycholysis, and the extent of the involved area. CONCLUSIONS: Our data suggest that nailfold capillary changes reflect microvascular changes of psoriasis and that the nailfold capillary pattern is a useful tool in evaluating nail involvement and the severity of psoriasis.

Adolescent↗
PubMed1994

Lipodystrophia centrifugalis abdominalis infantilis occurring in the neck.

We report a Japanese girl with atypical lipodystrophia centrifugalis abdominalis infantilis. The initial lesion developed on the neck as an area of erythema which showed centrifugal spread to the nape, submandibular area and upper breast and central fading to leave a residual depression and purplish brown pigmentation symmetrically. A central depression on the neck, nape, submandibular area and upper breast was surrounded by a distinctive erythematous, slightly elevated and indurated border. Histological examination of the erythematous border revealed inflammatory changes in the subcutaneous fat. Although this patient was affected in an unusual site, we concluded that she had lipodystrophia centrifugalis abdominalis infantilis, because of the overall features of the lesions.

Adipose Tissue↗
PubMed1994

Diabetic scleredema and scleroderma-like changes in a patient with maturity onset type diabetes of young people.

A 21-year-old housewife with maturity onset type diabetes of young people developed scleredema diabeticorum, scleroderma-like skin thickness on forearms and dorsum of hands, digital sclerosis and cheiroarthropathy. She had diabetes mellitus since the age of 11 years. Her grandfather on the mother's side, her mother and 3 of 5 her mother's brothers and sisters have diabetes mellitus. Blood glucose was 295 mg/dl. Urinary glucose was 5.3 g/day. Nail fold capillary microscopy revealed a progressive systemic sclerosis pattern. Histologically, hematoxylin and eosin sections from back and forearm skin demonstrated broad collagen bundles separated by widened clear spaces throughout the thickened dermis.

Adult↗
PubMed1994

[Scleroderma, dermatomyositis].

Systemic sclerosis (scleroderma, SSc) is a progressive and often fatal disorder characterized clinically by sclerotic changes in the skin, joints and internal organ systems such as the gastrointestinal tract, heart, lungs and kidneys, moreover pathologically by abnormalities of mucopolysaccharides, fibrous tissue deposition, atrophy of parenchymal structures in skin and various internal organs, and by vascular insufficiency. Little is known of its etiology and pathogenesis. Transforming growth factor-beta (TGF-beta), platelet derived growth factor-AA (PDGF-AA) and PDGF-alpha receptor interaction may play an important role in the pathogenesis of scleroderma. Furthermore, many of the proteoglycans act as modulators of growth factor activities. Dermatomyositis is also a complex connective tissue disease of unknown etiology, in which inflammatory change in the skin, muscle, and lung in association with vascular insufficiency and internal malignancy.

Blood Vessels↗
PubMed1992

Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts.

Transforming growth factor beta (TGF-beta), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-alpha receptor arm of that system. TGF-beta effects on PDGF alpha receptor expression were studied in vitro using ligand binding techniques in three human dermal fibroblast strains: newborn foreskin, adult skin, and scleroderma (systemic sclerosis, SSc). Each cell strain responded differently to TGF-beta. In newborn foreskin fibroblasts, PDGF alpha receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-beta (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF alpha receptor number by TGF-beta occurred consistently with SSc fibroblasts and low concentrations of TGF-beta (0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of alpha receptor subunit by TGF-beta in SSc fibroblasts correlated with increased new PDGF alpha receptor synthesis as demonstrated by radioimmunoprecipitation analysis of metabolically labeled cells and with increased steady-state levels of corresponding mRNAs. In normal adult skin fibroblasts, TGF-beta had no effect on either synthesis or mRNA expression of alpha receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-beta correlated positively with effects of TGF-beta on expression of alpha receptor subunit. Decreased mitogenic responses to PDGF-AA were observed in foreskin fibroblasts, small changes in responses in adult fibroblasts, and significant increases in SSc fibroblasts. Thus, costimulation with PDGF-AA and TGF-beta selectively enhanced proliferation of fibroblasts with the SSc phenotype. Immunohistochemical examination of SSc and control skin biopsies revealed the presence of PDGF-AA in SSc skin. Data obtained by ligand binding, immunoprecipitation, mRNA, and mitogenic techniques are consistent with the hypothesis that activation of the PDGF-AA ligand/alpha receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.

Adult↗
PubMed1992

Differential modulation of bFGF receptors by TGF-beta in adult skin, scleroderma skin, and newborn foreskin fibroblasts.

Effects of transforming growth factor beta (TGF-beta) on proliferative responses to basic fibroblast growth factor (bFGF) were studied in human diploid fibroblasts cell strains derived from three different sources: adult skin, scleroderma, and newborn foreskin. All three types of cell strains were similarly responsive to TGF-beta, whereas adult skin fibroblasts were significantly more responsive to bFGF. Incubation of cells with TGF-beta prior to bFGF addition substantially increased responsiveness of adult skin fibroblasts to this latter cytokine, slightly increased that of scleroderma fibroblasts, and decreased that of foreskin fibroblasts. Modulation of bFGF receptors by TGF-beta correlated positively with these mitogenic effects. Adult skin fibroblasts showed increases of both high- and low-affinity receptors and scleroderma fibroblasts showed small increases of high-affinity receptors only, whereas foreskin fibroblasts showed no changes. Heparitinase treatment of adult skin fibroblasts during TGF-beta pre-incubation resulted in reduced bFGF binding to low-affinity receptors and reduced mitogenic response to bFGF, suggesting that the TGF-beta-stimulated increase of low-affinity receptors in these cells contributes to the observed enhanced mitogenic effects of bFGF. Abnormal responses of scleroderma fibroblasts to TGF-beta/bFGF stimulation, particularly failure to synthesize low-affinity receptors in response to TGF-beta, adds a new characteristic to the fibrotic phenotype of scleroderma fibroblasts.

Adult↗