Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas T lymphocytes are essential for the initiation of acute graft-versus-host disease (aGVHD), it is not at all clear whether they or other cells or noncellular factors actually mediate the characteristic lesions. This report describes the in vivo effects of human NK cells, T cells, and cytokines on the induction of aGVHD in 4 Gy sublethally irradiated C.B-17 scid/scid (SCID) mice. Human NK and T lymphocytes were obtained separately by antibody- and complement-mediated negative selection from the peripheral blood of normal donors and expanded in medium containing rIL-2 and irradiated autologous feeder cells. The characteristics of the two groups of cells were analyzed before injection into SCID mice. Cytofluorometric phenotyping demonstrated that 70-95% of NK-enriched cells expressed CD3-, CD16+, CD56+, and CD8-dim+; ninety-seven per cent of T cells expressed CD3+, TCR-alpha/beta+, CD4+, or CD8-bright+. Analysis of K562 and Daudi cultured target cell lines demonstrated 40-50% higher cytotoxicity by NK-enriched cells as compared with activated T lymphocytes. TNF-alpha cytokine production was greatly increased in activated NK cells (250 pg/ml) as compared with T cells (25 pg/ml) and fresh PBMC (12.5 pg/ml). IFN-gamma was increased in both NK and T cells. After i.v. injection of 1-5 x 10(7) cells into irradiated SCID mice, minor to severe skin lesions, diarrhea, and weight loss occurred in NK- but not the T cell-injected animals. In NK-injected animals, thinning and focal loss of epithelium with pyknotic nuclear change and degeneration and loss of skin appendages were observed. Single cell necrosis, crypt abscess formation, and loss of glandular epithelium developed in the colon of NK but not in T cell-injected animals. These findings are very similar to allogeneic aGVHD in SCID mice injected with C57BL/6 mouse splenocytes. Immunohistological staining with anti-human CD56, CD3, TNF-alpha, and IFN-gamma antibodies demonstrated CD56+ cells in association with TNF-alpha and IFN-gamma secretion in the bowel of NK-injected animals. CD3+ cells were not found in the same tissues. These findings were not observed in T cell-injected and control mice. In summary, aGVHD-like lesions were induced by transplantation of xenogeneic human activated NK cells into SCID mice. We hypothesize that cytokines released from human NK cells play a central role in the pathogenesis of clinical aGVHD.
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PMID:Acute graft-versus-host-like disease induced by transplantation of human activated natural killer cells into SCID mice. 835 98

It is a major interest in the field of hematopoietic stem cell transplantation to reduce scarring of healing wounds with overdeposition of collagen due to radiation injury or graft-versus-host disease. Halofuginone (HF) inhibits collagen alpha1(I) gene expression and overdeposition of collagen. We examined the effect of HF on the healing of full-depth incision wounds inflicted in normal skin or skin areas compromised by local preirradiation with 18 Gy. Preirradiation significantly decreased the tensile strength of the healing wounds at day 14 (by approximately 60%, p < 0.0001). In contrast, HF treatment did not significantly decrease the strength of wounds inflicted in both normal and preirradiated skin. Histological evaluation revealed that HF induced moderate thinning of the dermis accompanied by elevated thickness of the epidermis and enhanced rejoining of subdermal muscles in the wound area. HF only minimally reduced total collagen deposition in both groups, with minor changes in the level of more matured fibrillar collagen network. Our study demonstrates that HF does not significantly affect wound strength. This encourages the possible use of HF as an antifibrotic agent with minimal complications for post-hematopoietic stem cell transplantation complications including radiation toxicity and graft-versus-host disease.
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PMID:Effect of halofuginone, a collagen alpha1(I) inhibitor, on wound healing in normal and irradiated skin: implication for hematopoietic stem cell transplantation. 1762 57

Longitudinal erythronychia is a linear red band on the nail plate that originates at the proximal nail fold, traverses the lunula, and extends to the free edge of the nail plate. Longitudinal erythronychia is classified based upon the number of nails affected and the number of red streaks present on each nail as follows: type Ia (monodactylous - single band), type Ib (monodactylous - bifid bands), type IIa (polydactylous - single band), and type IIb (polydactylous - multiple bands). Associated morphologic findings that can be present at the distal tip of the nail with longitudinal erythronychia include fragility, onycholysis, splinter hemorrhage, splitting, subungual keratosis, thinning, and V-shaped nick. Some patients with longitudinal erythronychia seek medical evaluation because of pain in the associated distal digit; however, the linear red nail plate dyschromia is often asymptomatic and the individual is concerned about the cosmetic appearance or distal nail fragility. Longitudinal erythronychia can be a clinical manifestation of an underlying local or systemic condition. Benign tumors (glomus tumor, onychopapilloma, and warty dyskeratoma), malignant neoplasms (malignant melanoma and squamous cell carcinoma), and other conditions (hemiplegia and postsurgical scar) can be associated with monodactylous longitudinal erythronychia or it may be idiopathic or the initial stage of polydactylous longitudinal erythronychia-associated systemic conditions. Polydactylous longitudinal erythronychia is most commonly reported in patients with Darier disease (keratosis follicularis); other associated conditions include acantholytic dyskeratotic epidermal nevus, acantholytic epidermolysis bullosa, acrokeratosis verruciformis of Hopf, amyloidosis, graft-versus-host disease, lichen planus, and pseudobulbar syndrome. Polydactylous longitudinal erythronychia has also been observed as an idiopathic finding. Biopsy of the nail matrix and nail bed may be necessary to establish the diagnosis of a longitudinal erythronychia-associated condition. Indeed, a biopsy should be seriously considered in patients aged more than 50 years who present with a monodactylous longitudinal red band to exclude squamous cell carcinoma. Treatment of longitudinal erythronychia depends on the etiology. For patients with longitudinal erythronychia-associated discomfort or severe nail splitting, a surgical excision may provide not only the underlying diagnosis of the nail dyschromia, but also relief of related symptoms.
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PMID:Longitudinal erythronychia: individual or multiple linear red bands of the nail plate: a review of clinical features and associated conditions. 2166 31

To explore ocular graft-versus-host disease (GVHD), anterior segment optical coherence tomography (AS-OCT) imaging of eyelids, tear meniscus, cornea and conjunctiva is performed in subsequent sessions on a patient who has ocular GVHD after allogeneic related donor stem cell transplant. The OCT results are presented together with those from a normal subject. OCT imaging is promising in visualizing several ocular GVHD manifestations, such as abnormal meibomian gland orifice (MGO), conjunctival keratinization, conjunctival hyperemia and chemosis, corneal epithelium opacification, thinning and sloughing. This case study demonstrates the capability of AS-OCT in the imaging and monitoring of ocular GVHD, which may be useful in the development of current ocular GVHD staging system and the clinical management for GVHD treatment.
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PMID:Anterior segment optical coherence tomography evaluation of ocular graft-versus-host disease: a case study. 2569 66

Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.
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PMID:Chronic rejection of human face allografts. 3031 35

Gastrointestinal graft-versus-host disease (GVHD) is a common complication after hematopoietic stem cell transplantation. Concomitant cytomegalovirus (CMV) enteritis worsens the prognosis of this condition. We report a case of small bowel perforation associated with gastrointestinal GVHD and CMV enteritis in a patient with leukemia who was successfully treated surgically. A 39-year-old man presented with intestinal perforation necessitating emergency surgical intervention. He was diagnosed with T-cell acute lymphoblastic leukemia and developed severe gastrointestinal GVHD and CMV enteritis after hematopoietic stem cell transplantation. His terminal ileum showed a perforation with diffuse wall thinning, and petechiae were observed over long segments of the distal ileum and the proximal colon. Small bowel segmental resection and a subtotal colectomy with a double-barreled ileocolostomy were performed. The patient recovered uneventfully after the operation. Based on reports described in the literature, surgery plays a minor role in the management of gastrointestinal GVHD; however, timely surgical intervention could be effective in selected patients.
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PMID:Small Bowel Perforation Associated With Gastrointestinal Graft-Versus-Host Disease and Cytomegalovirus Enteritis in a Patient With Leukemia: A Case Report With Literature Review. 3291 38