Biomedical subjects

Ya-Hui Chuang

Publications and source records attributed to Ya-Hui Chuang.

15 recordsLinked to original sources

PubMed2007

Short-term thallium intoxication: dermatological findings correlated with thallium concentration.

BACKGROUND: The dermatological features and skin biopsy findings of short-term thallium intoxication have been described. However, the correlation between the dermatological findings and the thallium concentration, the prognosis of peripheral neuropathy, and a cutaneous nerve biopsy study are lacking. OBSERVATIONS: Two patients initially developed perioral numbness, erythematous facial rashes, and polyneuropathy after ingesting thallium-containing water. Severe diffuse alopecia was noted, and a skin biopsy specimen revealed parakeratosis and vacuolar degeneration of the basal layer. Examinations of the hair mount demonstrated a tapered appearance of the anagen root. A serial cutaneous nerve biopsy study showed a loss of epidermal nerves 7 weeks and even 1 year after the thallium intoxication. A toxicology survey disclosed a high concentration of thallium (about 3124 mg/L) in the water. The clinical dermatological features subsided completely, but polyneuropathy with severe painful feet persisted. The blood and daily urinary thallium concentrations decreased slowly in the following 3-month period. CONCLUSIONS: The clinical dermatological features subsided completely, but painful polyneuropathy persisted. The series cutaneous nerve biopsy specimens showed persistent damage to the sensory nerve endings. The disappearance of the dermatological features and the appearance of Mees lines correlated with the decrease of blood and urinary thallium concentrations.

Alopecia↗

PubMed2006

Malignant cutaneous tumors of the scalp: a study of demographic characteristics and histologic distributions of 398 Taiwanese patients.

BACKGROUND: The scalp is a unique anatomic region, in which pilosebaceous follicles are concentrated. OBJECTIVE: We sought to investigate demographic characteristics and histologic distributions of malignant scalp tumors. METHODS: Primary and metastatic scalp malignancies diagnosed histopathologically between 1983 and 2003 were reviewed. Age at diagnosis, sex, and histologic types were analyzed. RESULTS: A total of 398 Taiwanese patients (200 males, 198 females) were selected. Age at diagnosis ranged from 3 to 103 years. Most malignant scalp tumors (69.8%) occurred in those 50 years or older. Basal (41.2%) and squamous (16.6%) cell carcinomas were the most common histologic types. Surprisingly, metastatic tumors (12.8%) came in third, in which lung cancers were the most frequent primary tumor in both male and female patients. LIMITATIONS: In our series, the case number of metastatic scalp malignancies was underestimated because not all patients with metastatic scalp tumors received a scalp skin biopsy. CONCLUSION: Because a wide spectrum of primary and metastatic malignancies can occur on the scalp, scalp inspection should be included in general screening for either skin or internal cancers.

Adolescent↗

PubMed2006

Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice.

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by lymphocytic infiltrates in portal tracts, selective destruction of biliary epithelial cells, and anti-mitochondrial Abs (AMAs). The elucidation of early events in the induction of tissue inflammation and autoimmunity in PBC has been hampered by the cryptic onset of the disease, the practical limitations in accessing the target tissue, and the lack of a suitable animal model. We demonstrate in this study that a mouse transgenic for directed expression of a dominant-negative form of TGF-beta receptor type II (dnTGFbetaRII), under the direction of the CD4 promoter, mimics several key phenotypic features of human PBC, including spontaneous production of AMAs directed to the same mitochondrial autoantigens, namely PDC-E2, BCOADC-E2, and OGDC-E2. The murine AMAs also inhibit PDC-E2 activity. Moreover, there is lymphocytic liver infiltration with periportal inflammation analogous to the histological profile in human PBC. Additionally, the serum cytokine profile of affected mice mimics data in human PBC. The concomitant presence of these immunopathological features in the transgenic mice suggests that the TGF-betaRII pathway is implicated in the pathogenesis of PBC. Finally, these data point away from initiation of autoimmunity by mechanisms such as molecular mimicry and more toward activation of an intrinsically self-reactive T cell repertoire in which necessary regulatory T cell influences are lacking.

Animals↗

PubMed2006

Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis.

Although the pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic, the immune system plays a key role in the initiation and subsequent development of pathology. Previous studies have indicated a critical role of the innate immune system. Importantly, natural killer (NK) cells are abundant in liver where they serve as sentinels of the immune system. In addition, NK cells have significant biologic activity based on their production of immunoregulatory cytokines. To address this issue, we have investigated several qualitative and quantitative activities of NK cells in patients with PBC as well as normal and liver diseased controls. We report herein a marked increase in the frequency and absolute number of blood and liver NK cells in PBC patients. Moreover, the cytotoxic activity and perforin expression by isolated NK cells were significantly increased in PBC patients associated with increased levels of plasma IL-8 and the expression of CD128a (IL-8 receptor) on NK cells. In contrast, the levels of IFN-gamma, IL-6 and IL-8 synthesized by NK cells were significantly decreased in PBC patients as compared to controls. In conclusion, data from this study provide compelling evidence supporting a biologic role of NK cells in the immunopathogenesis of PBC.

Adult↗

PubMed2006

Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen-specific T cells and airway inflammation in a murine model of asthma.

T cells expressing a type-2 T helper profile of cytokines (Th2 cells) have been demonstrated to play an important role in the initiation and progression of allergic asthma, and it is well known that Fas ligand (FasL) induces apoptosis when bound to its receptor, Fas. In the present study, we examined the possibility of modulating asthma manifestations by dendritic cells (DCs) genetically engineered to express FasL (DC-FasL), which could deliver a death signal to T cells in an antigen-specific manner. The delivery of DC-FasL into ovalbumin (OVA)-immunized allergic mice decreased the airway hyper-responsiveness (AHR). Moreover, we established a mouse model of airway inflammation by using an adoptive transfer of Th2 cells derived from ovalbumin T cell receptor transgenic mice to study the effect of DC-FasL on airway reactivity. The administration of DC-FasL in Th2-cell-induced allergic mice had significantly decreased AHR, airway inflammation, and IL-4, IL-5 and IL-13 production. Furthermore, the numbers of OVA-specific T cells were decreased in the lung of mice receiving DC-FasL. These results demonstrate that FasL-expressing dendritic cells might be applied for the modulation of allergic responses.

Adenoviridae↗

PubMed2006

Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis.

CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-alphabeta+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.

Autoimmunity↗

PubMed2006

IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis.

Recently, we identified a child born with a genetic deficiency of IL-2 receptor alpha (IL-2Ralpha, CD25) expression who had several clinical manifestations of primary biliary cirrhosis (PBC). In addition, there has been suggestive evidence in both patients with PBC and their first-degree relatives that a deficiency of regulatory T cells (Tregs) is an integral component for susceptibility to PBC. Based on these observations, we generated IL-2Ralpha/CD25 deficient (IL-2Ralpha(-/-)) mice and wild-type littermate controls and followed them longitudinally for the natural history of liver immunopathology and appearance of antimitochondrial antibodies (AMAs). The analyses included immunohistochemical staining of liver and portal tract infiltrates as well as FACS profiles of lymphoid subpopulations in liver and spleen. In addition, serum cytokine profiles were quantitated. Importantly, IL-2Ralpha(-/-), but not littermate controls, develop portal inflammation and biliary ductular damage similar to human patients with PBC. CD4(+) and CD8(+) T cells predominate among portal cell infiltrates and sera reflect a Th1 cytokine bias with increased levels of IFN-gamma, TNF-alpha, IL-2 and IL-12p40. Of importance is the finding that the IL-2Ralpha(-/-) mice not only develop significantly increased serum levels of IgG and IgA, but they also develop AMAs with specificity for PDC-E2, which maps to the inner lipoyl domain of the autoantigen, all characteristics which are hallmarks of human PBC. In conclusion, the IL-2Ralpha(-/-) mice should facilitate studies of the early events in PBC and especially the tantalizing connection between Treg deficiency and autoimmunity specifically directed to mitochondrially located PDC-E2 and subsequent biliary ductular cell damage.

Animals↗

PubMed2006

Effects of adenovirus-expressing IL-10 in alleviating airway inflammation in asthma.

BACKGROUND: Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic effects of IL-10 administration via adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)-induced murine model of asthma. METHODS: BALB/c mice were sensitized by intraperitoneal injections with OVA and challenged by nebulized OVA. The sensitized mice were given an intratracheal delivery of adenoviral vector expressing the murine IL-10 gene (AdIL-10), or mock adenoviral vector 4 days before the inhalation challenge of the OVA. Inflammatory parameters, such as the development of airway hyper-responsiveness (AHR), bronchial lavage fluid eosinophils, and chemokines were assayed. RESULTS: Intratracheal administration of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid of OVA-sensitized and challenged mice during the effector phase. CONCLUSIONS: Our data showed that the intratracheal transfer of the IL-10 gene could affect the recruitment of inflammatory cells during the challenge phase in a way that would result in the inhibition of airway inflammation. These findings suggest that the development of an immunoregulatory strategy based on IL-10 might shed light on more effective treatment.

Adenoviridae↗

PubMed2006

Early congenital syphilis and erythema multiforme-like bullous targetoid lesions in a 1-day-old newborn: detection of Treponema pallidum genomic DNA from the targetoid plaque using nested polymerase chain reaction.

A 1-day-old male newborn was born with respiratory distress, low birth weight, hepatosplenomegaly, and bullous targetoid skin lesions over the face, back, buttocks, and extremities. A diagnosis of early congenital syphilis was made based on a treponemal serologic test. Pathologic examination of the skin lesion showed scattered dyskeratotic cells in the epidermis and interface dermatitis consistent with erythema multiforme. No spirochete could be found in the skin sections staining with Warthin-Starry stain. Using nested polymerase chain reaction, treponemal genomic DNA fragments encoding DNA polymerase I were detected.

Biopsy↗

PubMed2005

Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives.

Infiltrating memory T cells play an important role in the destruction of the biliary tract in primary biliary cirrhosis (PBC) and inflammatory chemokines control lymphocyte traffic through their interactions with T cell chemokine receptors. In the present study, we measured plasma levels of chemokines interferon-gamma-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls. Interestingly, plasma IP-10 and MIG levels in PBC were increased significantly compared to controls and appeared to increase with disease progression. By immunohistochemistry, IP-10 and MIG expressions were evident in the portal areas in PBC. Further, the frequency of CXCR3-expressing cells in peripheral blood was also significantly higher in PBC, and CXCR3-positive cells were also found in the portal areas of diseased livers, primarily on CD4+ cells. Finally, the daughters and sisters of PBC patients also demonstrated increased plasma levels of IP-10 and MIG, but, in contrast, displayed normal frequency of CXCR3+ expressing peripheral blood lymphocytes. Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor.

Adult↗

PubMed2005

Autoantibodies against human epithelial cells and endothelial cells after severe acute respiratory syndrome (SARS)-associated coronavirus infection.

The severe acute respiratory syndrome (SARS) is caused by infection with the SARS-associated coronavirus (SARS-CoV) and characterized by severe pulmonary inflammation and fibrosis. In this study, the development of autoantibodies against human epithelial cells and endothelial cells in patients with SARS at different time periods (the first week: phase I, 1 month after the disease onset: phase II/phase III) were investigated. Antibodies in sera of patients and healthy controls against: (1) A549 human pulmonary epithelial cell-line, (2) human umbilical venous endothelial cells (HUVEC), (3) primary human pulmonary endothelial cells (HPEC) were detected by cell-based ELISA and indirect immunofluorescence staining. The results revealed that serum levels of IgG anti-A549 cells antibodies, IgG anti-HUVEC antibodies, and IgM anti-HPEC antibodies were significantly higher in SARS patients at phase II/phase III than those in healthy controls. Sera from SARS patients at phase II/phase III could mediate complement dependent cytotoxicity against some A549 cells and HPEC. It is concluded that some autoantibodies against human epithelial cells and endothelial cells would be developed after SARS-CoV infection and this phenomenon may indicate post-infectious cellular injury and also induce SARS-induced immunopathology.

Adult↗

PubMed2004

Treatment of murine lupus using nucleosomal T cell epitopes identified by bone marrow-derived dendritic cells.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies directed against intact nuclear structures, such as nucleosomes. The most prominent of these autoantibodies are those directed against double-stranded DNA (dsDNA) and histones. The majority are of the IgG isotype and show affinity maturation, both of which are known hallmarks of T cell help. Much evidence suggests that the nucleosome is a major candidate autoantigen in SLE. In this study, a novel strategy was used to identify the critical CD4+ T cell autoepitopes in nucleosomes. In addition, peptide-based therapy was then performed in a lupus animal model. METHODS: Bone marrow (BM)-derived dendritic cells (DCs) were used to examine the self-T cell responses against nucleosomes and to characterize the T cell epitope(s) of nucleosomes in (NZB x NZW)F1 (BWF1) mice. RESULTS: Several potential auto-T cell epitopes of core histone proteins (H2A, H2B, H3, and H4) were identified. Nucleosome-pulsed BM-derived DCs elicited release of interleukin-4 and interferon-gamma, representing a Th0 (i.e., mixed Th1 and Th2) pattern of cytokine production. In addition, intradermal immunization of BWF1 mice with the H3(111-130) peptide not only suppressed the level of anti-dsDNA and anti-single-stranded DNA IgG, but also significantly delayed the progress of glomerulonephritis in lupus-prone BWF1 mice. CONCLUSION: These results will help in understanding how pathogenic autoimmune responses develop in spontaneous SLE. This may potentially open the way to T cell-based immunotherapy for lupus.

Animals↗

PubMed2004

Multiple pigmented follicular cysts of the vulva successfully treated with CO2 laser: case report and literature review.

BACKGROUND: A pigmented follicular cyst is an uncommon epithelial cyst, typically occurring as a single asymptomatic pigmented papule or nodule on the head and neck of adult men. To the authors' knowledge, no previous cases of vulvar pigmented follicular cyst have been reported. Although benign, pigmented follicular cyst can affect quality of life when multiple and symptomatic. OBJECTIVE: The objective was to describe the clinicopathologic features of vulvar pigmented follicular cyst and to evaluate the efficacy of CO(2) laser therapy in this region. METHODS: A 62-year-old woman with multiple pigmented follicular cysts affecting the labia majora bilaterally is described. Owing to frequent inflammation and tenderness, continuous-wave CO(2) laser was used to treat the skin lesions under local anesthesia. RESULTS: All cystic nodules were successfully ablated with CO(2) laser. The patient tolerated the procedure well and had a satisfactory cosmetic outcome. CONCLUSION: CO(2) laser is a tolerable and effective therapeutic modality for multiple and symptomatic pigmented follicular cysts of the vulva.

Carbon Dioxide↗

PubMed2003

Vulvar syringoma: a clinicopathologic and immunohistologic study of 18 patients and results of treatment.

BACKGROUND: Syringoma of the vulva has been rarely reported. No effective treatment modality has been documented. OBJECTIVE: The purpose of this study was to describe the clinicopathologic features of vulvar syringoma, to investigate the hormonal influence on its growth, and to establish an effective treatment modality. METHODS: A total of 18 cases of vulvar syringoma were selected from the surgical pathologic file at Chang Gung Memorial Hospital. In all, 15 formalin-fixed, paraffin-embedded specimens were examined by immunohistochemical staining for estrogen receptor and progesterone receptor. RESULTS: The age of first presentation at our vulvar clinic ranged from 21 to 60 years with a median age of 29.5 years. Of patients, 13 (72%) had vulvar pruritus and 7 noticed aggravation during summer or during menstruation. The most common clinical appearance was multiple flesh-colored or brownish papules on bilateral sides of the vulva (9 of 18). One third of our series was found to have coexisting eyelid syringoma and 4 of them also had a family history of periorbital syringoma. Immunohistochemical stainings for estrogen receptor and progesterone receptor were all negative on the 15 cases studied. Of our patients, 7 with intense pruritus were treated with carbon dioxide laser vaporization. Their lesions resolved and pruritus subsided. CONCLUSION: Vulvar syringoma is not very rare and should be considered in the differential diagnosis of vulvar pruritus. In our study, estrogen receptor and progesterone receptor were not detected in vulvar syringoma. Carbon dioxide laser was an effective therapeutic modality in treating patients with intractable symptoms.

Adult↗

PubMed2002

In vivo tolerance breakdown with dendritic cells pulsed with U1A protein in non-autoimmune mice: the induction of a high level of autoantibodies but not renal pathological changes.

One of the hallmarks of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), is the immune response to nuclear autoantigens. Several studies have proposed that dendritic cells may acquire the nuclear autoantigens from the apoptotic cells to initiate the systemic autoimmune responses. To examine the immune response to a nuclear autoantigen induced by dendritic cells, bone marrow-derived dendritic cells (BMDCs) pulsed with U1 small nuclear ribonucleoprotein (snRNP)-A protein (U1A) were intravenously injected into non-autoimmune mice. The results showed that BMDCs pulsed with U1A proteins by intravenous injection into BALB/c (H-2d) and DBA-2xNZW F1 (H-2d/u) mice were capable of activating the autoreactive T cells and inducing a high titre of immunoglobulin G (IgG) anti-U1A antibodies. Both groups of mice with a high anti-U1A autoantibody titre also transiently developed IgG against double-stranded (ds) DNA. However, unlike NZBxNZW F1 (BWF1) (H-2d/u) mice, no obviously histopathological changes to the glomeruli were noted in the mice treated either with BMDCs or with U1A-pulsed BMDCs. Several months after immunization, all mice treated with U1A-pulsed BMDCs did develop IgG, but not the complement C3 deposit in the glomeruli. The cytokine profile produced by the U1A-specific T cells of primed DBA-2xNZW F1 mice was skewed toward the T helper type 1 phenotype compared with that of BWF1 mice. The model we describe here adds to the further understanding of the pathogenic mechanisms, such as self-antigen shifting, and the mechanisms that account for the different responses to self-antigens when in a normal or an autoimmune state.

Animals↗