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Biomedical subjects

Hsin-Su Yu

Publications and source records attributed to Hsin-Su Yu.

At least 37 records · Page 2Linked to original sources

Increased risk of preterm delivery in women residing near thermal power plants in Taiwan.

In this article, the researchers studied the prevalence of preterm births for women living near thermal power plants. The prevalence of delivery of preterm birth infants was significantly higher among women living within 3 km of a thermal power plant than among women living within 3-4 km of a plant. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, infant gender, and birth site), the adjusted odds ratio was 1.14 (95% confidence interval, 1.01-1.30) for delivery of preterm infants for women living close to the thermal power plants. These data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy, although a semiecological study cannot confirm a direct causal relationship.

Adult↗

Sculpting skin appendages out of epidermal layers via temporally and spatially regulated apoptotic events.

Complex skin appendages are built from the epidermal cells through various cell events. Here we used TUNEL and caspase-3 immuno-localization to examine apoptosis in feather morphogenesis. We deduced three modes. In Mode 1A, apoptosis occurs within the localized growth zone (LoGZ) to regulate growth (feather buds). In Mode 1B, morphogen secreting cells are present adjacent to LoGZ and apoptosis may work to remove such signaling centers (barb ridges). In Mode 2, keratinocytes apoptosed before terminal differentiation and left spaces between branches (marginal plate). In Mode 3A, keratinocytes cornified and flaked off to free skin appendages (feather sheath, pulp epithelium). In Mode 3B, keratinized apoptosed epithelial cells became permanent structures (rachis, ramus, barbules). Thus, different apoptotic modes can have different impacts on morphogenesis. We further tested effects of imbalanced Shh on apoptosis. Shh suppression reduced marginal plate apoptosis and caused abnormal differentiation of barbule plates. Shh over-expression enhanced proliferation in barb ridges. Expression of Patched in the barbule plate epithelia implies a paracrine mechanism. The current work complements our recent work on LoGZ to show how adding and removing cell masses in temporally and spatially specific ways are coordinated to sculpt skin appendages from epidermal layers.

Animals↗

Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes.

Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation of vitiligo lesions are not thoroughly clarified. The purpose of our study was to investigate the effects of narrow-band UVB irradiation on melanocyte proliferation and migration in vitro. Our results showed that the cell counts as well as [3H]thymidine uptake of melanocytes were significantly enhanced by narrow-band UVB-irradiated keratinocyte supernatants. In these supernatants, a significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1 (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated keratinocytes was significantly reduced by a selective endothelin-B (ET-B) receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte proliferation. Our results of time-lapse microphotography revealed a stimulatory effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK (p125(FAK)) expression on melanocyte was enhanced by narrow-band UVB irradiation. In this study, narrow-band UVB irradiation stimulated a significant increase in matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow-band UVB-irradiation-induced migration of melanocytes was significantly annihilated by the addition of p125(FAK) inhibitor (herbimycin-A) or MMP-2 inhibitor (GM6001). These results suggest that p125(FAK) and MMP-2 activity play important roles in narrow-band UVB-induced migration of melanocytes. Our results provide a theoretical basis for the effectiveness of narrow-band UVB irradiation in treating vitiligo.

Cell Movement↗

Elevated serum antimelanocyte antibody level in cerebriform intradermal nevus with vitiligo.

We describe a rare, but typical case of cerebriform intradermal nevus associated with vitiligo. A 45-year-old man had a patch of alopecia over his vertex scalp for 15 years. The microscopic findings of the biopsy revealed a typical deep-seated intradermal nevus and neuroid differentiation with a few pigments. Three hypopigmented patches developed on the forehead, cheek and index finger five years after the scalp lesion, with loss of both melanocytes and melanins. In addition, no dopa reactions were present. Compared to normal controls, the serum anti-melanocyte antibody level in the patient was elevated as determined by cellular enzyme-linked immunosorbent assay (cellular ELISA). This is the first reported case with elevation of serum antimelanocyte antibody level of cerebriform intradermal nevus with vitiligo. This antibody's presence may be related to the occurrence of the vitiligo in patient with cerebriform intradermal nevus.

Autoantibodies↗

Correlation of serum total IgE, eosinophil granule cationic proteins, sensitized allergens and family aggregation in atopic dermatitis patients with or without rhinitis.

Atopic dermatitis (AD) is a complex disease with both a genetic background and environmental interactions. Although multiple linkage-analyses about AD have been studied, there have been only a few family aggregation tests of AD or perennial allergic rhinitis (AR) to date. The association of allergen-specific IgE in AD and atopic dermatitis with allergic perennial rhinitis (ADR) have also been seldom discussed. The purpose of this study was to evaluate family aggregation and assess allergen-specific IgE in patients with AD and ADR. We also planned to investigate the effect of family history of AD on the prevalence of allergen-specific antibodies. The serum levels of IgE, eosinophil cationic protein (ECP) and major basic protein (MBP) were measured and compared in patients with AD and those with ADR. Proportional analysis compared allergen-specific IgE between AD and ADR. The family aggregation was conducted to estimate the odds ratio for various atopic diseases in different family members. Total IgE and allergen-specific antibodies in serum were compared between those patients who had AD with AR and those without. The result revealed that allergic rhinitis is the most common concomitant atopic disease associated with AD. The ADR group was more likely to have serum mite-, cockroach-, and feather-specific IgE. The positive rates for wheat, peanut and soybean were higher in those AD without rhinitis. In the family aggregation of AD, the odds ratio for siblings was higher than for parents, the ratios for brother and sister were 9.91 and 8.75, respectively. However, the odds ratio for parents of ADR was higher than siblings; the ratios for father and mother of ADR were 8.22 and 2.94, respectively. AD patients with family histories of AD were more likely to have mite-, soybean-, and peanut-specific antibodies in their serum. We concluded that aeroallergens are the most important allergens aggravating atopic diseases in Taiwan. Food plays an important role in the pathogenesis of AD. Measurement of serum total IgE combined with the MAST-CLA test could be helpful in the diagnosis of atopic diseases. The differential aggregation tendency for AD and ADR implicated the complexity of the gene-environment interaction in these atopic diseases.

Adult↗

Vascular permeability alterations induced by arsenic.

The impact of arsenic on the integrity of blood vessels in vivo via in situ exposure (local injection) of arsenic was investigated. Vascular permeability changes were evaluated by means of the Evans blue assay and the India ink tracer techniques. Rats were intravenously injected with Evans blue followed by intradermal injections of various doses of sodium arsenite on the back skins of the animals. Evans blue at different time points was extracted and assayed as indices of vascular leakage. Skin at various time point injection sites was sampled for arsenic measurement via graphite furnace atomic absorption spectroscopy. Our time course study with Evans blue technique demonstrated a biphasic pattern of vascular permeability change: an early phase of permeability reduction and a later phase of permeability promotion at all dose levels tested. The India ink tracer technique also demonstrated a time-correlated increase in vascular labelling in the tissues examined, signifying an increase in vascular leakage with time. Moreover, we found that despite an early increase in tissue arsenic content at time of injection, tissue arsenic declined rapidly and returned to near control levels after 30-60 min. Thus, an inverse correlation between tissue arsenic content and the extent of vascular permeability was apparent. This study provides the first demonstration that in situ exposure to arsenic will produce vascular dysfunction (vascular leakage) in vivo.

Animals↗

Effects of gallium on immune stimulation and apoptosis induction in human peripheral blood mononuclear cells.

Gallium is commonly used in the semiconductor industry and medical field. Biologically, gallium is able to interrupt iron metabolism. Exposure to gallium has been shown to affect the human immune system. The purpose of this study was to investigate the in vitro biological effects of different gallium concentrations on cultured human peripheral blood mononuclear cells (PBMCs) in terms of cell growth, cytokine release, and apoptosis induction. In addition, the in vivo effects of gallium were analyzed by Wistar rat model. Our results revealed that low concentrations (1-10 microg/ml) of gallium promoted cells to enter the S phase of cell cycle and enhanced cellular release of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, both in vitro and in vivo. In contrast, high concentrations of gallium (50-100 microg/ml) induced apoptosis. Furthermore, gallium-induced cytokine release and apoptosis could be inhibited by iron-saturated transferrin (Tf-Fe). These results suggest that the concentration-dependent effects of gallium on PBMCs are related to iron metabolism.

Adjuvants, Immunologic↗

Expression of nitric oxide synthases in keratinocytes after UVB irradiation.

The importance of nitric oxide (NO) in mediating vasodilation, neurotransmission, and immune and inflammatory responses has been demonstrated. Human keratinocyte express inducible nitric oxide synthase (iNOS) and the neuronal constitutive isoform of NOS (ncNOS). We established an in vitro model in keratinocytes to investigate changes in NO, iNOS and ncNOS expression after UVB exposure. We demonstrated a large induction of NO after UVB exposure and that the source of NO produced in UVB-exposed keratinocytes was increased expression of iNOS and ncNOS. The increased NO production with increased expression of iNOS and ncNOS may contribute to the pathological and physiological features of UVB-induced erythema and skin inflammation.

Cells, Cultured↗

Increased incidence of preterm delivery in mothers residing in an industrialized area in Taiwan.

The objective of this study was to determine whether women living in the vicinity of industrial districts where emission levels of air contaminants from multiple sources including petrochemical, petroleum, steel, and shipbuilding industries are highly correlated with increased incidence of preterm births. The prevalence of delivery of preterm-birth infants was significantly higher in mothers living in the industrial study area compared to control regions of Taiwan. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, infant gender, and birthplace), the adjusted odds ratio was 1.11 (95% CI = 1.02-1.21) for delivery of preterm infants in the industrial area. Data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy, although a semiecological study cannot confirm a direct causal relationship.

Adult↗

Biological evaluation of an antibiotic DC-81-indole conjugate agent in human melanoma cell lines.

Pyrrolo[2, 1-c][1, 4]benzodiazepines (PBDs) are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequences of DNA and form a labile covalent adduct. DC-81, an antitumor antibiotic produced by Streptomyces species, is a PBD. We combined DC-81 and an indole carboxylate moiety to synthesize a hybrid designed to have much higher sequence selectivity in DNA interactivity. In this paper, the cytotoxic potency of the hybrid in human melanoma cell lines was studied. XTT assay demonstrated that the DC-81-indole conjugate possessed cytotoxicity against human melanoma cell lines.

Antibiotics, Antineoplastic↗

Low concentrations of arsenic induce vascular endothelial growth factor and nitric oxide release and stimulate angiogenesis in vitro.

Arsenic (As) is widely distributed in nature, and its contamination in drinking water remains a major public health problem. Exposure to As may lead to degenerative peripheral vascular diseases. The purpose of this study is to clarify the role of As in modulating cell proliferation and in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs) and to scrutinize the contributing factors of these events. The results revealed that lower concentrations (up to 1 microM) of sodium arsenite stimulated HUVEC cell growth. An in vitro angiogenesis assay indicated that low concentrations of As increased vascular tubular formation, which was abrogated by hemoglobin, a potent nitric oxide scavenger. In contrast, higher concentrations of As (>5 micro M) revealed cytotoxicity and inhibition to angiogenesis. We also demonstrated that lower concentrations of As upregulated the expression of constitutive nitric oxide synthase (NOS3) at both transcriptional and translational levels and that lower concentrations of As implicated a modulatory role in vascular endothelial growth factor (VEGF) expression. In addition, low concentrations of As (<1 micro M) increased von Willebrand Factor (vWF) antigen expression, whose elevation paralleled the onset of angiogenesis and was considered an early indicator of endothelial activation in tumor metastasis. VEGF and basic fibroblast growth factor can synergistically upregulate the vWF gene expression. Therefore, we conclude that the treatment of HUVECs with As leads to cell proliferation and activation, which preferentially enhances angiogenesis in vitro, possibly via the VEGF-NOS signaling pathway. The molecular mechanism(s) by which As facilitates angiogenesis remains to be elucidated.

Arsenites↗

Helium-neon laser irradiation stimulates migration and proliferation in melanocytes and induces repigmentation in segmental-type vitiligo.

Low-energy helium-neon lasers (632.8 nm) have been employed in a variety of clinical treatments including vitiligo management. Light-mediated reaction to low-energy laser irradiation is referred to as biostimulation rather than a thermal effect. This study sought to determine the theoretical basis and clinical evidence for the effectiveness of helium-neon lasers in treating vitiligo. Cultured keratinocytes and fibroblasts were irradiated with 0.5-1.5 J per cm2 helium-neon laser radiation. The effects of the helium-neon laser on melanocyte growth and proliferation were investigated. The results of this in vitro study revealed a significant increase in basic fibroblast growth factor release from both keratinocytes and fibroblasts and a significant increase in nerve growth factor release from keratinocytes. Medium from helium-neon laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Furthermore, melanocyte migration was enhanced either directly by helium-neon laser irradiation or indirectly by the medium derived from helium-neon laser treated keratinocytes. Thirty patients with segmental-type vitiligo on the head and/or neck were enrolled in this study. Helium-neon laser light was administered locally at 3.0 J per cm2 with point stimulation once or twice weekly. The percentage of repigmented area was used for clinical evaluation of effectiveness. After an average of 16 treatment sessions, initial repigmentation was noticed. Marked repigmentation (>50%) was observed in 60% of patients with successive treatments. Basic fibroblast growth factor is a putative melanocyte growth factor, whereas nerve growth factor is a paracrine factor for melanocyte survival in the skin. Both nerve growth factor and basic fibroblast growth factor stimulate melanocyte migration. It is reasonable to propose that helium-neon laser irradiation clearly stimulates melanocyte migration and proliferation and mitogen release for melanocyte growth and may also rescue damaged melanocytes, therefore providing a microenvironment for inducing repigmentation in vitiligo.

Adolescent↗

Acupuncture, electrostimulation, and reflex therapy in dermatology.

Acupuncture is an old therapeutic method that includes both needle and nonneedle acupuncture. Nonneedle acupuncture includes moxibustion, cupping, and acupressure. In the field of dermatology, acupuncture has been reported to be beneficial for the treatment of acne, postherpetic neuralgia, psoriasis, atopic dermatitis, and urticaria. In acupuncture treatment of dermal diseases, both the filiform needle and the cutaneous needle are powerful tools. In the treatment of refractory dermal diseases, cutaneous needle acupuncture is usually followed by cupping to intensify the therapeutic effect. In cases where needle acupuncture is not possible, acupuncture-like transcutaneous electrical nerve stimulation (TENS) is a good alternative. In addition, reflex therapy based on foot reflex areas may also be an alternative. A lack of controlled studies is the main drawback for the methods mentioned above. However, the experiences from experts in this field may offer us new ideas to resolve refractory disorders in dermatology.

Acupuncture Therapy↗

Relapsing ulcerative papules over bilateral hands and scrotum in an Asian man: an atypical manifestation of primary cutaneous CD30-positive lymphoma.

A 33-year-old Taiwanese man presented at our clinic with multiple erythematous ulcerated papules over his bilateral hands. CD30-positive anaplastic large cell lymphoma (CD30+ ALCL) was diagnosed by an incisional biopsy. After a thorough survey for extracutaneous involvement, the diagnosis of primary cutaneous CD30+ ALCL was established. Due to spontaneous regression of some skin lesions, the patient refused therapeutic intervention. Subsequently, an ulcerative nodule arose over the scrotum. It spontaneously regressed 5 weeks later. Although histologically alarming, this particular lymphoma bears favorable prognosis. Thus, recognition of this entity is of great importance, because it may prevent patients from undergoing unnecessary aggressive treatment. To our knowledge, CD30+ ALCL has not been reported to evolve in the pattern similar as observed in our patient. Thus, this Asian man presents a rare presentation of CD30+ ALCL.

Adult↗

Arsenic induces tumor necrosis factor alpha release and tumor necrosis factor receptor 1 signaling in T helper cell apoptosis.

Long-term exposure to arsenic induces arsenical cancers in human beings. Arsenic has been shown to induce apoptosis in a variety of cell systems. Previous studies revealed that patients with arsenic-induced Bowen's disease showed a defective cell-mediated immunity and decreased percentages of T cell and T helper cell subpopulations in peripheral mononuclear cells. The purpose of this study was to investigate the effects of arsenic on T cell survival and function in mononuclear cells. Arsenic concentrations higher than 1 micro M induced tumor necrosis factor alpha release from mononuclear cells and caused a cytotoxic effect on T cells. When exposed to higher concentrations of arsenic, apoptosis was induced. CD4+ cells were the major apoptoic population in mononuclear cells. Tumor necrosis factor receptor 1 expression on CD4+ cells, but not Fas/FasL, was significantly enhanced by arsenic treatment compared to other mononuclear cells. Increased expressions of tumor necrosis factor receptor 1 related death domain proteins and activated caspases were observed. These findings indicate that tumor necrosis factor receptor 1 signaling is the major pathway in arsenic-induced T helper cell apoptosis.

Adult↗

Peripheral vascular diseases resulting from chronic arsenical poisoning.

Drinking water contaminated by arsenic remains a major public health problem. Long-term arsenic exposure has been found to be associated with peripheral vascular diseases in a variety of studies. Reports of vascular effects of arsenic in drinking water, which span almost 100 years, have been published in Taiwan, Chile, Mexico, and China. This paper reviewed the association of peripheral vascular diseases resulting from arsenic exposure to drinking water from the clinical and pathological points of view. An endemic peripheral vascular disorder called "blackfoot disease" has been noticed in a limited area in Taiwan. This disease results in gangrene in the extremities. It has been associated with the ingestion of high concentrations of arsenic-tainted artesian well water. Epidemiological studies confirmed a dose-response relationship between long-term arsenic exposure and the occurrence of blackfoot disease. Whereas arsenic has induced various clinical manifestations of vascular effects in Chile, Mexico and China, they do not compare in magnitude or severity to the blackfoot disease found in Taiwan. The pathogenesis of vascular effects induced by arsenic is still controversial. The possible mechanisms include endothelial cell destruction, arsenic-associated atherogenesis, carotene and zinc deficiency, and/or some immunological mechanism. Microcirculatory assessments revealed that deficits of capillary blood flow and permeability exist in clinically normal skin of patients with chronic arsenical poisoning. The vascular effects of chronic arsenic poisoning may involve cardiovascular and cerebrovascular systems as well. In view of the increasing public health problems caused by arsenic exposure, vascular effects should be included in the future study of health effects of arsenic.

Arsenic↗

Effect and correlation of serum total IgE, eosinophil granule cationic proteins and sensitized allergens in atopic dermatitis patients with or without rhinitis.

To understand the relevance of serological parameters and eliciting allergens in the patients with atopic dermatitis (AD) and patients with atopic dermatitis in combination with rhinitis (ADR), we compared the serum total IgE, major basic protein (MBP) and eosinophil cationic protein (ECP) levels and identified the sensitized allergens in these two groups. The serum levels of total IgE, MBP and ECP were not significantly different in these two groups. Patients with ADR had a higher positive rate of aeroallergens including housedust, mite (D.F), mite (D.P) and cockroach than patients with AD. However, a high positive rate of seafood allergens (include crab, shellfish and shrimp) was observed in patients with AD. The serum IgE level correlated well with serum MBP level (r = 0.603, P = 0. 019) in patients with ADR. There was a strong correlation between serum MBP and ECP level (r = 0.773, P = 0.005) in patients with AD and in patients with ADR (r = 0.721, P = 0.008). We also found that numbers of sensitized allergens correlated well with total IgE in patients with AD (r = 0.760, P = 0.001) and in patients with ADR (r = 0.487, P = 0.004). These results suggested that the aeroallergens are the most important allergens causing and aggravating atopic diseases in Taiwan. Seafood may play an important role in the pathogenesis of AD. We suggest the measurement of serum total IgE combined with Multiple Allergens Simultaneous Test-Chemiluminescent Assays(AST-CLA) test could be helpful in the diagnosis of atopic diseases.

Adolescent↗

Pseudoxanthoma elasticum with abnormal nailfold microcirculatory findings.

Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue. Here we report a 34-year-old male patient who developed multiple symptomless yellowish papules over his neck for several months. He visited our dermatologic out-patient-clinic because his sister had similar skin lesions and mild visual impairment. The pathologic features of the skin biopsy showed fragmented calcified elastic fibers in the mid-to-lower dermis under the H&E, Verhoeff-van Gieson and Von Kossa stains. Under electron microscopy, calcified degenerated elastic fibers were noted. No other internal organ involvement was found except angioid streaks on the fundus. In addition, morphological changes of the nailfold capillaries, including increased tortuosity, dilated venous limbs of capillary loops, and decreased red-blood-cell velocity, were observed under the capillaroscopy. Though former reports have indicated that cardiovascular manifestations are caused by degeneration of elastic fibers of blood vessels, this study is the first to emphasize the microcirculatory disturbance of nailfold capillary, including morphology and blood-cell velocity, in PXE.

Adult↗