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Biomedical subjects

H M Sheu

Publications and source records attributed to H M Sheu.

At least 19 recordsLinked to original sources
PubMed2006

Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne.

BACKGROUND: The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex-hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown. OBJECTIVE: We hypothesized that transcription factors involved in sex formation and regulation of steroidogenesis in the classical steroidogenic organs are also expressed in the sebaceous glands. Their possible role in the pathogenesis of acne were investigated. METHODS: We used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting to analyse the expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in cultured human sebocytes and the facial skin of acne patients. RESULTS: The in situ hybridization study showed SOX-9 mRNA mainly localized in basal keratinocytes, the basal layer of the sebaceous glands and eccrine glands. Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1 and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be higher in the acne-prone male patients, while DAX-1 was stronger in subjects without acne, although both were statistically insignificant. CONCLUSION: Our findings confirm the expression of some sex-determining genes in human sebaceous glands. Further studies on a larger patient population including the normal controls are needed to elucidate the functional significance of these transcription factors in the pathogenesis of acne.

Acne Vulgaris↗
PubMed2001

Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: implications for the permeability of compromised skin.

The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted hairless mouse skin as a model membrane. The effect of compound lipophilicity was studied using sucrose, caffeine, hydrocortisone, estradiol, and progesterone as model compounds. The results demonstrated that permeability barrier disruption by acetone treatment significantly enhanced the permeability of the skin to both hydrophilic and amphipathic compounds, including sucrose, caffeine and hydrocortisone. This effect was more prominent with caffeine and hydrocortisone at different transepidermal water loss (TEWL) levels. Acetone treatment, however, didn't appear to alter the percutaneous penetration of highly lipophilic compounds, such as estradiol and progesterone. The characteristics of skin permeability were described by parabolic relationships between log P(WS) (permeability coefficient of whole skin) and log K(O/W) (octanol/water partition coefficient) at different degrees of permeability barrier disruption. The optimal log K(O/W) of compounds for skin penetration appeared to decrease with an increase in TEWL levels. The maximal permeability achieved was similar through skin displaying different TEWL levels. In an attempt to explore the underlying mechanisms for the changes in skin permeability, the stratum corneum/normal saline partition coefficients of water, caffeine, and hydrocortisone either decreased or remained unaffected with an increase in TEWL. Electron microscopic examinations have revealed reductions in stratum corneum lipid content and alterations in intercellular membrane structures as a result of acetone treatment, whereas negligible changes in the number of horny layers were observed by safranin staining of the stratum corneum. We have concluded that the enhancement in skin permeability to both hydrophilic and amphipathic compounds by acetone treatment arose mainly because of the increase in stratum corneum diffusivity at higher TEWL levels. The results imply the possibility of using both TEWL and drug lipophilicity to predict alterations in skin permeability and hence the dose adjustment of topically applied medication for patients with impaired skin barrier function.

Acetone↗
PubMed2001

Molecular weight dependence of polyethylene glycol penetration across acetone-disrupted permeability barrier.

Previous studies have demonstrated that permeability barrier disruption by acetone treatment significantly enhances skin permeability to both hydrophilic and amphipathic compounds, but not to highly lipophilic compounds. The purpose of the present study was to investigate the dependence of permeability on molecular weight (MW) in acetone-disrupted hairless mouse skin in contrast to normal skin. Penetration of polyethylene glycol (PEG) 300, 600, and 1,000 over 12 h was measured using diffusion cells. High-performance liquid chromatographic methods with refractive index detection were used to separate and quantitate the individual oligomeric species in the PEG samples. Percutaneous penetration of PEGs exhibited slightly steeper MW dependency at a transepidermal water loss (TEWL) of 30-41 g/m2 per h in comparison with TEWLs of 0-10 (control skin), 10-20, and 20-30 g/m2 per h, with a higher percentage of smaller oligomer PEGs penetrating than larger ones. Increasing the TEWL of the skin increased the penetration of all the PEG oligomers, and the degree of the enhancement relative to penetration through control skin increased with MW and was maximal for oligomers with a MW ranging from 326 to 414 Da. Within the limit of quantitation of the assay, the MW cut-off for PEG penetration across mouse skin with TEWLs of 0-10, 10-20, and 20-30 g/m2 per h was 414, 590, and 942 Da, respectively, while all the measurable oligomers up to MW 1,074 Da were able to penetrate skin with TEWLs in the range 30-41 g/m2 per h. The results suggest that not only higher amounts but also more varieties of chemicals may penetrate skin with a compromised barrier than normal skin, implying a higher risk of intoxication and hypersensitization by environmental agents through diseased skin with impaired barrier function.

Acetone↗
PubMed2001

Morphology of glass fibers in electronics workers with fiberglass dermatitis--a scanning electron microscopy study.

BACKGROUND: Fiberglass is used as a reinforcement filler material in printed circuit boards (PCBs) which are widely used in the electronics industry. In a recent survey, we demonstrated that fiberglass dermatitis is the most common occupational dermatosis among electronics industry workers in Taiwan. Little is known, however, about the morphologic structures of the glass fibers which induce dermatitis. The purpose of this study was to assess the morphology of fiber spicules and to determine the relationship of this structure to fiberglass dermatitis. METHODS: Fourteen female patients with a diagnosis of fiberglass dermatitis were selected for study. The diagnosis was confirmed in all patients by positive skin stripping for glass fibers and matching with glass fibers from dust collected in work areas and from samples collected by scraping the edge of PCBs. Samples of collected glass fibers were analyzed by scanning electron microscopy (SEM). RESULTS: SEM of the fiberglass samples revealed that fibers were approximately 10 microm in diameter. In samples from both the edge of PCBs and from dust collected in work areas, SEM revealed that most of the fibers were in bundles of various sizes and lengths. All fibers collected from patients' skin by tape stripping showed a singular spicule, most had a sharp free end, and the lengths were in the range 50-150 microm . CONCLUSIONS: Singular glass fibers with a sharp free end and a length of 50-150 microm are most likely to induce fiberglass dermatitis.

Adult↗
PubMed2001

Photodynamic therapy for Bowen's disease (squamous cell carcinoma in situ) of the digit.

BACKGROUND: Surgical excision is the preferred method of eradicating Bowen's disease (BD). However, when BD occurs on the digit, surgical intervention can sometimes lead to scar contracture and loss of function of the digit. OBJECTIVE: To evaluate the effectiveness of photodynamic therapy (PDT) in eradicating BD of the digit while preserving the full function of the digit. METHODS: Four patients of chronic arsenism with biopsy-proven BD on the digit were treated with PDT by using a newly designed light-emitting diode (LED) array with a peak wavelength of 630 nm (630 +/- 40 nm; 40 mW/cm2 at skin surface). After partial removal of the thickened horny layer and 16 hours of occlusion with a 2% aminolevulinic acid (ALA) solution, each lesion was irradiated with 240 J/cm2 in two fractions with a 90-minute interval. RESULTS: All patients experienced a significant burning, tingling sensation that was tolerable during the procedure except one who needed local anesthesia. All treated digits healed without scarring in 2 weeks. Posttreatment biopsy in one patient showed normal epidermis and a slight fibrosis in the papillary dermis. Three patients remained free of recurrence (75%) at 15-17 months (average 16 months) after one treatment. One patient's BD recurred at 8 months, but was successfully treated without recurrence after 20 months. CONCLUSION: Our preliminary study suggests that PDT using 2% 5-ALA solution and an LED array is an effective, noninvasive method to treat digital BD with the benefit of scar-free contracture and loss of digital function. Among the various factors that would affect the results of PDT, we feel that partial removal of the thickened horny layer is the most important step to achieve sufficient therapeutic effect in digital BDs.

Aged↗
PubMed2000

Anticancer activity evaluation of the solanum glycoalkaloid solamargine. Triggering apoptosis in human hepatoma cells.

Solamargine, an herbal and molluscicidal medicine derived from Solanum incanum, is a steroidal alkaloid glycoside. To characterize the anticancer mechanism of solamargine on human hepatoma cells (Hep3B), changes of cell morphology, DNA content, and gene expression of cells after solamargine treatment were studied. The appearance in solamargine-treated cells of chromatin condensation, DNA fragmentation, and a sub-G(1) peak in a DNA histogram suggests that solamargine induces cell death by apoptosis. The maximum number of dead Hep3B cells was detected within 2 hr of incubation with constant concentrations of solamargine, and no further cell death was observed after an extended incubation with solamargine, indicating that the action of solamargine was irreversible. To determine the susceptibility of cell phases to solamargine-mediated apoptosis, Hep3B cells were synchronized at defined cell cycles by cyclosporin A, colchicine, and genistein, followed by solamargine treatment. The IC(50) values of solamargine for control, G(0)/G(1)-, M-, and G(2)/M-synchronized Hep3B cells were 5.0, > 10, 3.7, and 3.1 microg/mL, implying that cells in the G(2)/M phases are relatively susceptible to solamargine-mediated apoptosis. In addition, a parallel up-regulation of tumor necrosis factor receptor (TNFR)-I and -II on Hep3B cells was detected after solamargine treatment, and the solamargine-mediated cytotoxicity could be neutralized with either TNFR-I or -II specific antibody. Therefore, these results reveal that the actions of TNFR-I and -II on Hep3B cells may be independent, and both are involved in the mechanism of solamargine-mediated apoptosis.

Antibodies↗
PubMed2000

Quantitative determination of the expression of xeroderma pigmentosum F gene in human nonmelanoma skin cancers.

Nonmelanoma skin cancers (NMSC) has been evidenced with an impaired function in nucleotide excision repair (NER). However, malfunction of NER elements in NMSC has not been identified. Xeroderma pigmentosum F (XPF) is an essential subunit in NER and functions as a 5'-incision enzyme when repairing damaged DNA. So far, neither XPF's protein nor antibody is commercially available. To explore the expression of XPF in NMSC, the gene was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR). All the designed primers specifically amplified XPF cDNA as demonstrated by nested PCR, and one set of the primers was mimic constructed to form a controlled cDNA for the semiquantification of XPF gene in NMSC. The results indicated that the quantities of XPF expression of BCC and SCC specimens were approximately 57.0 and 76.4% less than that of normal skins, respectively. This paper indicates that the decrease expression of XPF gene may be one of mechanisms for impaired NER in NMSC, and the feasible and quantitative primers used in the experiments may explore the study of XPF in etiology of carcinogenesis.

Base Sequence↗
PubMed1999

A novel function of emodin: enhancement of the nucleotide excision repair of UV- and cisplatin-induced DNA damage in human cells.

Nucleotide excision repair (NER) is the main pathway by which mammalian cells remove carcinogenic DNA lesions caused by UV light and many other common mutagens. To explore the effect of emodin on NER, its influence on the repair of UV- and cisplatin-induced DNA damage in human fibroblast cells (WI38) was evaluated. Emodin increased unscheduled DNA synthesis (UDS) of UV-treated cells and reduced cisplatin-induced DNA adducts in WI38 in a concentration-dependent manner, indicating that emodin might promote NER capability in cells. The resultant NER complex is a cooperative assembly of XPF, ERCC1, XPA, RPA, and XPG subunits. The gene regulations of the subunits after emodin treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers. Among the subunits, the expression of ERCC1 in WI38 cells was up-regulated significantly after emodin treatment. All other expressions remained essentially unchanged. In addition, calcium influx in WI38 was increased in proportion to the concentration of emodin. Since UV-induced NER is Ca2+ dependent, elevation of calcium influx may be another mechanism by which emodin facilitates DNA repair. In conclusion, emodin can increase the repair of UV- and cisplatin-induced DNA damage in human cells, and elevated ERCC1 gene expression and Ca2+-mediated DNA repair processes may be involved in the repair mechanism of emodin.

Antineoplastic Agents↗
PubMed1999

Human skin surface lipid film: an ultrastructural study and interaction with corneocytes and intercellular lipid lamellae of the stratum corneum.

Sebum is a complex mixture of lipids, which is secreted by mammalian sebaceous glands, and forms a fluid film over the skin surface. After sebum is secreted, it becomes mixed with lipid from the keratinizing epithelium and forms the skin surface lipid film (SSLF). Until now, direct fine structural observation of the SSLF has been lacking. In the present work, we viewed the detailed structures of the human SSLF by ruthenium tetroxide staining. The results showed that the SSLF formed an amorphous sheet of variable thickness on the skin surface instead of forming lipid droplets, as had been the usual assumption. In general, its thickness was < 0.5 microm or even negligible in sebum-poor extremities. However, in the sebum-rich face, its thickness was > 4 microm in focal areas. Consistent with the thickness of SSLF, the sebum quantity showed great regional variation. It varied from 1 microg/cm2 (leg) to 189 +/- 42.7 microg/cm2 (mean +/- SD: face). The SSLF was composed of numerous fine granules of about 4-5 nm in a random orientation. Within the SSLF, variable amounts of deranged lipid lamellae derived from corneocytes were mixed with sebum. As well as on the skin surface, a similar amount of sebum was also found between the desquamating corneocytes in the uppermost several layers of the stratum corneum (SC). We also observed the presence of intercellular lipid lamellae in the outer layers of the SC: their lipid envelope remained intact even in desquamated corneocytes. Our results provide some new insights concerning the structure of the SSLF and its relationship with the SC.

Adult↗
PubMed1998

Expression of transposon LINE-1 is relatively human-specific and function of the transcripts may be proliferation-essential.

A new 1.7-kb LINE (L1) transcript has been discovered from the cDNA library of human small-cell lung cancer. The nucleotide sequence of 1.7-kb L1 transcript is 98.4% similar to that of open reading frame 2 (ORF2) found in consensus complete 6.5-kb L1. Although L1 DNA segments could be detected from both genomic DNAs of human and rodent cells by PCR, these L1 transcripts were not detectable from cellular RNA of rodent cells by RT-PCR and northern hybridization, implying that the expression of L1 was relatively human-specific. The functions of L1 transcripts in cells are not yet clear. This paper shows that L1 transcripts are essential for cell proliferation when determined by antisense oligonucleotides. Alternately, L1 transcripts exhibit in all human cells we have examined so far, and they map to all the human chromosomes. A sequence-similarity search in the GenBank database indicates that the major sequence of 1.7-kb L1 is integrated in human retinoblastoma (Rb), IL-2, and factor VIII genes. Since Rb and factor VIII genes have displayed high frequency of chromosomal deletions in various cancers and haemophilia A, the universal integration of long and homologous L1 segments in the genes and all chromosomes may be liable to promote abnormal DNA rearrangement.

Base Sequence↗
PubMed1998

Permeability barrier abnormality of hairless mouse epidermis after topical corticosteroid: characterization of stratum corneum lipids by ruthenium tetroxide staining and high-performance thin-layer chromatography.

Topical corticosteroids (TCS) are among the most frequently used topical therapeutics. Recently, it has been shown that TCS not only has antiproliferative actions, but also inhibits the differentiation of the epidermis and finally perturbates stratum corneum (s.c.) barrier function. It is well established that epidermal barrier function resides within the intercellular lipids of the SC. However, to date, little is known about the effects of TCS on the structure and composition of s.c. lipids. We therefore used hairless mouse skin to study the sequential changes of the s.c. permeability barrier and their intercellular lipids by ruthenium tetroxide staining and high-performance thin-layer chromatography (HPTLC) during topical use of corticosteroids. The results demonstrated a progressive increase in transepidermal water loss accompanied by a diminution in the SC intercellular lipid lamellae, which showed a normal structure of individual lamella. Analysis of lipid composition by HPTLC after a 6-week application of TCS also showed an obvious decrease in all the main components of s.c. lipids, which are known to constitute the permeability barrier of the skin. In light of these results, our work provides direct morphological evidence that TCS deteriorates the permeability barrier of epidermis when applied to normal skin.

Administration, Topical↗
PubMed1998

Use of tissue meshing technique to facilitate side to side closure of large defects.

BACKGROUND: Primary closure of a large wound usually needs flaps of sophisticated design or skin grafts, both require more skill and wound care. Motley and Holt first reported the use of meshed advancement flap, a relative simple technique to close large defects of the lower leg in five patients. OBJECTIVE: To report the use of tissue meshing technique to close large wounds with significant tension on various sites of the body. METHODS: Six patients with large benign or malignant neoplasms at various sites of the body were included. Tissue meshing technique was used to facilitate wound closure after elliptical excision of the tumors at office visits. RESULTS: The wound defects, ranging from 3.0-3.5 cm in width, were closed with satisfactory cosmetic results, except for the occurrence of transient small hypertrophic scars in one patient. There was no complication of wound dehiscence, ischemia, infection or hematoma. CONCLUSION: Tissue meshing technique is a simple procedure and appears to be a satisfactory alternative to facilitate the closure of large wounds under tension. This technique is suitable for most body sites excluding central face and neck because there may be a stippled appearance in the area of meshing.

Adult↗
PubMed1997

Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids.

The intercellular lipid lamellae of the stratum corneum (SC) is believed to provide the permeability barrier of the epidermis. Previous functional studies have demonstrated an increase in the transepidermal water loss (TEWL) after long-term use of topical corticosteroids (TCS): however, direct morphological confirmation of this barrier abnormality is still lacking. The aim of this study was to determine whether any abnormality could be detected in the structure of the SC intercellular lipid lamellae in patients after long-term TCS. Atrophic skin and untreated normal skin of 10 patients after long-term TCS were examined by transmission electron microscopy using ruthenium tetroxide-fixed tissue for the multilamellar lipid sheets of SC, and oil red O stain for neutral lipids of the SC. Layers of the SC were evaluated by 0.1% methylene blue stain after alkaline expansion, and TEWL was measured by Evaporimeter EP1. The TCS-treated atrophic skin had fewer layers of horny cells, mean 9.4 layers, than the normal control skin, 18 layers (P < 0.001) and increased TEWL of 21.3 g/m2 compared with the control skin TEWL of 6.7 g/m2 (P < 0.01). The mean neutral lipid content of the SC was also significantly lower (P < 0.001). Moreover, ultrastructural studies revealed a marked decrease in both the numbers of intercellular lipid lamellae of SC and membrane-coating granules of stratum granulosum in the atrophic skin. These results suggest that the diminution in the SC intercellular lipid lamellae and SC cell layers play an important part in the pathogenesis of barrier dysfunction after long-term use of TCS.

Administration, Topical↗
PubMed1997

Mouse skin damage caused by a recombinant extracellular metalloprotease from Vibrio vulnificus and by V. vulnificus infection.

Vibrio vulnificus wound infection is characterized by an intense acute cellulitis which spreads along the subcutaneous tissue with severe tissue destruction. Toxins produced by the bacteria appear to be involved in the pathogenesis of skin necrosis and to facilitate microbial dissemination in vivo. We report microscopic studies of mouse skin damage caused by a single intradermal injection of V. vulnificus or of an extracellular metalloprotease isolated from this organism. The gene encoding this metalloprotease has been cloned and expressed in Escherichia coli. The crude metalloprotease extract obtained from the periplasmic fraction by osmotic shock was used in this study. Intradermal injection of this preparation resulted in marked edematous changes of the skin, which extended throughout the dermis and subcutaneous tissues and into adjacent muscles. The collagen and elastic fibers degenerated and some muscle cells even appeared necrotic. Blood vessels became congested, with moderate perivascular neutrophil and mononuclear cell infiltration. There was no evidence of necrotic changes in the blood vessel itself. These results show that the damage to the connective tissues caused by V. vulnificus is at least partly attributable to its protease. Therefore, the protease seems to be an important virulence factor of this microbe.

Animals↗
PubMed1996

In vitro amplification of human basic fibroblast growth factor mRNA by RNA-specific exon-junction primers.

Highly sensitive and RNA-specific primers for the determination of human basic fibroblast growth factor (bFGF) gene expression by RT-PCR were identified. The RNA-specific primers could amplify bFGF mRNA from 10 pg to 1 ng of total cellular RNA without interfering with the presence of genomic DNA of the cell. The feasible temperatures of the primers annealed to the template were 55 degrees C, 60 degrees C and 65 degrees C. In addition, different locations of primers on the bFGF mRNA molecule yielded distinct amounts of RT-PCR products from the same concentration of RNA, suggesting that the mRNA secondary structure of bFGF affected the RT-PCR. Owing to high sensitivity and specificity of the primers to bFGF RNA, the RNA-specific primers may be potentially utilized for the determination of human bFGF gene expression by in situ RT-PCR.

Base Sequence↗