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Biomedical subjects

S Kang

Publications and source records attributed to S Kang.

At least 181 records · Page 10Linked to original sources

Prolonged occlusion in the treatment of psoriasis: a clinical and immunohistologic study.

BACKGROUND: An occlusive dressing that is both cosmetically acceptable and long term is needed for psoriasis treatment. The mechanisms that underlie the efficacy of occlusion in psoriasis are unknown. OBJECTIVE: We performed a clinical and immunohistologic study in patients with psoriasis of the effects of occlusion, topical corticosteroid alone, and occlusion plus corticosteroid, with a new prolonged dressing as the occlusive therapy. METHODS: Nineteen patients completed a 3-week study of efficacy of prolonged occlusion dressing, fluocinonide ointment, or a combination of the two. An immunohistologic study was performed in 10 patients with psoriasis treated for 1 week with prolonged occlusion. RESULTS: The combination of fluocinonide ointment and occlusion produced significantly more improvement than either treatment alone (p < 0.01). There was no significant difference between the efficacy of prolonged occlusion or fluocinonide ointment. On 4-week follow-up plaques treated with occlusion alone or combined fluocinonide and occlusion were still significantly improved (p = 0.05 and p < 0.001, respectively). None of the immunohistologic and proliferation markers assessed in psoriatic plaques was significantly affected by occlusion as compared with untreated plaques. CONCLUSION: Prolonged occlusion is an effective therapy for psoriasis either as monotherapy or in combination with a high-potency topical corticosteroid. However, the mechanism of action of prolonged occlusion alone in the improvement of psoriasis is unknown.

Administration, Cutaneous↗

Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli.

Several human hereditary neurological and neurodegenerative disease genes are associated with the expansion of CTG repeats. Here we show that the frequency of genetic expansions or deletions in Escherichia coli depends on the direction of replication. Large expansions occur predominantly when the CTGs are in the leading strand template rather than the lagging strand. However, deletions are more prominent when the CTGs are in the opposite orientation. Most deletions generated products of defined size classes. Strand slippage coupled with non-classical DNA structures may account for these observations and relate to expansion-deletion mechanisms in eukaryotic chromosomes for disease genes.

Base Sequence↗

The reconstruction locked nail for complex fractures of the proximal femur.

Thirty-seven patients with 37 proximal femoral fractures were treated with a reconstruction locked femoral nail. There were four ipsilateral intracapsular femoral neck and shaft fractures, two intertrochanteric fractures, 18 intertrochanteric fractures with diaphyseal extension, eight subtrochanteric fractures with involvement of the lesser trochanter, and five subtrochanteric fractures without involvement of the lesser trochanter. The overall union rate was 92%. Twenty-one complications developed in 13 patients (35%) which included three of the four femoral neck and shaft fractures, and six of 18 intertrochanteric fractures with diaphyseal extension. Of the five intertrochanteric fractures with diaphyseal extension in which anatomic reduction was not achieved, four developed a complication. Of the nine proximal screws in nine fractures, which were placed short (below the subchondral bone of the femoral head), six fractures developed a complication. The complications included three nonunions, one delayed union, two leg-length discrepancies of > 2.5 cm, two cases of varus deformity of > 10 degrees, two varus deformities < 10 degrees, four instances of revision surgery including one broken 13-mm nail, four proximal screws that backed out and required removal, two cases of pudendal nerve palsy, and one case of heterotopic ossification. Seven patients developed more than one complication. Eleven of the 13 patients with complications required a second surgery to treat the complication. We conclude that the reconstruction locked femoral nail is not a good choice for ipsilateral intracapsular neck and shaft fractures. Our recommendation is that anatomic reduction should be achieved for all cases using the reconstruction femoral nail, but it is absolutely required when treating the intertrochanteric fracture with diaphyseal extension. Reconstruction femoral nails have a high rate of complication due to the complex nature of the fractures as well as the device.

Adult↗

Identification, cloning, and characterization of PWL2, a gene for host species specificity in the rice blast fungus.

Genetic analysis of host specificity in the rice blast fungus (Magnaporthe grisea) identified a single gene, PWL2 (for Pathogenicity toward Weeping Lovegrass), that exerts a major effect on the ability of this fungus to infect weeping lovegrass (Eragrostis curvula). The allele of the PWL2 gene conferring nonpathogenicity was genetically unstable, with the frequent appearance of spontaneous pathogenic mutants. PWL2 was cloned based on its map position. Large deletions detected in pathogenic mutants guided the gene cloning efforts. Transformants harboring the cloned PWL2 gene lost pathogenicity toward weeping lovegrass but remained fully pathogenic toward other host plants. Thus, the PWL2 host species specificity gene has properties analogous to classical avirulence genes, which function to prevent infection of certain cultivars of a particular host species. The PWL2 gene encodes a glycine-rich, hydrophilic protein (16 kD) with a putative secretion signal sequence. The pathogenic allele segregating in the mapping population, pwl2-2, differed from PWL2 by a single base pair substitution that resulted in a loss of function. The PWL2 locus is highly polymorphic among rice pathogens from diverse geographic locations.

Alleles↗

All-trans retinoic acid induces cellular retinol-binding protein in human skin in vivo.

We examined the regulation of cellular retinol-binding protein (CRBP) mRNA and protein expression in human skin in vivo by all-trans retinoic acid and all-trans retinol. Treatment of human skin for 24 h with all-trans retinoic acid (0.1%) or all-trans retinol (1.6%) induced CRBP mRNA 5.5-fold (p < 0.01, n = 10) and 5.7-fold (p < 0.01, n = 5), respectively, compared with skin treated with vehicle or sodium lauryl sulfate (used as an irritant control). In vitro translation of poly A+ RNA from all-trans retinoic acid, all-trans retinol, sodium lauryl sulfate, and vehicle-treated human skin demonstrated that the observed increased CRBP mRNA in all-trans retinoic acid- and all-trans retinol-treated skin was able to direct increased (2.3-2.9-fold) CRBP protein synthesis. Riboprobe in situ hybridization revealed that CRBP mRNA was uniformly elevated throughout the epidermis and in dermal cells after all-trans retinoic acid treatment of human skin. Western analysis revealed that CRBP protein was elevated 3.2-fold (p < 0.01, n = 6) and 3.0-fold (p < 0.01, n = 6) after all-trans retinoic acid treatment of human skin in vivo for 24 and 96 h, respectively, compared with vehicle- and sodium lauryl sulfate-treated skin. In addition, functional CRBP levels measured by [3H]all-trans retinol binding were elevated 1.9-fold (p < 0.01, n = 6) and 3.5-fold (p < 0.01, n = 6) at 24 and 94 h, respectively, after all-trans retinoic acid treatment, compared with vehicle- or sodium lauryl sulfate-treated skin. Gel mobility shift analysis revealed that retinoid receptors in nuclear extracts from human skin formed a specific complex with a DNA probe containing the retinoic acid response element in the mouse CRBP gene. Monoclonal antibodies to nuclear retinoid receptors demonstrated that predominantly retinoic acid receptor-alpha/retinoid X receptor-alpha heterodimers bound to the CRBP retinoic acid response element. These data demonstrate that CRBP expression in human skin in vivo is regulated by exogenous all-trans retinoic acid and all-trans retinol.

Base Sequence↗

Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation.

We investigated the clinical, histologic, and molecular responses of normal human skin to all-trans-retinol (ROL) application, compared to those induced by topical all-trans-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6% ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone were applied in a double-blind fashion to normal buttock skin and occluded for 4 d. ROL produced from none to only trace erythema, which was clinically and statistically insignificant, whereas RA induced a significant 3.7-fold increase in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6% ROL, p < 0.01), similar to RA (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, compared with vehicle, also increased mRNA levels of cellular retinoic acid binding protein (CRABP-II) and cellular retinol binding protein (CRBP) genes as determined by Northern analysis (5-6-fold and 6-7-fold, respectively) and riboprobe in situ hybridization. CRABP-II and CRBP protein levels were also higher following ROL than vehicle treatment, as measured by ligand binding (3.2-fold, p < 0.001; n = 7) and Western analysis (3.6-fold, p < 0.003; n = 6), respectively. Epidermal retinyl ester (RE) content, measured after removal of stratum corneum, rose 240-fold (p < 0.005, n = 5) by 24 h of ROL occlusion. RA content, however, was undetectable or detectable only at trace amounts in all samples obtained at 0, 6, 24, and 96 h after ROL occlusion. Detectability of RA was not correlated with ROL treatment (compared to untreated normal skin, p = 0.86) or baseline skin ROL levels (average r = -0.1, p > 0.3). These data demonstrate that ROL application 1) produces trace erythema not significantly different from vehicle, whereas RA causes erythema; 2) induces epidermal thickening and enhances expression of CRABP-II and CRBP mRNAs and proteins as does RA; 3) causes marked accumulation of retinyl ester; and 4) does not significantly increase RA levels. Taken together, the data are compatible with the idea that ROL may be a prohormone of RA, because it produces changes in skin similar to those produced by RA but without measurable RA or irritation.

Administration, Cutaneous↗

Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams.

BACKGROUND AND DESIGN: The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n = 32), 0.025% tretinoin (n = 35), or vehicle (n = 32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. RESULTS: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. CONCLUSIONS: Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.

Aged↗

Tumor vascularity is not a prognostic factor for malignant melanoma of the skin.

Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most suitable vascular marker for this study. Our results indicate that there was no statistically significant difference between the two groups with regard to tumor vascularity. Even after identifying 15 cases of thin ( < 1.0 mm thick) melanoma, there was no significant difference in the number of microvessels between metastasizing and non-metastasizing tumors. Comparison of patterns of vascular microarchitecture also failed to discriminate between the two groups. Thus, our results indicate that tumor vascularity may not be an independent prognostic factor for cutaneous melanoma.

Adolescent↗

[VM-26 plus CCNU in the prevention of brain metastasis in lung cancer patients].

Brain metastasis is of frequent occurrence in patients with cancer of the lung. To ascertain if brain metastasis is preventable, 34 lung cancer patients without brain metastasis were treated with 4 cycles of VM-26 plus CCNU at 4-week intervals. As a control for comparison, an equal number of lung cancer patients free of brain metastasis were treated with chemotherapy protocol which did not include VM-26 and CCNU. The patients were monitored by clinical symptoms, signs and CT or MRI scan and were followed up for 4-12 months. The results indicate that none of the VM-26 plus CCNU-treated patients developed brain metastasis while brain metastasis occurred in 7 (20.5%) of 34 control patients. The difference was statistically significant (P < 0.05).

Adenocarcinoma↗

Congenital melanocytic nevi and DNA content. An analysis by flow and image cytometry.

BACKGROUND: Potential risk factors for the development of melanoma in congenital melanocytic nevi (CMN) are not well established. DNA aneuploidy may constitute such a risk factor but has not been sufficiently studied in CMN. METHODS: In the present study, DNA analysis of eight giant CMN, nine medium CMN (1.5-20 cm), and eight small CMN (< 1.5 cm) was assessed by flow cytometry and selected lesions (six nevi) by DNA image cytometry. DNA content was correlated with patient age, nevus size, and degree of cytologic atypia. RESULTS: DNA aneuploidy was detected by flow cytometry in two giant CMN from adult patients and in a small CMN from a child. DNA aneuploidy was not observed in any of the six CMN studied by image cytometry, although an increased S-phase was noted in a markedly atypical giant CMN. No DNA aneuploidy was detected in medium-sized CMN or in the CMN of nine patients 1 year of age or younger. CONCLUSION: In contrast to previous studies, it was observed that abnormal DNA content does tend to correlate with cytologic atypia, particularly in giant CMN with atypia or melanoma, in adults. Conversely, frank DNA aneuploidy in any CMN in children younger than 1 year of age, irrespective of histologic findings, was not detected. Finally, based on these limited studies, greater sensitivity of image over flow cytometry for detection of DNA aneuploidy cannot be verified.

Adolescent↗

Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene.

The expansion of CTG repeats in DNA occurs in or near genes involved in several human diseases, including myotonic dystrophy and Huntington's disease. Nucleosomes, the basic structural element of chromosomes, consist of 146 base pairs of DNA coiled about an octamer of histone proteins and mediate general transcriptional repression. Electron microscopy was used to examine in vitro the nucleosome assembly of DNA containing repeating CTG triplets. The efficiency of nucleosome formation increased with expanded triplet blocks, suggesting that such blocks may repress transcription through the creation of stable nucleosomes.

DNA↗

Zinc destabilizes DNA Watson-Crick pairs at AGCT.

Zinc, a component of a large number of enzymes and an abundant and essential trace metal, alters the structure of AGCT sites in negatively supercoiled DNA. Related sequences show little or no effect. Cobalt and cadmium show reactivities similar to zinc. The conformational change in DNA was fine mapped with haloacetaldehydes using chemical cleavage or primer extension methods. Since a many fold excess of zinc to AGCT sites is required to saturate the reaction, we propose that the zinc-AGT complex is preferentially accessible to the haloacetaldehyde probes due to a conformational deformation. Hence, zinc is the smallest ligand (by approximately 500-fold) that causes a perturbation of a specific DNA sequence.

Base Composition↗

Isolation of the mating-type genes of the phytopathogenic fungus Magnaporthe grisea using genomic subtraction.

Using genomic subtraction, we isolated the mating-type genes (Mat1-1 and Mat1-2) of the rice blast fungus, Magnaporthe grisea. Transformation of M. grisea strains of one mating type with a linearized cosmid clone carrying the opposite mating-type gene resulted in many "dual maters," strains that contain both mating-type genes and successfully mate with Mat1-1 and Mat1-2 testers. Dual maters differed in the frequency of production of perithecia in pure culture. Ascospores isolated from these homothallic crosses were either Mat1-1 or Mat1-2, but there were no dual maters. Most conidia from dual maters also had one or the other of the mating-type genes, but not both. Thus, dual maters appear to lose one of the mating-type genes during vegetative growth. The incidence of self-mating in dual maters appears to depend on the co-occurrence of strains with each mating type in vegetative cultures. In rare transformants, the incoming sequences had replaced the resident mating-type gene. Nearly isogenic pairs produced from three M. grisea laboratory strains were mated to investigate their fertility. One transformant with switched mating type appears to have a mutation that impairs the development of asci when its mating partner has a similar genetic background. The M. grisea Mat1-1 and Mat1-2 genes are idiomorphs approximately 2.5 and 3.5 kb in length, respectively.

Ascomycota↗

Distinction of class II MHC+ Langerhans cell-like interstitial dendritic antigen-presenting cells in murine dermis from dermal macrophages.

Dermal cells are capable of initiating contact-hypersensitivity responses but the precise identification of the antigen-presenting cell within murine dermis is lacking. Class II major histocompatibility complex (MHC)+ cells with dendritic shape and lacking endothelial factor VIII but expressing the dendritic antigen-presenting cell marker NLDC-145 were observed in the perivascular and interstitial dermis of BALB/c and C3H/HeN skin. The heterogeneous class II MHC+ cells could be divided into two subsets: each was class II MHC+ CD45+ (bone marrow derived) GR-1- (non-neutrophil/macrophage) CD3- (non T), but one subset was CD11b+ (beta 2 integrin) and the other was CD11b-. Ultrastructural examination of class II MHC+ cells revealed the presence of a Langerhans cell-like/indeterminant cell subset with indented nuclei, dendritic morphology, active cytoplasm, and dense intermediate filaments. Phagolysomes and Birbeck granules were not observed in such cells, indicating these were distinct from dermal macrophages and from classical epidermal Langerhans cells, respectively. Cells with a monocyte/macrophage ultrastructural appearance were also noted, likely representing the class II MHC subset expressing CD11b and Ly6c (monocyte/endothelial antigen). Dermal cells in suspension were capable of processing and presenting large protein antigens to antigen-specific T-cell hybridomas; dermal cells also induced the syngeneic mixed lymphocyte reaction. The dermal antigen-presentation activities were totally abrogated by removal of class II MHC+ cells, but not by removal of CD11b+ cells or Ly6c+ cells, indicating that potent antigen-presenting cell activity was restricted to the class II MHC+ CD11b- Ly6c- subset (Langerhans cell-like/indeterminant cells). In conclusion, within a complex array of dermal leukocytes a murine dermal class II MHC+ cell population expressing a Langerhans cell-like/dendritic antigen-presenting cell phenotype and exhibiting potent antigen processing and presenting activity can be identified. The positioning of potent interstitial dendritic antigen-presenting cells at the interface of the vasculature with the dermal interstitium provides rapid access to an antigen-presenting cell as T cells first egress into the skin.

Animals↗

Characterization of the high mannose asparagine-linked oligosaccharides synthesized by microfilariae of Dirofilaria immitis.

This report describes the structures of high-mannose-type N-linked oligosaccharides in glycoproteins synthesized by the microfilariae of Dirofilaria immitis. Microfilariae of D. immitis were incubated in vitro in media containing 2-[3H] mannose to allow metabolic radiolabeling of the oligosaccharide moieties of newly synthesized glycoproteins. Glycopeptides were prepared from the radiolabeled glycoproteins by digestion with pronase and fractionation by chromatography on concanavalin A-Sepharose. Thirty eight percent of 2-[3H] mannose incorporated into the microfilariae of D. immitis glycopeptides was recovered in high mannose-type asparagine-linked oligosaccharides which were bound to the immobilized lectin. Upon treatment of 2-[3H] mannose labeled glycopeptides with endo-beta-N-acetylglucosaminidase H, the high mannosetype chains were released and their structures were determined by high performance liquid chromatography and exoglycosidase digestion. The major species of high mannosetype chains synthesized by microfilariae of D. immitis have the composition Man5GlcNAc2, Man6ClcNAc2, Man7GlcNAc2, and Man8GlcNAc2. Structural analyses indicate that these oligosaccharides are similar to high mannose-type chains synthesized by vertebrates.

Animals↗

PPOs: moving from fee-for-service to accepting financial risk.

Introducing a new acronym for the health care delivery environment--the RPO. As PPOs prepare to accept risk in their relationships with payers and providers, new, more-integrated organizations will evolve to be better prepared to assume risk-bearing contracts.

Capitation Fee↗

Melanoma risk in individuals with clinically atypical nevi.

BACKGROUND AND DESIGN: A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole. The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this subspecialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study. RESULTS: A total of 155 such individuals were identified. The mean (+/- SEM) age of the patients at first evaluation was 26 +/- 1 years. The group was followed for 7 +/- 1 years. The male-female ratio was 1:1. A family history of melanoma was present in 71 subjects (46%). Of the 155 patients, two developed melanoma. The thickness of the tumors in both patients was less than or equal to 0.8 mm. Twenty-five patients (16%), including the two with melanoma, had at least one nevus removed that showed "severe nuclear atypia." CONCLUSIONS: The risk of melanoma in individuals with atypical nevi is significantly greater than expected. The elevated risk was demonstrated even though careful, regular evaluations and removal of more atypical lesions were performed. This study provides evidence that, compared with no surveillance, the meticulous monitoring of patients with clinically atypical nevi is more likely to result in the detection of melanoma at thin stages, with an attendant improved prognosis.

Adolescent↗