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N J Korman

Publications and source records attributed to N J Korman.

At least 19 recordsLinked to original sources
PubMed1998

Decreased mRNA expression of several basement membrane components in basal cell carcinoma.

The biologic factors that control the behavior of basal cell carcinoma are poorly understood. This study was undertaken to elucidate the mechanisms responsible for the altered protein levels of several basement membrane components found in basal cell carcinoma. RNA was isolated from papulonodular basal cell carcinoma, normal human epidermal keratinocytes, and normal human skin, reverse transcribed to cDNA and amplified by the polymerase chain reaction utilizing primers specific for the 230 kDa bullous pemphigoid antigen (BPAG1), the 180 kDa bullous pemphigoid antigen (BPAG2), the alpha6 and beta4 chains of the alpha6beta4 integrin complex, and the beta3 chain of laminin 5. Southern blots probed with internal oligonucleotides confirmed that each polymerase chain reaction was specific for the basement membrane component amplified. The mRNA expressions of basement membrane components were indistinguishable between normal human epidermal keratinocytes and normal human skin, and subsequent experiments used normal human epidermal keratinocytes as controls. Quantitation of polymerase chain reaction products indicated that all basement membrane specific mRNA were significantly decreased in basal cell carcinoma as compared with normal human epidermal keratinocytes. The mean polymerase chain reaction product intensities were significantly less in the basal cell carcinoma as compared with the normal human epidermal keratinocytes at the following levels: p < 0.001 for alpha6 and beta4 integrins and the beta3 chain of laminin 5; p < 0.01 for BPAG1; and p < 0.05 for BPAG2. Our results demonstrate that decreased protein levels of basement membrane components in basal cell carcinoma are due at least partially to a downregulation of basement membrane mRNA species. We speculate that these alterations may lead to a structurally incompetent basement membrane that facilitates the basal cell carcinoma ability to invade tissues.

Antigens, CD↗
PubMed1997

Protective effects of silymarin against photocarcinogenesis in a mouse skin model.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer among humans; solar UV is its major cause. Therefore, it is important to identify agents that can offer protection against this cancer. PURPOSE: We evaluated the protective effects of silymarin, a flavonoid compound isolated from the milk thistle plant, against UVB radiation-induced nonmelanoma skin cancer in mice and delineated the mechanism(s) of its action. METHODS: For long-term studies, three different protocols of treatment were employed, each evaluating protection by silymarin at a different stage of carcinogenesis. Female SKH-1 hairless mice were subjected to 1) UVB-induced tumor initiation followed by phorbol ester-mediated tumor promotion, 2) 7,12-dimethylbenz[a]anthracene-induced tumor initiation followed by UVB-mediated tumor promotion, and 3) UVB-induced complete carcinogenesis. Forty mice were used in each protocol and were divided into control and treatment groups. Silymarin was applied topically at a dose of 9 mg per application before UVB exposure, and its effects on tumor incidence (% of mice with tumors), tumor multiplicity (number of tumors per mouse), and average tumor volume per mouse were evaluated. In short-term studies, the following parameters were measured: formation of sunburn and apoptotic cells, skin edema, epidermal catalase and cyclooxygenase (COX) activities, and enzymatic activity and messenger RNA (mRNA) expression for ornithine decarboxylase (ODC), a frequently observed marker at tumor promotion stage. Fisher's exact test was used to evaluate differences in tumor incidence, two-sample Wilcoxon rank sum test was used for tumor multiplicity and tumor volume, and Student's t test was used for all other measurements. All statistical tests were two-sided. RESULTS: In the protocol with UVB-induced tumor initiation, silymarin treatment reduced tumor incidence from 40% to 20% (P = .30), tumor multiplicity by 67% (P = .10), and tumor volume per mouse by 66% (P = .14). In the protocol with UVB-induced tumor promotion, silymarin treatment reduced tumor incidence from 100% to 60% (P<.003), tumor multiplicity by 78% (P<.0001), and tumor volume per mouse by 90% (P<.003). The effect of silymarin was much more profound in the protocol with UVB-induced complete carcinogenesis, where tumor incidence was reduced from 100% to 25% (P<.0001), tumor multiplicity by 92% (P<.0001), and tumor volume per mouse by 97% (P<.0001). In short-term experiments, silymarin application resulted in statistically significant inhibition in UVB-caused sunburn and apoptotic cell formation, skin edema, depletion of catalase activity, and induction of COX and ODC activities and ODC mRNA expression. CONCLUSIONS AND IMPLICATION: Silymarin can provide substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. Clinical testing of its usefulness is warranted.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Paraneoplastic pemphigus: report of a case.

A 56-year-old male with chronic lymphocytic leukemia developed extensive erosive mucocutaneous lesions with histologic acantholysis. Immunopathologic studies showed IgG deposition at the intercellular space, C3 deposition at both the intercellular space and the dermo-epidermal junction, and reactivity of the serum to rat urinary bladder epithelium. Autoantibodies in the serum to human epidermal proteins of 210 kD and 190 kD were shown by Western blotting and to proteins of 250 kD, 210 kD, and 190 kD by immunoprecipitation. All these data suggest the diagnosis of paraneoplastic pemphigus. Repeated plasmapheresis resulted in re-epithelialization of the mucocutaneous lesions and reduction in antibody titer from 1:1280 to 1:20. Although this mucocutaneous disease was established as a new autoimmune bullous disease by Anhalt et al. (1990), cases have rarely been reported from Japan. The present patient demonstrates the major characteristics of paraneoplastic pemphigus.

Autoantibodies↗
PubMed1996

Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

Animals↗
PubMed1996

Stump pemphigoid.

Stump pemphigoid is a localized variant of bullous pemphigoid characterized by specific clinical, pathological, and immunofluorescent characteristics. The early diagnosis of this entity guides treatment toward this specific immunologically mediated inflammatory process and away from treatment of unrelated conditions with similar clinical findings.

Amputation Stumps↗
PubMed1996

Immune-mediated subepithelial blistering diseases of the mucous membranes. Improving the detection of circulating autoantibodies by the use of concentrated serum samples.

BACKGROUND AND DESIGN: Comparison of detection of circulating autoantibodies before and after concentration of serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes. We determine whether the use of concentrated serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes improves diagnostic sensitivity for circulating antibodies. We studied 13 patients from a university-based referral practice who had no skin lesions and a scarring subepithelial blistering disease of the mucous membranes. Three of these patients had detectable circulating autoantibodies and 10 had negative indirect immunofluorescence study results using standard techniques. The main outcome measures after concentration of serum samples were detection of circulating autoantibodies on salt-split skin by indirect immunofluorescence, immunoblotting, and immunoprecipitation. RESULTS: Of the 10 patients in whom circulating autoantibodies had not been detectable with standard techniques, circulating IgG antibodies were detected in 5 (50%) and circulating IgA antibodies in 3 (30%). Of the 3 patients in whom circulating autoantibodies had been detectable with standard techniques, 1 (33%) had circulating IgA antibodies that immunoblotted the 97-kd linear IgA bullous disease antigen only when concentrated serum samples were used. CONCLUSIONS: The use of concentrated serum samples can improve our ability to detect the presence and antigenic specificity of circulating autoantibodies in patients with suspected but unclassifiable immune-mediated subepithelial blistering diseases of the mucous membranes.

Autoantibodies↗
PubMed1995

Inhibition of 12-O-tetradecanoylphorbol-13-acetate and other skin tumor-promoter-caused induction of epidermal interleukin-1 alpha mRNA and protein expression in SENCAR mice by green tea polyphenols.

Recent studies have shown that topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to murine skin results in increased expression of the highly inflammatory cytokine interleukin (IL)-1 alpha in the epidermis. This has led to the suggestion that IL-1 alpha directly or indirectly mediates the inflammatory and hyperplastic responses elicited by TPA and possibly by other skin tumor promoters. In the current study, we investigated the effect of skin application of a polyphenolic fraction isolated from green tea (GTP) to SENCAR mice on skin tumor-promoter-caused induction of cutaneous edema and hyperplasia, and IL-1 alpha mRNA expression. Pretreatment of the skin with GTP 30 min before that of anthralin, benzoyl peroxide, mezerein, and TPA resulted in a significant (p < 0.05) inhibition of cutaneous edema and epidermal hyperplasia caused by each of these tumor promoters. Northern blot analysis indicated that topical application of TPA, anthralin, mezerein, or benzoyl peroxide to SENCAR mice resulted in an increased expression of epidermal IL-1 alpha mRNA. Pretreatment of the skin with GTP or individual epicatechin derivatives (ECDs) present therein, 30 min before that of TPA, resulted in a significant inhibition of enhanced expression of epidermal IL-1 alpha mRNA caused by skin application of TPA. These inhibitory effects were found to be dependent on the dose of GTP. Among four epicatechin derivatives present in GTP, (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate were more effective than (-)-epigallocatechin and (-)-epicatechin in affording this inhibition. Preapplication of GTP was also found to afford inhibition against anthralin-, benzoyl peroxide-, and mezerein-caused increased expression of epidermal IL-1 alpha mRNA and protein. Our study suggests that the inhibition of tumor-promoter-induced IL-1 alpha mRNA and protein expression in mouse epidermis by green tea in combination with other inhibitory effects may be responsible for the anti-tumor-promoting and anti-inflammatory effects of GTP.

Animals↗
PubMed1995

In situ-bound antibodies eluted from the skin of patients with bullous pemphigoid are preferentially directed against the 230-kD bullous pemphigoid antigen.

Two bullous pemphigoid antigens (BPAs) have been identified: a 230-kD intracellular hemidesmosome-associated molecule and a 180-kD transmembrane hemidesmosome-associated molecule. Although patients with bullous pemphigoid (BP) have been shown to have circulating antibodies directed against one or both BPAs, the antigenic specificity of tissue-bound BP autoantibodies has not been studied. Because these skin-bound antibodies may play an important role in disease initiation, we sought to determine their antigenic specificity. In situ-bound BP antibodies were eluted with glycine from salt-split perilesional skin biopsy specimens and subjected to immunoprecipitation. Ten of 13 patients had glycine-eluted antibodies that recognized the 230-kD BPA, whereas four of 13 patients had glycine-eluted antibodies that recognized the 180-kD BPA. When these glycine-eluted BP skin specimens were sequentially eluted with urea, we found either antibodies of the same specificity or loss of reactivity to one of the BPAs, but no reactivity to any BPAs previously undetected with glycine elution. Sequential elution with sodium dodecylsulfate revealed no detectable BP antibodies. The heavy- and light-chain isotypes of the circulating, tissue-bound, and eluted BP antibodies were very similar, suggesting that we are not eluting certain subsets of BP antibodies. Sera from these patients contained circulating antibodies that recognized either one or both BPAs. Our observations demonstrate that in situ-bound antibodies eluted from the skin of patients with BP are preferentially directed against the 230-kD BPA.

Aged↗
PubMed1995

Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis.

We investigated the antigen molecules for six clinically typical cases of paraneoplastic pemphigus (PNP) using immunofluorescence, immunoprecipitation, and immunoblotting. All the PNP sera showed a clear reactivity with transitional epithelia of rat urinary bladder and immunoprecipitated the 250-kD, 230-kD, 210-kD, 190-kD, and 170-kD proteins in various combinations, confirming the diagnosis of PNP. Immunoblot analysis demonstrated slightly different reactivity from that of immunoprecipitation. With immunoblotting of normal human epidermal extract, bovine desmosome preparation, and extract of cultured squamous cell carcinoma cells, all the PNP sera reacted with a characteristic doublet of the 210-kD and 190-kD proteins. However, immunoblotting detected the 250-kD desmoplakin I and the 230-kD bullous pemphigoid antigen less frequently and did not detect the 170-kD protein. Further immunoblot studies indicated that the 210-kD protein is different from desmoplakin II and that the 190-kD protein is most frequently detected by PNP sera. Two of the six PNP sera specifically reacted with the extracellular domain of recombinant pemphigus vulgaris antigen protein, indicating that pemphigus vulgaris antigen may be involved in PNP. In future studies to unravel the complex mechanisms of the PNP antigens, the immunoblot technique may be a useful tool.

Autoantigens↗
PubMed1995

Erythrodermic bullous pemphigoid is a clinical variant of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin. Several variants of BP have been described but until recently the relationship of these variants to generalized BP was unclear. Several studies have shown that pemphigoid nodularis, pemphigoid vegetans, localized BP and vesicular pemphigoid are true variants of BP as the circulating antibodies in these patients recognize the same 230 kDa BP antigen as found in patients with generalized BP. Erythrodermic BP is a very unusual variant characterized by an erythroderma along with blister formation. We describe the third known patient to develop erythrodermic BP and characterize the antigenic specificity of the circulating antibodies in both our newly reported patient with erythrodermic BP and in one of the two other previously reported cases of erythrodermic BP. Both patients with erythrodermic BP had circulating IgG antibodies which bound to the epidermal side of salt-split human skin in a pattern identical to two patients with immunopathologically proven generalized BP. Sera from four erythrodermic patients without blisters and from a healthy normal volunteer, as controls, failed to demonstrate detectable circulating IgF autoantibodies. Immunoprecipitation studies revealed that both patients with erythrodermic BP had circulating IgG autoantibodies which recognized, to varying degrees, the same 230 and 180 kDa BP antigens as recognized by sera from two patients with immunopathologically proven generalized BP. Sera from four erythrodermic patients without blisters and from a healthy normal volunteer, as controls, failed to recognize any specific polypeptides. These observations demonstrate that erythrodermic BP is a distinct clinical variant of BP.

Aged↗
PubMed1995

Paraneoplastic pemphigus: the first case report from Japan.

Paraneoplastic pemphigus is a rare skin disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. A 54-year-old Japanese man, who had received chemotherapy and radiation therapy due to a diagnosis of non-Hodgkin's lymphoma, developed marked stomatitis, conjunctivitis and blisters. Histologic examination showed suprabasal cleft formation with acantholysis and keratinocyte necrosis. Direct immunofluorescence revealed the deposition of IgG at the cell surface of the keratinocytes and C3 at the basement membrane zone. Indirect immunofluorescence on normal human skin and rat bladder sections revealed circulating autoantibodies to the cell surface of both keratinocytes and transitional epithelia. Immunoprecipitation disclosed antibodies reactive to the 250-kD, 230-kD, 210-kD and 170-kD proteins. From these results, a diagnosis of paraneoplastic pemphigus was made. This is the first report of paraneoplastic pemphigus from Japan.

Animals↗
PubMed1994

Hypocomplementemic urticarial vasculitis syndrome in identical twins.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a syndrome of recurrent urticarial vasculitis, arthralgia/arthritis, and hypocomplementemia. Angioedema, ocular inflammation, glomerulonephritis, and obstructive lung disease are other clinical findings. Although the etiology of HUVS is unknown, its resemblance to systemic lupus erythematosus (SLE) suggests a similar pathogenesis. SLE is known to occur in identical twins. This is the first report of a pair of identical twins with HUVS. Concordance for HUVS in identical twins suggests that the pathogenesis of the disease involves abnormal genetic immunoregulation.

Adult↗
PubMed1993

Erythema annulare-like acantholytic dermatosis (EAAD): nonbullous pemphigus or a new entity?

This article describes a case of unusual annular erythema-like dermatosis, with histological features of pemphigus foliaceus (subcorneal acantholysis) and IgG antibodies in circulation and bound in vivo to the keratinocyte surface. The reactivity of the antibodies, restricted to human squamous epithelium, was unique, differing from that of all known forms of pemphigus. This also was confirmed by immunoprecipitation. The problem is that these circulating antibodies could be missed if not determined on human substrate. It is to be established whether such cases present a new type of pemphigus or a unknown dermatosis with an autoimmune response of a pemphigus type.

Acantholysis↗
PubMed1993

Basal cell carcinomas display extensive abnormalities in the hemidesmosome anchoring fibril complex.

We have employed a panel of antibodies directed against several newly-defined and well-characterized components of the epidermal basement membrane (BM) to investigate the biology of basal cell carcinoma (BCC) by indirect immunofluorescence and to determine whether alterations in BM components may play a significant role in BCC tumor invasion. We found that the 230 KD bullous pemphigoid antigen (BPA) was either not detected (13/16) or significantly diminished (3/16) in BCC tumor BM. While the 180 KD BPA revealed less intense staining of the normal overlying epidermal BM than did the 230 KD BPA, the 180 KD BPA was uniformly undetectable in BCC tumor BM (16/16). Epiligrin was either not detected (9/15) or minimally detected (6/15) in BCC tumor BM. alpha 6 integrin was not detected (15/16) or minimally detected (1/16) in BCC tumor BM, whereas beta 4 integrin was uniformly undetectable in BCC tumor BM (16/16). Type VII collagen was also not detected (9/16) or was significantly diminished (4/16) in BCC tumor BM. Laminin and type IV collagen were both at least as strong in BCC tumor BM as in adjacent normal BM. All of these components were present both in the epidermis of normal skin as well as in the normal epidermal BM overlying BCC tumor nests. Our findings reveal extensive alterations in numerous components of the hemidesmosome anchoring fibril complex of BCC's. As this complex is thought to play an important part in epidermal cell adhesion to the BM, our findings suggest that these extensive BM abnormalities may facilitate or contribute to BCC tumor invasion.

Actin Cytoskeleton↗
PubMed1993

Exuberant conjunctival pseudopolyposis in a patient with dermatomyositis.

Dermatomyositis is a disease of unknown cause, characterized by a diffuse inflammatory myopathy and skin changes consisting of heliotrope eruption, Gottron's papules, periungual telangiectasia with dystrophic cuticles, skin telangiectasia, and atrophy. Ocular involvement may consist of conjunctival edema, nystagmus, extraocular muscle imbalance (when associated with myasthenia gravis), iritis, cotton-wool spots, and optic atrophy. Conjunctival avascularity and membranous conjunctivitis also have been reported. We describe an unusual conjunctival finding with secondary corneal surface disturbances in a patient with dermatomyositis.

Basement Membrane↗
PubMed1993

Bullous pemphigoid.

Bullous pemphigoid is an acquired subepidermal blistering disease of the elderly characterized by tense blisters. Patients with bullous pemphigoid have circulating and tissue-bound antibodies that are directed against a normal component of the epidermal basement membrane. The course of bullous pemphigoid tends to be self-limited, and effective treatment is often affected with systemic glucocorticosteroids.

Diagnosis, Differential↗