Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease first named by Anhalt, et al. in 1990. The disease is characterized by such distinctive clinical symptoms and signs as severe, painful mucosal erosions, polymorphous skin lesions, histopathology hallmarks, and immunological findings. The situation typically presents in patients with lymphoproliferative diseases and primarily malignancies. A main challenge of the study is the relationship between the existence of associated tumors and the autoimmune reaction to the skin. Some researchers suspected that the possible expression of foreign antigens on the tumor can cross react with epidermal antigens inducing the auto-reactive clones of T-lymphocytes. Some speculated that the type of tumors associated with PNP may produce plakin proteins that result in initiation of the immune response. Other reports believed the autoimmune reaction is related to the epitope spreading or to the changing of cytokines. We analyzed 12 PNP patients diagnosed in our department in the past few years. An intensive study to the B cells in the PNP associated with tumors demonstrated that the tumors have structural basis to produce antibody. The similar immunoglobulin heavy chain genes of tumor B-cells in 7 patients strongly suggested that the B cell clones were functional and recognized the same antigen epitope. The autoantibodies secreted by the tumor can react against specific plakin proteins in epidermis, lead to the impairment of cell-cell adhesion, and cause the mucocutanous lesions. The clinical significance of the results indicates the importances of early finding and total resection of the associated tumors, and the usage of IVIG pre or during operation to prevent Bronchitis Obliterans. The new finding is also important for the study of other antibody mediated autoimmune diseases.

Intracellular calcium is one of the crucial signalings that modulate various physiological and pathological processes.Abnormal calcium signaling is closely associated with invasion and migration of neoplasms.Calcium regulates focal adhesion turnover,cytoskeletal reorganization and other processes about tumor cell movement through contacting with multiple downstream proteins,such as calpain,PYK2 and S100 protein family.Several calcium entry channels including store-operated calcium channels and transient receptor potential channels participate in the invasion and migration of tumor cells.Pathological calcium signaling may be a potential target in anti-invasion and anti-migration therapy.

Objective To identify gene mutations of two cases of epidermolytic hyperkeratosis ichthyosis.Methods Punch biopsies were taken from typical lesions for histopathological examination by light microscopy and transmission electron microscopy.Genomic DNA was extracted from blood samples.Mutations of keratin1(K1)and keratin10(K10)were detected by polymerase chain reaction(PCR)and DNA sequencing;Frequencies of the alleles were screened by PCR-based allele-specific assays(PASA)and restriction fragment-length polymorphism(RFLP)in normal controls.Results There was a single heterozygous point mutation in either K1or K10genes,i.e.2140G→A of K10gene and4226G→A of K1gene,leading to an amino acid alteration of arginine to histidine(K10R156H)and glutamic acid to lysine(K1E477K),respectively.These substitutions were not found in normal controls.Conclusion K10R156H and K1E477K mutations were the cause of the phenotypes in these two cases.

Objective To report the first case of ectodermal dysplasia/skin fragility syndrome in China. Methods The clinical data, transmission electron microscopic examination and immunohistochemical analysis of this patient were evaluated. Results The patient was a 3-year-old girl who presented increased skin fragility with trauma-induced, blisters and erosions, combined with short and sparse hair, finger-and toe-nail dystrophy and palmoplantar keratoderma. Transmission electron microscopy showed a loss of keratinocyte-keratinocyte adhesion, widening of intercellular spaces and a reduced number of hypoplastic desmosomes. Immunohistochemical analysis revealed a complete absence of staining for plakophilin 1. Conclusion Ectodermal dysplasia/skin fragility syndrome is a rare autosomal recessive inherited disease characterized by clinical manifestations as well as electron microscopic features and immunohistochemical evidence.

Bullous pemphigoid antibodies can recognize two autoantigens-BPAG1 (220 000-240 000 ) and BPAG2 (160 000 -180 000). With two specific primers, we successfully amplified a 588bp cDNA fragment of 160 000 BP antigen from human keratinocyte cDNA library in this paper. The result confirmed that lip antigens were synthesized by keratinocyte at a molecular level. This cDNA fragment could not be amplified with epidermal DNA Templets. We suggest that BP antigen gene may be separated by some introns. We will prepare cDNA probes and recombinant antigens using PCR product in order to elicit autoimmunity mechanism of BP.

The purpose of this study is to ascertain the significance of diagnosis of human papillomavirus (HPV) infection and the histological pattern of distriution of HPV in condylomata acuminata(CA) by direct in situ PCR (ISPCR) technique. of the 25 patients with BA, all 10 cases with typical histopathological features of CA gave a positive reaction in tile upper layers of the epithelium. HPV was also detected in the granular ladyer and whole prickle cell layer of 11 cases of CA with no typical koilocytes. In the direct ISPCR oligonucleotides labelled with bio tin were incorporated in situ during amplification, then immunohistochemical method was used for detection. In this technique the viral existence in paraffin sections can be directly compared with the histologic changes, and can help pathologist to analyze the possibility that HPV is present in the suspected lesions.

Objective To report a pedigree of generalized atrophic benign epidermolysis bullosa (GABEB),a special type of junctional epidermolysis bullosa(JEB). This is the first case report in China. Methods The clinical, histologic, electron microscopic, and immunofluorescence changes of the disease were evaluated. Results Besides the symptom of inherited epidermolysis bullosa, the patient had special clinical manifestations such as atrophic alopecia and dental dysplasia. The disease was inherited in an autosomal recessive mode in this pedigree. Electron－ microscopy found the fissure in lamina lucida, accompaning with dysplasia and sparse hemidesmosome. Immunofluorescence study did not show BPAg2 in the basement membrane zone, indicating that mutation in the gene encoding BPAg2 leading to the disease in this family. Conclusions The case is diagnosed as GABEB, a special type of JEB. Although GABEB has its characteristic, clinical manifestations, electron microscopy and immunofluorescence study are important for confirmative diagnosis and classification, and will guide the study of mutation detection.

0.05).The correlation was WBCr=0.98(P

In order to study the relationship of keratin 5 gene and Weber-Cockayne epidermolysis bullosa simplex (WC-EBS), we use polymerase chain reaction (PCR) amplification combined with single strand conformation polymorphism (SSCP) methods and DNA sequenceing to detect the point mutation of keratin 5 in a family of WC-EBS. The results showed that there is a G→T substitution at the third base pair of codon 327, which caused methionine changed into isoleucine. This abnormality of keratin structure makes the normal assembly of tonofilaments impossible. Furthermore, the above change resulted in blister formation and epidermolysis clinically. This indicates that PCR-SSCP is useful for the gene and prenatal diagnosis of genodermatoses and also provides the basis of theroies for gene therapy.

Objective To identify the gene mutations and mu tating patterns in a pedigree with X-linked anhidrotic ectodermal dysplasia(EDA)so as to provide a basis for gene diagn osis and genetic counselling of this disorder.Methods Polymerase chain reaction-single s trand conformation polymorphism(PCR-SSCP)analysis and DNA sequencing of amplified prod ucts were performed to screen mutati ons and mutating patterns of EDA1gen e,responsible for EDA pathogenesis,i n a X-linked EDA family of Han people.Results Abnormal single strand bands were found in the amplified fra gments as well of exon 1of EDAgene in t he patients as well as their mothers,the carriers.The DNAsequencing of ampl ified products revealed a point muta tion at nucleotide 404(C→Gtransversion)in the proband compared with that of t he normal controls,which resulted i n the transversion of histidine with glutamine at codon 54in the ectodysplasin-A(H54Q).Meanwhile there were heterozyous double peaks of nucleotide Cand Gat the same position in his mother.Conclusion A missense mutation(404C→G)in exon 1of EDA1gene has been determined in the pedigree with X-linked EDA,which is probably one of the molecular bases of EDA pathogenesis.