外阴硬化性苔癣组织P53、PCNA表达、DNA含量及与细胞增殖的关系

探讨外阴硬化性苔癣组织中的 P5 3、PCNA表达 ,DNA含量与细胞增殖的关系。免疫组化方法测定 2 0例外阴硬化性苔癣组织和 10例正常外阴皮肤中 P5 3、 PCNA蛋白表达 ;图像分析技术检测两组基底层细胞核形态及 DNA含量。结果显示 ,外阴硬化苔癣组 P5 3阳性表达率为 40 % ,与正常皮肤比较 P<0 .0 5 ,PCNA阳性表达率为 70 % ,与正常皮肤比较 P>0 .0 5 ,阳性表达主要分布于棘层、颗粒层 ;基底细胞核显著变小和 DNA含量降低 (P<0 .0 5 )。结果表明外阴硬化性苔癣组织中存在细胞增殖异常     

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus

Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1 and IL-1, and therefore is a powerful endogenous anti-inflammatory molecule. The gene encoding IL-1ra (designated IL-1RN) has a variable number tandem repeat polymorphism in intron 2. There are five alleles of the gene corresponding to 2, 3, 4, 5 and 6 repeats of an 86-bp sequence. We have determined allele frequencies in a control population and a group of 78 patients with lichen sclerosus. The frequency of one of the alleles is related to increasing disease severity. Thus, IL-1RN may be a candidate gene or severity factor for lichen sclerosus or may possibly be a linked marker to another, as yet undefined, gene.     

Unexplained hepatitis following halothane.

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.     

Risk for Coexistent Autoimmune Diseases in Familial and Sporadic Type 1 Diabetes is Related to Age at Diabetes Onset

ObjectiveType 1 diabetes (T1D) is frequently associated with other autoimmune diseases (AIDs). Although most of T1D patients are sporadic cases (S-T1D), 10% to 15% have a familial form (F-T1D) involving 2 or more first-degree relatives. This study evaluated the effect of T1D family aggregation and age onset on AIDs occurrence.MethodsIn this observational, cross-sectional, case-control, single center study, we enrolled 115 F-T1D and 115 S-T1D patients matched for gender, age, T1D age onset, and duration. With respect to T1D age onset (before or after 18 years), both groups were further subdivided into young- or adult-onset F-T1D and young- or adult-onset S-T1D. The presence of organ-specific antibodies and/or overt AIDs was evaluated.ResultsThe F-T1D group had a higher percentage of AIDs (29.8% vs 18.4%, P = .04) and a significant earlier onset of AIDs at Cox regression analysis (P = .04) than the S-T1D group. Based on multivariate analysis, the adult-onset F-T1D subgroup had the highest prevalence of both additional organ-specific antibodies (60.5%) and overt AIDs (34.9%), whereas the adult S-T1D subgroup was the least frequently involved (29.1% and 12.7%, respectively). In F-T1D patients, offsprings develop T1D and AIDs earlier than their parents do.ConclusionsIn T1D patients, familial aggregation and adult-onset of T1D increase the risk for coexistent AIDs. These clinical predictors could guide clinicians to address T1D patients for the screening of T1D-related AIDs.     

Affections dermatologiques de la muqueuse genitale masculine et de la verge

A wide variety of infectious, inflammatory or dysplasic disorders may affect both male genital skin and mucous membranes. We review here the clinical patterns or the most common disorders. The diagnosis is based upon the existence of erythematous balanitis, erosions or ulcerations. Among infections, candidiosis, genital herpes, HPV papillomas are the most common. Most of inflammatory skin disorders may affect the male organ, especially psoriasis, lichen planus or erosive lichen planus, allergic dermatitis, auto-immune bullous dermatoses, drug-reactions. Chronic balanitis, or recurrent inflammatory balanitis, lichen sclerosus may lead to the emergence of intraepithelial neoplasias (PIN) or invasive carcinomas. The management of genital lesions needs in fact: the observation or oral mucous membrances and of the skin it-self with a special attention to very peculiar body sites for the presence of typical skin disease lesions; a surgical biopsy for microscopic observation; in some cases immunopathology with direct and indirect immunofluorescence for the diagnosis of auto-immune disorders.     

Long spacing collagen in dermal disorders

Electron microscopic studies of biopsy material from the vulva of six patients with lichen sclerosus et atrophicus and two patients with condyloma latum, and from the skin of the back and shoulder of one patient with scleromyxoedema and the forearm of one patient with macular amyloidosis revealed the presence of long spacing collagen (LSC) of one patient with macular amyloidosis revealed the presence of long spacing collagen (LSC) intermingled with an increased amount of ground substance and extracellular microfibrils. The presence of LSC in condyloma latum is believed not to have been reported previously. The LSC displayed an axial periodicity varying from 1000 to 2000 A. Our studies support the contention that the appearance of LSC is not specific of any disorder, and the formation of LSC is associated with the presence of increased amounts of glycosaminoglycan-rich ground substance and the abundance of microfilaments in the extracellular space.     

Lichen planus and liver diseases: a multicentre case-control study. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED).

OBJECTIVE--To assess the association of lichen planus with liver complaints and with known aetiological factors of liver diseases. DESIGN--Multicentre case-control study. Interviews were conducted by trained medical investigators on the basis of a structured questionnaire. At the interview patients and controls were asked for consent to blood samples being taken to determine transaminase activities and the presence of hepatitis B virus surface antigen. SETTING--Outpatient departments of 27 Italian general and teaching hospitals that were collaborating in the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). SUBJECTS--Incident cases and controls were eligible. A total of 577 patients with lichen planus and 1031 controls with dermatological diseases other than lichen planus were interviewed. Less than 1% of the people contacted refused to participate. Patients and controls were matched for sex and age in five year intervals. RESULTS--The risk of lichen planus was higher in patients with a history of liver diseases requiring hospital admission or specialist consultation (relative risk = 1.6; 95% confidence interval = 1.2 to 2.2), those who had had liver biopsy (5.5; 1.9 to 15.6), and those with a history of viral hepatitis (1.9; 1.1 to 3.1). High activities of liver enzymes and positive results of tests for hepatitis B virus surface antigen were also associated with lichen planus. The association with alcohol consumption was not clearly confirmed by a dose-risk relation. CONCLUSION--This study adds quantitative epidemiological evidence to the clinical observation that liver disease is a risk factor for lichen planus although not a specific marker of it.     

Surgical treatment of balanitis xerotica obliterans

Balanitis xerotica obliterans, or kraurosis penis, is a chronic progressive scleroatrophic process of the penis, prepuce, and urethral meatus. This syndrome is due to lichen sclerosus et atrophicus of the genital region. We have observed 32 patients, whose ages ranged from 24 to 78, with different clinical and pathologic findings. Clinical symptomatology consisted of painful erection with secondary impotence, burning, itching, and urinary disorders. The treatment in the early stages is pharmacologic; stenosis of the meatus, phimosis, scar adhesions, fissures, and erosions of glans and prepuce prescribe a surgical treatment. We have performed modified circumcision, meatotomy and meatoplasty, removal of the scleroatrophic tract and subsequent grafting. The functional results were satisfactory.     

Evidence that type I diabetes and thyrogastric autoimmunity have different genetic determinants.

The prevalences of autoimmune endocrine disease and relevant organ-specific autoantibodies were determined in 141 patients with type I (insulin-dependent) diabetes and their families. All available members of the families were genotyped for HLA. Islet-cell antibody was found in 10 (4%) out of 248 unaffected siblings, all of whom were genetically potential cases of diabetes. One developed classical symptoms six months later. In contrast, thyroid and gastric parietal-cell antibodies occurred independent of the HLA-linked susceptibility to diabetes. These results suggest that different genes control the production of these autoantibodies and the susceptibility to type I diabetes.     

Autoimmunity in juvenile diabetics and their families.

Pancreatic islet cell, thyroid, and gastric antibodies were studied in 116 young insulin-dependent diabetics and 257 relatives. Seventy-four per cent of the diabetics studied within three months of diagnosis had islet-cell antibodies but only 20% of those studied three years or more after diagnosis. Persistence of these antibodies was associated with a high prevalence of thyrogastric autoimmunity, which suggests that some cases have an aetiology similar to that of "polyendocrine" autoimmune disease. Retinopathy or nephropathy, or both, was present in 10 diabetics, who were all members of "autoimmune" families, in which one or more members had organ-specific antibodies. Nine of the 10 healthy relatives with islet-cell antibodies and all families with more than one diabetic were also in this autoimmune group. These data suggest that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications.     

Organ-specific autoantibodies in children with Helicobacter pylori infection

BACKGROUND: We compared the prevalence of organ-specific autoantibodies in a group of Helicobacter pylori infected children and a group of uninfected children and investigated the relationship between the presence of relevant autoantibodies and the status of the target organs. PATIENTS AND METHODS: One hundred and twenty-four children with dyspepsia (54 boys, 70 girls; mean age 10.5 years; range 4-19) underwent gastroscopy: 56 had H. pylori infection (31 girls, 25 boys), while 68 (37 girls and 31 boys), were H. pylori-negative. All sera were tested for the presence of: parietal cell autoantibodies (PCA), intrinsic factor autoantibodies (IFA), microsomial autoantibodies, thyroglobulin autoantibodies, islet cell autoantibodies, glutamic acid decarboxylase autoantibodies, adrenal cortex autoantibodies, steroid-producing cell autoantibodies; gastrin, pepsinogen A, pepsinogen C and anti-H. pylori antibodies. The histological features and the ureA and cagA genes were also considered. RESULTS: The frequency of organ-specific autoantibodies was higher in patients with H. pylori infection than in uninfected patients (chi2-test p < .0001). Specifically gastric autoantibodies were significantly higher: seven of the 56 H. pylori-positive children were PCA-positive and one was IFA-positive (chi2-test p = .0004). The presence of autoantibodies was not associated with any clinical or biohumoral signs of disease. CONCLUSIONS: Our study detected a relationship between H. pylori infection in childhood and the presence of organ-specific autoantibodies unassociated with any clinical or biohumoral signs of disease. Helicobacter pylori infection in childhood could trigger the onset of clinical autoimmune gastritis, and/or other clinical autoimmune diseases.     

Klebsiella pneumoniae secreted protein-containing antigens in the system of adaptive immunity

The study was aimed at the evaluation of the antigenic properties of K. pneumoniae secreted protein-containing antigens with a molecular weightt of 21 and 34-35 kD, obtained from supernatant culture fluid. As confirmed by the method of flow cytofluorimetry, the protein-containing fractions belonged to the secreted components of the microbial cell. The fraction with a molecular weight of 34-35 kD possessed high antigenic activity and contributed to the formation of specific antibodies after the immunization of mice. At the same time none of the protein fractions lead to an increase in the level of autoantibodies in mouse blood sera to organ-unspecific and organ-specific antigens. As revealed by the method of solid-phase, in 6 (27.3%) from 22 patients of patients with rhizomelic spondylitis had an increased level of IgG to K. pneumoniae cell-wall antigens with a molecular weight of 34-35 kD. An increase in the level of IgG to the secreted protein-containing fraction with a molecular weight of 34-35 kD was detected only in one patient (4.5%) (p<0.05).     

Association of HLA-te22 antigen with anti-nuclear antibodies in Chinese patients with erosive oral lichen planus

The purpose of this study was to determine the frequencies of the presence of serum anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) in 76 patients with oral lichen planus (OLP), in 77 patients with other oral mucosal diseases, and in 41 healthy control subjects. HLA phenotypes in some of the patients with OLP and recurrent aphthous ulcers (RAU) were determined to show whether there was an association of HLA antigens with the presence of autoantibodies. Indirect immunofluorescence techniques with mouse liver or stomach as the substrate were used to detect the serum ANA or SMA, respectively. The B lymphocytes isolated from peripheral blood were used for HLA typing by means of a standard microcytotoxicity assay. We found that the positive rate of serum ANA in patients with OLP (29%, p < 0.01), especially in patients with erosive OLP (34%, p < 0.001), was significantly higher than that in the normal control subjects (5%). The frequency of serum SMA in patients with OLP (20%, p < 0.01), in patients with RAU (17%, p < 0.01), or in patients with oral squamous cell carcinomas (41%, p < 0.001) was also significantly higher than that in normal control individuals (0%). In the erosive OLP group, the HLA-Te22 antigen occurred more frequently in patients with positive ANA (75%, p < 0.05) than in those with negative ANA (25%). We conclude that there is an association of HLA-Te22 antigen with ANA in Chinese patients with erosive OLP.     

Islet cell antibodies and other autoantibodies in South African blacks and indians with insulin dependent diabetes mellitus (IDDM)

The presence or absence of islet cell antibodies and other autoantibodies was determined in 47 African and 34 Indian patients with IDDM and 37 controls. Islet cell antibodies (ICA-IgG) were found in over a third of the patients and in only 2 controls. Complement fixing antibodies (ICA-Cf) were found in 10% of patients, but in none of the controls. Persistence of ICA beyond 3 years was more frequent in Black compared to Indian patients. Parietal cell antibodies were found more often in patients (20%) than controls (5%) as were thyroid microsomal antibodies (11% vs. 0%). None of the patients or controls had adrenal antibodies.     

Detection of serum antibodies to Bartonella henselae and Coxiella burnetii from Japanese children and pregnant women

The participation of Bartonella henselae and Coxiella burnetii in the pathogenesis of fever of unknown origin (FUO) and lymphadenopathy has not been completely clarified. Prevalence of these two agents in Japanese children is also unknown. Serum IgG and IgM antibodies to B. henselae and to C. burnetii were examined by the indirect fluorescence antibody assay. Enzyme immunoassay kits were used to detect serum IgG and IgA antibodies against Chlamydia trachomatis. Out of 200 healthy normal pregnant women, two (1.0%) had serum IgG antibodies to B. henselae, four (2.0%) to C. burnetii and 49 (24.5%) to C. trachomatis. Out of 29 patients with FUO, one (3.4%) had serum IgG antibodies to B. henselae, four (13.8%) to C. burnetii and none to C. trachomatis. Out of 31 patients with cervical lymphadenopathy, three (9.6%) had serum IgG antibodies to B. henselae, two (6.5%) to C. burnetii and none to C. trachomatis. Out of 22 patients with generalized lymphadenopathy, one (4.5%) had serum IgG antibodies to B. henselae, three (13.6%) to C. burnetii and none to C. trachomatis. Prevalences of serum antibodies to C. burnetii in the patients with FUO and generalized lymphadenopathy and to B. henselae in the patients with cervical lymphadenopathy were significantly higher than those of normal pregnant women (Welch's t-test; P<0.01). These two agents may have some roles in the pathogenesis of FUO and lymphadenopathy in Japanese children.     

Australian Antigen and Autoantibodies in Chronic Hepatitis

The sera of 110 patients with chronic hepatitis and adequate controls were examined for antibodies to smooth muscle (S.M.), mitochondria (M.), and for antinuclear factors by the immunofluorescence method, and for Australia (Au(1)) antigen by a modified micro-Ouchterlony immunodiffusion technique. Twelve out of 13 patients with primary biliary cirrhosis had M. antibodies, two had antinuclear factor, and none had Au(1) in their sera. In chronic aggressive hepatitis 23·5% of the sera contained antinuclear factor, 13% S.M. antibodies, 10·5% M. antibodies, and 22% Au(1) antigen. Of the 12 patients with chronic persistent hepatitis, one had antinuclear factor, one S.M. antibodies, and three Au(1) antigen.The most striking finding was a mutual exclusion between Au(1) antigen and M. and S.M. antibodies. None of the 33 patients with one or the other form of chronic hepatitis and M. or S.M. antibodies had Au(1) antigen; 22 out of 77 (28%) patients without such antibodies were positive.     

Richness of Lichen Species,Especially of Threatened Ones,Is Promoted by Management Methods Furthering Stand Continuity

Lichens are a key component of forest biodiversity. However, a comprehensive study analyzing lichen species richness in relation to several management types, extending over different regions and forest stages and including information on site conditions is missing for temperate European forests. In three German regions (Schwäbische Alb, Hainich-Dün, Schorfheide-Chorin), the so-called Biodiversity Exploratories, we studied lichen species richness in 631 forest plots of 400 m² comprising different management types (unmanaged, selection cutting, deciduous and coniferous age-class forests resulting from clear cutting or shelterwood logging), various stand ages, and site conditions, typical for large parts of temperate Europe. We analyzed how lichen species richness responds to management and habitat variables (standing biomass, cover of deadwood, cover of rocks). We found strong regional differences with highest lichen species richness in the Schwäbische Alb, probably driven by regional differences in former air pollution, and in precipitation and habitat variables. Overall, unmanaged forests harbored 22% more threatened lichen species than managed age-class forests. In general, total, corticolous, and threatened lichen species richness did not differ among management types of deciduous forests. However, in the Schwäbische-Alb region, deciduous forests had 61% more lichen species than coniferous forests and they had 279% more threatened and 76% more corticolous lichen species. Old deciduous age classes were richer in corticolous lichen species than young ones, while old coniferous age-classes were poorer than young ones. Overall, our findings highlight the importance of stand continuity for conservation. To increase total and threatened lichen species richness we suggest (1) conserving unmanaged forests, (2) promoting silvicultural methods assuring stand continuity, (3) conserving old trees in managed forests, (4) promoting stands of native deciduous tree species instead of coniferous plantations, and (5) increasing the amount of deadwood in forests.     

Candida biotypes in patients with oral leukoplakia and lichen planus

Prevalence of yeasts in 35 leukoplakia and 34 oral lichen planus patients was compared with that observed in persons without oral diseases. Serotype and morphotype were determined on Candida albicans isolates. Yeasts were isolated from the oral cavity specimens of 43.7% of the patients. C. albicans (serotype A) was the predominant species (76% in leukoplakia, 88.2% in lichen planus and 60.8% in healthy persons). Sixteen morphotypes were encountered on malt extract agar, being 732, 733, 734, 753 and 754 the most frequently found. Morphotypes SP1N and SP1Y were the most common on Sabouraud-trypheniltetrazolium agar (68.4% of the isolates from leukoplakia and 73.3% from lichen planus, but only 46.6% of the isolates from healthy oral mucosa showed SP1N morphotype). Presence of oral lesions was associated with a marked reduction in the yeast species and C. albicans biotypes, suggesting that C. albicans and particularly some of its biotypes, show a high potential of adaptation to the changes associated with the development of oral leukoplakia and lichen planus.     

Circulating anti-p53 antibodies in lung cancer and relationship to histology and smoking

Anti-p53 antibodies were examined in the plasma of 112 lung cancer patients by ELISA in order to study the distributions in lung cancer patients and the determinants of these antibodies in relation to lung cancer. Twenty (17.9 %) lung cancer patients were found to have anti-p53 antibodies. The distribution of the antibodies by histological type was 7/48 (14.6 %) adenocarcinoma, 8/32 (25.0 %) squamous cell carcinoma, 3/7 (42.9 %) small cell lung cancer, 0/4 large cell carcinoma, 0/8 adenosquamous cell carcinoma and 2/13 (15.4 %) other types. By ethnicity, 8/44 (18.2 %) Caucasians, 4/20 (20.0 %) Hispanics and 8/48 (16.7 %) African-Americans were positive for anti-p53 antibodies, with no significant differences among the groups (p=0.5137). The antibody positivity rates were higher in lung cancer patients 55 years or older (21.2 %) than in the patients under 55 years (7.4 %). The positive rates of the antibodies were 14.3 % in non-smokers, 16.7 % in ex-smokers and 19.1 % in current smokers, with heavy smokers (41 pack-years) having the highest positive rate (28.6 %), but none of these differences were statistically significant (p > 0.05). Seven controls who had anti-p53 antibodies were all ex-smokers or current smokers and some had occupational exposures. No anti-p53 antibodies were found in 41 non-smoking controls. These results suggest that the development of anti-p53 antibodies in pulmonary carcinogenesis and its association with smoking and other carcinogenic exposures deserve further study.     

Image cytometric evaluation of nuclear texture features and DNA content of the reticular form of oral lichen planus

OBJECTIVE: To analyze image cytometric chromatin changes reflected in nuclear texture features and DNA ploidy of oral lichen planus in relation to the normal buccal mucosa and buccal mucosa expressing malignancy-associated changes in cancer patients. STUDY DESIGN: Twenty-eight patients with the reticular form of oral lichen planus, with a follow-up period of 25 years, 50 healthy controls and 50 lung cancer patients were included in the study. Scrapings of buccal mucosa were suspended in transport medium. Monolayer filter preparations were Feulgen-thionin stained. Image cytometric analysis was performed by Cyto-Savant. RESULTS: All oral lichen planus specimens in our study were diploid. In univariate analysis, differences between the normal buccal mucosa and oral lichen planus were found in several nuclear texture features, which gave an 80% correct classification rate in multivariate analysis. In the second part of the study, the classifier that recognizes malignancy-associated changes on the buccal mucosa of patients with lung cancer correctly recognized > 80% of oral lichen planus samples as normal buccal mucosa. CONCLUSION: Our results indicate that chromatin changes in oral lichen planus exist compared to normal cells; however, the chromatin structure of the reticular form of oral lichen planus does not express malignancy-associated changes and is more similar to normal squamous cells.