Cytogenetic abnormalities in dyskeratosis congenita—report of five cases

Five patients with dyskeratosis congenita arc described. The cytogenetic studies showed varying frequencies of chromosomal abnormalities which included gaps, chromatid breaks and pulverizations, ranging from 4 to 22%. These findings suggest that chromosomal breakage may be of fundamental importance in the etiology of dyskeratosis congenita and it could represent a genetic marker for the disease.     

Sister chromatid exchanges in lymphocytes of psoriatics after treatment with 8-methoxypsoralen and long wave ultraviolet radiation

Sister chromatid exchange rates in cultured cells from the blood of patients receiving photochemotherapy have been examined as an indicator of possible genetic hazards of the treatment to patients with psoriasis. Lymphocytes of untreated patients with psoriasis appear to have sister chromatid exchange rates after 72 h of culture indistinguishable from normal subjects and there is no evidence from these studies that sister chromatid exchanges are significantly increased in the lymphocytes of patients receiving photochemotherapy. Cells from blood taken from patients who had been given 8-methoxypsoralen orally 2 h before and then irradiated with UV-A in vitro were found to have an increased exchange rate which could be related to the presence of the drug in the peripheral circulation.     

寻常性银屑病外周血染色体不稳定性的研究

目的探讨体细胞染色体异常在银屑病发病机制中的作用。方法选取40例寻常性银屑病患者,根据临床资料分为初发组(18例)和经过系统治疗组(22例),并选取16例健康正常人作为对照组。以全血细胞体外培养后制备中期染色体,采用常规细胞遗传学方法染色体G显带行核型分析和姐妹染色单体互换实验,比较初发寻常性银屑病组和经过系统治疗组的差异。结果 40例寻常性银屑病患者及16例健康正常人外周血淋巴细胞中期染色体G显带均未发现异常核型;初发寻常性银屑病患者和经过系统治疗的寻常性银屑病患者外周血淋巴细胞的姐妹染色单体互换频率比正常人明显增加,差异均有统计学意义(P均<0.01);但初发的和经过系统治疗的银屑病患者间的外周血淋巴细胞姐妹染色单体互换频率比较,两者差异无统计学意义(P>0.05)。结论寻常性银屑病患者体细胞染色体存在不稳定性,其外周血淋巴细胞的姐妹染色单体互换频率明显高于正常人。     

Sister chromatid exchange analysis in patients with psoriasis

Abstract:  Psoriasis is a common, chronic inflammatory skin disease with unknown aetiology. An increased reactive oxygen species (ROS) and insufficient antioxidant activity have been determined in psoriatic lesions. The analysis of sister chromatid exchange (SCE) is a cytogenetic technique used to show DNA damage caused by an exchange of DNA fragments between sister chromatids. The study aimed to determine the rates of SCE in psoriatic patients (17 female and 19 male) and healthy controls (15 female and 15 male) as well as superoxide dismutase (SOD), glutathione peroxidase (GP) and catalase (CAT) activity in both groups. We found significantly higher SCE rates in the patients ( P  < 0.00001). In addition, statistically significant decreased levels of erythrocyte SOD and CAT activities were noted in the patients( P  < 0.001 and P  < 0.05 respectively). Furthermore, a statistically significant increased erythrocyte GP activity was found in the psoriasis group ( P  < 0.05). Our results indicate that chromosomal instability may play an important part in the aetiology of psoriasis. In addition, the results support the hypothesis of an imbalance in the oxidant-antioxidant system in psoriasis.     

系统性红斑狼疮的外周血细胞周期动力学与姊妹染色单体互换频率的研究

采用外周血淋巴细胞培养方法对39例系统性红斑狼疮(SLE)患者和22例一级亲属进行淋巴细胞姊妹染色单体互换(SCE)频率和细胞周期动力学(CK)测定,发现SLE患者和亲属的SCE频率明显增高,细胞周期延长,细胞增殖率下降,提示SLE患者存在着淋巴细胞质和量的异常,遗传因素在SLE发病中起重要作用;这种遗传素质的来源不仅存在于亲代亲属之间,而且存在于同胞亲属。     

Periungual capillaroscopic aspects in Beh?et's disease. Apropos of 30 cases

Nailed capillaroscopy was systematically performed in 30 patients with Behcet's disease to search capillary dystrophies with paradoxal normal number of capillary loops; some indirect signs of microvascular disease were noted: pallor of the background; petechiae; sludge; abnormal visibility of the venous plexus and of irregularly arranged venules. Eight patients had a normal capillaroscopy: thirteen had direct signs of microvalvular abnormalities (nine cases with two direct signs and at least two indirect signs; and four cases with two direct and one indirect, or one direct and three indirect signs). Nine patients had only sludge and/or petechiae. We never observed any abnormality in the number of the capillaries, in the sweat droplets nor in the circulatory speed. Two patients had megacapillaries resembling those seen in scleroderma. The petechiae were observed in 50 p. 100 of the cases. We found no correlation between the capillaroscopic abnormalities and the age, sex, duration of the disease, or ethnic background. However, the presence of aphthosis the day of the capillaroscopy seems to be correlated with the cutaneous microvascular abnormalities. Thus, there exist frequent capillaroscopic abnormalities in Behcet's disease. Although aspecific, they point out the vascular tropism of this disease, resembling that of the vascularite. The prognostic importance of the capillaroscopy in Behcet's disease is under study.     

Investigations of chromosomal stability in the Gorlin-Goltz syndrome

Summary Chromosomal studies were carried out on nine patients with the Gorlin-Goltz syndrome using recently developed methods on cultured lymphocytes. In addition, the dermatoglyphics of these patients were examined. No evidence of a characteristic chromosome aberration was found in banded prometaphase-chromosome preparations, nor could increased chromosome breakage be demonstrated in eight of the patients. One proposita showed frequent breaks of Chromosome 1 at p22. Increased chromosome instability in these patients was suggested by higher spontaneous and mitomycin-C-induced sister chromatid exchange rates in patients than in controls. Although the dermatoglyphic findings cannot be regarded as specific for the Gorlin-Goltz syndrome, an increased occurrence of whorl patterns and white lines in patients' fingerprints was noted.Abbreviations SCE sister chromatid exchange - MMC mitomycin C - BrdU bromodeoxyuridine Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 70th birthday     

Chromosomal instability associated with a novel BLM frameshift mutation (c.1980‐1982delAA) in two unrelated Tunisian families with Bloom syndrome

The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980‐1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.     

Frequency of sister chromatid exchanges in the lymphocytes of patients with atopic dermatitis

The combination of genetic susceptibility and environmental factors can induce allergic sensitization and subsequent local inflammation, resulting in atopic dermatitis (AD). Sister chromatid exchange (SCE) is a sensitive method that may reflect an instability in DNA or a deficiency in DNA repair. The aim of the present study was to investigate whether patients with AD have defects in DNA repair and whether SCE frequency can be used as a genetic marker in the pathogenesis of AD. Between September 2004 and July 2005, SCE was analyzed in the peripheral blood lymphocyte chromosomes of 32 patients with AD and 28 control subjects at the Dermatology Unit of Erzurum State Hospital. This study found that the SCE frequency was significantly increased in patients with AD (P < 0.00001). The prevalence of SCE was not correlated with patient age, sex, disease duration or AD disease severity. Our results indicate that increased chromosome instability may play an important role in the etiology of AD.     

Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet's disease

Inflammation in Behcet's disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. In this study, we tried to determine serum interleukin (IL)-18 and tumour necrosis factor (TNF)-alpha levels of patients with Behcet's disease. Twenty-seven patients with active Behcet's disease, and 20 healthy control subjects were included in this study. Differences between mean serum IL-18 and TNF-alpha level of patients with Behcet's disease were significantly increased when compared with the control group. A significant correlation was found between serum IL-18 and TNF-alpha levels of Behcet patients (rs = 0.627, P < 0.0001). IL-18 and TNF-alpha levels may be related to disease pathogenesis. Increased levels of IL-18 also support Th1 predominance in Behcet's disease.     

Bloom's syndrome

Bloom's syndrome is a rare autosomal recessive disorder that characteristically shows a telangiectatic, sun-sensitive facial rash in conjunction with stunted growth. These patients are prone to respiratory and gastrointestinal infections along with immunologic abnormalities. Chromosomal aberrations include an elevated frequency of sister chromatid exchange in cultured lymphocytes, a phenomenon pathognomonic for this disorder. These patients exhibit a great tendency for neoplasia, particularly acute leukemia and lymphoma. Three cases are reported, including a follow-up of a patient diagnosed 16 years ago.     

N-acetyltransferase 2 polymorphisms in patients with Behcet's disease

It is possible that dietary, environmental factors and/or genetic polymorphisms in xenobiotic-metabolizing enzymes may contribute to the development of Behcet's disease. As N-acetyltransferase (NAT) 2 is an important xenobiotic-metabolizing enzyme and theoretically the nonacetylated xenobiotics may induce an autoimmune mechanism, the aim of the present study was to investigate whether the genetic polymorphism of NAT2 plays a role in susceptibility to Behcet's disease. Forty Behcet's disease patients and 82 control subjects were enrolled in the study. NAT2*5A, NAT2*6A, NAT27*A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). The NAT2*5A and NAT2*6A mutant genotypes carried an increased risk of developing Behcet's disease [odds ratio (OR) = 66.29, 95% confidence interval (CI) = 8.21-535.33; and OR = 24; 95% CI = 2.04-304.98, respectively]. The NAT2*7A/B and NAT2*14A gene polymorphisms were not an increased risk for developing Behcet's disease. As a result of this study we conclude the NAT2 slow acetylator status may be a determinant in susceptibility to Behcet's disease. This finding may have implications for the theories of the pathogenesis of the disease as well as for therapeutic aspects.     

Bloom syndrome in an Indian child

A girl presented with severely stunted growth, photosensitivity, and a characteristic facies. Cytogenetic studies were suggestive of Bloom syndrome. This disorder has not been previously documented in the literature in an Indian child. Minor variations in characteristics in this patient have been highlighted. Cytogenetically, she was found to be a low sister chromatid exchange mosaicism of Bloom syndrome.     

Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters

The study was designed to investigate the possible correlation between some oxidative stress parameters in Behcet's disease and the clinical manifestations of the disease as well as the possible correlation with the disease severity. Seventy-six patients diagnosed according to the International Study Group criteria for Behcet's disease were included in the study. Sixty patients had mild-to-moderate disease and 16 patients had severe disease. Sixty matched control subjects were also included. After a full history and examination from each subject, 10 mL blood was drawn from each for analysis. Serum malondialdehyde, glutathione, ceruloplasmin, copper and zinc levels were determined. Patients with Behcet's disease showed increased levels of serum malondialdehyde and copper while glutathione and zinc levels were decreased. Comparison between these parameters in patients with mild-to-moderate disease with those with severe disease showed only that serum zinc levels were lower in severe Behcet's disease. Serum malondialdehyde levels were found to be significantly positively correlated with oral ulcer size, duration and frequency. Glutathione levels were found to be inversely correlated with the clinical manifestation index and all oral ulcer parameters. Zinc levels were found to be inversely correlated with the clinical manifestation index and pathergy test positivity grades. Copper levels were found to be positively correlated with oral ulcer number. Although the parameters of oxidative stress did not show correlation with disease severity, they were correlated with the disease manifestations. This points out the importance of oxidative stress in Behcet's disease.     

Familial Behcet's disease

There are very few reports of Behetaet's disease from India. Familial aggregation of Behetaet's disease has been reported with restricted geographical distribution. We report here familial Behcet's disease from India in two brothers aged 30 and 32 years. Both patients had recurrent oral and genital ulcers for approximately five years. They also had arthralgias on and off along with fever. Pathergy test was positive in both cases. Their younger brother and a sister had recurrent oral aphthous ulcers.     

Serum Levels of IL-4, IL-10, IL-12, IL-13 and IFN-gamma in Behçet's disease

Behçet's disease (BD) is an inflammatory disease of unknown etiology. Although its pathogenesis is not fully understood, recent studies have suggested that immunological abnormalities and neutrophil hyperfunction may be involved in its etiology and pathophysiology. The immune system in BD can be characterized as a divergent cytokine production profile of the mixed Th1/Th2 cell type. In this study, we investigated the levels of interleukin (IL)‐4, IL‐10, IL‐12, IL‐13 and interferon‐γ in the sera of patients with BD, in comparison with recurrent aphthous stomatitis and healthy controls, to determine the Th1/Th2 profile of the disease. The levels of IL‐4, IL‐10 and IL‐13 were found to be high in active BD patients, and IL‐12 and interferon‐γ levels were lower in active BD patients than in inactive BD, recurrent aphthous stomatitis, and control patients.     

The nevoid basal cell carcinoma syndrome: sensitivity to ultraviolet and x-ray irradiation

Demographic studies in patients with skin cancer have demonstrated the importance of exposure to ultraviolet and x-ray irradiation. This paper describes in vitro studies in peripheral lymphocytes from three patients with the nevoid basal cell carcinoma syndrome. Particular stress was placed on the following factors: (1) the distribution of the lymphocyte subsets, (2) the frequency of spontaneous sister chromatid exchange, (3) the effect of ultraviolet C (UVC) (254 nm) on deoxyribonucleic acid (DNA) synthesis, (4) the effect of UVC on the phytohemagglutinin-stimulated lymphocyte proliferation, and (5) the capacity to repair x-ray-induced DNA damage. Our data indicate that the distribution of the peripheral lymphocytes was normal, while the frequency of spontaneous sister chromatid exchange was high. The capacity of the lymphocytes to repair x-ray-induced DNA damage was low in all three patients. In two patients the UVC-induced DNA synthesis was reduced, while an increased UVC-induced inhibition of lymphocyte proliferation was observed. These cellular responses in vitro to ultraviolet and x-ray irradiation correspond to the clinical features of the nevoid basal cell carcinoma syndrome. A clearly defective in vitro cellular response to x-ray irradiation, reflecting the clinically evident x-ray sensitivity in the nevoid basal cell carcinoma syndrome, has not been reported previously.     

Lymphocyte function and chromosome aberrations in patients with early mycosis fungoides and parapsoriasis en plaques

Thirteen patients with stage I or II mycosis fungoides (MF) and 10 patients with large-plaque parapsoriasis en plaques (PEP) were examined for immunologic and cytogenetic disturbances. Total lymphocyte counts and immunoglobulin concentrations in the blood were normal. In vitro lymphocyte responses to polyclonal activators and various antigens in standard concentrations were normal. However, titration of phytohemagglutinin and concanavalin A (ConA) disclosed significantly lowered responses to suboptimal concentrations in the patient group, most pronounced in patients with MF II. ConA-induced leukocyte migration inhibitory factor (LIF) production, tested in an indirect leukocyte migration inhibitory assay, was low in the patient group. Furthermore spontaneous LIF production in vitro and small amounts of serum LIF were demonstrated in a few patients. The chromosomal banding pattern, sister chromatid exchange, and break frequency were within normal limits except for 3 translocations in the MF group. It is concluded that even in early-stage MF a pathologic function of blood lymphocytes can be demonstrated, when sensitive methods are applied. The findings might be important for monitoring disease activity and effect of treatment.     

New clinical syndromes in dermatology

Dermatologists are in the unique position to be able to diagnose serious systemic diseases through skin findings; in addition, cutaneous manifestations can be associated with internal symptoms and clarify the pathogenesis and treatment of challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic Arteriolopathy, primarily affects patients with end-stage renal disease with concomitant hyperphosphatemia, increased calcium-phosphate product and hyperparathyroidism, skin biopsy and wound care are crucial parts of the diagnosis and treatment. Hyperhomocysteinemia may play a very important role in many cutaneous and systemic diseases including, chronic cutaneous wounds, systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin biopsy and biochemical analysis of the proteoglycans accumulation it may be possible to diagnose a new systemic mucinosis and prevent sudden death in patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a newly described fibrosing disorder occurring in patients with end stage renal disease, the etiology and pathogenesis are still unknown, and the ultimate course of this disease has not been defined.     

The alteration of sister chromatid exchange frequencies in Behçet''s disease with and without HLA-B51

Background The analysis of sister chromatid exchange (SCE) is a cytogenetic technique used to show DNA damage as a result of an exchange of DNA fragments between sister chromatids. It is known that there is an increased SCE frequency in Behçet's disease (BD). Objective To investigate whether human leucocyte antigen (HLA)‐B51‐positive patients with Behçet's disease exhibit higher SCE frequencies than those without HLA‐B51. Methods Lymphocytes from 75 patients (38 women, 37 men) and from 50 controls (28 women, 22 men) were cultured in darkness for 72 h in the presence of bromodeoxyuridine. Metaphase chromosomes were stained with a fluorescence plus Giemsa technique after a standard harvest procedure. For HLA‐B51 typing, DNA was extracted from ethylenediaminetetraacetic acid blood samples and HLA‐B5 allele genotyping was performed by the polymerase chain reaction (PCR)–sequence specific primer method. Results Thirty‐nine of 75 patients with BD (52%) and 15 of 50 controls (30%) were found HLA‐B51‐positive. The SCE frequencies in HLA‐B51‐positive patients were higher than in HLA‐B51‐negative ones (P < 0.001), whereas no difference was detected in the control group. Conclusion This study revealed that there was a significant association between elevated SCE frequencies and existence of HLA‐B51 patients with BD.