四种遗传性鱼鳞病临床表型和组织病理的比较研究

目的：比较四种鱼鳞病（寻常型鱼鳞病；X-连锁鱼鳞病；板层状鱼鳞病；大疱性鱼鳞病）临床表型和组织病理的差异。方法：对鱼鳞病患者进行临床表型分析、皮损组织病理和电镜检测。结果：1．寻常型鱼鳞病：浅褐色多角形鳞屑，组织病理角化过度伴局灶性角化不全，颗粒层变薄；电镜示透明角质颗粒数量减少且结构异常。2．X-连锁鱼鳞病：粗大深褐色鳞屑，组织病理中度角化过度，颗粒层正常或稍增厚。3．板层状鱼鳞病：粗大黑色板样鳞屑，组织病理致密板层状角化过度伴灶性角化不全，局灶颗粒层增厚，棘层不规则增生肥厚；电镜示角质包膜异常。4．大疱性鱼鳞病：棕色疣状鳞屑，组织病理致密角化过度，颗粒层显著增厚，颗粒层及棘层中上部细胞核周空泡改变。电镜可见异常角蛋白分布于基底层以上全部表皮，棘细胞松解，颗粒层细胞核周围有异常聚集的角蛋白丝。结论：四种鱼鳞病患者临床表型、组织病理和严重程度有明显差异。     

银屑病和鱼鳞病患者血清必需脂肪酸分析

为了探讨必需脂肪酸与鳞屑性皮肤病的关系，用气相质谱法分析了寻常型银屑病，性联隐性鱼鳞病，寻常型鱼鳞病和正常对照组的血清和血清磷脂脂肪酸的组成，结果：银屑病组Ｃ＾４２０、Ｃ＾４２２、Ｃ＾５２２显著低于正常，而Ｃ＾２１８、Ｃ＾３１８及Ｃ＾３２０明显升高。     

男性生殖器疱疹病毒的检测和治疗

目的：研究生殖器疱疹（ＧＨ）的治疗和探讨其病原学。方法：采用聚合酶链反应（ＰＣＲ）检测生殖器皮肤粘膜及精液中的单纯疱疹病毒（ＨＳＶ），并用盐酸万乃洛韦（ＶＣＶ）与阿昔洛韦（ＡＣＶ）对照治疗６０例ＧＨ患者。结果：发现生死器皮肤粘膜ＨＳＶ－Ⅱ阳性率高于精液中。ＶＣＶ疗效与ＡＣＶ相当，但ＶＣＶ起效时间明显快于ＡＣＶ（Ｐ〈０．０１）。结论：ＶＣＶ和ＡＣＶ适合治疗ＧＨ；泌尿生殖器标本ＨＳＶ－Ⅱ的检测，对了解ＧＨ的病原很重要。     

性联隐性鱼鳞病和常染色体显性遗传...

用类固醇硫酸酯酶基因的ｃＤＮＡ为探针对１９例性联隐性鱼鳞病和１１例常染色体显性遗传（常显）鱼鳞病分别进行Ｓｏｕｔｈｅｒｎ杂交，发现８４％性联隐性鱼鳞病患者的ＳＴＳ基因缺失，且为全长ＳＴＳ基因缺失；常显鱼鳞病组均正常。此实验室检查对鱼鳞病的基因论断，携带者检测及产前诊断有较的意义。     

获得性鱼鳞病研究进展

获得性鱼鳞病在临床和组织学上类似于常染色体显性遗传性寻常型鱼鳞病，但生物学表现不同。前者主要表现为皮肤干燥、粗糙和显著的鳞屑；组织病理检查显示：表皮角化过度，颗粒层变薄或缺失。获得性鱼鳞病与多种系统性疾病和某些药物有关，治疗上主要是消除致病因素和对症处理。     

某些炎症介质拮抗剂抗过敏作用的实验研究

目的：为了探讨抗组胺药及抗５ 羟色胺（５ ＨＴ）药对迟发型超敏反应（ＤＨＲ）的作用及其机制。方法：我们观察了扑尔敏、特非那丁、多虑平、利血平、赛庚啶、苯噻啶对小鼠变应性接触性皮炎（ＡＣＤ）及真皮肥大细胞（ＭＣ）、表皮郎格罕细胞（ＬＣＳ）的影响。结果：发现这６种药物对小鼠ＡＣＤ均有不同程度的抑制作用，提示这些药物的抗过敏作用不限于Ⅰ型变态反应疾病，对Ⅳ型变态反应疾病亦可有效。受试药物中扑尔敏、特非那丁、多虑平、利血平、赛庚啶等５种能减少真皮ＭＣ数，扑尔敏、多虑平、利血平等３种能减少表皮ＬＣＳ数。结论：提示这些药物抑制ＤＨＲ的机制至少部分地与减少真皮ＭＣ数及／或减少表皮ＬＣＳ数有关。     

应用原位聚合酶链反应检测淋病患者HSV-Ⅱ感染情况的报告

为了解淋病患者ＨＳＶ Ⅱ的感染情况，应用原位聚合酶链反应（ＩＳＰＣＲ）和ＰＣＲ技术对５８例淋病患者进行ＨＳＶ Ⅱ检测。结果两种方法ＨＳＶ ⅡＤＮＡ阳性检出率均为５３．４５％（３１／５８）。ＩＳＰＣＲ显示，１１例有皮损者中，９例阳性信号存在于上皮细胞核及胞浆，既往有疱疹皮损者６例，阳性信号均存在于细胞核，４１例无明显皮损者，１６例阳性，其中１２例阳性信号在细胞核，４例在胞核及胞浆。结果提示，淋病患者合并有高的ＨＳＶ Ⅱ感染率。应用ＩＳＰＣＲ不仅可以敏感特异地检测ＨＳＶ Ⅱ，而且可以定位，为临床诊断和治疗提供重要依据     

局部应用他扎罗汀治疗先天性鱼鳞病

先天性鱼鳞病是一组角化异常的遗传性疾病 ,除了Ｘ性联隐性遗传鱼鳞病 (ＸＲＩ)、常染色体显性遗传寻常鱼鳞病 (ＡＤＩＶ) ,还有几种无相关疾病的板层状鱼鳞病或表皮松解性鱼鳞病。常染色体隐性遗传板层状鱼鳞病可区分为红皮型和非红皮型 (ＮＥＡＲＬＩ)。表皮松解角化过度是Ｂｒｏｃｑ大疱性先天性鱼鳞病样红皮症和Ｓｉｅｍｅｎｓ大疱性鱼鳞病 (ＩＢＳ)的共同特征。该文主要评价局部外用他扎罗汀治疗先天性鱼鳞病的临床疗效和耐受性。方法和结果 :共有 1 2例患者参与了这项半侧、自身对照、开放性研究。其中有 4例ＸＲＩ,3例ＮＥＡＲＬＩ,3…     

1,25（OH）2维生素D3对小鼠郎格罕细胞和接触变态反应的影响

研究了不同浓度的１，２５（ＯＨ）２维生素Ｄ（ＶＤ３）外涂对小鼠表皮郎格罕细胞（ＬＣ）的影响及对接触变态反应（ＣＨＳ）的局部和系统抑制作用。结果表明随着１，２５（ＯＨ））２ＶＤ３浓度的增加，ＬＣ树枝状减少，呈现卵圆或圆形细胞并且细胞数量下降。局部使用治疗剂量的１，２５（ＯＨ）２ＶＤ３能直接抑制小鼠的ＣＨＳ。并且，接受此种处理的小鼠脾细胞后，受体小鼠的ＣＨＳ亦同样抑制。这提示与诱导体内抑制性淋巴细胞的     

无毛小鼠(hr/hr)外用维生素C和E可抑制UVR诱导的晒黑及免疫抑制反应

目前认为维生素Ｃ和维生素Ｅ可形成一种具有自我调节的协同的ＮＡＤＨ依赖系统，以保护哺乳动物的皮肤免受紫外线辐射（ＵＶＲ）的伤害。以往的实验主要集中在维生素Ｃ和维生素Ｅ单独使用或合用后抑制ＵＶＲ对白化猪造成的红斑和光损伤方面的研究。对实验结果的观察也主要是记录皮肤外观的变化或记录表皮角质形成细胞的组织学变化。最近的研究表明：在人体，外用或内服维生素Ｃ和维生素Ｅ可抑制ＵＶＲ照射诱发的红斑，但对色素的变化情况未作报道。 该作者采用Ｃ３ＨＢＹＢ／Ｗｑ无毛小鼠（ｈｒ／ｈｒ）作为实验材料，用ＵＶＲ照射１５天后…     

Simplified method of determination of serum cholesterol sulfate by reverse phase thin-layer chromatography

A new method for determination of cholesterol sulfate (CS) and dehydroepiandrosterone sulfate (DHEAS) from 1 ml serum by reverse phase thin-layer chromatography (TLC) is described. The method comprises an isolation step of sulfated steroids by means of octadecylsilane-bonded (C18) reverse phase column chromatography, a solvolysis step for desulfation of sulfated steroids, and a C18 TLC step for measurement on a photodensitometer. This method is much simpler and more rapid than the methods previously reported, since neither a radioisotope is needed, nor any steps of saponification, derivatization, tedious scraping from a TLC plate, and time-consuming conventional column chromatography are not required. The present method allowed us to distinguish recessive X-linked ichthyosis (RXLI) very easily from ichthyosis vulgaris (IV) by the size and gradation of clearly visible blue chromogen derived from CS on a TLC plate in RXLI. By photodensitometer scanning, the CS levels in patients with RXLI were about 10 times higher than those of patients with IV and healthy subjects, whereas the DHEAS level was normal in the RXLI patients. The present simplified method proved to be useful in diagnosis of RXLI.     

Simplified determination of serum cholesterol sulfate by gas-liquid chromatography combined with cyclohexylsilane-bonded phase column purification

Summary A new gas-liquid chromatographic (GLC) determination of cholesterol sulfate (CS) and dehydroepiandrosterone sulfate (DHEAS) for a biochemical diagnosis of recessive X-linked ichthyosis (RXLI) is described. Although the GLC method for determination of CS is known to be more sensitive than the thin layer chromatographic (TLC) method, the former method has not been widely employed because of its complicated pre-purification steps. The present method allows us to measure the serum levels of CS and DHEAS without tedious purification steps such as multiple conventional column chromatography and preparative thin layer chromatography. Sulfated steroids are rapidly purified with a commercially available mini disposable cyclohexylsilane-bonded phase (CH) column, CH BOND ELUT, and the purified steroids after desulfation are converted to water-resistant tert-butyldimethylsilyl ether derivatives for the GLC analysis on dual 2 m glass columns packed with 2% XE-60 on Chromosorb W.By the present method, serum CS concentrations in RXLI patients were shown to be about 10 times higher than those in patients with ichthyosis vulgaris, carriers of RXLI, and healthy subjects. This method is more suitable not only for a biochemical diagnosis of RXLI but also for studies on the metabolism of sulfated steroids than the previous time-consuming GLC methods.     

Interactions of cholesterol and cholesterol sulfate with free fatty acids: Possible relevance for the pathogenesis of recessive X-linked ichthyosis

Summary Whereas the stratum corneum contains large amounts of unesterified cholesterol and minimal amounts of cholesterol sulfate, in recessive X-linked ichthyosis (RXLI), levels of cholesterol decrease while cholesterol sulfate content increases. To study the molecular basis for abnormal shedding in RXLI, we compared the interaction of cholesterol and cholesterol sulfate with the free fatty acid, hexadecanoic acid, by differential scanning calorimetry (DSC). While cholesterol and the free fatty acid formed a eutectic mixture, such an interaction did not occur upon mixing of cholesterol sulfate with hexadecanoic acid. In addition, and unexpectedly, free cholesterol appeared to undergo progressive autoxidation during repeated DSC measurements at only slightly supraphysiologic temperatures. These studies may provide a molecular mechanism for the abnormal desquamation that occurs in RXLI. The regular formation of oxidation products of cholesterol observed here, if matched by equivalent molecular events in vivo, may have important implications for epidermal pathophysiology.     

X-linked ichthyosis: relation between cholesterol sulphate, dehydroepiandrosterone sulphate and patient's age

Steroid sulphatase deficiency is a feature of recessive X-linked ichthyosis (RXLI) that causes the accumulation of sulphated steroids (SS) in various organs and cells. In a previous study, we detected elevated cholesterol sulphate (CS) and dehydroepiandrosterone sulphate (DHEAS) serum levels in a group of 15 RXLI patients selected in a narrow age range. In the present study both CS and DHEAS serum levels were qualitatively and quantitatively determined using gas-chromatographic analysis in a group of 33 RXLI patients ranging in age from 3 to 70 years. The levels of CS and DHEAS were significantly increased in all patients. Variations in SS were related both to patients' ages and clinical course of the disease. Serum SS levels start to increase in early infancy, peak at puberty, remain elevated in adults and decrease slightly in the elderly.     

Basis for abnormal desquamation and permeability barrier dysfunction in RXLI

Mutations in the gene for steroid sulfatase (SSase), are responsible for recessive x-linked ichthyosis (RXLI). As a consequence of SSase deficiency, its substrate, cholesterol sulfate (CSO4), accumulates in the epidermis. Accumulation of this amphipathic lipid in the outer epidermis provokes both a typical scaling phenotype and permeability barrier dysfunction. Research on RXLI has illuminated several, potentially overlapping pathogenic mechanisms and provided insights about the role of SSase and CSO4 in normal differentiation, barrier maintenance, and desquamation. We now show here that SSase is concentrated in lamellar bodies (LB), and secreted into the SC interstices, along with other LB-derived lipid hydrolases. There, it degrades CSO4, generating some cholesterol for the barrier, while the progressive decline in CSO4 (a serine protease (SP) inhibitor) permits corneodesmosome (CD) degradation leading to normal desquamation. Two molecular pathways contribute to disease pathogenesis in RXLI: 1) excess CSO4 produces nonlamellar phase separation in the stratum corneum (SC) interstices, explaining the barrier abnormality. 2) The increased CSO4 in the SC interstices inhibit activity sufficiently to delay CD degradation, leading to corneocyte retention. We also show here that increased Ca++ in the SC interstices in RXLI could contribute to corneocyte retention, by increasing CD and interlamellar cohesion. RXLI represents one of the best understood diseases in dermatology--from the gene to the SC interstices, its etiology and pathogenesis are becoming clear, and assessment of disease mechanisms in RXLI led to new insights about the role of SSase and CSO4 in epidermis terminal differentiation.     

Steroid sulphatase deficiency in patients initially diagnosed as ichthyosis vulgaris or recessive X-linked ichthyosis

Twenty-one patients with ichthyosis were classified as either ichthyosis vulgaris (IV) (five cases) or recessive X-linked ichthyosis (RXLI) (sixteen cases) by using a steroid sulphatase assay of plantar callus and peripheral leukocytes. The patients had presented with various clinical manifestations, which had resulted in some initial misdiagnoses. Cases which initially resemble IV may in fact be RXLI, although we found that if a case is initially diagnosed as RXLI it is unlikely to be a case of IV.     

Stratum corneum lipid abnormalities in ichthyosis. Detection by a new lipid microanalytical method

Although the biochemical diagnosis of the ichthyoses is still in its infancy, the two recessively inherited types, recessive X-linked ichthyosis (RXLI) and nonbullous congenital ichthyosiform erythroderma (CIE), are accompanied by stratum corneum lipid abnormalities. However, in RXLI, cholesterol sulfate accumulates; in CIE, massive quantities of n-alkanes accumulate. The diagnosis of these disorders has required large quantities of scale for sequential, quantitative thin-layer chromatography (TLC). In this study, we sought to confirm the previously described lipid abnormalities with the use of a rapid, recently developed microchromatographic technique that employs silica gel-coated quartz rods and flame ionization detection (Iatroscan). The cholesterol sulfate content of RXLI (n = 5) scale and the n-alkane content of CIE (n = 8) scale were determined by both TLC and the microchromatographic technique. Less than 10 mg of scale and even single punch biopsy specimens sufficed for the microchromatographic technique, whereas more than 50 mg of scale were required for TLC. Since the microchromatographic technique can rapidly detect diagnostic biochemical abnormalities from readily obtainable, small tissue samples, this method could eventually supplant or supplement standard lipid biochemical techniques for the diagnosis of cutaneous lipidoses.     

Cholesterol sulphate levels in the hair and nails of patients with recessive X-linked ichthyosis

Cholesterol sulphate (CS) has been suggested as an intercellular glue for corneocyte-corneocyte cohesion from studies on patients with recessive X-linked ichthyosis (RXLI). Pathological stratum corneum of RXLI patients was found to show a significant elevation of CS. In the present study hair and nails, unaffected keratinized tissues in RXLI patients, were examined for CS levels. The results demonstrated significantly elevated CS levels in both tissues in RXLI patients (P less than 0.001). In particular the mean CS level in the hair of RXLI patients was five times greater than normal. The present study suggests that hair is a useful material for the diagnosis of RXLI.     

Excretion of (sulfated) steroids in the urine and excretion of cholesterol sulfate in the feces of boys with recessive X-linked ichthyosis

Summary The excretion of sulfated steroids was investigated in the urine and feces of six boys aged 9 months to 7 years and 10 months who had recessive X-linked ichthyosis. Profiles of urinary total steroids as well as sulfated steroids were normal. Cholesterol sulfate excretion in the urine was not elevated. In the feces 2–20% of total cholesterol was cholesterol sulfate, whereas in the feces of 28 healthy children no cholesterol sulfate was demonstrable. In the 6 patients total cholesterol excretion (500–2,500 mol/kg feces) was also elevated in comparison with the 28 healthy controls (150–700 mol/kg feces, mean 365 mol/kg feces)