77例不明原因肝功能异常患者的临床与病理特点

目的探讨不明原因肝功能异常患者的临床与病理特点。方法75例不明原因肝功能异常患者行1秒钟肝穿刺,2例外科手术肝活检,标本均送免疫组化双标记及HE染色、Masson染色、网状纤维染色、罗丹宁铜染色、普鲁士蓝染色,进一步分析其临床及病理特点。结果77例病因不明肝功能异常患者除6例无诊断学异常及3例非特异性炎症外,其余68例（88．31％）经肝组织病理检查分别诊断为急慢性肝炎12例、自身免疫性肝病27例、代谢性肝病4例、脂肪性肝病11例、药物性肝损伤10例、先天性肝纤维化及肝小静脉闭塞病各1例。结论肝组织病理检查在不明原因肝功能异常患者诊断价值较高,但由于病理检查存在一定的局限性,如果重视临床资料收集,通过临床及病理特点相结合的方法可进一步提高临床确诊率。     

Clinical and molecular genetic features of ARC syndrome

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is an autosomal recessive multisystem disorder that may be associated with germline VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion by interacting with SNARE proteins, and evidence of abnormal polarised membrane protein trafficking has been reported in ARC patients. We characterised clinical and molecular features of ARC syndrome in order to identify potential genotype-phenotype correlations. The clinical phenotype of 62 ARC syndrome patients was analysed. In addition to classical features described previously, all patients had severe failure to thrive, which was not adequately explained by the degree of liver disease and 10% had structural cardiac defects. Almost half of the patients who underwent diagnostic organ biopsy (7/16) developed life-threatening haemorrhage. We found that most patients (9/11) who suffered severe haemorrhage (7 post biopsy and 4 spontaneous) had normal platelet count and morphology. Germline VPS33B mutations were detected in 28/35 families (48/62 individuals) with ARC syndrome. Several mutations were restricted to specific ethnic groups. Thus p.Arg438X mutation was common in the UK Pakistani families and haplotyping was consistent with a founder mutation with the most recent common ancestor 900–1,000 years ago. Heterozygosity was found in the VPS33B locus in some cases of ARC providing the first evidence of a possible second ARC syndrome gene. In conclusion we state that molecular diagnosis is possible for most children in whom ARC syndrome is suspected and VPS33B mutation analysis should replace organ biopsy as a first line diagnostic test for ARC syndrome.     

Clinical and molecular features of human rhinovirus C

A newly discovered group of human rhinoviruses (HRVs) has been classified as the HRV-C species based on distinct genomic features. HRV-Cs circulate worldwide, and are important causes of upper and lower respiratory illnesses. Methods to culture and produce these viruses have recently been developed, and should enable identification of unique features of HRV-C replication and biology.     

Clinical, biochemical and molecular genetic features of Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) has traditionally been considered a disease causing severe and permanent visual loss in young adult males. In nearly all families with LHON it is associated with one of three pathogenic mitochondrial DNA (mtDNA) mutations, at bp 11778, 3460 or 14484. The availability of mtDNA confirmation of a diagnosis of LHON has demonstrated that LHON occurs with a wider range of age at onset and more commonly in females than previously recognised. In addition, analysis of patients grouped according to mtDNA mutation has demonstrated differences both in the clinical features of visual failure and in recurrence risks to relatives associated with each of the pathogenic mtDNA mutations. Whilst pathogenic mtDNA mutations are required for the development of LHON, other factors must be reponsible for the variable penetrance and male predominance of this condition. Available data on a number of hypotheses including the role of an additional X-linked visual loss susceptibility locus, impaired mitochondrial respiratory chain activity, mtDNA heteroplasmy, environmental factors and autoimmunity are discussed. Subacute visual failure is seen in association with all three pathogenic LHON mutations. However, the clinical and experimental data reviewed suggest differences in the phenotype associated with each of the three mutations which may reflect variation in the disease mechanisms resulting in this common end-point.     

Clinical features, diagnosis and molecular studies of familial central diabetes insipidus

BACKGROUND: Familial central diabetes insipidus (DI) is rare and is characterised by polydipsia and polyuria with a variable age of onset. The evaluation of arginine vasopressin (AVP) secretion in these individuals has been reported infrequently and only in adulthood. OBJECTIVE: To describe the clinical features, diagnosis and molecular investigation of children affected by familial central DI. METHODS: Functional studies of AVP secretion were undertaken in children from two kindreds with familial central DI. The AVP-neurophysin II (AVP-NPII) gene was also sequenced in symptomatic individuals. RESULTS: In affected individuals, the result of the water deprivation test may be inconclusive. However, the hypertonic saline test identified both the severe and partial forms of AVP deficiency. A novel mutation of the AVP-NPII gene was identified by direct gene sequencing in both families. CONCLUSIONS: This report highlights the progressive decline in AVP secretion with increasing age in this disorder and the usefulness of mutational analysis in these families. In symptomatic individuals, the hypertonic saline test may be a useful second-line investigation for functional studies of AVP secretion where molecular diagnostics are unavailable.     

MERRF: Clinical features, muscle biopsy and molecular genetics in Brazilian patients

Myoclonic epilepsy with ragged red fibers (MERRF) is a mitochondrial disease that is characterized by myoclonic epilepsy with ragged red fibers (RRF) in muscle biopsies. The aim of this study was to analyze Brazilian patients with MERRF. Six patients with MERRF were studied and correlations between clinical findings, laboratory data, electrophysiology, histology and molecular features were examined. We found that blood lactate was increased in four patients. Electroencephalogram studies revealed generalized epileptiform discharges in five patients and generalized photoparoxysmal responses during intermittent photic stimulation in two patients. Muscle biopsies showed RRF in all patients using modified Gomori-trichrome and succinate dehydrogenase stains. Cytochrome c oxidase (COX) stain analysis indicated deficient activity in five patients and subsarcolemmal accumulation in one patient. Molecular analysis of the tRNA(Lys) gene with PCR/RFLP and direct sequencing showed the A8344G mutation of mtDNA in five patients. The presence of RRFs and COX deficiencies in muscle biopsies often confirmed the MERRF diagnosis. We conclude that molecular analysis of the tRNA(Lys) gene is an important criterion to help confirm the MERRF diagnosis. Furthermore, based on the findings of this study, we suggest a revision of the main characteristics of this disease.     

Congenital toxoplasmosis: epidemiologic features and control.

Toxoplasmosis is caused by the parasite Toxoplasma gondii. It is acquired from undercooked meat or from food or fomites contaminated by cat feces. The disease can be transmitted to the fetus only during maternal parasitemia, which is associated with primary infection. Extrapolation from current data suggests that there are 140 to 1400 cases of congenital toxoplasmosis per year in Canada and that 70 to 280 of the infants are severely affected at birth; many of the others suffer sequelae later in life. Serologic diagnosis of primary infection in the mother is quite sensitive and specific. Diagnosis in the infant is more difficult and may take several months. Prenatal treatment of the woman and postnatal treatment of the infant are hampered by the lack of proven efficacy as well as ethical and compliance problems. Preventive serologic screening and prophylaxis have the same drawbacks. Educating young women to avoid infection is an inexpensive, low-risk intervention that would be the preferred preventive strategy if it could be shown to be effective. Immunization may prove to be the most cost-effective method of preventing congenital toxoplasmosis if a safe and effective vaccine is developed.     

Clinical, epidemiologic, and environmental surveillance for ehrlichiosis and anaplasmosis in an endemic area of northern California.

Two forms of tick-borne leukocytotropic rickettsioses have been recognized in California since the mid-1990s: human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis and human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum. Between 1997 and 1999, two cases of HME and four cases of HGA were diagnosed in residents of southern Humboldt County, California. Environmental followup at case-patients' residences revealed dense populations of Ixodes pacificus ticks, particularly in grassy roadside areas. PCR evidence of A. phagocytophilum was detected in approximately 2.0% of I. pacificus; E. chaffeensis was not detected in any of 625 ticks tested. Serologic antibody to A. phagocytophilum was detected in two of 54 participants in a community epidemiologic study; one of these also had antibody to E. chaffeensis. Over 85% of study participants reported finding a tick on themselves in the preceding 12 mo. Residents of southern Humboldt County are at significant risk of tick bites and should take appropriate prevention measures to avoid infection with rickettsia and other tick-transmitted pathogens.     

Automated area calculation of histopathologic features using SIVQ

Recently, with the advent of the 7th edition of the AJCC Cancer Staging manual, at least one set of criteria (e.g. breast) were modified to now require the measurement of maximal depth of stromal invasion. With the current manual interpretive morphological approaches typically employed by surgical pathologists to assess tumor extent, the specialty now potentially has stumbled upon a crossroads of practice, where the diagnostic criteria have exceeded the capabilities of our commonly available tools. While whole slide imaging (WSI) technology holds the potential to offer many improvements in clinical workflow over conventional slide microscopy including unambiguous utility for facilitating quantitative diagnostic tasks with one important example being the determination of both linear dimension and surface area. However, the availability of histology data in digital form is of little utility if time-consuming and cumbersome manual workflow steps are necessarily imposed upon the pathologist in order to generate such measurements, especially as encountered with the complex and ill-defined shapes inherent to infiltrative tumors. In this communication, we demonstrate the utility of the recently described SIVQ algorithm to serve as the basis of a highly accurate, precise and semi-automated tool for direct surface area measurement of tumor infiltration from WSI data sets. By anticipating the current trend in cancer staging that emphasizes increasingly precise feature characterization, as witnessed by the recent publication of AJCC's 7th edition of the Cancer Staging Manual, this tool holds promise to will be of value to pathologists for clinical utility.     

Diet, alcohol and liver cirrhosis: an epidemiologic study

A retrospective case-control study was conducted over three years in a Gastroenterology Department. Alcohol consumption and dietary habits of 152 male patients with liver cirrhosis and 304 hospital controls selected in the same age range, were assessed from a standardized questionnaire by a highly trained dietician. The variations of the relative risk of liver cirrhosis as a function of the estimated mean daily intakes of alcohol, fats, carbohydrates and proteins were studied using stratified conditional logistic regression models. Thus the relative risk of liver cirrhosis was found to be positively correlated with alcohol and fat consumption. Whereas in the control group, the calorie percentage from fats was 33.8, it was 39.6 in the cirrhotic group (87.11 g/d vs. 102.1 g/d). In contrast, the relative risk of liver cirrhosis was found to be negatively correlated with the mean daily carbohydrate and protein intakes. These findings indicate that in addition to alcohol consumption, dietary habits and in particular daily fat intake, should be considered for studying liver cirrhosis and for monitoring these patients.     

Osteoarthrosis in guinea pigs: histopathologic and scanning electron microscopic features

Spontaneous cartilage degeneration of the femorotibial joint of male Hartley guinea pigs, 61 to 365 days old, was studied by light microscopy (LM) and scanning electron microscopy (SEM) to determine the incidence, age at onset, and to characterize the early changes. Knee joints of 61 day old animals were histologically and ultrastructurally normal. Focal minimal degeneration characterized by cell and proteoglycan loss with surface fibrillation was first observed by LM on the medial tibial plateau (MTP) in two of five 89 day old animals. Mild lesions characterized by focal surface disruption, primarily in the area of medial tibial plateau not covered by the meniscus, were observed in three of five 89 day old animals by SEM. Light microscopic alterations in knee joints of 4, 5, and 6 month old animals consisted of varying degrees of focal chondrocyte death, decreased toluidine blue matrix staining, and surface fibrillation. Small chondrocytic clones were first observed in medial tibial cartilage of 6 month old animals with moderate focal degeneration. Ultrastructurally, 4, 5, and 6 month old animals generally had moderate to severe fibrillation involving primarily the area of the medial tibial plateau not covered by the meniscus. Tibial osteophyte formation, mild synovial hyperplasia, medial femoral and meniscal cartilage degeneration, were first seen by LM in 9 month old animals. Lesions in 1 year old animals were similar, but more severe and included subchondral sclerosis of medial tibial and femoral bone. Bilateral fibrillation of greater than 50% of the medial tibial articular surface was observed in all 1 year old animals by SEM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Several epidemiologic features of the spread of chickenpox and herpes zoster]

Epidemiological and statistical data of herpes zoster and chickenpox by such indices as morbidity level, periodicity and month-by-month changes in the incidence of these diseases were compared. The study included 2345 herpes zoster and 11116 chickenpox cases in the course of 5 years (1972--1976). In comparison with herpes zoster, the intensity of chickenpox spread among the population was on the average 4.7 times greater. Of the total number of chickenpox cases the percentage of herpes zoster contituted 21.0. Chickenpox morbidity had marked seasonal cyclic nature with the amplitude of seasonal variations of about 8; as to herpes zoster--there was no annual or seasonal cyclicity. Thus, in the development of chickenpox and herpes zoster epidemic process there was revealed a peculiar tendency inherent to each of these infections; no common epidemiological and statistical regularities in the spread intensity, annual periodicity and seasonal cyclicity were detected.     

Characterization of molecular recognition features, MoRFs, and their binding partners

Molecular Recognition Features (MoRFs) are short, interaction-prone segments of protein disorder that undergo disorder-to-order transitions upon specific binding, representing a specific class of intrinsically disordered regions that exhibit molecular recognition and binding functions. MoRFs are common in various proteomes and occupy a unique structural and functional niche in which function is a direct consequence of intrinsic disorder. Example MoRFs collected from the Protein Data Bank (PDB) have been divided into three subtypes according to their structures in the bound state: alpha-MoRFs form alpha-helices, beta-MoRFs form beta-strands, and iota-MoRFs form structures without a regular pattern of backbone hydrogen bonds. These example MoRFs were indicated to be intrinsically disordered in the absence of their binding partners by several criteria. In this study, we used several geometric and physiochemical criteria to examine the properties of 62 alpha-, 20 beta-, and 176 iota-MoRF complex structures. Interface residues were examined by calculating differences in accessible surface area between the complex and isolated monomers. The compositions and physiochemical properties of MoRF and MoRF partner interface residues were compared to the interface residues of homodimers, heterodimers, and antigen-antibody complexes. Our analysis indicates that there are significant differences in residue composition and several geometric and physicochemical properties that can be used to discriminate, with a high degree of accuracy, between various interfaces in protein interaction data sets. Implications of these findings for the development of MoRF-partner interaction predictors are discussed. In addition, structural changes upon MoRF-to-partner complex formation were examined for several illustrative examples.     

社区获得性肺炎非典型病原体分布及其流行特征

目的 了解社区获得性肺炎(CAP)非典型病原体感染的分布情况及其流行特征.方法 收集确诊为社区获得性肺炎患者278例,间接免疫荧光法(IFA)检测人血清中呼吸道9种主要的非典型性病原体的IgM抗体.结果 病原体检测阳性者150例,总阳性率54.O％.单一病原体感染中,肺炎支原体(MP) 125例(45.0％)、呼吸道合胞病毒( RSV) 27例(9.7％)、腺病毒22例(7.9％)、副流感病毒1、2和3型19例(6.8％)、乙型流感病毒16例(5.8％)、嗜肺军团菌血清1型13例(4.7％)、肺炎衣原体2例(0.7％)和甲型流感病毒1例(0.4％).混合感染共63例(22.7％),其中61例(21.9％)为MP与其他病原体的混合感染,病毒感染以RSV最常见,共27例(9.7％).CAP患者患有基础疾病共139例(50％),其余为无基础疾病者.基础疾病中以循环疾病和呼吸疾病最常见,各占总CAP患者的15,1％和13.0％.所有受检者MP阳性率最高,达45％,其中未成年组3～18岁中MP阳性率高达60.2％,而成人组18 ～50岁中MP阳性率高达81.8％.CAP春季病原体阳性检出率为46.9％,冬季病原体阳性检出率为63.8％(x2=7.752,P＜0.05).结论 非典型性病原体(特别是MP)感染在CAP患者中比例较大,其流行与分布跟病原体种类、基础疾病、年龄、季节等有一定的关系.