Antigenic challenge in the etiology of autoimmune disease in women

Infection has long been implicated as a trigger for autoimmune disease. Other antigenic challenges include receipt of allogeneic tissue or blood resulting in immunomodulation. We investigated antigenic challenges as possible risk factors for autoimmune disease in women using the Health and Retirement Study, a nationally representative longitudinal study, linked to Medicare files, years 1991–2007. The prevalence of autoimmune disease (rheumatoid arthritis, Hashimoto’s disease, Graves’ disease, systemic lupus erythematosus, celiac disease, systemic sclerosis, Sjögren syndrome and multiple sclerosis) was 1.4% in older women (95% CI: 1.3%, 1.5%) with significant variation across regions of the United States. The risk of autoimmune disease increased by 41% (95% CI of incidence rate ratio (IRR): 1.10, 1.81) with a prior infection-related medical visit. The risk of autoimmune disease increased by 90% (95% CI of IRR: 1.36, 2.66) with a prior transfusion without infection. Parity was not associated with autoimmune disease. Women less than 65 years of age and Jewish women had significantly elevated risk of developing autoimmune disease, as did individuals with a history of heart disease or end-stage renal disease. Antigenic challenges, such as infection and allogeneic blood transfusion, are significant risk factors for the development of autoimmune disease in older women.     

Noninvasive tests in the initial evaluation of heart murmurs in children

We prospectively examined the usefulness of electrocardiography, chest radiography, and M-mode echocardiography in discriminating between the presence and absence of heart disease in 280 children older than one month and newly referred for evaluation of a heart murmur. After taking a history and performing a physical examination but before reviewing diagnostic tests, we categorized the children as having "no heart disease" (142), "possible heart disease" (34), or "definite heart disease" (104). Among the children initially thought to have no heart disease, the diagnosis was changed after a review of diagnostic tests in eight--three with mitral-valve prolapse, two with possible cardiomyopathy, and three with no heart disease on follow-up. Among those initially thought to have possible heart disease, the tests changed the diagnosis to definite heart disease in four, of whom only one had heart disease (mitral-valve prolapse) on follow-up. In no case did a review of tests change the diagnosis of definite heart disease. We conclude that the results of diagnostic tests are unlikely to change the clinical diagnosis of no heart disease or definite heart disease, when made by a qualified pediatric cardiologist in children newly referred for evaluation of a heart murmur.     

The frequency distribution of cardiovascular diseases in 13 hospital admitted patients in Korea. Korean Society of Circulation

The frequency distribution of cardiovascular disease are changing recently due to the development of living environment. Unfortunately there are few epidemiological studies of cardiovascular diseases in general population, we tried to estimate the recent trend of cardiovascular diseases studying hospitalized patients in nationwide 13 large hospitals during a year of 1985. The hypertensive disease (24.1%) was the most common cardiovascular disease and the next were cerebrovascular disease (15.8%), arrhythmias (12.2%), ischemic heart disease (9.7%), congenital heart disease (9.1%), and rheumatic heart disease (5.4%) in order. This results showed that hypertensive disease and cerebrovascular disease are still the major cardiovascular disease and ischemic heart disease and arrhythmias are increased. But chronic rheumatic heart disease is declined compared with previous studies in hospitalized patients.     

Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons.

In Parkinson's disease and other Lewy-body-associated disorders, the substantia nigra pars compacta undergoes degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy-body-associated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation, and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and diseased cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. The finding of neuronal death by apoptosis may have relevance for the development of new treatment strategies for Parkinson's disease and related disorders.     

肺心病左室舒张功能障碍发病机制的研究进展

近年来肺心病的发病率逐年上升,以往认为肺心病对心脏的影响主要以右心功能障碍为主,不影响左心功能,左心功能障碍主要为原发左心病变所致,但近年来不少文献指出由慢阻肺长期发展引起的肺心病在早期即可合并左心功能障碍,主要以左室舒张功能障碍为主。本文主要从五个不同方面阐述由慢阻肺长期发展引起的肺心病患者左室舒张功能障碍的原因,结合相关文献做一综述。     

The significance of disease-independence in Mikulicz's disease--revival interests in Mikulicz's disease]

Mikulicz's disease represents a unique condition involving enlargement of the lacrimal and salivary glands. Mikulicz's disease has been considered part of primary Sj?gren's syndrome because both diseases were histologically similar. However, the gland swellings in Mikulicz's disease are persistent, and its decreased secretional function is good responsiveness to glucocorticoid. Serologically, Mikulicz's disease is characterized by few autoantibody including anti-SS-A and anti-SS-B antibodies. Recently, it is revealed elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the lacrimal and salivary glands in Mikulicz's disease. Prominent IgG4-positive plasma cells are also detected in systemic lymph tissues. We cannot detect the phenomenon in Sj?gren's syndrome. In complications with Mikulicz's disease, there are autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, autoimmune hypophysitis, Riedel's thyroiditis, which are related to IgG4 in its pathogenesis. Mikulicz's disease is different from Sj?gren's syndrome, and may be a systemic IgG4-related plasmacytic disease.     

Fibrinolytic activity in malignant disease.

Resting fibrinolytic activity and fibrinolytic capacity were compared in 31 patients with malignant disease and in 24 control subjects without malignant disease. Patients with malignant disease had a lower mean fibrinolytic activity: this was particularly marked in those with disseminated disease. In contrast, patients with malignant disease had a fibrinolytic capacity which did not differ from that of the control subjects.     

Plasma viscosity in inflammatory bowel disease.

AIMS: To assess the relation of plasma viscosity to disease activity in patients with inflammatory bowel disease. METHODS: Crohn's disease (n = 60) and ulcerative colitis (n = 71) were diagnosed on the basis of typical histological or radiological features. Active Crohn's disease was defined as a Crohn's disease activity index of 150 or over. Active ulcerative colitis was defined as a liquid stool passed three times a day or more with blood. Blood samples were assessed for haemoglobin concentration, total white cell count, platelets, plasma viscosity, erythrocyte sedimentation rate, serum albumin, and C-reactive protein. RESULTS: Plasma viscosity was higher in those with active Crohn's disease compared with those with inactive Crohn's disease or active ulcerative colitis. Plasma viscosity correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and platelet count in patients with Crohn's disease. In ulcerative colitis plasma viscosity correlated only with serum C-reactive protein. Plasma viscosity showed a low sensitivity for detecting active Crohn's disease, with 48% of those with active disease having a plasma viscosity within the laboratory reference range. CONCLUSIONS: Plasma viscosity is related to disease activity in Crohn's disease, but is insufficiently sensitive for it to replace erythrocyte sedimentation rate as a measure of the acute phase response in Crohn's disease.     

A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease

To search for a genetic marker for type 2 Gaucher's disease (acute neuronopathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher's disease with a normal gene. We found only a single base substitution (T----C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the NciI restriction endonuclease. We analyzed NciI enzymatic digests of genomic DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher's disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher's disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine----proline) in patients with neuronopathic Gaucher's disease, detectable by the NciI RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher's disease.     

Synaptophysin expression abnormalities in Hirschsprung's disease

Hirschsprung's disease is defined by the congenital absence of ganglion cells in enteric plexuses. Immunostaining of synaptophysin after formalin fixation may be used to identify hyperplasia of nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease. The aim of the study was to evaluate semi-quantitatively the expression of synaptophysin in Hirschsprung's disease, in correlation with morphologic features. This retrospective study included 3 controls, 42 surgical rectal biopsies performed for suspicion of Hirschsprung's disease in children presenting with lower digestive occlusion or severe chronic constipation, including 18 Hirschsprung's disease, and 23 surgical specimens of Hirschsprung's disease. In the absence of Hirschsprung's disease, synaptophysin-positive fibers were numerous but thin in the muscularis mucosae, thin and scarce in the mucosa and submucosa. Neuromuscular junctions were thin and numerous in the muscularis propria. In Hirschsprung's disease, synaptophysin-positive fibers were coarse, and increased in number on each side of the muscularis mucosae. Plexuses were enlarged, weakly stained, and associated in the connective tissue of the muscularis propria with coarse and intensely stained fibers. In conclusion, staining for synaptophysin could be useful to demonstrate abnormalities of enteric innervation in rectal biopsies performed for suspected Hirschsprung's disease in the absence of acetylcholinesterase staining on frozen sections, in transmural biopsies performed for guiding surgery in Hirschsprung's disease, and in cases of extensive Hirschsprung's disease.     

Group B Streptococcal Bacteremia in Nonpregnant Adults with Hepatic Disease in Korea

Sixty-seven cases of group B streptococcal bacteremia in adults were retrospectively reviewed during the period 1991-2000. Not one case occurred in pregnant women. The mean age of the patients was 57 years, and 67.2% were men. Of the 67 cases of illness, 25.4% were hospital acquired and 11.9% were polymicrobial. Common predisposing diseases included hepatic disease (55.2%), diabetes mellitus (28.4%), malignancy (20.9%), and cardiovascular diseases (17.9%). Primary bacteremia, peritonitis, bone and joint infections, and skin and soft tissue infections accounted for most presentations. Peritonitis was a more common presentation in patients with hepatic disease (P<0.001), whereas skin and soft tissue infection was more common in patients with nonhepatic disease (P=0.008). More patients with hepatic disease had polymicrobial bacteremia than did patients with nonhepatic disease (P=0.018). Death occurred in 9.8% of cases, and mortality did not differ between patients with hepatic disease and those with nonhepatic disease. Hepatic disease was found to be an important predisposing condition in adults with group B streptococcal bacteremia. However, mortality for patients with hepatic disease was similar to that for patients with nonhepatic disease. Electronic Publication     

Low frequency of RET mutations in Hirschsprung disease in Sweden

Hirschsprung disease is a congenital malformation, where absence of intramural ganglia in the hindgut results in a defect in the coordination of peristaltic movement. This leads to ileus in the newborn or, more often, constipation in children and adults. The disease affects one in 5000 live births. Siblings of affected cases are at an increased risk (4%) of developing the disease. Among cases, males are affected more often than females.
The first major susceptibility gene for Hirschsprung disease is the RET proto-oncogene on 10q11.2. Germline RET mutations in Hirschsprung disease are mainly inactivating, and have been reported to account for up to 20 and 50% of sporadic and familial cases, respectively. We have screened Swedish population-based samples from 62 sporadic cases and seven familial cases of Hirschsprung disease with single strand conformation polymorphism (SSCP), and found five mutations.     

Cultured skin fibroblasts in lipidoses. Enzymatic, histochemical, and ultrastructural relationship in Fabry's Tay-Sachs, and Sandhoff's diseases

Enzymatic, histochemical, and ultrastructural studies were performed on cultured skin fibroblasts from patients with Fabry's disease, Tay-Sach's disease, and Sandhoff's disease and from their families (carriers). alpha-Galactosidase activity was deficient in the proband with Fabry's disease (lower in the homozygotes than in the heterozygote). Levels of hexosaminidase A in the patient with Tay-Sachs disease and hexosaminidase A and B in the patient with Sandhoff's disease were deficient and were lower in her mother than in the control subject. Lysosome-like structures were observed in cultured fibroblasts from the patients with each disease, as well as in the heterozygote with Fabry's disease and the carrier with Tay-Sach's disease. The amount of the accumulating arrays in the lysosome-like structures was related to low level of enzymatic activity.     

The appendix in inflammatory bowel disease in children.

The morphologic characteristics of the colon in ulcerative colitis and Crohn's disease are well established, but specific appendiceal pathology is less clearly defined. In addition, the frequency of appendiceal involvement in children with inflammatory bowel disease has also not been delineated. We have determined the prevalence of appendiceal involvement in 41 children with inflammatory bowel disease (24 with Crohn's disease and 17 with ulcerative colitis) who required colonic resection and have defined the histopathologic characteristics of the appendix in these diseases. All appendices were abnormal. Specific changes of Crohn's disease or ulcerative colitis were observed respectively in 50% and 56% of the appendices in our patient population. Nonspecific changes only such as fibrous obliteration, serosal fibrosis and lymphoid and/or neuronal hyperplasia were noted in the remaining appendices. The severity of ileocolonic and appendiceal inflammation was similar in about two thirds of the patients with either type of inflammatory bowel disease.     

Autoantibodies in celiac disease

Autoantibody production is an important feature of many autoimmune disorders, signifying a breakdown of immune tolerance to self-antigens. In celiac disease, an autoimmune enteropathy with multiple extra-intestinal manifestations, autoantibody reactivity to transglutaminase 2 (TG2) has been shown to closely correlate with the acute phase of the disease. It serves as a specific and sensitive marker of celiac disease, and is highly useful in aiding diagnosis and follow-up. Immune reactivity to other autoantigens, including transglutaminase 3, actin, ganglioside, collagen, calreticulin and zonulin, among others, has also been reported in celiac disease. The clinical significance of these antibodies is not known, although some may be associated with specific clinical presentations or extra-intestinal manifestations of celiac disease. This review examines the presence of anti-TG2 and other autoantibodies in celiac disease, discussing their diagnostic value, their potential role in disease pathogenesis and current hypotheses that explain how their release may be triggered.     

Genetic risk factors in Alzheimer's disease.

Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease.     

Kawasaki disease in a postpartum patient

Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a multisystem disease. It usually affects children below the age of five, but it occasionally affects adults. There are less than 50 English-reported adult cases in the literature, and only five reported cases of Kawasaki disease and pregnancy, as of 2003. The cases associated with pregnancy involved patients who had a history of Kawasaki disease during childhood and addressed how the complications of the illness (i.e,. coronary artery aneurysms) were managed during pregnancy and delivery. There are no reported cases of Kawasaki disease in postpartum patients. This article presents a case of Kawasaki disease in a 21-year-old, four-week postpartum patient who initially responded to intravenous (IV) antibiotic therapy. This paper will review the diagnosis and treatment of Kawasaki disease as well as the multiple outside variables that impact the management of adult postpartum patients with Kawasaki disease.     

炎性细胞因子在系统性红斑狼疮中的作用

系统性红斑狼疮是一个全身性自身免疫病，常伴多器官受累，许多炎性细胞因子参与了系统性红斑狼疮的发病与发展，该病的活动性及器官损伤程度与不同的细胞因子相关。     

Genetic risk factors in Alzheimer''s disease.

Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease.