Single nucleotide polymorphisms of the very low density lipoprotein receptor (VLDLR) gene

The very low density lipoprotein receptor (VLDLR) has a potentially important role in lipoprotein metabolism and Alzheimer's disease. We developed amplification primers for most of the coding region and 3′-untranslated region of VLDLR and used sequencing of genomic DNA to examine these regions of VLDLR in subjects with familial combined hyperlipidemia and in normal controls. We identified ten novel single nucleotide polymorphisms (SNPs) for VLDLR. We also found one rare coding sequence variant, S>R153, in a subject with familial combined hyperlipidemia, which was absent from 2360 normal alleles. The identification of intron–exon boundaries, amplification primers, and SNPs provides tools to investigate VLDLR for genetic association and linkage studies. Received: April 30, 2001 / Accepted: May 1, 2001     

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture- or PCR-confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South-Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100,000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring-like in 31.8% and homogeneous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture-positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogeneous than ring-like. B. burgdorferi may disseminate early without generalized symptoms.     

Diabetes mellitus in Huntington disease

There have been conflicting reports that individuals with Huntington disease (HD) are prone to abnormalities of carbohydrate metabolism. In this study information about the incidence and control of diabetes mellitus in 620 probands (278 living, 332 deceased) with HD and in their first and second degree relatives was obtained by questionnaire method from participants of the National HD Research Roster. Among the probands, 65 individuals (10.5%) were identified by the informant or verified by examination of Roster family records as diabetic. The prevalence of diabetes, particularly among those less than 50 years of age, is significantly greater than corresponding figures among the general U.S. Caucasian population (Scott 1977, Krolewski & Warram 1985). Incidence rates were not calculated because of ascertainment and other biases in the data. Results from the analysis of family data indicate that HD affected relatives of an HD proband with diabetes are 7 times as likely to have diabetes over the proband's non-HD relatives. A non-diabetic HD proband is equally likely to have an HD or non-HD relative with diabetes.     

Gm markers in celiac disease

The association of Ig allotypes with celiac disease was analyzed in a sample of 95 Italian patients typed for HLA polymorphisms. No significant association was found for any Gm, A2m, or Km specificity when the overall sample was considered. However, significant different sex ratios were shown by patients' fnb positive and fnb negative genotypes, with a relative risk of 10.7 for this haplotype in males, suggesting that sex and Gm influence the penetrance of the HLA-linked genes. The significance of this finding is strengthened by the recent report that H-2 and Ig allotypes intervene in the genetic control of murine immune response to A-gliadin (M.F. Kagnoff, Nature 296:158, 1982).     

Psychopathology and Public Policy

An effective definition of psychopathology would be helpful in distinguishing between normal and abnormal behavior and would provide guidance for important public policy decisions. Overinclusive definitions, such as the capacity/disability formulation, do not provide meaningful direction for defining need or assessing eligibility for insurance or other entitlements. Coping failures due to lack of skill, inadequate preparation, or other factors should be distinguished from those due to dysfunction or disturbance of psychological mechanisms. The capacity/disability formulation encourages confusion between different performance decrements and gives no guidance for appropriate boundaries for psychotherapy.     

Pathogenesis of pancreatic perilobular necrosis in patients with liver disease.

We often see perilobular necrosis of the pancreas in patients with liver disease at autopsy. This study was undertaken to determine the frequency and the mechanism of development of pancreatic perilobular necrosis in patients with liver disease. Pancreatic perilobular necrosis was seen in 21 per cent of 261 autopsied patients: in 41 per cent of 73 autopsied patients with liver disease and in 13 per cent of 188 autopsied patients without liver disease. Moreover, splanchnic congestion was present in 90 per cent of 30 pancreatic perilobular necrosis patients with liver disease. These data indicate that patients with liver disease develop perilobular necrosis of the pancreas more often than patients without liver disease, and that the high frequency may be a sequela of splanchnic congestion; that is, congestion of the pancreas and endotoxaemia due to congestion of the gut.     

Light and ultrastructural features of lymphoepithelial lesions of the salivary glands in Mikulicz's disease

This investigation deals with the histogenesis of the so-called 'epimyoepithelial islands' in Mikulicz's disease of the major salivary glands and is based on light and electron microscopic study in six patients. The 'epimyoepithelial islands' represent collapsed acini prior to their complete involution and disappearance, the intraductal cellular proliferation, stratification and differentiation into luminal and peripheral myoepithelial cells with partial and complete obliteration of their lumina and finally, cord-like proliferation and formation of nests of residual pluripotential cells showing squamous metaplasia and occasional myoepithelial cell differentiation. A pink, homogeneous and hyaline material on light microscopic examination is multilayered and extracellular and is in close association with the basal lamina when viewed with electron microscope.     

Peripheral blood mononuclear cell proliferative responses to soluble and particulate heat shock protein 65 in health and inflammatory bowel disease

Objectives: The aims of this study were to determine, in peripheral blood mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified cell proliferative response compared to soluble antigen and (ii) a dysfunctional response in cells derived from patients with chronic inflammation and specifically in those with inflammatory bowel disease (IBD). Subjects: Healthy volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17) were recruited from St Thomas’ and Guys’ Hospital, London, UK. Methods: Following optimisation of experimental conditions (0.1–10.0 μg/ml antigen), PBMC were stimulated with (i) 10.0 μg/ml recombinant soluble heat shock protein 65 (hsp 65) and (ii) 1.0 and 10.0 μg/ml hsp 65 conjugated to microparticles (0.5 μm diameter). PBMC proliferative responses were measured by ³H-Thymidine incorporation at day 5 and results compared between groups using unpaired t-test. Results: Conjugation to microparticles of low dose hsp 65 significantly increased overall proliferative responses by 2–11 fold compared to soluble antigen alone (p < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells from subjects with IBD. Conclusions: Low dose antigen, in microparticulate form, leads to amplified cell proliferation in primary human cells, as showed previously in cell lines and animal studies. However there is no abnormal proliferative response in cells from subjects with IBD. Received 8 February 2006; returned for revision 7 March 2006; accepted by G. Wallace 25 October 2006     

建立一种用重组蛋白检测抗口蹄疫病毒抗体的间接ELISA方法

目的研究以重组蛋白作为包被抗原检测口蹄疫病毒（FMDV）感染后的动物血清中特异性抗体的可能性,为建立一种非病毒颗粒的ELISA检测试剂盒提供实验依据。方法利用自行构建表达的O型口蹄疫病毒VP1表位肽重组蛋白（VP1epi）作为包被抗原,采用间接ELISA方法确定抗原的最佳工作浓度和包被方法,优化各项实验条件,并以FMDV感染后的豚鼠血清作为标准阳性血清确定ELISA方法的特异性和灵敏度。结果FMDV感染后的阳性豚鼠血清可以很好地识别VP1epi重组蛋白,用此蛋白包被检测抗FMDV抗体的灵敏度可达1∶3200,并证明所检测的抗体是FMDV特异性的。结论VP1epi重组蛋白可以替代FMDV颗粒用于建立检测抗FMDV抗体的ELISA试剂盒。