Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells

BACKGROUND: Sera of patients with IgA nephropathy (IgAN) contain circulating immune complexes (CIC) composed of galactose-deficient IgA1 complexed with antiglycan antibodies. The role of these CIC in the pathogenesis of IgAN is not known. METHODS: We studied how proliferation of cultured mesangial cells (MC) is affected by CIC prepared from sera of IgAN patients and healthy control subjects using size-exclusion chromatography. CIC-containing fractions were added to serum-starved MC in culture, and cell proliferation was measured using (3)H-thymidine incorporation. The results were confirmed by staining MC using an antibody against proliferating cell nuclear antigen. RESULTS: The incubation of starved MC with serum fractions with M(r) 800 to 900 kD, rich with galactose-deficient IgA1, stimulated proliferation, while fractions with smaller complexes were inhibitory. Furthermore, CIC-containing larger molecular mass fractions isolated from serum of an IgAN patient collected during an episode of macroscopic hematuria stimulated MC proliferation more than CIC obtained during a subsequent quiescent phase. To examine the role of IgA, we removed IgA1 from serum before fractionation. The resultant IgA1-depleted fractions were devoid of stimulatory IgA-CIC. Sera of IgAN patients were also fractionated after addition of desialylated galactose-deficient polymeric IgA1 to form additional immune complexes. Supplementation with a small quantity of this IgA1 increased cellular proliferation in assays using serum fractions of M(r)>/=800 to 900 kD; uncomplexed IgA1 did not affect MC proliferation significantly. In contrast, supplementation with a larger quantity of this IgA1 inhibited cellular proliferation in assays using serum fractions of M(r) 700 to 800 kD. CONCLUSION: Overall, these findings suggest that CIC containing aberrantly glycosylated IgA1 affect proliferation of MC in vitro and, thus, likely play a role in the pathogenesis of IgAN.     

家庭医生的新挑战——躯体化障碍

有研究提示,在初级保健中,有20%~25%的就诊者可能有心理或精神方面的问题,也就是说这些病人的症状不是真正的病理问题,而是情感上或是行为上的问题。美国Oliver Oyama等提出约有50%的病人具有不能用医学解释的症状,其中某些病人为躯体化障碍,首先要排除病人是否存在着躯体疾病,来就诊的病人可为器官疾病与心理问题共存,这时,我们要下两个诊断;有些人因为心理问题长期未得到解决,而转化为躯体症状。如何应对这些病例或案例对全科医生来说是一种挑战。     

Fibroblasts in Dermal Tissue Repair

ABSTRACT: The cellular dynamics of dermal regeneration were studied in nonsutured cutaneous wounds of female pigs and monkeys with electron microscopy and immunohistochemistry to demonstrate the origin and the development of fibroblasts forming granulation tissue. The results indicate that fibroblasts do not originate from histiocytes but from resting fibroblasts in the wound margins. These resting fibroblasts first become undifferentiated mesenchymal cells termed “X” cells. The “X” cells then multiply, migrate, and invade the wound defect in approximately 3 days, transforming into highly active fibroblasts. The active fibroblasts are endowed with the capacity of further transformation to fibroclasts and myofibroblasts. The latter two cell populations then effectively cause remodeling of newly formed tissue and contraction of wound margins.     

Primary localized cutaneous nodular amyloidosis successfully treated with cyclophosphamide

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle‐aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.     

Chondromyxoid fibroma of the mastoid facial nerve canal mimicking a facial nerve schwannoma

Chondromyxoid fibroma of the skull base is a rare entity. Involvement of the temporal bone is particularly rare. We present an unusual case of progressive facial nerve paralysis with imaging and clinical findings most suggestive of a facial nerve schwannoma. The lesion was tubular in appearance, expanded the mastoid facial nerve canal, protruded out of the stylomastoid foramen, and enhanced homogeneously. The only unusual imaging feature was minor calcification within the tumor. Surgery revealed an irregular, cystic lesion. Pathology diagnosed a chondromyxoid fibroma involving the mastoid portion of the facial nerve canal, destroying the facial nerve. Laryngoscope, 2009     

Rapamycin for treatment of refractory dysthyroid compressive optic neuropathy

We report a patient with dysthyroid optic neuropathy refractory to steroids and orbital decompression treated with rapamycin, a fibroblast and T cell inhibitor. Symptoms, visual acuity, color plate testing, and visual fields improved. Aside from hypercholesterolemia, no complication related to this therapy was observed. By addressing the pathogenesis of thyroid eye disease, rapamycin may represent an alternative when standard treatments fail. Further investigation of rapamycin for treatment of dysthyroid orbitopathy is warranted.     

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

Effect of Posterior Tracheopexy on Risk of Recurrence in Children after Recurrent Tracheo-Esophageal Fistula Repair

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