273 research outputs found
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and IgA nephropathy
Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia
BACKGROUND: Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). CASE PRESENTATION: A 20-year-old man was diagnosed with XLA 3Â months after birth and subsequently received periodic Îł-globulin replacement therapy. Renal dysfunction developed at 19Â years of age in association with high urinary ÎČ2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary ÎČ2-MG and serum creatinine concentrations improved. CONCLUSION: Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the Îł-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane
Evidence of mature adipocyte proliferation regulated by proliferin
Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2′-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF
Very low-density lipoprotein-apoprotein CI is increased in diabetic nephropathy: Comparison with apoprotein CIII
Very low-density lipoprotein-apoprotein CI is increased in diabetic nephropathy: Comparison with apoprotein CIII.BackgroundRecent studies have suggested that apoprotein (apo) CI in very low-density lipoprotein (VLDL) plays an important role in causing hypertriglyceridemia independent of apo CIII, which is associated with coronary heart disease (CHD). Because the incidence of CHD is increased in diabetic patients and is even higher when diabetic nephropathy is developed, we measured apo CI levels in VLDL from type 2 diabetic patients, with various degree of nephropathy, and compared the results with those for healthy controls or nondiabetic patients with chronic renal failure (CRF).MethodsThis study enrolled healthy control subjects, type 2 diabetic patients with normoalbuminuria, microalbuminuria, overt proteinuria, and CRF on hemodialysis and nondiabetic hemodialyis patients. VLDL (density <1.006) was separated by ultracentrifugation. Then the apo CI, CIII, and B concentrations in VLDL were measured by enzyme-linked immunosorbent assay (ELISA).ResultsThe apo CI, CIII, and B concentrations in VLDL were respectively 3-, 2-, and 2-fold higher, respectively, in diabetic patients with overt proteinuria than in controls. Hemodialysis patients with diabetic nephropathy had levels of apo CI, CIII, and B in VLDL that were 2.6-, 2.7- and 2-fold higher, respectively, than those in controls. Nondiabetic hemodialysis patients also had a 2.7-fold higher level of VLDL apo CIII, whereas VLDL apo CI and VLDL apo B were not significantly increased. VLDL apo CI was significantly correlated with VLDL apo B independently of VLDL apo CIII level.ConclusionAn increase of VLDL apo CIII is a prominent feature of dyslipidemia in CRF patients, regardless of whether they are diabetic or nondiabetic, whereas an increase of VLDL apo CI is more specific to diabetic nephropathy and is closely associated with an increase of VLDL particle numbers, a new risk factor for CHD
Maggot debridement therapy for a patient with critical limb ischaemia and severe cardiac dysfunction: possibility of limb salvage
Ischaemic skin ulcer occurred on the foot of a 73-year-old man who had a history of fulminant myocarditis with severe cardiac dysfunction. We attempted wound bed preparation by maggot debridement therapy and salvaged his limb. It can be one of the adjuvant treatment strategies for critical limb ischaemia
Elevated C-met in Thymic Dendritic Cells of New Zealand Black Mice
New Zealand Black (NZB) mice are a well-known animal model of human autoimmune disease. Although the mechanism for development of autoimmunity is unclear, NZB mice are well known for severe thymic microarchitecture abnormalities. It is thought that thymic dendritic cells (DC) may play a role in thymic education and contribute to the autoimmune process. To address this issue and, in particular, that qualitative and/or quantitative differences exist in thymic DC, we took advantage of a novel restriction analysis system that allow definition of differences in the expression of tyrosine kinases using highly enriched populations of thymic DC from NZB compared to BALB/c and C57BL/6 mice. The method chosen, restriction analysis of gene expression, allowed the determination of protein tyrosine kinase transcription profiles. We report herein that NZB mice have a significant upregulation of C-met compared to the control strains. The abnormality of the C-met transcription was confined to thymic DC. We believe that its abnormal expression reflects the resistance of thymic cells to apoptosis, which will ultimately lead to defects and/or abnormal signaling by the interaction of thymic DC and thymocytes. Further studies involving such interactions are under way
Thermal abundance of non-relativistic relics with Sommerfeld enhancement
We propose an analytic treatment for computing the relic abundances of
non-relativistic particles whose annihilation rate at chemical decoupling is
increased by Sommerfeld enhancement. We find approximate rational functions
that closely fit the thermal average of Sommerfeld-enhanced cross sections in
the massless limit of force carriers for s- and p-wave annihilations. We
demonstrate that, with the approximate thermally-averaged cross sections
implemented, the standard analytic method for the final relic abundances
provides accuracy to within 1% even for the case of Sommerfeld enhancement.Comment: 12 pages, 3 figures; discussions and references adde
Higgs Boson Mass and Electroweak-Gravity Hierarchy from Dynamical Gauge-Higgs Unification in the Warped Spacetime
Dynamical electroweak symmetry breaking by the Hosotani mechanism in the
Randall-Sundrum warped spacetime is examined, relations among the W-boson mass
(m_W), the Kaluza-Klein mass scale (M_{KK}), and the Higgs boson mass (m_H)
being derived. It is shown that M_{KK}/m_W = (2 pi kR)^{1/2} (pi/theta_W) and
m_H /m_W = 0.058 kR (pi/theta_W), where k^2, R, and theta_W are the curvature
and size of the extra-dimensional space and the Wilson line phase determined
dynamically. For typical values kR = 12 and theta_W = (0.2 to 0.4) pi, one
finds that M_{KK} = (1.7 to 3.5) TeV, k = (1.3 to 2.6) x 10^{19} GeV, and m_H =
(140 to 280) GeV.Comment: 14 pages. The argument below (22) was elaborate
Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine
Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research
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