Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential to yield its crystalline ...precipitation in urine and renal interstitial tissues, leading to crystalluria, urolithiasis, acute kidney injury (AKI) or chronic kidney disease (CKD). In epidemiological studies, atazanavir/ritonavir alone or in combination with tenofovir has been associated with increased risk of progression to CKD. However, renal biopsies were not provided in these studies. Case reports showing an association between atazanavir use and tubulointerstitial nephritis among HIV-infected individuals provide clues as to the potential causes of atazanavir nephrotoxicity. We now review atazanavir-related kidney disease including urolithiasis, renal dysfunction and interstitial nephritis and illustrate the review with a further case of atazanavir-associated kidney injury with sequential renal biopsies. There are two forms of atazanavir-associated tubulointerstitial nephritis: acute tubulointerstitial nephritis that may develop AKI rapidly (in weeks) after initiation of atazanavir, and chronic tubulointerstitial nephritis that may develop progressive CKD slowly (in years) with granuloma and intrarenal precipitation of atazanavir crystals as well as crystalluria. Caution should be exercised when prescribing atazanavir to patients at high risk of CKD, and therapy should be reevaluated if renal function deteriorates, especially associated with crystalluria and hematuria.
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease. Cortical tubers are one of the standard intracranial hallmarks of TSC, they comprise subependymal hamartomas ...protruding into the ventricles, cortical and white matter hamartomas, and giant cell tumors. The clinical course of TSC varies from asymptomatic to severe, with epileptic seizures and psychomotor retardation. We discuss here the correlation between clinical manifestation and features on 1H-MR spectroscopy ( 1H-MRS) of the white matter involving cortical tubers in patients with TSC. Statistical analysis of the N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI)/creatinine (Cr) ratios between tubers and normal controls showed decreased NAA/Cr and increased mI/Cr ratios (P<0.05) in tubers, but no significance difference in Cho/Cr. The significance of the clinical appearance is associated with a decreased ratio of NAA/Cr in tubers with TSC. An elevated ratio of mI/Cr in tuber does not parallel the severity of the clinical features of TSC. These findings suggest that 1H-MRS may be useful for the evaluation of the clinical severity and prognostic diagnosis of TSC.
The B motif is a signature of type-B response regulators (ARRs) involved in His-to-Asp phosphorelay signal transduction systems in Arabidopsis. Homologous motifs occur widely in the GARP family of ...plant transcription factors. To gain general insight into the structure and function of B motifs (or GARP motifs), we characterized the B motif derived from a representative ARR, ARR10, which led to a number of intriguing findings. First, the B motif of ARR10 (named ARR10-B and extending from Thr-179 to Ser-242) possesses a nuclear localization signal, as indicated by the intracellular localization a green fluorescent protein-ARR10-B fusion protein in onion epidermal cells. Second, the purified ARR10-B molecule binds specifically in vitro to DNA with the core sequence AGATT. This was demonstrated by several in vitro approaches, including PCR-assisted DNA binding site selection, gel retardation assays, and surface plasmon resonance analysis. Finally, the three-dimensional structure of ARR10-B in solution was determined by NMR spectroscopy, showing that it contains a helix-turn-helix structure. Furthermore, the mode of interaction between ARR10-B and the target DNA was assessed extensively by NMR spectroscopy. Together, these results lead us to propose that the mechanism of DNA recognition by ARR10-B is essentially the same as that of homeodomains. We conclude that the B motif is a multifunctional domain responsible for both nuclear localization and DNA binding and suggest that these insights could be applicable generally to the large GARP family of plant transcription factors.
We have discovered an unusual α-galactosylation using phenylthioglycoside of 4,6-
O-di-
tert-butylsilylene (DTBS)-protected galactose derivatives as a glycosyl donor, which was not hampered by the ...neighboring participation of C-2 acyl functionality such as NTroc and OBz. The power of the DTBS effect has been exemplified by the coupling reaction with various glycosyl acceptors.
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We studied recovery of the ectomycorrhizal species Cenococcum geophilum (Cg) after urea treatment in two types of vegetation. The recovery was as quick as 6 months after the treatment and overlapped ...the fruiting period of ectomycorrhizal ammonia fungi. Ectomycorrhizas investigated as Cg belonged to a single species irrespective of treatment and vegetation type. Cg ectomycorrhizas were significantly more abundant in density in nontreated soil than in treated soil. Between vegetation types, Cg ectomycorrhizas were significantly more in density in broad-leaved deciduous forest than in broad-leaved evergreen forest. Moreover, Cg was dominant in the nontreated soils of the former type of forest.
We have succeeded in the facile synthesis of 4-methylumbelliferyl T-antigen as a substrate for endo-α-N-acetylgalactosaminidase by exploiting the combination of the di-tert-butylsilylene effect and ...the Mitsunobu reaction.
Peroxisome biogenesis disorders (PBDs) are severe autosomal recessive neurological diseases caused by a defect of peroxisomal assembly factors. Zellweger syndrome, the most severe phenotype, is ...characterized by hypotonia, psychomotor retardation and neuronal migration disorder. Neonatal adrenoleukodystrophy and infantile Refsum disease are milder phenotypes of this disease. Thirteen complementation groups have been established since the genetic heterogeneity of PBDs was elucidated in 1988. Eleven genes for PBDs have been identified either by a functional complementation cloning or by EST homology searches. In 1992, the first gene for PBDs, PEX2, was identified. It encodes peroxisomal integral membrane protein with a RING finger domain. PEX5 and PEX7 are the genes for peroxisomal targeting signal (PTS)‐1 and ‐2 receptors, respectively. PEX3, PEX16 and PEX19 are considered to be required for the early stage of peroxisome biogenesis. PEX13 protein has an SH3 docking site that binds to the PTS‐1 receptor. PEX1 and PEX6 encode ABC protein, and PEX10 and PEX12 also encode integral membrane protein, with RING finger. Temperature‐sensitivity, whereby peroxisomal biogenesis and metabolic dysfunctions are restored at 30°C in cells from mild phenotypes, is a useful event for predicting the clinical severity and for elucidation of peroxisome biogenesis. Investigations using knockout mice are expected to facilitate understanding of migration disorders.
Abstract Objective: Few cases of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy (APH)-like morphological changes during the recovery process have been reported. Patient: A ...56-year-old woman diagnosed with Takotsubo cardiomyopathy showed a morphology similar to that of APH during recovery. We examined this patient using 2D speckle-tracking echocardiography based on the method used for hypertrophic cardiomyopathy, which suggested that the circumferential strain (CS) of the middle wall indicated myocardial function of the left ventricle, and the CS of the inner wall was associated with left ventricular chamber function. Results: We measured the CS of the endocardial, middle, and epicardial layers and found that the apical inner layer CS (CSinner), middle layer CS, and outer layer CS were all decreased at the onset. CSinner showed a strong tendency to recover on echocardiography performed when APH-like morphology was observed. Conclusion: The morphology of the apex in our case likely contributed to the maintenance of chamber function.
Intracranial pial arteriovenous fistula (pAVF) is uncommon, accounting for approximately 1.6% of all intracranial vascular malformations. High flow pressure renders varices and AVF highly susceptible ...to rupture and life-threatening hemorrhage.A 15-year-old girl who presented with headache and visual disturbance was diagnosed with an intracranial pAVF associated with a giant varix in the right occipital lobe. Imaging studies showed anomalous dilatation of the right posterior cerebral artery, a 53 mm thrombosed and calcified varix in the right occipital lobe, and drainage into the transverse sinus. We planned a combined surgery with the goal of reducing the mass and curing the pAVF. The patient underwent coil embolization for the obliteration of an angiographic shunt point; however, shunt flow appeared from the new feeders. We resected the giant varix with an angiographic shunt point completely and safely, with embolization the following day. The patient was discharged without any postoperative intracranial complications. The pathological shunt point was confirmed.Recently, reports on endovascular surgery for pAVF have increased. Combined surgery that includes safe excision, particularly in cases with mass effects, is required.
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