Cyclosporine A inhibits the adaptive responses to hypertonicity: a potential mechanism of nephrotoxicity.

Cell survival in the hypertonic environment of the renal medulla is dependent on the intracellular accumulation of protective organic solutes through the induction of genes whose transcriptional regulation is mediated in part by interaction between osmotic response elements and the transcription nuclear factor of activated T lymphocyte 5. It is shown that cyclosporine A (CsA) prevents the nuclear translocation of the transcription nuclear factor of activated T lymphocyte 5 and inhibits osmotic response element-mediated reporter gene expression. The expression of mRNA for hypertonicity-induced genes (aldose reductase, betaine/gamma-amino-n-butyric acid transporter 1, and heat shock protein 70) is also decreased in the medulla of CsA-treated rats.

Diagnosing primary and metastatic renal cell carcinoma: the use of the monoclonal antibody 'Renal Cell Carcinoma Marker'.

The diagnosis of primary or metastatic renal cell carcinoma (RCC) can be difficult, especially in small biopsies, because of the wide variety of histologic appearances and clinical presentations that RCC can assume. An immunomarker specific for RCC is currently not available. We tested the relevant diagnostic use of the Renal Cell Carcinoma Marker (RCC Ma), a monoclonal antibody, against a normal human proximal tubular brush border antigen.

Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature.

Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies.

Ectopic expression of CCAAT/enhancer binding protein beta (C/EBPbeta) in long-term bone marrow cultures induces granulopoiesis and alters stromal cell function.

CCAAT/enhancer binding proteins (C/EBP) have been demonstrated to impact directly the development of multiple hematopoietic lineages. However, the role of C/EBPbeta in the differentiation of various hematopoietic lineages has not been thoroughly examined. We used primary bone marrow cultures to assess directly the ability of C/EBPbeta to influence myelopoiesis.

Renal cell apoptosis in chronic obstructive uropathy: the roles of caspases.

Background: Apoptosis of tubular and interstitial cells is well documented in kidneys with chronic obstructive uropathy (COU) and probably plays an important role in the pathogenesis of this condition. The molecular control of apoptosis in COU remains poorly understood. Apoptosis in general is known to proceed initially along distinct pathways, which later converge into a common arm characterized by orderly activation of caspases.

Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats.

Objectives: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage.

Methods: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry.

Role of p53-dependent activation of caspases in chronic obstructive uropathy: evidence from p53 null mutant mice.

Chronic obstructive uropathy (COU) created by unilateral ureteric ligation is associated with increased renal cell apoptosis and p53 expression. Genetically engineered mice were used to examine the role of p53 in renal cell apoptosis in COU and the involved molecular pathways. Obstructed kidneys in p53+/+, p53+/-, and p53-/- mice were examined at days 4, 7, 15, 20, and 30 for apoptosis, and mRNA were examined for p53, members of the bcl-2 family, the death receptor family, and the common effectors of apoptosis.

Cloning of two pectate lyase genes from the marine Antarctic bacterium Pseudoalteromonas haloplanktis strain ANT/505 and characterization of the enzymes.

A marine Antarctic psychrotolerant bacterium (strain ANT/505), isolated from sea ice-covered surface water from the Southern Ocean, showed pectinolytic activity on citrus pectin agar. The sequencing of the 16S rRNA of isolate ANT/505 indicates a taxonomic affiliation to Pseudoalteromonas haloplanktis. The supernatant of this strain showed three different pectinolytic activities after growth on citrus pectin.

Aspiration biopsy of osseous metastasis of retroperitoneal paraganglioma. Report of a case with cytologic features and differential diagnostic considerations.

Background: Paragangliomas are uncommon tumors, only 10% of which are malignant, as evidenced by metastatic disease. It is rare for paraganglioma to present with symptomatic osseous metastases.

Case: A retroperitoneal paraganglioma presented in a 52-year-old man as painful metastases in the rib and vertebrae.

Long-term bone marrow cultures provide access to early lymphoid progenitors.

Long-term bone marrow cultures provide defined systems for studying and manipulating hematopoietic progenitors. Myeloid bone marrow cultures harbor early lymphoid progenitors; however, the nature and phenotype of these progenitors has not been investigated. Phenotypic and molecular markers associated with lymphopoiesis were used to characterize the lymphoid population maintained in these cultures.

Renal lymphoma. The diagnostic and therapeutic roles of fine-needle aspiration.

This study focused on 19 patients with renal lymphoma (RL) from whom 20 initial (1 patient with fine-needle aspiration [FNA] specimens of masses in both kidneys) and 1 repeated FNA specimen were obtained. Of the 19 patients, 10 had secondary RL, 8 primary RL, and 1 transplant RL. The FNA samples were studied by smears (all cases), tissues (11), phenotyping by immunostaining (13) or flow cytometry (4), and gene rearrangement (3).

Absolute bioavailability of 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides following intraduodenal instillation in rats.

Three modified 20-mer antisense oligonucleotides targeted to human intercellular adhesion molecule-1 mRNA were characterized for their presystemic stability and oral bioavailability compared with a first-generation phosphorothioate oligodeoxynucleotide (PS ODN), ISIS 2302. The three modified oligonucleotides contained 2'-O-(2-methoxyethyl) (2'-O-MOE) ribose sugar modifications on a portion, or on all of the nucleotides in the antisense sequence. In vitro metabolism studies conducted in various gastrointestinal and digestive tissue preparations indicated substantial improvement in stability of 2'-O-MOE-modified oligonucleotides.

Pharmacokinetic properties of 2'-O-(2-methoxyethyl)-modified oligonucleotide analogs in rats.

Plasma pharmacokinetics, biodistribution, excretion, and metabolism of four modified 20-mer antisense oligonucleotides targeted to human intercellular adhesion molecule-1 mRNA have been characterized in rats and compared with a first-generation phosphorothioate oligodeoxynucleotide (PS ODN), ISIS 2302. The modified oligonucleotides contained 2'-O-(2-methoxyethyl) (2'-O-MOE) ribose sugar modifications on all or a portion of the nucleotides in the antisense sequence. The 2'-O-MOE-modified oligonucleotides were resistant to nuclease metabolism in both plasma and tissue.

Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney: altered expression of vascular endothelial growth factor.

Chronic tubulointerstitial injury (CTI) including tubular atrophy and interstitial fibrosis represents one major determinant for the progression of chronic renal disease regardless of cause. Although peritubular capillaries (PTCs) are essential to maintain the normal structure and function of renal tubules, little is known about the role of PTCs in the development of CTI. The integrity of PTCs seems to be regulated by growth factors.

Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-beta in human renal epithelial cells.

Heme oxygenase-1 (HO-1), a 32-kDa microsomal enzyme, is induced as a beneficial and adaptive response in cells/tissues exposed to oxidative stress. Transforming growth factor-beta1 (TGF-beta1) is a regulatory cytokine that has been implicated in a variety of renal diseases where it promotes extracellular matrix deposition and proinflammatory events. We hypothesize that the release of TGF-beta1 via autocrine and/or paracrine pathways may induce HO-1 and serve as a protective response in renal injury.

Cryptococcal osteomyelitis. Report of a case with aspiration biopsy of a humeral lesion with radiologic features of malignancy.

Background: Osteomyelitis due to Cryptococcus neoformans typically exhibits lytic lesions on radiographs. Extensive periosteal reaction is an uncommon feature.

Case: A 68-year-old man presented with pain and swelling in the left elbow.

Mechanism of chronic obstructive uropathy: increased expression of apoptosis-promoting molecules.

Background: We have demonstrated that renal tubular and interstitial cells undergo pronounced apoptosis during the course of chronic obstructive uropathy (COU). Apoptosis is a complex cellular process consisting of multiple steps, each of which is mediated by families of related molecules. These families may include receptor/ligand molecules such as Fas, Fas ligand, tumor necrosis factor receptor-1 (TNFR-1), and TNF-related apoptosis inducing ligand (TRAIL); signal transduction adapter molecules such as Fas-associated death domain (FADD), TNFR-1 associated death domain (TRADD), receptor-interacting protein (RIP), Fas-associated factor (FAF), and Fas-associated phosphatase (FAP); or effector molecules such as caspases.

Osmotically relevant membrane signaling complex: association between HB-EGF, beta(1)-integrin, and CD9 in mTAL.

The integral membrane proteins cluster of differentiation-9 (CD9), beta(1)-integrin, and heparin-binding epidermal growth factor-like (HB-EGF) exist in association in many cell lines and are linked to intracellular signaling mechanisms. Two of the proteins (CD9 and beta(1)-integrin) are induced by hypertonicity, suggesting that their related signaling processes may be relevant to osmotic stress. The validity of this hypothesis rests upon coexpression and physical association between these molecules in nephron segments that are normally exposed to high and variable ambient osmolality.

Expression of adhesion molecules in kidney with experimental chronic obstructive uropathy: the pathogenic role of ICAM-1 and VCAM-1.

Background: Chronic obstructive uropathy induced by maintained unilateral ureter ligation in the rat is characterized morphologically by interstitial inflammation, interstitial fibrosis, and tubular atrophy. Infiltrating mononuclear inflammatory cells, particularly T lymphocytes and macrophages, may contribute to the progression of this lesion by mediating tubular injury and by the activation of interstitial fibroblasts, with resultant tubular atrophy and interstitial fibrosis, respectively. Altered expression and activation of adhesion molecules by leukocytes, vascular endothelial cells, and parenchymal cells likely contributes both to the infiltration of inflammatory cells into the tubulointerstitial compartment and to the interaction of activated inflammatory cells with parenchymal cells.

"Pauci-Immune" proliferative and necrotizing glomerulonephritis with thrombotic microangiopathy in patients with systemic lupus erythematosus and lupus-like syndrome.

In the glomerulonephritides of systemic lupus erythematosus (SLE), the number of subendothelial deposits, when present, generally corresponds to the degree of light microscopic glomerular hypercellularity; only very rarely are no or few such deposits present in cases of focal (WHO class III) or diffuse (WHO class IV) proliferative lupus nephritis. We have recently encountered five cases of active diffuse proliferative glomerlonephritis with no subendothelial and few or no mesangial deposits and thrombotic microangiopathy (TMA) in four patients with SLE and one patient with lupus-like syndrome. Three of the five patients were tested for circulating lupus anticoagulants or anticardiolipin antibodies, and two were positive.

Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis.

Heme oxygenase-1 (HO-1) is a 32-kDa microsomal enzyme that catalyzes the conversion of heme to biliverdin, releasing iron and carbon monoxide. Induction of HO-1 occurs as a protective response in cells/tissues exposed to a wide variety of oxidant stimuli. The chemotherapeutic effects of cis-diamminedichloroplatinum(II) (cisplatin), a commonly used anticancer drug, are limited by significant nephrotoxicity, which is characterized by varying degrees of renal tubular apoptosis and necrosis.

Unilocular retroperitoneal cyst of mesothelial origin presenting as a renal mass.

We report the first 2 cases, to our knowledge, of retroperitoneal cysts with features of mesothelial differentiation that clinically mimic renal masses. The first lesion occurred in a 71-year-old man who presented with flank pain. Ultrasound and magnetic resonance imaging studies showed a unilocular cystic structure arising from the upper pole of the left kidney.

Thin basement membrane disease with heavy proteinuria or nephrotic syndrome at presentation.

Thin basement membrane disease (TBMD) is a condition originally defined as diffuse thinning of the glomerular basement membrane (GBM) associated with hematuria in all patients. Although proteinuria has been described in up to 60% of patients with TBMD, it is almost always mild, with a 24-hour excretion mostly of less than 500 mg. We describe eight patients (four men and four women between 32 and 66 years of age) with TBMD who presented with heavy proteinuria or nephrotic syndrome.

Absorption of antisense oligonucleotides in rat intestine: effect of chemistry and length.

An in situ single-pass perfusion model was used to assess the effect of chemical modification and length on permeability and absorption of various oligonucleotides in rat intestine. Phosphorothioate oligodeoxynucleotides (PS-ODN) were compared with oligoribonucleotides with 2'-methoxyethyl (MOE) or 2'-O-methyl (OMe) modifications. A 25-mer PS-OMe-modified oligonucleotide showed relatively poor permeability in this model, as did unmodified 20-mer PS-ODN (permeability coefficient [P(eff)] = 2-8 X 10(-6)cm/sec).