Urinary protein markers in lupus nephritis: the need for concurrent calibration and discrimination statistics in predictive models.
Explore the source record for details and available documents.
Biomarkers↗
Biomedical subjects
P Chu
Publications and source records attributed to P Chu.
Bilateral nephrocalcinosis in short bowel syndrome.
Explore the source record for details and available documents.
Adult↗
Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis.
BACKGROUND: Acute renal failure (ARF) is a life-threatening entity that frequently complicates advanced liver disease. This study documents a number of factors that may predispose to or precipitate ARF and influence outcomes in patients with advanced liver disease. Comparisons are also made between subgroups of patients with viral and alcohol-induced liver cirrhosis in those with ARF. PATIENTS AND METHODS: We conducted a retrospective chart review over one year of 127 consecutive hospital admissions in 82 patients who were diagnosed with advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A diagnosis of ARF was made in 29 admissions and another 98 admissions not complicated by ARF served as controls. This study evaluated different etiologies of ARF and developed a database which included clinical features, biochemical parameters, the etiology of cirrhosis, possible predisposing factors, and precipitating events. Version II of the Acute Physiology and Chronic Health Physiology Scoring system (APACHE II) was applied to predict short-term hospital mortality rates. RESULTS: ARF occurred in 29 admissions over the one-year study period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73% were men. The patients with ARF had significant hyponatremia and higher levels of serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white cell counts on admission than the controls. Patients who developed ARF were more likely to have had infection, especially septicemia, and gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients with viral cirrhosis and ARF were found to have higher leukocyte counts, serum bilirubin levels, and more frequent incidence of infection, septicemia and GI bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those with viral hepatitis were also significantly older and had more frequent incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and less frequent incidence of encephalopathy. CONCLUSIONS: The risk of ARF is significantly increased in patients with advanced liver cirrhosis presenting with marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and GI bleeding. The presence of ARF leads to higher mortality rates in both viral and alcohol-induced liver cirrhosis.
Acute Kidney Injury↗
The halo sign and peripancreatic fluid: useful CT signs of hypovolaemic shock complex in adults.
AIM: To report two new, useful computed tomography (CT) signs of the hypovolaemic shock complex (HSC) in adults admitted after blunt abdominal trauma: the halo sign (ring of fluid around a collapsed intra-hepatic inferior vena cava (IVC)), and peripancreatic retroperitoneal fluid. MATERIALS AND METHODS: CT images of 498 consecutive patients admitted after blunt abdominal trauma were reviewed, of which 27 had CT signs of the HSC. The CT images of these 27 patients were analysed. A control group of 101 patients examined using CT for suspected blunt abdominal trauma who did not have the HSC were chosen for comparison. RESULTS: The most common features involved the vascular compartment: diminished IVC diameter n = 27 a positive halo sign n = 21 diminished anteroposterior diameter of the aorta n = 13 and abnormal vascular enhancement n = 10. Peripancreatic retroperitoneal fluid in the absence of pancreatic injury, pancreatitis or pancreatic disease was observed in eight patients. Hollow visceral abnormalities included: diffuse increased mucosal enhancement of both the small and large bowel n = 19 diffuse thickening of the small bowel wall n =11 and small bowel dilatation n = 7. Solid visceral abnormalities included both decreased and or increased enhancement. Several concomitant intra- and extra-abdominal injuries were also identified. CONCLUSION: In the setting of blunt abdominal trauma, early abdominal CT can show diffuse abnormalities due to the HSC, which occasionally may alert clinicians of unsuspected shock. Recognition of these signs as distinguished from injured viscera is important in order to avoid unnecessary laparotomy. Two new signs are described: the halo sign and peripancreatic retroperitoneal fluid.
Abdominal Injuries↗
Aberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemia.
The retinoic acid receptor alpha (RARA) gene is disrupted by PML/RARA fusion in acute promyelocytic leukemia (APL). The P2 promoter of RARA, controlling the RARalpha2 isoform, contains an RA-responsive element and may be targeted in APL. To test whether aberrant methylation of P2 was involved, 47 APL at diagnosis, 16 APL at first relapse, 50 acute myeloid leukemia (AML) and 22 acute lymphoblastic leukemia (ALL) were tested by methylation-specific polymerase chain reaction. RARA P2 methylation was highly associated with APL (APL: 25/63 vs AML/ALL: 2/75, P<0.0001). P2 methylation occurred at similar frequencies in APL at diagnosis and relapse, suggesting it was an initiating leukemogenic event. In the APL line NB4, RARalpha2 was not expressed, with the untranslocated RARA shown to be P2 methylated. 5-Azacytadine treatment of NB4 led to progressive P2 demethylation and re-expression of RARalpha2, confirming that RARA methylation collaborated with PML/RARA in totally suppressing RARalpha. In APL, RARA P2 methylation was unrelated to gender, age, presenting leukocyte counts and additional cytogenetic aberrations. For APL patients receiving all-trans retinoic acid for induction, P2 methylation did not affect the complete remission rates and survivals. RARA is the first myeloid-specific transcription factor shown to be dysregulated by both translocation and aberrant methylation.
Acute Disease↗
Rocks in the head: extensive intracranial calcification.
Explore the source record for details and available documents.
Brain Diseases↗
Apoptotic markers on lymphocytes and monocytes are unchanged during single hemodialysis sessions using either regenerated cellulose or polysulfone membranes.
BACKGROUND: There is an increased rate of apoptosis of peripheral blood mononuclear cells (PBMCs) in patients undergoing hemodialysis (HD), but little is known about how different dialysis membranes may contribute to the process. We, therefore, studied the influence of two different dialysis membranes on apoptotic markers during HD. METHODS: 8 healthy controls and 8 patients on regular HD 3 times per week were enrolled in this cross-controlled study. Patients received HD using polysulfone and then regenerated cellulose dialysis membranes for one week each, sequentially. Serum was collected for C-reactive protein (CRP) detection; flow cytometry with dual antibody staining was used to measure the apoptotic markers Fas (CD95), FasL (CD 178) and TNF-R2 (CD120b) in T cells (CD3+), B cells (CD19+), and monocytes (CD14+) at 0, 15, 120 and 240 min after starting HD. We also measured total leukocyte numbers and differential white cell counts. RESULTS: Hemodialysis patients revealed lymphocytopenia, monocytopenia, higher CRP levels and higher Fas and TNF-R2 expression on lymphocytes and monocytes at baseline when compared with normal controls. Leukocyte numbers, including neutrophils, lymphocytes and monocytes, dropped significantly after 15 min of dialysis. There were no significant differences in Fas levels during hemodialysis on T and B lymphocytes or on monocytes. T lymphocyte FasL (CD 178) levels remained unchanged throughout the process. There was a significantly lower overall level of CD120b at 15 min of HD, whereas this marker was higher on monocytes after dialysis. There were no significant differences in the levels of apoptotic markers between the two membranes. CONCLUSION: Our results suggest that uremia itself contributes to PBMC apoptosis. The two different dialysis membranes used in this study did not influence apoptotic markers on PBMCs significantly, but increased TNF-R2 expression on monocytes during a single dialysis session.
Adult↗
Localization and physical property experiments conducted by Opportunity at Meridiani Planum.
The location of the Opportunity landing site was determined to better than 10-m absolute accuracy from analyses of radio tracking data. We determined Rover locations during traverses with an error as small as several centimeters using engineering telemetry and overlapping images. Topographic profiles generated from rover data show that the plains are very smooth from meter- to centimeter-length scales, consistent with analyses of orbital observations. Solar cell output decreased because of the deposition of airborne dust on the panels. The lack of dust-covered surfaces on Meridiani Planum indicates that high velocity winds must remove this material on a continuing basis. The low mechanical strength of the evaporitic rocks as determined from grinding experiments, and the abundance of coarse-grained surface particles argue for differential erosion of Meridiani Planum.
Extraterrestrial Environment↗
Localization and physical properties experiments conducted by Spirit at Gusev Crater.
The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.
Extraterrestrial Environment↗
Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation.
We assayed helper T-lymphocyte precursor frequencies (HTLPf), interferon (IFN)-gamma-producing cell frequencies (IFN-gammaPf) and CTL precursor frequencies (CTLPf) to see if they could predict the severity of acute graft-versus-host disease (aGVHD) and disease relapse after transplantation. In all, 48 bone marrow transplantation (BMT) patients and their HLA-identical sibling (n=29) or matched unrelated donors (MUD) (n=19) were recruited. HTLPf, IFN-gammaPf and CTLPf were measured using a limiting dilution assay (LDA). Patients were followed prospectively to assess the severity of aGVHD and the status of the primary disease after BMT. High (>5 x 10(-6)) HTLPf, CTLPf and IFN-gammaPf were significantly associated with the occurrence and severity of aGVHD in patients who received transplants from HLA-identical sibling. Among patients receiving BMT from MUD, HTLPf and CTLPf, but not IFN-gammaPf, were associated with aGVHD. Five patients had disease relapse post-BMT and the risk was not significantly associated with HTLPf, CTLPf or IFN-gammaPf. Patients with high (>5 x 10(-6)) HTLPf, IFN-gammaPf or CTLPf before BMT are at higher risk of developing aGVHD after transplantation from both matched sibling donors and MUD. Whether these parameters can predict disease relapse would have to be investigated with a larger cohort of patients.
Adult↗
Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases.
AIMS: To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs). METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma. CONCLUSIONS: Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.
Adolescent↗
LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats.
AIMS/HYPOTHESIS: Advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including diabetic nephropathy. LR-90, a new advanced glycation endproduct inhibitor, was investigated for its effects on the development of renal disease in diabetic rats. METHODS: Diabetic animals were randomly allocated into groups receiving LR-90 or vehicle (untreated). Age- and weight-matched non-diabetic rats were studied concurrently. Body weight, plasma glucose, glycated haemoglobin, urinary albumin and creatine excretions were measured serially. Kidney histopathology, AGE accumulation in cells and tissues, protein oxidation, were also examined. In vitro assays were used to assess the possible mechanism of action of LR-90. RESULTS: LR-90 inhibited the increase in albumin and creatinine concentrations, and concentrations of circulating AGE in diabetic rats without any effect on glycaemic control. LR-90 treated-rats also showed higher body weights than untreated diabetic rats. LR-90 prevented glomerulosclerosis, tubular degeneration and collagen deposition in the kidney. AGE-induced cross-linking and fluorescence of tail collagen were reduced by LR-90 treatment. LR-90 also decreased AGE accumulation in kidney glomeruli and nitrotyrosine deposition in the renal cortex. In vitro, LR-90 was capable of reacting with reactive carbonyl compounds and was a more potent metal chelator than pyridoxamine and aminoguanidine. CONCLUSION/INTERPRETATION: LR-90 reduces in vivo AGE accumulation, AGE-protein cross-linking and protein oxidation, and could be beneficial in preventing the progression of diabetic nephropathy. The AGE inhibitory and therapeutic effects of LR-90 could be attributed, at least in part, to its ability to react with reactive carbonyl species and/or potent metal chelating activity that inhibits glycoxidative-AGE formation.
Animals↗
Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling.
In an effort to identify novel therapeutic targets for autoimmunity and transplant rejection, we developed and performed a large-scale retroviral-based functional screen to select for proteins that inhibit antigen receptor-mediated activation of lymphocytes. In addition to known regulators of antigen receptor signaling, we identified a novel adaptor protein, SLAP-2 which shares 36% sequence similarity with the known Src-like adaptor protein, SLAP. Similar to SLAP, SLAP-2 is predominantly expressed in hematopoietic cells. Overexpression of SLAP-2 in B and T cell lines specifically impaired antigen receptor-mediated signaling events, including CD69 surface marker upregulation, nuclear factor of activated T cells (NFAT) promoter activation and calcium influx. Signaling induced by phorbol myristate acetate (PMA) and ionomycin was not significantly reduced, suggesting SLAP-2 functions proximally in the antigen receptor signaling cascade. The SLAP-2 protein contains an NH2-terminal myristoylation consensus sequence and SH3 and SH2 Src homology domains, but lacks a tyrosine kinase domain. In antigen receptor-stimulated cells, SLAP-2 associated with several tyrosine phosphorylated proteins, including the ubiquitin ligase Cbl. Deletion of the COOH terminus of SLAP-2 blocked function and abrogated its association with Cbl. Mutation of the putative myristoylation site of SLAP-2 compromised its inhibitory activity and impaired its localization to the membrane compartment. Our identification of the negative regulator SLAP-2 demonstrates that a retroviral-based screening strategy may be an efficient way to identify and characterize the function of key components of many signal transduction systems.
Adaptor Proteins, Signal Transducing↗
Heterologous inhibition of G protein-coupled receptor endocytosis mediated by receptor-specific trafficking of beta-arrestins.
We have observed an unexpected type of nonreciprocal "cross-regulation" of the agonist-induced endocytosis of G protein-coupled receptors by clathrin-coated pits. Isoproterenol-dependent internalization of beta2-adrenergic receptors in stably transfected HEK293 cells was specifically blocked (>65% inhibition) by vasopressin-induced activation of V2 vasopressin receptors co-expressed at similar levels. In contrast, activation of beta2 receptors caused no detectable effect on V2 receptor internalization in the same cells. Several pieces of evidence suggest that this nonreciprocal inhibition of endocytosis is mediated by receptor-specific intracellular trafficking of beta-arrestins. First, previous studies showed that the activation of V2 but not beta2 receptors caused pronounced recruitment of beta-arrestins to endocytic membranes (Oakley, R. H., Laporte, S. A., Holt, J. A., Barak, L. S., and Caron, M. G. (1999) J. Biol. Chem. 274, 32248-32257). Second, overexpression of arrestin 2 or 3 (beta-arrestin 1 or 2) abolished the V2 receptor-mediated inhibition of beta2 receptor internalization. Third, mutations of the V2 receptor that block endomembrane recruitment of beta-arrestins eliminated the V2 receptor-dependent blockade of beta2 receptor internalization. These results identify a novel type of heterologous regulation of G protein-coupled receptors, define a new functional role of receptor-specific intracellular trafficking of beta-arrestins, and suggest an experimental method to rapidly modulate the functional activity of beta-arrestins in intact cells.
Arginine Vasopressin↗
Pathobiologic findings in DCIS of the breast: morphologic features, angiogenesis, HER-2/neu and hormone receptors.
With the increasing incidence of ductal carcinoma in situ (DCIS) of the breast and its relationship to invasive breast carcinoma, it is important to understand the biology of this entity. We report on a hospital-based survey of 219 case subjects with DCIS of the breast without associated invasive carcinoma diagnosed between 1982 and 1994. The cases of DCIS were analyzed for architectural type, size, nuclear grade, necrosis, calcification, periductal fibrosis, neovascularization, estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu expression. Periductal neovascularization was associated with tumor size, microcalcifications, periductal fibrosis, and HER-2/neu overexpression. Expression of ER and PR was observed in 60 and 62% of the cases, respectively, and HER-2/neu overexpression in 28% of the cases. ER and PR expression were both inversely associated with comedo histology and nuclear grade. HER-2/neu overexpression was positively associated with comedo histology, high nuclear grade, and periductal neovascularization and was inversely correlated with both ER and PR expression. High nuclear grade was positively associated with comedocarcinoma, necrosis, microcalcification, and periductal fibrosis. The role of these molecular/pathologic markers in the biology of DCIS and their potential clinical implications are discussed.
Breast Neoplasms↗
Development of perfluorocarbon (PFC) primary standards for monitoring of emissions from aluminum production.
An EPA Voluntary Aluminum Industrial Partnership (VAIP) program has been formed to help US primary producers focus on reducing the emissions of two perfluorocarbons (PFCs), tetrafluoromethane (CF4) and hexafluoroethane (C2F6), during the production of aluminum. To ensure comparability of measurements over space and time, traceability to national sources was desirable. Hence, the EPA approached the NIST to develop a suite of primary standards to cover a mole fraction (concentration) range of 0.1 to 1400 micromol mol(-1) for CF4 and 0.01 to 150 micromol mol(-1) of C2F6. A total of eight gravimetric PFC gas standards were prepared with relative expanded uncertainties of < or = 0.52% (approximately 95% confidence level). These primary standards were ultimately used to assign values to a series of secondary gas standards at three mole-fraction levels with relative expanded uncertainties ranging from +/- 0.7% to 5.3% (approximately 95% confidence level). This series of secondary standards was used within the aluminum industry to calibrate instruments used to make emission measurements. Assignment of values to the secondary standards was performed by use of gas chromatography with flame-ionization detection (GC-FID) and Fourier transform infrared spectrometry (FTIR). Real time pot-line and stack samples from a local aluminum plant were also obtained and sub-samples sent to each participating facility for analysis. The data generated from each facility were sent to NIST for analysis. The maximum difference between the NIST and individual facilities' values for the same sub-sample was +/- 26%.
Journal Article↗
A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.
The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.
Acute Disease↗
Histological and immunohistochemical characterization of extranodal diffuse large-cell lymphomas with prominent spindle cell features.
AIMS: To describe five cases of diffuse large-cell lymphoma with prominent spindle cell components involving skin, nasal-ocular mucosa, and soft tissue. Because of the spindle cell morphology, such cases must be differentiated from true sarcomas arising in or metastasizing to soft tissue, skin, bone, lymph node, or other organs and sites. METHODS AND RESULTS: Formalin-fixed paraffin-embedded archival tissue from five consultation cases of diffuse large-cell lymphoma with prominent spindle cell features involving the skin, nasal-ocular mucosa, and soft tissue in three male and two female patients was studied by histology and immunohistochemistry. Clinicopathological findings were also reviewed for all the patients. By morphology, initial evaluation of the cases suggested spindle cell sarcoma in two cases, inflammatory pseudotumour in one case, large-cell lymphoma in another case, and one case was considered suspicious for malignant lymphoma. Immunohistochemistry demonstrated a B-cell lineage in four of the spindle cell lesions, with a diagnosis of primary cutaneous CD30+ anaplastic large cell lymphoma made for the fifth case. Four of five cases also showed actin reactivity. CONCLUSIONS: Although extremely rare, lymphomas with prominent spindle cell morphology can be encountered in daily surgical pathology practice, and should be included in the differential diagnosis of spindle cell lesions in skin and soft tissue. The observed actin reactivity in four of the five spindle cell lymphomas may lead to a misdiagnosis of leiomyosarcoma if lymphoid markers are not included in the immunohistochemical panel.
Adult↗