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Oncocytic Papillary Renal Cell Carcinoma (OPRCC) is a rare variant of renal cell carcinoma with overlapping characteristics type 1 and 2 of papillary renal carcinoma. Based on the literature, OPRCC is predominantly present in adult males. OPRCC has a specific genetic affiliation with the Fumarate Hydratase gene requiring all patients diagnosed with OPRCC to undergo genetic testing. There isn't any agreement for the treatment of OPRCC due to the rarity of the disease; however, a radical nephrectomy poses as a possible modality. Therefore, we present the rare case of an 11-year-old female found to have OPRCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Hospital accreditation can be an incentive to improve occupational health and safety (OHS) performance., Objective: This study assesses the relationship between status of accreditation among private Lebanese hospitals and compliance with OHS accreditation standards., Methods: A survey was administered to 68 private Lebanese hospitals to assess accreditation status and specific indicators related to each of the 9 OHS codes in the Lebanese accreditation manual. Chi-square, Fisher's exact test, and independent sample t-tests compared the OHS standards between accredited and non-accredited hospitals., Results: Fifty-six percent of participating private hospitals were accredited. Accredited hospitals reported statistically better OHS performance than non-accredited hospitals based on the standards outlined in the accreditation manual. However, there was inconsistent performance on numerous OHS indicators among participating hospitals., Conclusion: The gaps in OHS performance suggest the need for strengthened OHS guidelines in the national accreditation process to safeguard workers' health. Strategies to fortify OHS performance include tying service reimbursement to OHS compliance and linking OHS standards with national labor legislation.

Combining congenic mapping with microarray expression profiling offers an opportunity to establish functional links between genotype and phenotype for complex traits such as type 1 diabetes (T1D). We used high-density oligonucleotide arrays to measure the relative expression levels of >39,000 genes and ESTs in the NOD mouse (a murine model of T1D and other autoimmune conditions), four NOD-derived diabetes-resistant congenic strains, and two nondiabetic control strains. We developed a simple, yet general, method for measuring differential expression that provides an objective assessment of significance and used it to identify >400 gene expression differences and eight new candidates for the Idd9.1 locus. We also discovered a potential early biomarker for autoimmune hemolytic anemia that is based on different levels of erythrocyte-specific transcripts in the spleen. Overall, however, our results suggest that the dramatic disease protection conferred by six Idd loci (Idd3, Idd5.1, Idd5.2, Idd9.1, Idd9.2, and Idd9.3) cannot be rationalized in terms of global effects on the noninduced immune system. They also illustrate the degree to which regulatory systems appear to be robust to genetic variation. These observations have important implications for the design of future microarray-based studies in T1D and, more generally, for studies that aim to combine genome-wide expression profiling and congenic mapping.

gammadelta T lymphocytes in the intestinal intraepithelial layer (gammadelta IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of gammadelta IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8(+) alphabeta T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8(+) alphabeta T cells must be activated to become cytotoxic effectors, gammadelta IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that gammadelta IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. gammadelta IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general.

Self-tolerance is achieved by deleting or regulating self-reactive lymphocytes at a series of cellular checkpoints placed at many points along the developmental pathways to plasma cells and effector T cells. At each checkpoint, what are the molecular pathways that determine whether a lymphocyte remains quiescent, begins dividing, differentiates or dies? In splenic B cells, the decision between quiescence, tolerance by anergy, and activation provides a tractable setting to explore these issues by global gene expression profiling on DNA microarrays. Here we discuss the application of microarrays to illuminate a set of cell fate decisions that appear to be determined by summation of numerous small changes in expression of stimulatory and inhibitory genes. Many genes with known or predicted inhibitory functions are highly expressed in naive, quiescent B cells, notably the signal inhibitor SLAP and DNA-binding proteins of the Kruppel family (LKLF, BKLF, GKLF), Tsc-22, GILZ, Id-3, and GADD45. Activation of naive B cells, triggered by acute binding of antigen to the B-cell receptor, involves a rapid decrease in expression of these inhibitory genes. Promitotic genes are induced in parallel, including c myc, LSIRF/IRF4, cyclin D2, Egr-1 and Egr-2, as are the anti-apoptotic gene A1 and genes for the T-cell-attracting chemokines MIP-1alpha and beta. B-cell tolerance through the process of anergy, induced by chronic binding of self antigen, maintains expression of the inhibitory genes found in quiescent B cells and induces an additional set of inhibitory genes. The latter include inhibitors of signaling - CD72, neurogranin, pcp4 - and additional inhibitors of gene expression such as SATB1, MEF2C, TGIF and Nab-2. The effects of tolerance, the immunosuppressive drug FK506 and other modulators of calcium or MAPK signaling allow individual gene responses to be linked to different signal transduction pathways. The global molecular profiles obtained illustrate how quiescence and anergy are actively maintained in circulating B cells, how these states are switched to clonal expansion and how they could be better emulated by pro-tolerogenic drugs.

Immunologists are already comfortable with the need for monitoring many different gene products simultaneously. It is a common challenge to remember what CD-one-hundred-and-something is, and an ever-increasing number of colours are required for identification on the flow cytometer. Gene expression arrays now offer the possibility of extending this approach beyond the cell surface and expanding it dramatically to survey the entire catalogue of gene transcripts in a lymphoid cell.

Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH pedigrees from Amish, Venezuelan and Utah populations) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles. There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.

A highly reliable and efficient technology has been developed for high-throughput DNA polymorphism screening and large-scale genotyping. Photolithographic synthesis has been used to generate miniaturized, high-density oligonucleotide arrays. Dedicated instrumentation and software have been developed for array hybridization, fluorescent detection, and data acquisition and analysis. Specific oligonucleotide probe arrays have been designed to rapidly screen human STSs, known genes and full-length cDNAs. This has led to the identification of several thousand biallelic single-nucleotide polymorphisms (SNPs). Meanwhile, a rapid and robust method has been developed for genotyping these SNPs using oligonucleotide arrays. Each allele of an SNP marker is represented on the array by a set of perfect match and mismatch probes. Prototype genotyping chips have been produced to detect 400, 600 and 3000 of these SNPs. Based on the preliminary results, using oligonucleotide arrays to genotype several thousand polymorphic loci simultaneously appears feasible.

Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.

The effectiveness of heart failure management in clinical practice is limited by physicians' suboptimal utilization of effective medications, patients' poor adherence to dietary sodium limitation and optimal drug therapy, and the lack of systematic monitoring of patients after hospitalization. The present study evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse-mediated, home-based system for heart failure management that implements consensus guidelines for pharmacologic and dietary therapy using a nurse manager to enhance dietary and pharmacologic adherence and to monitor clinical status by frequent telephone contact. Fifty-one patients with the clinical diagnosis of heart failure were followed for 138 +/- 44 days. Daily dietary sodium intake fell by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses increased significantly (lisinopril: 17 to 23 mg, p <0.001; hydralazine: 140 to 252 mg, p = 0.01). Functional status and exercise capacity improved significantly (p = 0.01). Compared with the 6 months before enrollment and normalized for variable follow-up, the frequency of general medical and cardiology visits declined by 23% and 31%, respectively (both p <0.03); emergency room visits for heart failure and for all causes declined 67% and 53%, respectively (both p <0.001). Hospitalization rates for heart failure and for all causes declined 87% and 74%, respectively (p = 0.001), compared with the year before enrollment. The MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy for heart failure in clinical practice, improving clinical outcomes and reducing medical resource utilization.

Thirteen of 32 patients with coronary heart disease who also exhibited symptoms and signs of severe time urgency and hostility (the two overt components of type A behavior [TAB]) were found to exhibit multiple episodes of silent myocardial ischemia over a 48-hour period of Holter monitoring as indicated by electrocardiogram ST depressions. Ten of these 13 patients were given 14 months of TAB counseling in an attempt to diminish the intensity of their time urgency and hostility. The remaining three patients served as controls. After counseling, the intensity of the time urgency and hostility of the 10 counseled patients diminished 53% and 59%, respectively, as measured by the videotaped clinical examination. The time urgency and hostility of the three uncounseled control patients did not significantly change. The mean frequency of ischemic episodes in the 10 patients who received TAB counseling significantly declined from an initial 6.6 to 3.1 ischemic episodes per 24 hours. However, the mean frequency of ischemic episodes did not significantly decline in 2 of the 3 uncounseled patients. The third uncounseled patient developed a conduction defect in the 14-month interlude, making an analysis of his repeat 48-hour electrocardiogram for episodes of ST depression impossible.

This article presents a new Type A Videotaped Clinical Examination scale that measures insecurity. This scale was validated against an existing insecurity measure in a sample of 204 individuals. The results indicated that this new scale is a valid measure of insecurity. The relation between insecurity and type A behavior was examined in a sample of 3013 people. In this large population insecurity showed a strong positive correlation to type A behavior and to each of the two overt behavioral components, time urgency and free-floating hostility.

Objective: To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification., Design: Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction., Setting: 5 Kaiser Permanente Medical Centers in the San Francisco Bay area., Patients: 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction., Intervention: In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy., Outcome: Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction., Results: In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively., Conclusion: In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.

The objective of this investigation was to develop a medically oriented examination (including a search for physical signs in addition to elicitation of symptoms) for the accurate diagnosis of type A and type B behaviors. Comprising the study were 99 post-myocardial infarction patients, 15 clinically well persons in whom clinical coronary heart disease subsequently developed, and 23 healthy type B subjects. All participants were subjected to a videotaped clinical examination during which, in addition to eliciting responses to questions, 14 possible physical or psychomotor signs (many of which are newly discovered) of type A behavior were also observed. Each physical sign and symptom was given an arbitrarily weighted score (according to its observed frequency of occurrence in previously studied and authenticated type A behavior). These total scores were then statistically analyzed to obtain a critical "diagnostic score" for the presence of type A behavior. The medically oriented videotaped clinical examination detected the presence of type A behavior in 97 of 99 (98%) successively examined postinfarction patients and in 14 of 15 (93%) subjects who were clinically well at the time of their videotaped clinical examination but who subsequently had clinical coronary heart disease. Conversely type A behavior was diagnosed by videotaped clinical examination in only 1 of 23 (4%) healthy men who previously had been found to exhibit type B behavior by prior diagnostic procedures.

Background: An estimated 40 million Americans have serum cholesterol levels that warrant medically supervised dietary intervention. Although registered dietitians are expected to play an important role in treating these patients, current treatment practices in the community are largely unknown., Methods: A questionnaire concerning treatment practices was mailed to all 377 registered dietitians listed in the directories of the American Dietetic Association for two large California districts. Number of patients seen and length and content of dietary counseling were ascertained for three types of patients: (a) hypercholesterolemic outpatients without heart disease, (b) hypercholesterolemic outpatients who have heart disease, and (c) inpatients with myocardial infarction., Results: A return rate of 59% (n = 252) was obtained for the questionnaire. A total of 44% of the registered dietitians counseled hypercholesterolemic patients in any of the categories surveyed. About 30% of the respondents counseled hypercholesterolemic outpatients without heart disease. They saw an average of 4.9 such patients a week, spent an average of 53 min in an initial session, and usually did not see the patient again in follow-up. Fewer than 10% of patients had as many as four sessions. About 27% of the respondents saw hypercholesterolemic outpatients with heart disease, averaging 3.5 such contacts per week. The reported practices were similar to those provided to noncardiac outpatients. About 22% of registered dietitians worked with hospitalized myocardial infarction patients. They spent an average of a total of 41 min over 2.5 visits with each patient., Conclusion: Currently, outpatient registered dietitian counseling for hypercholesterolemia appears to be limited in both the number of patients reached and the duration of the counseling. Further research into the impact of, barriers to, and efficacy of alternative delivery methods of dietary counseling is needed.

DNA sequences of the human, mouse, and rabbit immunoglobulin kappa-gene (J-C regions) are compared with respect to various DNA patterns, including dyad symmetry pairings, runs of nucleotides, repeat clusters, and repeats that occur with unusually high frequency. The significant dyad symmetry pairings within each of the sequences emphasize the two "control-enhancer" elements of the J5-C intron. Dyad symmetry pairs between the J-C region and a number of kappa variable (V)-gene domains suggest differences in the affinities between the V and J segments. It is the "consensus heptamer" rather than the "consensus nonamer" that embodies the longest V-J dyad symmetry combinations. In the rabbit there are long runs and repeat clusters of the sequences that identify regions of high duplication; these regions are absent in the human and mouse sequences. High-frequency oligonucleotides feature the consensus nonamer 5' to the J segments, especially in the mouse sequence.

Efficient algorithms are described for identifying local molecular sequence features including repeats, dyad symmetry pairings and aligned matches between sequences, while allowing for errors. Specific applications are given to the genomic sequences of the Epstein-Barr virus, Varicella-Zoster virus and the bacteriophages lambda and T7.