tbuckley/cabot-search huggingface dataset:
Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1
Authors: A. L. Hughes
Journal: Molecular Biology and Evolution (1998)

There are 10 gene families that have members on both human chromosome 6 (6p21.3, the location of the human major histocompatibility complex [MHC]) and human chromosome 9 (mostly 9q33-34). Six of these families also have members on mouse chromosome 17 (the mouse MHC chromosome) and mouse chromosome 2. In addition, four of these families have members on human chromosome 1 (1q21-25 and 1p13), and two of these have members on mouse chromosome 1. One hypothesis to explain these patterns is that members of the 10 gene families of human chromosomes 6 and 9 were duplicated simultaneously as a result of polyploidization or duplication of a chromosome segment ("block duplication"). A subsequent block duplication has been proposed to account for the presence of representatives of four of these families on human chromosome 1. Phylogenetic analyses of the 9 gene families for which data were available decisively rejected the hypothesis of block duplication as an overall explanation of these patterns. Three to five of the genes on human chromosomes 6 and 9 probably duplicated simultaneously early in vertebrate history, prior to the divergence of jawed and jawless vertebrates, and shortly after that, all four of the genes on chromosomes 1 and 9 probably duplicated as a block. However, the other genes duplicated at different times scattered over at least 1.6 billion years. Since the occurrence of these clusters of related genes cannot be explained by block duplication, one alternative explanation is that they cluster together because of shared functional characteristics relating to expression patterns.
Decline in CA19-9 During Chemotherapy Predicts Survival in Four Independent Cohorts of Patients with Inoperable Cholangiocarcinoma.
Authors: M. Grunnet, I. Christensen, U. Lassen, L.H. Jensen, M. Lydolph, J. Knox, M. McNamara, M. Jital, H. Wasan, J. Bridgewater, J. Valle, M. Mau-Sørensen
Journal: Annals of Oncology (2014)
Fas and Fas ligand: expression and soluble circulating levels in cutaneous malignant melanoma
Authors: P. Redondo, T. Solano, B. VAzquez, A. Bauza, M. Idoate
Journal: British Journal of Dermatology (2002)

The Fas/Fas ligand (FasL) system plays a key part in maintaining tissue homeostasis via the induction of apoptosis. Functional impairment of the Fas/FasL system is associated with the development and progression of malignancies. Malignant melanoma cells and tissues have been shown to express Fas and FasL to variable extents.To demonstrate the expression and the presence of soluble circulating levels of Fas and FasL in cutaneous malignant melanoma.Biopsy specimens of 42 patients with primary melanoma and nine patients with cutaneous metastatic melanoma were obtained for immunohistochemistry studies. All patients were followed for at least 5 years. In another 46 patients with melanoma (15 stage I and II; 11 stage III; and 20 stage IV) and in 10 healthy volunteer control subjects circulating levels of Fas and FasL were analysed with commercial ELISA tests.FasL was strongly positive in 38 (90%) of 42 primary melanomas; two of nine metastases did not express FasL. In the primary melanomas Fas was strongly or intensely positive in 17 (40%), moderately or weakly positive in 10 (24%) and negative in 15 (36%) of 42 melanomas. Soluble Fas plasma levels in patients with metastatic malignant melanoma were significantly elevated over those in the control group (P = 0.01).The absence of Fas in most of the thick melanomas that did not metastasize, and in insitu melanomas, might be taken as a theoretical factor for a good prognosis. Soluble Fas is increased in patients with metastatic melanoma and might be associated with poor prognosis.
VISIT-TO-VISIT VARIABILITY OF SYSTOLIC BLOOD PRESSURE PREDICTS OUTCOMES MAINLY IN THE ACTIVE TREATMENT GROUP RATHER THAN THE PLACEBO GROUP IN THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM: PATHOPHYSIOLOGIC IMPLICATIONS
Authors: John B. Kostis, Jeanine E. Sedjro, Javier Cabrera, Nora M. Cosgrove, Sara Pressel, Barry R. Davis
Journal: Journal of the American College of Cardiology (2013)
Cognitive assessment of older people
Authors: J. Young, D. Meagher, A. MacLullich
Journal: BMJ (2011)

points Dementia, depression, and delirium are common and serious clinical syndromes in older people that are underdiagnosed in routine care Formal detection of these syndromes may enable identification of treatable conditions, is associated with better outcomes for patients, and requires routine cognitive assessmentCognitive assessment requires integration of information acquired from observing the patient and talking with carers, and from the results of an assessment instrument Cognitive assessment instruments are brief, easy to use, and sensitive to cognitive impairment, but an overall clinical assessment is needed to establish the underlying causeThe character and time frame of cognitive problems are key considerations in establishing an accurate diagnosis and a coherent management plan Case scenario: part 1A woman aged 89 years attends your clinic accompanied by her daughter.The daughter explains that her mother has not been herself over the past few months, that she is less interested in her usual activities, has poor concentration during conversation, and forgets day to day events.Two days ago she became incontinent of urine, which was unusual for her, and was noted to be confused and sleepy.
Pathogenic Role of Endothelin 1 in Hemodynamic Dysfunction in Experimental Acute Pulmonary Thromboembolism
Authors: JI-HYUN LEE, YONG-GAM CHUN, IN-CHUL LEE, RUBIN M. TUDER, SANG-BUM HONG, TAE-SUN SHIM, CHAE-MAN LIM, YOUNSUCK KOH, WOO-SUNG KIM, DONG-SOON KIM, WON-DONG KIM, SANG-DO LEE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ETA receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ETA receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ETA receptor antagonists might constitute a useful therapeutic tool for APE.
Relation between ventricular repolarization duration and cardiac cycle length during 24-hour Holter recordings. Findings in normal patients and patients with long QT syndrome.
Authors: M Merri, A J Moss, J Benhorin, E H Locati, M Alberti, F Badilini
Journal: Circulation (1992)

BACKGROUND The interval from the R wave to the maximum amplitude of the T wave (RTm) contains the heart rate dependency of ventricular repolarization. METHODS AND RESULTS A computer algorithm was developed to quantify the RTm and preceding RR intervals for each of more than 50,000 beats on 24-hour ambulatory electrocardiographic (Holter) recordings to evaluate the dynamic relation between repolarization duration and cycle length. The relation of RTm to the preceding RR interval (RTm/RR slope) was determined by the best-fit linear regression equation between these two parameters. Eleven normal subjects and 16 patients with long QT syndrome (LQTS) were investigated. Six of the normal subjects had Holter recordings obtained before and after beta-blocker therapy. beta-Blockers were associated with a significant (p = 0.005) reduction in the RTm/RR slope from 0.13 +/- 0.02 to 0.10 +/- 0.02. The mean value of the RTm/RR slope was significantly (p = 0.003) larger in the LQTS patients (0.21 +/- 0.08) than in normal subjects (0.14 +/- 0.03). CONCLUSIONS These findings indicate that 1) quantification of the dynamic relation between ventricular repolarization and RR cycle length can be obtained on a large number of Holter-recorded heart beats; 2) beta-blockers reduce the RTm/RR slope in normal patients; and 3) LQTS patients have an exaggerated delay in repolarization at long RR cycle lengths.
High-density lipoprotein, beta cells, and diabetes
Authors: A. von Eckardstein, C. Widmann
Journal: Cardiovascular Research (2014)

High-density lipoproteins (HDLs) exert a series of potentially beneficial effects on many cell types including anti-atherogenic actions on the endothelium and macrophage foam cells. HDLs may also exert anti-diabetogenic functions on the beta cells of the endocrine pancreas, notably by potently inhibiting stress-induced cell death and enhancing glucose-stimulated insulin secretion. HDLs have also been found to stimulate insulin-dependent and insulin-independent glucose uptake into skeletal muscle, adipose tissue, and liver. These experimental findings and the inverse association of HDL-cholesterol levels with the risk of diabetes development have generated the notion that appropriate HDL levels and functionality must be maintained in humans to diminish the risks of developing diabetes. In this article, we review our knowledge on the beneficial effects of HDLs in pancreatic beta cells and how these effects are mediated. We discuss the capacity of HDLs to modulate endoplasmic reticulum stress and how this affects beta-cell survival. We also point out the gaps in our understanding on the signalling properties of HDLs in beta cells. Hopefully, this review will foster the interest of scientists in working on beta cells and diabetes to better define the cellular pathways activated by HDLs in beta cells. Such knowledge will be of importance to design therapeutic tools to preserve the proper functioning of the insulin-secreting cells in our body.
Cholangitis and Endoscopic Drainage
Authors: Jeffrey L. Barnett
Journal: Hepatology (1992)

ABSTRACT Background. Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment. Methods. During a 43–month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis. Results. Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 treated with surgery (34 vs. 66 percent, P &gt; 0.05). The time required for normalization of temperature and stabilization of blood pressure was similar in the two groups, but more patients in the surgery group required ventilatory support. The hospital mortality rate was significantly lower for the patients who underwent endoscopy (4 deaths) than for those treated surgically (13 deaths) (10 vs. 32 percent, P &lt; 0.03). The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups. Conclusions. Endoscopic biliary drainage is a safe and effective measure for the initial control of severe acute cholangitis due to choledocholithiasis and to reduce the mortality associated with the condition.
Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function.
Authors: W M Holleran, Y Takagi, G K Menon, G Legler, K R Feingold, P M Elias
Journal: Journal of Clinical Investigation (1993)

The interstices of the mammalian stratum corneum contain lipids in a system of continuous membrane bilayers critical for the epidermal permeability barrier. During the transition from inner to outer stratum corneum, the content of polar lipids including glucosylceramides, decreases while ceramide content increases. We investigated whether inhibition of glucosylceramide hydrolysis would alter epidermal permeability barrier function. Daily topical applications of bromoconduritol B epoxide (BrCBE) to intact murine skin selectively inhibited beta-glucocerebrosidase, increased glucosylceramide content of stratum corneum with ceramide content remaining largely unchanged, and caused a progressive, reversible decrease in barrier function. Histochemistry of inhibitor-treated epidermis revealed persistence of periodic acid-Schiff-positive staining in stratum corneum cell membranes, consistent with retention of hexose moieties. Electron microscopy of inhibitor-treated samples revealed no evidence of toxicity or changes in the epidermal lipid delivery system. However, immature membrane structures persisted in the intercellular spaces throughout the stratum corneum, with reappearance of mature membrane structures progressing outward from the lower stratum corneum upon termination of BrCBE. Finally, the induced barrier abnormality was not reversed by coapplications of ceramide. These data demonstrate that glucosylceramide hydrolysis is important in the formation of the epidermal permeability barrier, and suggest that accumulation of glucosylceramides in stratum corneum intercellular membrane domains leads to abnormal barrier function.
THE ACCUMULATION OF IRON IN TUBERCULOUS AREAS
Authors: Valy Menkin, Miriam F. Menkin
Journal: The Journal of Experimental Medicine (1931)

Repeated daily intravenous injections of ferric chloride solution are followed by an accumulation of iron in tuberculous areas of lungs. The iron accumulates in the caseous areas of tubercles and is demonstrable by the Prussian blue reaction. Quantitative determinations corroborate these results and show that the iron content of lung tissue in tuberculous animals injected with ferric chloride exceeds that in normal animals injected with this salt, as well as that in non-injected tuberculous animals.
Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD
Authors: Moumita Barua, Onur Cil, Andrew D. Paterson, Kairon Wang, Ning He, Elizabeth Dicks, Patrick Parfrey, York Pei
Journal: Journal of the American Society of Nephrology (2009)

Mutations of PKD1 and PKD2 account for 85 and 15% of cases of autosomal dominant polycystic kidney disease (ADPKD), respectively. Clinically, PKD1 is more severe than PKD2, with a median age at ESRD of 53.4 versus 72.7 yr. In this study, we explored whether a family history of renal disease severity predicts the mutated gene in ADPKD. We examined the renal function (estimated GFR and age at ESRD) of 484 affected members from 90 families who had ADPKD and whose underlying genotype was known. We found that the presence of at least one affected family member who developed ESRD at age < or =55 was highly predictive of a PKD1 mutation (positive predictive value 100%; sensitivity 72%). In contrast, the presence of at least one affected family member who continued to have sufficient renal function or developed ESRD at age >70 was highly predictive of a PKD2 mutation (positive predictive value 100%; sensitivity 74%). These data suggest that close attention to the family history of renal disease severity in ADPKD may provide a simple means of predicting the mutated gene, which has prognostic implications.
A Form of the Metabolic Syndrome Associated with Mutations in<i>DYRK1B</i>
Authors: Ali R. Keramati, Mohsen Fathzadeh, Gwang-Woong Go, Rajvir Singh, Murim Choi, Saeed Faramarzi, Shrikant Mane, Mohammad Kasaei, Kazem Sarajzadeh-Fard, John Hwa, Kenneth K. Kidd, Mohammad A. Babaee Bigi, Reza Malekzadeh, Adallat Hosseinian, Masoud Babaei, Richard P. Lifton, Arya Mani
Journal: New England Journal of Medicine (2014)

Genetic analysis has been successful in identifying causative mutations for individual cardiovascular risk factors. Success has been more limited in mapping susceptibility genes for clusters of cardiovascular risk traits, such as those in the metabolic syndrome.
Biostatistical Implications of Design, Sampling, and Measurement to Health Science Data Analysis
Authors: Gary G. Koch, Dennis B. Gillings, Maura E. Stokes
Journal: Annual Review of Public Health (1980)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Electrophoretic Variation and Sex Dimorphism of the Major Urinary Protein Complex in Inbred Mice: A New Genetic Marker
Authors: J. S. Finlayson, Michael Potter, Charles R. Runner
Journal: JNCI Journal of the National Cancer Institute (1963)

The urinary proteins of both sexes from 19 inbred strains of mice and 2 hybrids were examined by agar-gel electrophoresis and Immunoelectrophoresis with rabbit antisera. The mice excreted several different proteins, but amounts of the major urinary protein (MUP) greatly exceeded all others. At pH 5.5, three different electrophoretic components of MUP could be distinguished. In any inbred strain only 2 of the components were evident, and they varied in relative amounts. On this basis several MUP phenotypes were designated. Although 2 male and 4 female phenotypes were seen, only 4 male-female combinations were observed in the 19 strains examined. When 2 parental strains of similar phenotype were mated, the MUP components of the respective F1 hybrids were like those of the parent of the same sex. When 2 unlike parental strains were mated, the F1 hybrids of both sexes had a different phenotype from either parent, all 3 components being present. Ovariectomized, testosterone-treated females exhibited the MUP phenotype characteristic of the males of the strain, but the pattern returned to the female phenotype when testosterone injections were discontinued. Castrated males had the pattern characteristic of females. The MUP complex thus provides a suitable system for the study of genetic and hormonal influences on protein synthesis.
Staphylococcus aureus in the lesions of atopic dermatitis
Authors: JAMES J. LEYDEN, RICHARD R. MARPLES, ALBERT M. KLIGMAN
Journal: British Journal of Dermatology (1974)

Quantitative aerobic cultures were obtained from fifty patients with chronic plaques, and from twenty with exudative lesions of atopic dermatitis. In the former, Staphylococcus aureus was isolated from 90% and the density exceeded 1 × 106/cm2 in 45% of the samples. In the exudative form, Staph. aureus was recovered in every case with a mean density of 14 × 106 organisms per cm2. Staph. aureus was the dominant organism not only in the lesions but in nearby clinically normal skin. Despite these high numbers, clinical signs of infection were lacking. Systemic and topical antibiotic therapy pro‐duced a profound decrease in Staph. aureus density. It is proposed that high numbers of Staph. aureus may aggravate the underlying lesion and be the source of Staph. aureus infections in contacts.
Human SNPs Reveal No Evidence of Frequent Positive Selection
Authors: Liqing Zhang, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2005)

We compared the single-nucleotide polymorphisms (SNPs) in humans in 182 housekeeping and 148 tissue-specific genes. SNPs were divided into rare and common polymorphisms based on their frequencies. We found that housekeeping genes tend to be less polymorphic than tissue-specific genes for both rare and common SNPs. Using mouse as a second species for computing sequence divergences, we found no evidence of positive selection: for both housekeeping and tissue-specific genes, the ratio of nonsynonymous to synonymous common SNPs per site showed no significant difference from that of divergence. Similarly, we observed no evidence of positive selection for the 289 and 149 genes that have orthologs available for divergence calculation between humans and chimpanzees and between humans and Old World monkeys, respectively. A comparison with previous SNP studies suggests that approximately 20% of the nonsynonymous SNPs in the human population are nearly neutral and that positive selection in the human genome might not be as frequent as previously thought.
Identification of alpha-naphthyl butyrate esterase as a plasma membrane ectoenzyme of monocytes and as a discrete intracellular membrane-bounded organelle in lymphocytes.
Authors: M J Bozdech, D F Bainton
Journal: The Journal of Experimental Medicine (1981)

A reaction for an esterase, with a nonhalogenated, short-chain naphthyl ester (alpha-naphthyl butyrate or alpha-naphthyl acetate) as the substrate, has been used to identify mononuclear phagocytes by light microscopy. By analyzing techniques used in the collection, separation, fixation, processing, and embedding of human blood leukocytes for electron microscopy, we adapted the light microscopic method for use in determining the fine structural localization of this reaction. In monocytes, the reaction product covered the external surface of the plasma membrane. This distribution indicated that monocytic esterase is an ectoenzyme. The addition of NaF completely inhibited the monocytic reaction. In lymphocytes, the reaction product was localized in membrane-bounded intracellular organelles, similar to those previously shown to contain phospholipid and called Gall bodies. These organelles correspond with the punctate densities or focal reaction product observed by light microscopy. Other investigators believe that this distribution of enzyme in lymphocytes marks a subset of T cells, the Tmicro. The lymphocytic reaction was not inhibited by NaF.
EARLY AND PERIODIC SCREENING, DIAGNOSIS, AND TREATMENT AND MANAGED CARE
Authors: Margo L. Rosenbach, Norma I. Gavin
Journal: Annual Review of Public Health (1998)

▪ Abstract This paper presents evidence on the performance of Medicaid managed care organizations (MCOs) in providing Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) services to children under age 21. States face considerable challenges in integrating EPSDT into managed care. For example, MCOs rarely offer all services required under federal law. Also, MCOs often are unable to meet state reporting requirements. On the other hand, MCOs offer children a medical home, often for the first time, that may encourage timely preventive care. The literature generally shows no differences in the performance of MCOs relative to traditional FFS providers in the EPSDT participation rate. Future needs include improving the specificity of contract language, more precisely defining the EPSDT benefit package, evaluating the adequacy of EPSDT payments, monitoring the capacity of MCO provider networks, establishing the effectiveness of outreach and enabling services, developing standardized MCO reporting requirements, documenting program outcomes, and assessing benchmarks for accountability.