tbuckley/cabot-search huggingface dataset:
Characterization of a protein cofactor that mediates protein kinase A regulation of the renal brush border membrane Na(+)-H+ exchanger.
Authors: E J Weinman, D Steplock, Y Wang, S Shenolikar
Journal: Journal of Clinical Investigation (1995)

Activation of cAMP-dependent protein kinase A inhibits the renal proximal tubule brush border membrane Na(+)-H+ exchanger by a process involving participation of a regulatory cofactor (NHE-RF) that is distinct from the transporter itself. Recent studies from this laboratory reported a partial amino acid sequence of this putative cofactor (Weinman, E. J., D. H. Steplock, and S. Shenolikar. 1993. J. Clin. Invest. 92:1781-1786). The present experiments detail the structure of the NHE-RF protein as determined from molecular cloning studies. A codon-biased oligonucleotide probe to a portion of the amino acid sequence of the putative cofactor was used to isolate a 1.9-kb cDNA from a rabbit renal library. The encoded protein is 358 amino acids in length and is rich in proline residues. Search of existing data bases indicates that NHE-RF is a unique protein. Using a reticulocyte lysate, the cDNA translated a product of approximately 44 kD, which was recognized by an affinity-purified polyclonal antibody to NHE-RF. Potential phosphorylation sites for protein kinase A are present. The mRNA for the protein is expressed in kidney, proximal small intestine, and liver. Reverse transcription/PCR studies in the kidney indicate the presence of mRNA for NHE-RF in several distinct nephron segments including the proximal tubule.
Adherence to the DASH Diet Is Inversely Associated With Incidence of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study
Authors: Angela D. Liese, Michele Nichols, Xuezheng Sun, Ralph B. D'Agostino, Steven M. Haffner
Journal: Diabetes Care (2009)

OBJECTIVE The Dietary Approaches to Stop Hypertension (DASH) diet has been widely promoted; however, little is known about its impact on type 2 diabetes. RESEARCH DESIGN AND METHODS We evaluated the association of the DASH diet with incidence of type 2 diabetes among 862 participants of the Insulin Resistance Atherosclerosis Study (IRAS) who completed a 1-year food frequency questionnaire at baseline. Type 2 diabetes odds ratios (ORs) were estimated at tertiles of the DASH score. RESULTS An inverse association was observed in whites (tertile 2 vs. tertile 1, OR 0.66 [95% CI 0.29–1.48]) that became significant for the most extreme contrast (tertile 3 vs. tertile 1, 0.31 [0.13–0.75]), with adjustment for covariates. No association was observed in blacks or Hispanics (tertile 2 vs. tertile 1, 1.16 [0.61–2.18 ]; tertile 3 vs. tertile 1, 1.34 [0.70–2.58 ]). CONCLUSIONS Adherence to the DASH dietary pattern, which is rich in vegetables, fruit, and low-fat dairy products, may have the potential to prevent type 2 diabetes.
Analysis of the Use of HIV Antibody Testing in a Minnesota Hospital
Authors: Keith Henry
Journal: JAMA (1988)

We retrospectively studied the clinical use of human immunodeficiency virus (HIV) antibody serology at one 450-bed medical center and affiliated clinics from April 1985 through August 1986. No restrictions were placed on the use of HIV antibody serology during that time, although it was recommended that consent be obtained and risk-reduction information be provided. Testing was performed for 275 patients; results for 25 (9%) of these were positive. Nearly half (44%) of the patients had no recognized risk factor for HIV infection recorded in their charts. For an additional 44% of the patients, the test was medically indicated but consent and counseling were not documented. For only 10% of HIV antibody tests was there notation that consent was obtained and that risk-reduction information was provided. These results indicate that HIV antibody testing is often done without consent and that opportunities to provide risk-reduction counseling are being missed. (<i>JAMA</i>1988;259:229-232)
Multimedia: Management of Acute and Chronic Pain
Authors: Mathew Zacharias
Journal: BMJ (1999)

Ed Narinder Rawal


BMJ Books, £25, pp 240 




ISBN 0 7279 1193 7

———————

Rating: ★★

In the past two decades we have seen a thorough change in the medical profession’s attitude towards pain and its control. Recent publications on pain suggest the growing demand for information.

To study the mechanisms we must journey through a maze of neurotransmitters, chemical modulators, and neural pathways. If we make the effort to cross this labyrinth the reward is a clearer understanding of referred pain, secondary hyperalgesia, placebo response, and the like.

Evaluation and quantification of pain are important. All those who deal with acute pain should be able to achieve adequate pain control with the wide selection of drugs and techniques available. Children and neonates are the most challenging.

While management of cancer pain has undergone major changes in the past decade, and the WHO analgesic ladder is the simplest and most useful management aid, epidural analgesia has become the optimal method for pain relief during parturition.

The striking lack of success in the management of chronic pain, however, has forced us to consider a variety of treatments that include drugs, interventional techniques, and psychological approaches along with the proliferation of multidisciplinary pain clinics.

A few factual mistakes in the book (particularly in drug doses) could pose problems to those not familiar with the topic. Thus, the book is probably most suitable for ageing anaesthetists like myself, who will benefit from the challenges to our grey matter and from the recapitulation of some long forgotten truths.
On the Employment of Dead Bacteria in the Serum Diagnosis of Typhoid and Malta Fever, and on an Easy Method of Extemporising a Blowpipe Flame for Making Capillary Sero-Sedimentation Tubes
Authors: A. E. Wright, D. Semple
Journal: BMJ (1897)

2 in good health after nearly three years, i after one year and nine months, 3 after one year, i after six months, and I after three months; i case has not been seen since leaving the hospital.E. H. Taylor, of Dublin, in an excellent article in the
Characterizing and measuring bias in sequence data
Authors: Michael G Ross, Carsten Russ, Maura Costello, Andrew Hollinger, Niall J Lennon, Ryan Hegarty, Chad Nusbaum, David B Jaffe
Journal: Genome biology (2013)

DNA sequencing technologies deviate from the ideal uniform distribution of reads. These biases impair scientific and medical applications. Accordingly, we have developed computational methods for discovering, describing and measuring bias.We applied these methods to the Illumina, Ion Torrent, Pacific Biosciences and Complete Genomics sequencing platforms, using data from human and from a set of microbes with diverse base compositions. As in previous work, library construction conditions significantly influence sequencing bias. Pacific Biosciences coverage levels are the least biased, followed by Illumina, although all technologies exhibit error-rate biases in high- and low-GC regions and at long homopolymer runs. The GC-rich regions prone to low coverage include a number of human promoters, so we therefore catalog 1,000 that were exceptionally resistant to sequencing. Our results indicate that combining data from two technologies can reduce coverage bias if the biases in the component technologies are complementary and of similar magnitude. Analysis of Illumina data representing 120-fold coverage of a well-studied human sample reveals that 0.20% of the autosomal genome was covered at less than 10% of the genome-wide average. Excluding locations that were similar to known bias motifs or likely due to sample-reference variations left only 0.045% of the autosomal genome with unexplained poor coverage.The assays presented in this paper provide a comprehensive view of sequencing bias, which can be used to drive laboratory improvements and to monitor production processes. Development guided by these assays should result in improved genome assemblies and better coverage of biologically important loci.
Remission of symptoms during long term treatment of metastatic pancreatic endocrine tumours with long acting somatostatin analogue.
Authors: J L Ch'ng, J V Anderson, S J Williams, D H Carr, S R Bloom
Journal: BMJ (1986)

Five patients with metastatic pancreatic endocrine tumours injected a long acting somatostatin analogue (SMS 201-995) 50 micrograms subcutaneously every 12 hours and were followed up for three to six months. Treatment aimed at controlling excess secretion of hormone by the tumours thereby bringing symptomatic relief. Four patients showed a significant reduction in tumour related hormone concentrations but in none did values return to normal. All five patients, however, noted definite symptomatic improvement and in one this was dramatic (disappearance of life threatening diarrhoea and correction of metabolic acidosis and hypokalaemia within 48 hours). Mild worsening of symptoms and increasing fasting tumour related hormone concentrations after three to six months of treatment were reversed by doubling the 12 hourly dose. The treatment was well tolerated and had no deleterious effect on fasting blood glucose concentrations. This somatostatin analogue seems a promising non-invasive treatment for metastatic pancreatic endocrine tumours.
"ATTITUDE OF CHRISTIAN SCIENTISTS IN THE PRESENT EPIDEMIC OF INFLUENZA"
Authors: C. B. Burr
Journal: JAMA (1918)

<h3>To the Editor:</h3> —"The churches in Boston were not ordered closed by health authorities—merely requested," writes Walter H. Van Zwoll toThe Journal, November 9. What were the Eddyites waiting for? A club? Mr. Hoover's early requests for food conservation were accepted at once by a large proportion of the American people. The more definite regulations and prohibitions did not appear until some time later. This cheerful compliance was a source of marvel to the New York correspondent of<i>L'Illustration</i>, Paris, who thereupon made the flattering comment, "I have said not once but twenty times that this is the best disciplined nation on the face of the earth—a request from the top is all that is necessary." According to Carl Ackerman, the Eddyites in Berlin also believed in food conservation, but for an altogether different purpose. Immediately after the outbreak of war they laid by in store provisions in such
Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries.
Authors: M J Liptay, W C Parks, R P Mecham, J Roby, L R Kaiser, J D Cooper, M D Botney
Journal: Journal of Clinical Investigation (1993)

Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal extracellular matrix gene expression, suggesting regulation by local factors. Though the factors responsible for inducing matrix gene expression in atherosclerotic lesions are largely unknown, several observations suggest macrophages may be a focal source of those factors. Immunohistochemistry confirmed the presence of macrophages in the neointima of atherosclerotic elastic pulmonary arteries from patients with unexplained pulmonary hypertension. Areas of neointima containing dense clusters of macrophages were separated by sparsely populated areas. Foamy macrophages resided more deeply within the neointima than nonfoamy macrophages, which were found more often subjacent to the endothelium or within the lumenal one-third of the neointima. Combined immunohistochemistry-in situ hybridization indicated neointimal fibronectin and type I procollagen gene expression was intimately associated only with nonfoamy neointimal macrophages. These observations suggest that: (a) nonfoamy neointimal macrophages participate in the local regulation of extracellular matrix gene expression in atherosclerotic pulmonary arteries; (b) foamy macrophages, which are not associated with matrix gene expression, have undergone modulation of their secretory phenotype.
Tissue Factor Modulates the Thrombogenicity of Human Atherosclerotic Plaques
Authors: Vincenzo Toschi, Richard Gallo, Maddalena Lettino, John T. Fallon, S. David Gertz, Antonio Ferna´ndez-Ortiz, James H. Chesebro, Lina Badimon, Yale Nemerson, Valentin Fuster, Juan J. Badimon
Journal: Circulation (1997)

The thrombogenicity of a disrupted atherosclerotic lesion is dependent on the nature and extent of the plaque components exposed to flowing blood together with local rheology and a variety of systemic factors. We previously reported on the different thrombogenicity of the various types of human atherosclerotic lesions when exposed to flowing blood in a well-characterized perfusion system. This study examines the role of tissue factor in the thrombogenicity of different types of atherosclerotic plaques and their components.Fifty human arterial segments (5 foam cell-rich, 9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal, nonatherosclerotic segments) were exposed to heparinized blood at high shear rate conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial specimens was assessed by 111In-labeled platelets. After perfusion, specimens were stained for tissue factor by use of an in situ binding assay for factor VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0 to 3. Platelet deposition on the lipid-rich atheromatous core was significantly higher than on all other substrates (P = .0002). The lipid-rich core also exhibited the most intense tissue factor staining (3 +/- 0.1 arbitrary units) compared with other arterial components. Comparison of all specimens showed a positive correlation between quantitative platelet deposition and tissue factor staining score (r = .35, P < .01).Our results show that tissue factor is present in lipid-rich human atherosclerotic plaques and suggest that it is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption.
Peptide-mediated inactivation of recombinant and platelet plasminogen activator inhibitor-1 in vitro.
Authors: D T Eitzman, W P Fay, D A Lawrence, A M Francis-Chmura, J D Shore, S T Olson, D Ginsburg
Journal: Journal of Clinical Investigation (1995)

Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator, is an important regulator of the blood fibrinolytic system. Elevated plasma levels of PAI-1 are associated with thrombosis, and high levels of PAI-1 within platelet-rich clots contribute to their resistance to lysis by t-PA. Consequently, strategies aimed at inhibition of PAI-1 may prove clinically useful. This study was designed to test the hypothesis that a 14-amino acid peptide, corresponding to the PAI-1 reactive center loop (residues 333-346), can rapidly inhibit PAI-1 function. PAI-1 (0.7 microM) was incubated with peptide (55 microM) at 37 degrees C. At timed intervals, residual PAI-1 activity was determined by addition of reaction mixture samples to t-PA and chromogenic substrate. The T1/2 of PAI-1 activity in the presence of peptide was 4 +/- 3 min compared to a control T1/2 of 98 +/- 18 min. The peptide also inhibited complex formation between PAI-1 and t-PA as demonstrated by SDS-PAGE analysis. However, the capacity of the peptide to inhibit PAI-1 bound to vitronectin, a plasma protein that stabilizes PAI-1 activity, was markedly attenuated. Finally, the peptide significantly enhanced in vitro lysis of platelet-rich clots and platelet-poor clots containing recombinant PAI-1. These results indicate that a 14-amino acid peptide can rapidly inactivate PAI-1 and accelerate fibrinolysis in vitro. These studies also demonstrate that PAI-1 function can be directly attenuated in a physiologic setting and suggest a novel approach for augmenting fibrinolysis in vivo.
Exogenous surfactant in acute respiratory distress syndrome: more is better
Authors: A. Anzueto
Journal: European Respiratory Journal (2002)

Pulmonary surfactant is a complex of highly active phospholipids and proteins that cover the alveolar epithelial surface of the lungs 1. Surfactant is synthesized in the alveolar type-II cells, stored in the lamellar bodies, and secreted to the alveolar space where it undergoes complex changes 2. The composition of lung surfactant in humans is very constant, although it may change in disease states 3. Phospholipids account for 85% of its composition and the main component is dipalmitoylphosphatidylcholine (DPPC). In addition, surfactant contains different apoproteins, neutral lipids, and carbohydrates 4.

Pulmonary-surfactant dysfunction can lead to acute lung injury and is characterized by alveolar instability, floating, and collapse. These abnormalities have been shown to occur in acute respiratory distress syndrome (ARDS) 5, 6 and infant respiratory distress syndrome (IRDS) 7. Since the initial report of ARDS by Ashbaugh et al. 5, abnormalities of the surfactant system have been recognized. Petty and co-workers 8, 9, later reported both qualitative and quantitative abnormalities in the surfactant content of ARDS patients. It is now known that surfactant dysfunction plays a major role in the pathophysiology of ARDS 6, 10, and functional changes have been described not only in patients with established ARDS, but also in patients at risk 10–12. The main biochemical abnormalities include an 80% fall in the total phospholipid content, decline in the fractional content of DPPC and phosphatidylglycerol and …
A Visual Index of Thyroid Function
Authors: SAMUEL SOSTRE, SHIRISH PARIKH
Journal: Clinical Nuclear Medicine (1979)

A visual index of thyroid uptake (VITU) is introduced as a qualitative measure of thyroid trapping. This index is determined from the 20-minute 99mmTc-pertechnetate scan by visually comparing the relative tracer uptake between the thyroid and salivary glands. Three categories are defined: low, normal and elevated. The VITU correctly identified the functional status of the thyroid in 94% of 123 patients studied and agreed with the 24-hour radioiodine uptake (RAIU) in 89%. The VITU is a very simple but highly accurate, reliable and reproducible test. It was primarily designed to complement other tests of thyroid function by contributing qualitative information about the thyroidal trapping mechanism, but it can also be useful in confirming blood tests of thyroid function in cases in which one would prefer to avoid 131I administration for RAIU studies.
Some Relations Among Psychiatric Symptoms, Organic Illness, and Social Class
Authors: DEWITT L. CRANDELL, BRUCE P. DOHRENWEND
Journal: American Journal of Psychiatry (1967)

Two major investigations of the prevalence of psychiatric disorder in community groups, the Midtown and Stirling County studies, relied heavily on symptoms the researchers considered psychophysiological. Both found the highest rates of psychiatric disorder in the lowest status groups. The present study of a sample of 1,710 adults in Washington Heights, New York City, indicates that the previous findings are in part a function of a distinct tendency for lower-class groups to express psychological distress in physiological terms. The present results also suggest that the higher rates are confounded with organic illness.
The Risks of Phenacetin Use
Authors: Paul D. Stolley
Journal: New England Journal of Medicine (1991)

ALMOST 25 years ago, Dubach and his colleagues noted that many women working in Swiss watch factories took large amounts of analgesic drugs daily because of occupation-related aches and pains. The relation between abuse of analgesics and renal disease had been reported, but here was a unique opportunity to study the problem longitudinally. Thus began one of the more remarkable prospective cohort studies of recent decades.1 In this issue of the Journal, Dubach et al. report on 20 years of follow-up of this cohort, and their findings are disturbing.2 The essence of a cohort investigation is the division of . . .
High levels of CD44 expression distinguish virgin from antigen-primed B cells.
Authors: R L Camp, T A Kraus, M L Birkeland, E Puré
Journal: The Journal of Experimental Medicine (1991)

The in vitro polyclonal stimulation of B cells through their surface immunoglobulin (Ig) induces substantial increases in CD44 protein levels within 24 hours, whereas other stimuli (e.g., lipopolysaccharide, phorbol 12,13 dibutyrate, and interleukin 4) fail to significantly upregulate CD44. The marked increase in CD44 protein expression on anti-Ig-treated B lymphocytes correlates with an increase in CD44-specific mRNA. Cell sorting experiments with B cells isolated from trinitrophenyl-keyhole limpet hemocyanin-immunized mice demonstrate that both short-term antigen-specific, IgG-secreting cells and long-term antigen-primed B cells are exclusively CD44high. We speculate that the rapid and sustained increase in CD44 expression mediated by surface Ig stimulation may alter the homing properties of antigen-primed B cells.
Occurrence of Groupable Beta-Hemolytic Streptococci
Authors: W. Channing Nicholas
Journal: JAMA (1962)

Throat swabbings were taken weekly and cultured for groupable beta-hemolytic streptococci from September, 1960, through May, 1961, from 260 children in the first 6 grades of all schools in Bismarck. None of the children followed developed rheumatic fever or glomerulonephritis. One new case of rheumatic fever occurred during the study making an incidence of 0.0037% for the entire city. There was no significant seasonal variation in the weekly group A streptococcal prevalence rates. The average group A prevalence rate for the entire study was 16.6%, and the range in the weekly rates was 12%-21%. Group A streptococci were not isolated in a random pattern from these children. Of the 260 children followed 146 were found to have group A at least once during the study, and 35 children contributed over half of the cultures positive for group A.
MPs deplore poor progress in combating childhood obesity
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

The government's attempts to tackle childhood obesity have been beset by “dithering,” “confusion,” and “little coordination” by three key departments, the MP charged with investigating progress on the matter has said. Unless concerted action is taken promptly the proportion of children who are obese will rise sharply, he warns. 

Edward Leigh MP, chairman of the public accounts committee, was commenting on the committee's latest report. The committee took evidence on how the Departments of Health; Education and Skills; and Culture, Media, and Sport planned to halt the rise in obesity in children and what they are doing to harness the support of parents and influence …