tbuckley/cabot-search huggingface dataset:
Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia
Authors: Hiroshi Kawaguchi, Noriyo Manabe, Chisato Miyaura, Hirotaka Chikuda, Kozo Nakamura, Makoto Kuro-o
Journal: Journal of Clinical Investigation (1999)

We recently identified a new gene, klotho, which is involved in the suppression of multiple aging phenotypes. The mouse homozygous for a disruption of the klotho locus (kl/kl) exhibited multiple pathological conditions resembling human aging. Histomorphometric analysis revealed low-turnover osteopenia in kl/kl mice. The decrease in bone formation exceeded that of bone resorption, resulting in a net bone loss. The number of osteoblast progenitors determined by ex vivo bone marrow cultures was reduced in kl/kl mice. In addition, cultured osteoblastic cells derived from kl/kl mice showed lower alkaline phosphatase activity and matrix nodule formation than those from wild-type mice. Osteoclastogenesis in the coculture of marrow cells and osteoblastic cells was decreased only when marrow cells originated from kl/kl mice independently of the origin of osteoblastic cells. We also found that the expression of osteoprotegerin, an osteoclastogenesis inhibitor, was significantly upregulated in kl/kl mice. We conclude that a defect in the klotho gene expression causes the independent impairment of both osteoblast and osteoclast differentiation, leading to low-turnover osteopenia. Because this state represents a characteristic feature of senile osteoporosis in humans, kl/kl mice can be regarded as a useful model for investigating cellular and molecular mechanisms of age-related bone loss.
CRP as a Mediator of Disease
Authors: Edward T.H. Yeh
Journal: Circulation (2004)

Of the various hypotheses offered to explain atherosclerosis, inflammation now appears to provide a key to this pathological process. Inflammation has been shown to play a major role in precipitating a cascade of events from formation of the atheromatous lesion in response to vascular injury through lipid ingestion by macrophages, to subsequent rupture of the lesion, and myocardial infarction. Atherosclerosis shares many inflammatory features with rheumatoid arthritis (RA), an autoimmune disease, and drugs that block the inflammatory cytokine pathway now provide effective treatment for RA. In animal models, blockers of the inflammatory cytokine pathway appear to block mononuclear cell binding to arterial plaque. C-reactive protein (CRP), an inflammatory marker, may also play a proinflammatory role in activating monocyte chemotactic protein. Antiatherosclerotic drugs may be exerting some of their beneficial effects by inhibiting the harmful effects of CRP.
The Accuracy of Spirographic Recording at High Respiratory Rates
Authors: L. Bernstein, D. Mendel
Journal: Thorax (1951)

Spirometers were designed and used originally for the measurement of metabolic rate or such respiratory constants as vital capacity.Such measurements are made at low rates of respiration (up to about 40 breaths per minute) or with single inspiratory or expiratory efforts.There has been no reason to suspect the accuracy of records made under these conditions.Since Hermannsen (1933) first described the maximum breathing capacity test (M.B.C.) many investigators have used the spirometer to record tidal air at consider- ably higher rates of breathing.During an investigation into the M.B.C. of a series of subjects D' Silva and Mendel (1950) noted that at respiratory rates higher than 55 breaths per minute the oscillatory movements of the water in their spiro- meter were of such violence that very often water was aspirated into the tubes connecting the subject to the instrument, and that aspiration invariably occurred at these high respiratory rates if the tidal air was large.The large movements of the water column which they noted must have been either the cause, or the result, of considerable pressure changes within the spirometer bell, and it seemed that these pressure changes might affect the excursions of the bell and so invalidate the M.B.C. estimations.It was decided therefore to investigate the response of the spirometer at various respiratory rates in order to determine: (a) the magnitude of the errors produced, if any, and (b) whether it would be possible to construct a calibration curve for the instrument so that the errors could be corrected.DESCRIPTION OF THE SPIROMETER This was the same instrument as that used by D'Silva and Mendel in their experiments.It is of the Knipping type (manufactured by C. F. Palmer), and the CO2 absorber and circulating pump had been removed.Details of the moving parts of the instrument, except the pulleys, are given in Table I. METHODFirst the accuracy of the instrument as a volume recorder under static conditions was checked over the full range, from 0 to 6 litres, by introducing known small incre- mental volumes of air and recording the movements of the bell on the special charts provided.Secondly the accuracy as a volume recorder under dynamic conditions was studied by measuring the excursion of the bell produced by pumping a constant volume of air into and out of the spirometer at different repetitive rates.In order to avoid alteration in rate or volume, or any subjective compensations for restraint offered by on July 13,
Herpes Zoster and Chicken-pox
Authors: E. Lodge
Journal: BMJ (1957)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Herpes Zoster and Chicken-pox Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Papaverine inhibits bile acid excretion in isolated perfused rat liver
Authors: Tomoyuki Kumai, Makoto Hoshino, Tomihiro Hayakawa, Katsuyoshi Higashi
Journal: Hepatology (1994)

We investigated the effects of papaverine on bile acid excretion into bile in the presence of infusions of taurocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodehydrocholic acid in a single-pass, isolated perfused rat liver model. Although continuous infusion of papaverine (1.6 mumol/min) did not reduce bile acid excretion in the presence of low-dose (1.0 mumol/min) infusions of taurocholic acid or tauroursodeoxycholic acid, papaverine significantly inhibited biliary excretion of bile acids in the presence of low-dose taurochenodeoxycholic acid (-50%) and high-dose (3.0 mumol/min) taurocholic acid (-54%), tauroursodeoxycholic acid (-37%) and taurodehydrocholic acid (-31%). During continuous infusion of taurocholic acid (3 mumol/min), a 15-min infusion of papaverine (3.2 mumol/min) reduced bile acid excretion significantly; however, total uptake of bile acid was slightly decreased by the papaverine infusion. Bile acid excretion increased over the baseline value after the papaverine infusion was stopped and then returned to baseline. These results suggest that papaverine does not affect the uptake phase of bile acids at the sinusoidal membrane but may affect the intracellular transport phase or the excretory phase at the bile canalicular membrane. When taurocholic acid was infused at a constant rate of 3 mumol/min for 20 min without papaverine and then stopped, bile acid excretion decreased gradually and was nearly zero by 52 min. Cumulative bile acid excretion in the 52 min after the end of the infusion reached 3.3 +/- 0.2 mumol/gm liver and represented the storage capacity of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
A CLINICAL STUDY OF URETERS
Authors: ALEXANDER HAMILTON PEACOCK
Journal: JAMA (1923)

The ureter is a subject of great interest to the abdominal surgeon as well as to the urologist. More and more are surgeons learning that abdominal pain, either right or left sided, is often caused by lesions of the ureter. In all obscure pains of this region, the condition of the ureters and kidneys should be determined. In going over my consultation records, I am greatly impressed by the patients who have been unsuccessfully operated on for abdominal pain, only to find a urologic condition present, such as stricture of the ureter, regurgitation from the bladder up the ureter, dilatation, nephroptosis, kinks of the ureter and impacted calculus. My object in this paper is not to report any new or rare pathologic lesions, but to demonstrate just what things are discovered by routine pyelograms; at the same time, it is also urged that the ureters be more carefully studied, for
825. Primary Canine Marrow Cells Support HIV-1 Vector Mediated Expression of Functional Human Factor VIII
Authors: Michail Zaboikin, Srinivas N. Kumar, Tatiana Zaboikina, Friedrich G. Schuening
Journal: Molecular Therapy (2006)

We have tested primary canine marrow mononuclear cells (MNC) as a potential target for gene therapy of hemophilia A by investigating their ability to support the expression of functional transgenic factor VIII (FVIII). . To this end, B-domain deleted human FVIII (BDFVIII) transgene was expressed in HIV-1 vectors from the viral LTR promoter or constitutively active internal cellular promoters: the mouse phosphoglycerate kinase (PGK) or elongation factor 1α (EF1α) promoters. The vector that expressed BDFVIII from the LTR also encoded a functional single-exon Tat protein (Tat72) [Srinivasakumar and Schuening (2000) J. Virol. 74:6659-6668]. The promoters expressed transgenes at high levels in hematopoietic cells, as has been previously shown [Srinivasakumar et. al., (2002). J. Virol. 76:7334-7342]. Vector stocks for each of the above vectors were prepared by transient transfection of 293T cells [Srinivasakumar (2002) Methods Mol. Med. 69:275-302] and their titers were determined by real-time quantitative PCR of genomic DNA isolated from vector infected indicator cells. Each vector stock was then used for infection of primary canine marrow MNC by three spin-infections over 2 days on CH296-coated 6-well plates. The medium was replaced at the end of the transduction procedure. Conditioned medium was harvested 3-days after transduction and assayed for functional FVIII activity using the Coamatic Factor VIII kit (Chromogenix, Monza, Italy). Measured factor VIII activity in conditioned medium was normalized to input vector titer. The results, shown in the figure below, indicate that vector-derived FVIII could be detected in the supernatants of canine marrow MNCs transduced with any of the three HIV-1 vectors. Highest levels of functional FVIII were obtained with the Tat-encoding bicistronic HIV-1 vector. These results demonstrate that canine marrow MNC support expression and secretion of functional human FVIII. Further experiments are warranted to determine if the levels of FVIII observed in vitro will translate into therapeutic benefit in vivo in canine models of hemophilia A.
The New York State Examination Act.
Authors: William Warren Potter
Journal: JAMA (1890)

<h3>To the Editor:</h3> —Under the above title a correspondent ofThe Journal, Dr. Alfred Ludlow Carroll, of 30 West Fifty-ninth street, New York —we cheerfully give his name and address in full —offers extended criticism in your issue of August 23, 1890, of the recent statute enacted by the legislature of this State creating boards of medical examiners for the license to practice. In the third paragraph of this singularly clear, logical and concise communication occurs one sentence to which I beg briefly to reply. It is worded as follows: According to its report for 1889, its members numbered less than 200.......Yet from this small circle are to be exclusively appointed the arbiters of questions which concern the whole profession throughout the United States. This refers to the Medical Society of the State of New York, which by the statute above referred to, is charged with the duty of nominating
Endotoxin and Endotoxemia
Authors: Jack Levin
Journal: New England Journal of Medicine (1973)

Endotoxins — lipopolysaccharides that form a portion of the cell walls of gram-negative bacteria — cause alterations of blood coagulation, complement and kallikrein, and often hypotension and death in a variety of laboratory animals.1 Endotoxin has been considered a likely cause of some of the pathophysiological alterations that often lead to death of patients with bacteremia due to gram-negative organisms. However, proof that endotoxin actually produces these effects in man is lacking. In addition, a test sensitive enough to detect endotoxin in blood or other body fluids has not been available in the past, and gram-negative sepsis has been equated . . .
Dose-response relationships for carcinogens: a review.
Authors: L Zeise, R Wilson, E A Crouch
Journal: Environmental Health Perspectives (1987)

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites.
Abstract 3493: A single-tube, multiplexed, transcript-based assay to detect ALK, ROS1 and RET fusions in lung cancer.
Authors: Maruja Lira, Yoon-La Choi, Shibing Deng, Donghui Huang, Mark Ozeck, Joungho Han, Ji Yun Jeong, Keunchil Park, Jhingook Kim, Myung-Ju Ahn, Mao Mao
Journal: Cancer Research (2013)

Abstract Oncogenic fusions involving ALK, ROS1 and RET define a small subpopulation (∼7%) of non-small cell lung carcinomas (NSCLC). Tumors harboring ALK and ROS1 rearrangements are highly sensitive to crizotinib whereas RET inhibitors may be of potential benefit for the treatment for RET-fusion positive tumors1. Current methods for detection of ALK, ROS1, and RET rearrangements involve fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) or RT-PCR, each test offering its own advantages and disadvantages, and making it difficult for screening large numbers of patient samples for all three targetable fusions. To explore screening modalities for the simultaneous detection of ALK, ROS1 and RET fusions from a single analyte, we designed a multiplexed, transcript-based assay to detect for presence or absence of fusions. Utilizing a combined 3’ over-expression and fusion-specific detection strategy, we developed a single-tube multiplex assay with a quantitative scoring modality that is highly sensitive, reproducible and capable of detecting low abundant ALK, ROS1 and RET fusion transcripts. We successfully validated the assay in 273 NSCLC specimens. For ALK, our results were highly concordant (97.4%) to prior results obtained by IHC (n=189). We confirmed ROS1 (n=7) and RET (n=11) fusion-positive tumors by RT-PCR plus sequencing. There is a significant enrichment for ROS1 and RET fusions in triple negative NSCLC (i.e. KRAS/EGFR/ALK wildtype) (Table 1). ALK, ROS1, RET, KRAS and EGFR mutations are mutually exclusive in this study. Our assay offers an easy to perform, high-throughput, and FFPE-compatible screening method for detection of ALK, ROS1 and RET fusions. Table 1. Incidence of ALK, ROS1 and RET fusions cohorts clinical/molecular feature # cases ALK+ ROS1+ RET+ Set 1 ALK IHC+, Kras/EGFR wt 95 91 0 0 Set 2 ALK IHC−, Kras/EGFR wt 94 1 5 11 Set 3 never smokers 84 10 2 1 Citation Format: Maruja Lira, Yoon-La Choi, Shibing Deng, Donghui Huang, Mark Ozeck, Joungho Han, Ji Yun Jeong, Keunchil Park, Jhingook Kim, Myung-Ju Ahn, Mao Mao. A single-tube, multiplexed, transcript-based assay to detect ALK, ROS1 and RET fusions in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3493. doi:10.1158/1538-7445.AM2013-3493
The Elderly and Poor in the Medical Outcomes Study
Authors: Peter Juhn
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The report of health outcomes for elderly and poor, chronically ill patients<sup>1</sup>provoked alarming headlines in the lay press: "Aged, Poor Fare Worse in HMOs, Study Says."<sup>2</sup>However, the data presented by the authors support neither the conclusions of the article nor the subsequent headlines. We are especially troubled by this study's potential negative impact on the physician-patient relationships of the nation's 3.6 million Medicare risk beneficiaries. Our major concern about this study is the unequivocal language regarding the association between prepaid financing and worse health outcomes. In this study, changes in average physical and mental health scores were not statistically significant across either the age or poverty categories. Presumably, the sample size estimate was based on this analysis. It is the standard approach to analyzing such data, and it showed no difference. For this finding to be omitted from the "Results" section of the
Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice
Authors: Jørgen F.P. Wojtaszewski, Yasuki Higaki, Michael F. Hirshman, M. Dodson Michael, Scott D. Dufresne, C. Ronald Kahn, Laurie J. Goodyear
Journal: Journal of Clinical Investigation (1999)

Physical exercise promotes glucose uptake into skeletal muscle and makes the working muscles more sensitive to insulin. To understand the role of insulin receptor (IR) signaling in these responses, we studied the effects of exercise and insulin on skeletal muscle glucose metabolism and insulin signaling in mice lacking insulin receptors specifically in muscle. Muscle-specific insulin receptor knockout (MIRKO) mice had normal resting 2-deoxy-glucose (2DG) uptake in soleus muscles but had no significant response to insulin. Despite this, MIRKO mice displayed normal exercise-stimulated 2DG uptake and a normal synergistic activation of muscle 2DG uptake with the combination of exercise plus insulin. Glycogen content and glycogen synthase activity in resting muscle were normal in MIRKO mice, and exercise, but not insulin, increased glycogen synthase activity. Insulin, exercise, and the combination of exercise plus insulin did not increase IR tyrosine phosphorylation or phosphatidylinositol 3-kinase activity in MIRKO muscle. In contrast, insulin alone produced a small activation of Akt and glycogen synthase kinase-3 in MIRKO mice, and prior exercise markedly enhanced this insulin effect. In conclusion, normal expression of muscle insulin receptors is not needed for the exercise-mediated increase in glucose uptake and glycogen synthase activity in vivo. The synergistic activation of glucose transport with exercise plus insulin is retained in MIRKO mice, suggesting a phenomenon mediated by nonmuscle cells or by downstream signaling events.
Management of Septic Arthritis
Authors: Joseph M. Mylotte
Journal: JAMA (1982)

<h3>To the Editor.—</h3> I initially read with interest the article by Ho and Su entitled "Therapy for Septic Arthritis" (1982;247:797). It is apparent that the title of this article is deceiving. There is little or no information about specific therapy, but, rather, a brief analysis of prognostic factors related to outcome. The authors of this article conclude that the time to sterilize the synovial fluid correlates with outcome of therapy. They arrive at this conclusion based on the results of serial synovial fluid cultures in only 13 patients. Although the authors make the statement that they have tried "to minimize the number of variables that may skew interpretation of the data," they have, in fact, selected a biased sample from which to make conclusions. It is well known that patients with underlying joint disease (rheumatoid arthritis, osteoarthritis) and septic arthritis have a poorer outcome than those with infection without underlying
Changes of Mean Spatial QRS and T Vectors and of Conventional Electrocardiographic Items in Hard Anaerobic Work
Authors: K. A. KAHN, E. SIMONSON
Journal: Circulation Research (1957)

In 35 normal men, conventional and vectorial electrocardiographic items were studied after severe, anaerobic exercise over a recovery period of 8 min. The changes, especially of the T vector, are pronounced, but are different from those observed in coronary insufficiency. The hypothesis is advanced that the changes in anaerobic exercise are due to general myocarclial hypoxia, in contrast to the localized ischemia in coronary insufficiency.
Oroileal transit of slow release 5-aminosalicylic acid.
Authors: H Goebell, U Klotz, B Nehlsen, P Layer
Journal: Gut (1993)

The predominant active anti-inflammatory moiety in chronic inflammatory bowel disease is 5-aminosalicylic acid (5-ASA). As unprotected 5-ASA is rapidly absorbed in the upper gastrointestinal tract several slow release preparations have been developed to permit passage of 5-ASA to the lower small bowel and to the colon. To investigate luminal kinetics and extent of the release of 5-ASA intraluminal concentrations and loads of this compound together with that of its main metabolite acetyl-5-aminosalicylic acid (ac-5-ASA) were studied, over 15 hours after giving the slow release preparation Salofalk at a dose of 500 mg orally together with a test meal. Plasma concentrations and urinary excretion were also measured. Six healthy volunteers swallowed an 11 lumen oroileal tube, which allowed marker perfusion, aspiration of luminal content from the duodenum, mid-jejunum, and ileum, and recording of intestinal motility. Emptying of 5-ASA into the duodenum started after emptying of the meal, together with the first phase III of interdigestive motility. Mean luminal concentrations of 5-ASA and ac-5-ASA increased continuously from duodenum (both: 15 to 30 micrograms/ml) to ileum (60 to 110 micrograms/ml and 80 to 150 micrograms/ml respectively) over three hours and decreased over the next three hours. During 10 hours after eating, 30% of the total dose passed the ileum in solution and another 10% were excreted in urine. Thus about 60% reached the colon unreleased from tablets and another 30% were in solution. The ratio of 5-ASA and ac-5-ASA in solution was about 1:1 in the duodenum and 1:1.5 to 1:2 in the more distal small intestine. The data suggest that the large quantities of intraluminal ac-5-ASA are generated in the intestinal mucosa and reach the lumen by back diffusion. The results show that most of the 5-ASA from this slow release preparation is delivered into the colon, which explains its effectiveness in ulcerative colitis. The considerable luminal concentrations already present in the distal ileum might justify therapeutic trials in Crohn9s disease.
Platelet-activating factor stimulates a rapid accumulation of inositol (1,4,5)trisphosphate in guinea pig eosinophils: Relationship to calcium mobilization and degranulation
Authors: Claus Kroegel, Edwin R. Chilvers, Mark A. Giembycz, R.A.John Challiss, Peter J. Barnes
Journal: Journal of Allergy and Clinical Immunology (1991)