tbuckley/cabot-search huggingface dataset:
Copper Resistant Human Hepatoblastoma Mutant Cell Lines Without Metallothionein Induction Overexpress Atp7b
Authors: Michael L. Schilsky, Richard J. Stockert, Amanda Kesner, Giridhar R. Gorla, Gregg S. Gagliardi, Kunihiko Terada, Naoyuki Miura, Mark J. Czaja
Journal: Hepatology (1998)

Mutant human hepatoblastoma cell lines resistant to copper toxicity were isolated from mutagenized HuH7. Two copper resistant cell lines (CuR), CuR 23 and CuR 27, had reduced basal expression of metallothionein (MT) messenger RNA (mRNA) and exhibited minimal or no increase in resistance to cadmium or zinc toxicity. Copper uptake, efflux of newly transported copper, glutathione content, and efflux rate were comparable with HuH7, whereas holoceruloplasmin synthesis and secretion were slightly decreased. Subcellular distribution of copper at steady–state showed an increase in organelle and membrane fractions with a reduction in cytosol. Expression of ATP7B mRNA was fivefold increased, and ATP7B protein approximately threefold increased in both CuR 23 and 27. Another cell line, CuR 41, showed increased basal expression of MT and ATP7B mRNA but not ATP7B protein, and resistance to cadmium and zinc toxicity. Copper uptake in CuR 41 was comparable with HuH7, but initial rates of efflux of copper and glutathione were reduced. The synthesis of holoceruloplasmin but not ceruloplasmin peptide was markedly diminished in CuR 41. Subcellular distribution of copper showed an increase in cytosolic and decreased organelle and membrane–associated copper. These data suggest that cellular resistance to copper toxicity was achieved in two independent cell lines without MT induction and that the induction of ATP7B may lead to the enhanced intracellular sequestration of copper by organelles.
Similar response patterns to topical minoxidil foam 5% in frontal and vertex scalp of men with androgenetic alopecia: a microarray analysis
Authors: P. Mirmirani, M. Consolo, P. Oyetakin-White, E. Baron, P. Leahy, P. Karnik
Journal: British Journal of Dermatology (2014)

There are regional variations in the scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions have been less well studied. To determine whether scalp biopsies from men with AGA show variable gene expression before and after 8 weeks of treatment with minoxidil topical foam 5% (MTF) vs. placebo. A placebo‐controlled double‐blinded prospective pilot study of MTF vs. placebo was conducted in 16 healthy men aged 18–49 years with Hamilton–Norwood type IV–V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for 8 weeks. Stereotactic scalp photographs were taken at the baseline and final visits, to monitor global hair growth. Scalp biopsies were taken at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo, and microarray analysis was performed using the Affymetrix GeneChip HG U133 Plus 2.0. Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of patients with AGA. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin‐associated genes and decreased the expression of epidermal differentiation complex and inflammatory genes in both scalp regions. These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of patients with AGA.
How to do it. Conduct an interview.
Authors: G Dick
Journal: BMJ (1979)

When taking interviews I often recall a reproduction in one of my school books of Yeames's painting "And when last did you see your father" which showed a party of Roundheads "interviewing" a little boy while his royalist family wait in fear in case the boy's answers to questions lead to disaster.The picture looks more like an inquisition, which many medical interviews resemble but which fortunately carry no punishment and only the hope of success. Personal interviewsAll I wish to say about personal interviews is that a dated record (including the year) should be kept in the form of notes taken of the discussions and of any conclusion or recommended action.I keep a separate notebook for this purpose. Interviewing panelsMembers of an interviewing panel sitting round a table should each be identifiable to the candidate by a nameplate in large letters which also indicates whom they represent.(Nothing elaborate is required-a folded piece of stiff paper and a felt pen is all you need.)Unless they are all well known to each other, the chairman should be given a seating list of the committee: if this is not provided he should make his own.He should ensure that all members of the interviewing committee and any administrators in attendance know each other.The chairman of the panel should indicate how he proposes to conduct the meeting and, in my experience, the fairest way is to withhold discussion about any of the candidates until all have been interviewed.The chairman should also indicate for how long he expects each candidate to be interviewed and that he hopes the business will be finished at a given time.If the usual procedure is not known, arrangements should be made with administrative officers to ensure that the candidates arrive at intervals of 20 to 30 minutes.After agreement on procedure the first candidate is summoned.
A METHOD FOR THE DEMONSTRATION OF CALIBRE CHANGES IN THE BRONCHI IN NORMAL RESPIRATION
Authors: Peter Heinbecker
Journal: Journal of Clinical Investigation (1927)

An investigation of the literature indicates that changes occurring in the calibre of the bronchi during the normal respiratory move- ments have never been demonstrated.In a review of the subject by von Skramlik (1925) it is remarked that one would anticipate a widening during inspiration, a narrowing during expiration, but that in quiet respiration these differences are obviously too small to record.In forced respiratory movements as in cough it is known (Briinings, 1912) that a narrowing in the bronchi occurs just at the instant that the vocal chords are forced apart. METHODSWithin the past few years lipiodol has permitted the outlining of the bronchial tree in the living subject with great accuracy and detail (Forestier, 1926).It was therefore decided to investigate the pos- sibility of using this substance to demonstrate any changes in the size of the bronchi which might occur during normal respiration.For the observations on living subjects, one cat, two dogs, and five human subjects were employed.The animals were anesthetized with urethane and the oil administered by tracheal puncture.In man the films were taken in the course of diagnostic procedures.No anesthetic was required, the technique described by Singer (1926) being employed.After injection of the oil, x-ray films were taken in man during the actual process of breathing and also while holding the breath at the end of inspiration and at the end of expiration.
Urticaria and Angioedema
Authors: JOHN S. THOMPSON
Journal: Annals of Internal Medicine (1968)

Urticaria may be the sole symptom of a minor reaction or it may be a manifestation of a progressive, fatal connective tissue or neoplastic disease. At least five basic pathogenetic pathways may initiate histamine release from mast cells. These are complement factors; chemical liberators; immunologic mechanisms; biologic, physical, and neurogenic factors; and general modifying phenomena. The interrelationship of these pathways has been shown, particularly stressing the potential significance of chemical liberators and complement-mediated events in several mechanisms. Implication that hormonal and neurohumoral substances may modify the entire mast-cell degranulating system has been entertained as important speculation awaiting confirmation. Diagnosis and therapy is discussed using these principles. In addition to a careful history and physical exam, determination of blood eosinophiles, total complement activity, quantitation of isolated complement components, selected skin tests, elimination regimes, and controlled provocative tests may be useful in individual cases. Although antihistamines constitute the principal means of therapy, their method of action impairs an early effect, and beta adrenergic amines must be given when shock or potentially fatal angioedema occur. Corticoids and immunosuppressive agents may be necessary for control in some of the serious underlying disorders. Three modes of experimental therapy are also discussed.
Phosphorylation of Steroid Hormone Receptors*
Authors: EDUARDO ORTÍ, JACK E. BODWELL, ALLAN MUNCK
Journal: Endocrine Reviews (1992)

Many observations with intact cells as well as cell-free systems suggest that receptors of the steroid hormone superfamily, along with other transcription factors, are regulated by phosphorylation. All receptors that have been analyzed carefully so far have turned out to be phosphoproteins. They are basally phosphorylated in the absence of ligand, and in many cases become hyperphosphorylated in the presence of hormone or other agonists, and sometimes of antagonists. Several studies indicate that hyperphosphorylation of receptors follows activation, and may require nuclear binding of the receptor. Serines are the predominant phosphorylated residues detected in receptors, with minor amounts of threonine. Tyrosine phosphorylation of the estrogen receptor is a subject of controversy. With various receptors, evidence has been found for phosphorylation in vivo of the N-terminal, hormone-binding, and DNA-binding domains, as well as of the hinge region. All but one of the phosphorylated sites identified in progesterone and glucocorticoid receptors by phosphopeptide mapping and sequencing are in the N-terminal domain; one is in the hinge region. Even after hormone treatment most of those sites are only partly phosphorylated, which means that several subpopulations of receptors, characterized by different states of phosphorylation and potentially different biological activities, must coexist. The majority of identified phosphorylated sites lie in consensus sequences for the PDPK. Many parallels can be discerned between phosphorylation of receptors and of other transcription factors. For example, several transcription factors become hyperphosphorylated on stimulation, and much indirect evidence points to regulation of both receptors and transcription factors by kinases and phosphatases, with cycling between different phosphorylated states. Functions of receptors that are regulated by phosphorylation are only beginning to be investigated. With transcription factors a substantial body of information is already available, and functions that appear to be thus regulated include dimerization, interactions with other proteins, binding to DNA, nuclear-cytoplasmic localization, and transcriptional activity. These and other functions may be found to be regulated by phosphorylation of receptors.
Sex hormones, sex hormone binding globulin, and lung cancer: a 12 year prospective study in a cohort of men aged 50-79
Authors: A. Calciano, K.-T. Khaw, E. Barrett-Connor, C. Garland
Journal: BMJ (1988)

Sex hormones, sex hormone binding globulin, and lung cancer: a 12 year prospective study in a cohort of men aged 50-79 Four case-control studies have shown that patients with lung cancer have lower serum testosterone concentrations than healthy controls.`-4 One study also showed considerably higher concentrations of sex hormone binding globulin in patients with lung cancer.4These studies included severely
Problems in the use of indices of myocardial contractility
Authors: G. C. V. D. BOS, G. ELZINGA, N. WESTERHOF, M. I. M. NOBLE
Journal: Cardiovascular Research (1973)

We have tested the validity of the following indices of myocardial contractility: the maximum acceleration of blood from the left ventricle, the maximum rate of rise of left ventricular pressure (LV dP/dt max), LV dP/dt max/left ventricular pressure at the time of LV dP/dt max (LV dP/dt max)/P, the maximum of the instantaneous ratio of the rate of rise of left ventricular pressure [(LV dP/dt/P) max], and the X-Y plot of LV dP/dt/P against P. In the isolated cat heart, the filling and resistance to ejection of the left ventricle were controlled directly. The other preparations were: the open chest anaesthetized dog, the closed chest anaesthetized dog with and without denervated heart, and the conscious dog with and without denervated heart. In these preparations, the effect of increased load was studied by constricting the aorta between beats and the effect of increased heart size was studied in subsequent beats during ventricular distention. It was found that none of the indices was insensitive to increased load and heart size under all circumstances. We were unable to find a satisfactory method of extrapolating the plot of LV dP/dt/P against P to zero P to obtain Vmax. [f a linear relationship was assumed, P was found to be a complex function of time (t), namely Po/[l+(Po/Pd-1)e-Vmaxt] where Po = P when dP/dt/P=0 and Pd = end-diastolic pressure.
Pharmacokinetics of Lidocaine
Authors: Carl Lawyer
Journal: JAMA (1977)

<h3>To the Editor.—</h3> This letter refers to the article "Pharmacokinetic Approach to the Clinical Use of Lidocaine Intravenously" (236:273, 1976) by Greenblatt et al. I would like to call attention to a possible problem with the data on which they base their approach. Greenblatt and colleagues base their analysis on the data in an article by Rowland et al.<sup>1</sup>Unfortunately, Rowland and his colleagues did not do a least-squares regression of the distribution volume versus body weight; they instead assumed a 0 intercept and divided by body weight. Figure 1 is a least-squares regression of their data which I did of body weight versus distribution volume. The dashed line is the least-squares plot; the solid line is the plot that Rowland et al assumed and on which the article by Greenblatt and colleagues is based. It is clear that the solid line is not justified by the data. Yet
Mice Lacking the 110-kD Isoform of Poly(ADP-Ribose) Glycohydrolase Are Protected against Renal Ischemia/Reperfusion Injury
Authors: Nimesh S.A. Patel, Ulrich Cortes, Rosanna Di Poala, Emanuela Mazzon, Helder Mota-Filipe, Salvatore Cuzzocrea, Zhao-Qi Wang, Christoph Thiemermann
Journal: Journal of the American Society of Nephrology (2005)

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD(+) and subsequently, ATP, leading to cellular dysfunction and, ultimately, cell death. The key enzyme involved in polymer turnover is PARG, which possesses mainly exoglycosidase activity but can remove olig(ADP-ribose) fragments via endoglycosidic cleavage. Thus, the aim of this study was to investigate whether the absence of PARG(110) reduced the renal dysfunction, injury, and inflammation caused by I/R of the mouse kidney. Here, the renal dysfunction and injury caused by I/R (bilateral renal artery occlusion [30 min] followed by reperfusion [24 h]) in mice lacking PARG(110), the major nuclear isoform of PARG, was investigated. The following markers of renal dysfunction and injury were measured: Plasma urea, creatinine, aspartate aminotransferase, and histology. The following markers of inflammation were also measured: Myeloperoxidase activity, malondialdehyde levels, and plasma nitrite/nitrate. The degree of renal injury and dysfunction caused by I/R was significantly reduced in PARG(110)-deficient mice when compared with their wild-type littermates, and there were no differences in any of the biochemical parameters measured between sham-operated PARG(110)(-/-) mice and sham-operated wild-type littermates. Thus, it is proposed that endogenous PARG(110) plays a pivotal role in the pathophysiology of I/R injury of the kidney.
Arterial stiffness by pulse wave velocity in COPD: reliability and reproducibility
Authors: Isabelle Vivodtzev, Clémence Minet, Renaud Tamisier, François Arbib, Jean-Christian Borel, Jean-Philippe Baguet, Patrick Lévy, Jean-Louis Pépin
Journal: European Respiratory Journal (2013)

Arterial stiffness by pulse wave velocity in COPD: reliability and reproducibilityTo the Editor:Cardiovascular diseases are the most common cause of mortality in chronic obstructive pulmonary disease (COPD) [1].Arterial stiffness certainly plays a role in the increased cardiovascular risk of these patients [2,3].Arterial pulse wave velocity (PWV) constitutes a useful and safe non-invasive method [4] for assessing central arterial stiffness.The carotid-femoral PWV is considered as the gold standard method by the European Society of Hypertension/European Society of Cardiology [5] and is a strong predictor of future cardiovascular events and all-cause mortality, supporting its implementation into clinical research and daily practice [6].In patients with COPD, feasibility and validity of this marker of arterial stiffness have been confirmed [2] and PWV is now used in studies evaluating cardiovascular risk and/or the efficacy of new bronchodilators and rehabilitation programmes [3,7,8].However, little is known about its variability and reproducibility studies are lacking in the COPD population.Here we report on the variability of PWV measurements between baseline, day 15 and day 42 in stable COPD patients.The carotid-femoral PWV was assessed using the Complior device (Alam Medical, Vincennes, France) and pulmonary function, blood pressure, metabolic and inflammatory markers were systematically measured at each evaluation.Pearson or Spearman correlation coefficients and intraclass correlation coefficient (ICC) allowed comparison of PWV at day 0 versus day 15 (short-term) and day 42 (middle-term reproducibility).From 62 stable patients enrolled in the study, four patients dropped out (withdrawal of study participation) and 20 patients were excluded from the analysis due to exacerbations during the follow-up evaluations (day 15 and day 42) or absence of at least one of the datasets at day 0, day 15 and day 42.Among the remaining patients, the majority were in Global Initiative for Chronic Obstructive Lung Disease stage II and III, but three patients were in stage I and two patients in stage IV at baseline.18 (47%) patients presented with a history of at least one cardiovascular risk factor and nine (24%) patients had two or more cardiovascular risk factors.
Neurobiologic Aspects of Autism
Authors: Fred R. Volkmar, Donald J. Cohen
Journal: New England Journal of Medicine (1988)

In this issue of the Journal, Courchesne et al. report on an association of cerebellar vermal hypoplasia with autism.1 Although proper interpretation of this finding, which was based on magnetic resonance imaging in a relatively small number of patients with a limited degree of impairment, cannot yet be made, it is likely to stimulate further interest in the neurobiologic bases of autism and should be viewed within the broader context of research on this devastating disorder.In 1943 Leo Kanner described 11 children with an apparently inborn disturbance of social development or "affective contact."2 These children showed profound social . . .
In-flight Medical Emergencies
Authors: Joseph J. Cottrell
Journal: JAMA (1989)

Recent regulations require commercial US aircraft to carry an enhanced medical kit. We reviewed kit use on United Airlines during the initial year of the regulations. We also surveyed passengers who became ill during flight and health care providers who used the new kit. The medical kit was used 362 times on 361 flights (once in every 1900 flights or one use for every 150 000 air travelers). Health care providers indicated that the kit was useful in more than 80% of emergencies and was occasionally lifesaving. In the emergencies in which the kit was used, 70% fell into one of seven major diagnostic groupings, including syncope/near syncope (29%), cardiac/chest pain (16%), asthma/lung disease/shortness of breath (10%), and allergic reactions (5%). With 450 million domestic air travelers per year, we would expect 3000 in-flight medical emergencies annually, and conclude that the enhanced medical kit is beneficial and propose that its effectiveness would be improved by the addition of a bronchodilator for inhalation.  ( JAMA . 1989;262:1653-1656)
The effect of myocardial force on coronary transmural flow distribution
Authors: G. A. KLASSEN, D. T. ZBOROWSKA-SLUIS
Journal: Cardiovascular Research (1979)

The role of myocardial force as a determinant of transmural coronary flow distribution was examined in the presence and absence of autoregulation by infusing calcium chloride into a segment of the left coronary system. The concentration of calcium used was adequate to increase force but did not alter coronary pressure or endoventricular pressure. No alterations in transmural gradients of flow were observed following increased regional force. These results suggest that increases in regional force are not of importance as a determinant of transmural blood flow.
Lung Fluid Dynamics in Awake Newborn Lambs
Authors: Richard D. Bland, Douglas D. McMillan
Journal: Journal of Clinical Investigation (1977)

We measured steady-state lung lymph flow, lymph protein flow, and simultaneous pulmonary vascular pressures in 12 1-wk-old unanesthetized lambs and compared these measurements to those of previous studies, performed under similar conditions, on nine awake adult sheep. The purpose of these experiments was to compare newborn and adult sheep with respect to transvascular filtration of fluid and microvascular permeability to plasma proteins. We prepared the lambs surgically to isolate and collect lung lymph and measure average pulmonary arterial and left atrial pressures, allowing at least 2 days for the lambs to recover from surgery before studies began. Lambs had higher pulmonary arterial and left atrial pressures, lower lymph and plasma protein concentrations, and 57% more lymph flow per gram of dry bloodless lung than sheep; the difference in protein flow between lambs and sheep was not significant. Protein concentration in lymph relative to that in plasma was significantly lower in lambs than in sheep; but the ratio of albumin concentration to globulin concentration in both lymph and plasma was almost identical in the two groups of animals. Extravascular lung water per gram of dry bloodless lung was greater in lambs (4.82±0.11 g) than in sheep (4.45±0.08 g), but there was no histologic evidence of pulmonary edema in either group of animals. These findings suggest that lambs have more transvascular filtration of fluid per unit lung mass than sheep, but that microvascular sites for protein exchange do not differ appreciably in lambs and sheep. To test this conclusion, we measured steady-state lymph flow in three lambs before and after raising pulmonary microvascular pressure by rapid intravenous infusion of saline. Lymph flow increased as a function of the net transvascular driving pressure (hydraulic pressure gradient—protein osmotic pressure gradient). This response was almost identical to that of four sheep with pulmonary microvascular pressure augmented by inflation of a balloon in the left atrium. In eight lambs we measured the time for intravenously injected 125I-albumin to equilibrate in lymph at half the specific activity of plasma: the protein tag equilibrated faster than in sheep. This difference could be explained partly by the higher pulmonary arterial and left atrial pressures of lambs than sheep, and possibly by the presence of more microvascular sites for protein exchange relative to the volume of distribution of protein in the lung of the younger animals.