tbuckley/cabot-search huggingface dataset:
Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog
Authors: Noboru Sato, Philip L. Leopold, Ronald G. Crystal
Journal: Journal of Clinical Investigation (1999)

Hair follicles form in prenatal skin and mature in the postnatal period, establishing a growth cycle in 3 phases: telogen (resting), anagen (growth), and catagen (regression). Based on the knowledge that Sonic hedgehog (Shh) expression is necessary for the embryonic development of hair follicles, and that anagen in the postnatal cycling follicle has morphologic similarities to the epithelial invagination process in embryonic skin, we hypothesized that localized, but transient, enhanced expression of the Shh gene in postnatal skin would accelerate initiation of anagen in the hair follicle cycle, with concomitant accelerated hair growth. To assess this concept, an E1– adenovirus vector, AdShh, was used to transfer the murine Shh cDNA to skin of postnatal day 19 C57BL/6 mice. The treated skin showed increased mRNA expression of Shh, Patched (the Shh receptor), and Gli1 (a transcription factor in the Shh pathway). In mice receiving AdShh, but not in controls, acceleration into anagen was evident, since hair follicle size and melanogenesis increased and the hair-specific keratin ghHb-1 and the melanin synthesis–related tyrosinase mRNAs accumulated. Finally, C57BL/6 mice showed marked acceleration of the onset of new hair growth in the region of AdShh administration to skin 2 weeks after treatment, but not in control vector–treated or untreated areas. After 6 months, AdShh-treated skin showed normal hair and normal skin morphology. Together, these observations are consistent with the concept that upregulation of Shh activity in postnatal skin functions as a biologic switch that induces resting hair follicles to enter anagen with consequent hair growth.
Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor
Authors: Holger Tönnies, Stefanie Huber, Jörn-Sven Kühl, Antje Gerlach, Wolfram Ebell, Heidemarie Neitzel
Journal: Blood (2003)
Experience with the surgical treatment of coarctation of the aorta in India.
Authors: W J Perianayagam, S Muralidharan, P S Jairaj, S Krishnaswamy, I P Sukumar, G Cherian, R Mansfield, S John
Journal: Thorax (1980)

Between 1961 and 1977, 51 patients underwent operations for coarctation of the aorta. The average age of presentation of these cases was higher than in other series. Only three were asymptomatic, a finding which is not seen in reports from the West. Operative procedures included resection and graft interposition, resection and end-to-end anastomosis, and bypass grafting. However, the technique of patch angioplasty, routinely performed in the last three years of this review, seemed by far the most satisfactory procedure. The overall operative mortality was 9.8%. Hypertension did not regress in some cases in spite of a successful operation. Recoarctation was not seen in this series. Associated defects influenced results adversely. The overall results of operation for coarctation of the aorta have been very satisfactory and comparable with those in other recorded series.
Loss of the common "A" determinant of hepatitis B surface antigen by a vaccine-induced escape mutant.
Authors: J A Waters, M Kennedy, P Voet, P Hauser, J Petre, W Carman, H C Thomas
Journal: Journal of Clinical Investigation (1992)

A previous study (Carman, W. F., A. R. Zanetti, P. Karayiannis, J. A. Waters, G. Manzillo, E. Tanzi, A. J. Zuckerman, and H. C. Thomas. 1990. Lancet. 336:325-329) demonstrated a variant hepatitis B surface antigen (HBsAg) in a vaccinated child born to a hepatitis B virus-infected mother. A substitution of arginine for glycine at amino acid 145 in HBsAg was observed. In this study the effect of this substitution on the common "a" determinant of this protein, against which protective immunity is directed, is investigated. Using recombinant HBsAg with and without the amino acid substitution, the binding of monoclonal antibodies that recognize different epitopes of the "a" determinant, was shown to be destroyed by the presence of arginine at amino acid 145. In convalescent and vaccinee sera, antibody binding to HBsAg was not inhibited by the variant HBsAg. Immunization with the variant HBsAg, although eliciting a high titer antibody that recognized the variant, produced a low titer of antibody recognizing the native protein. Studies in mice demonstrate that the immunogenicity of the variant protein is also substantially altered. The data presented here demonstrate that this variant evades the known protective anti-HBs response and lends support to the suggestion that this mutation arose as the result of immune pressure.
Fibronectin is produced by human macrophages.
Authors: K Alitalo, T Hovi, A Vaheri
Journal: The Journal of Experimental Medicine (1980)

Monocyte-enriched cultures were prepared from human blood mononuclear leukocytes by adherence to growth substratum. Synthesis and secretion of fibronectin was detected in these cultures concomitantly with morphological differentiation, starting on day 3--5. Production of fibronectin by macrophages was documented by metabolic labeling followed by immunoprecipitation and gel electrophoresis, radioimmunoassay specific for human fibronectin, and by indirect immunofluorescence. Fibronectin was detected mainly intracellularly but was also detected pericellularly only in minute amounts. No production of collagenous proteins was seen in these cultures. Macrophage fibronectin might act in vivo as a nonspecific opsonin and promote cell adhesion during macrophage migration in tissues.
Inflammation and lipid profile in rheumatoid arthritis: bridging an apparent paradox
Authors: Miguel A González-Gay, Carlos González-Juanatey
Journal: Annals of the Rheumatic Diseases (2014)

Several pieces of evidence indicate that rheumatoid arthritis (RA) is a proatherogenic disease associated with increased cardiovascular (CV) mortality.1 ,2 Besides genetic and traditional CV risk factors,3 ,4 chronic inflammation has emerged as a pivotal component implicated in the development of this process. A chronic inflammatory burden, determined by the mean values of C-reactive protein (CRP) over the extended follow-up of patients with RA, was associated with subclinical atherosclerosis and increased risk of CV events.5 ,6 In keeping with these observations, in a large retrospective cohort study, CV disease-related mortality was increased in RA patients with elevated measures of inflammation markers.7 These findings are in accordance with data from the general population that showed that CRP could be an independent predictor of CV disease with CRP values ≥3 mg/L defining high CV-risk individuals.8 With respect to this, levels of the proinflammatory cytokine interleukin-6, the main inducer of CRP, also predict outcome following hospitalisation for unstable angina.9

Despite some similarities, there are also some differences between patients with chronic inflammatory diseases and the general population. While the risk to develop atherosclerosis increases progressively with increasing low-density lipoprotein (LDL) cholesterol levels and declines with increasing levels of high-density lipoprotein (HDL) cholesterol in healthy individuals,10 the presence of a proinflammatory state leads to a decrease of total cholesterol, HDL cholesterol and LDL cholesterol in patients with RA.11

Paradoxically, anti-inflammatory therapies increase total cholesterol, HDL cholesterol and LDL cholesterol to variable degrees in patients with RA.11 ,12 This lipid increase is not associated with a rise in the number of CV events in these patients. On the contrary, probably due to the anti-inflammatory effect, conventional disease-modifying antirheumatic drugs, such as methotrexate, and different biological agents have demonstrated a reduction of the CV …
The Heart and Cardiac Conduction System in Thrombotic Thrombocytopenic Purpura
Authors: REN L. RIDOLFI
Journal: Annals of Internal Medicine (1979)

The relation between the heart lesions of thrombotic thrombocytopenic purpura and clinical cardiac dysfunction was studied in 17 autopsied patients. Thirteen of the 17 patients had extensive small-vessel thromboses and in some instances hemorrhages and focal necroses within the heart. Congestive heart failure was present in nine of the 17 patients. Thrombotic microcirculatory cardiac lesions and anemia-related high cardiac output may have contributed to cardiac dysfunction. Serial histologic sections of the cardiac conducting system in 10 patients showed microthrombi in seven and associated hemorrhages in five. Lesions were localized to the atrioventricular node and His bundle parts of the system with sparing of the sinoatrial node and bundle branches. Two patients had electrocardiographic evidence suggesting lesions within conducting tissues. Thrombi and hemorrhages are common findings in the conducting tissues in thrombotic thrombocytopenic purpura and may account for cardiac arrest or transient rhythm disturbances.
Book: Guns, Germs and Steel: A Short History of Everybody for the Last 13,000 Years
Authors: A. Brooks
Journal: BMJ (1999)

Jared Diamond Vintage, £8.99, pp 480 ISBN 0099302780 ——————— Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> “Why is it that you white people developed so much cargo and brought it to New Guinea, but we black people had little cargo of our own?” Jared Diamond, a professor of physiology who also writes about ecology and evolutionary biology, has written this book in response to the above question. The 400 pages wade through 13 000 years of history to explain why the Spanish conquistador Francisco Pizarro destroyed the Atahuallpa's … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Role of Seroconversion in Confirming Cure of &lt;EMPH TYPE="ITAL"&gt;Helicobacter pylori&lt;/EMPH&gt; Infection
Authors: Mark Feldman, Byron Cryer, Edward Lee, Walter L. Peterson
Journal: JAMA (1998)

Context.—The role of serologic testing to confirm cure of Helicobacter pylori infection after antimicrobial therapy is not completely defined.Objective.—To determine the utility of serologic testing in confirming cure of H pylori infection more than 1 year after therapy.Design.—A prospective, before-after interventional trial.Setting.—An outpatient clinical research laboratory in an academic, urban Veterans Affairs medical center.Participants.—Twenty-three otherwise healthy men and women with active H pylori infection demonstrated by gastric biopsy and with positive H pylori serologic findings.Intervention.—A 14-day course of bismuth, tetracycline, and metronidazole.Main Outcome Measures.—Determination of IgG serum antibodies to H pylori at baseline, 1 month, 3 months, and approximately 18 months after completion of therapy compared with serial gastric mucosal biopsy specimens with stains for H pylori and for histologic examination as the criterion standard.Results.—Fifteen (65%) of 23 subjects were cured of their H pylori infection as assessed by gastric biopsy, with elimination of gastritis; median antibody levels declined from 92.5 U/mL at baseline to undetectable levels at 18 months. The other 8 subjects (35%) were not cured and had persistent gastritis at 18 months; median antibody levels declined from 130.6 U/mL at baseline to 89.7 U/mL at 18 months. Sensitivity and specificity of seroconversion (from a positive to negative test result) in detecting cure of H pylori infection were 60% and 100%, respectively.Conclusion.—Undetectable antibody levels beyond the first year of therapy accurately confirm cure of H pylori infection in initially seropositive healthy subjects, with reasonable sensitivity.
Hormone replacement therapy quadruples risk of breast cancers
Authors: Susan Mayor
Journal: BMJ (2008)

Postmenopausal women taking combined oestrogen and progestin hormone replacement therapy for three years or longer run four times the risk of developing lobular breast cancer, finds US research. This is shorter than the time associated with an increased risk of other types of breast cancer ( Cancer Epidemiology, Biomarkers & Prevention 2008;17:43-50).

The study included 1044 women between the ages of 55 and 74 who had been diagnosed as having invasive breast cancer between 2000 and 2004 and entered into the cancer surveillance system in Washington state. They were compared with 469 age matched …
THE GERMICIDAL EFFICIENCY OF COMMERCIAL PREPARATIONS OF HYDROGEN PEROXID
Authors: P. G. HEINEMANN
Journal: JAMA (1913)

Hydrogen peroxid has been recommended for germicidal purposes for many years. Its application has been advocated for rendering water and milk safe, for disinfection of sewage; it has been applied in medicine, surgery, dentistry, hair-dressing, etc. The chief advantage claimed for hydrogen peroxid over many other germicides is the fact that the decomposition products are harmless. It has also been claimed that toxins, such as diphtheria and tetanus toxins, are destroyed by it.<sup>1</sup>Its use for treating water and milk is, therefore, of considerable interest. There are some objections, however, to the use of this chemical. It decomposes rapidly. The presence of small amounts of acid prevents decomposition to some extent. Some commercial preparations contain acids, acetanilid, or arsenic, barium salts, etc. The amount of acid, corresponding to about 0.2 per cent. hydrochloric acid, is perhaps harmless, and according to Croner<sup>2</sup>increases the germicidal effect. In neutral and
Transcriptional activation and DNase I hypersensitive sites are associated with selective expression of the gastrin-releasing peptide gene.
Authors: S Markowitz, G Krystal, A M Lebacq-Verheyden, J Way, E A Sausville, J Battey
Journal: Journal of Clinical Investigation (1988)

The gastrin-releasing peptide (GRP) is a neuropeptide hormone and growth factor produced normally by neural and neuroendocrine cells, as well as by human small-cell lung cancer (SCLC) tumors and derived cell lines. This study compares the structure of the human prepro-GRP gene in four SCLC cell lines that express variable levels of steady-state GRP mRNA. The regulation of GRP gene expression appears to be at the level of primary transcription based on nuclear run on studies. In the two SCLC cell lines expressing GRP we find a single transcription start site for GRP mRNA, and near this site we find four DNase I hypersensitive sites. These hypersensitive sites are absent in the two cell lines that do not express GRP. The presence of DNase hypersensitive sites in the promoter region of the GRP gene is the structural feature that best correlates with transcriptional activation. These four DNase hypersensitive sites are candidates for cis acting regulatory regions, which may be important in determining the level of transcription of the human prepro GRP gene.
PHONOGRAPHIC RECORDING OF HEART SOUNDS
Authors: Paul D. White
Journal: JAMA (1942)

<h3>To the Editor:—</h3> There has been some correspondence inThe Journalin recent weeks about phonographic recording of heart sounds. For historical interest, I would add that Dr. Richard Cabot made such recordings from Oct. 31, 1925 to Jan. 6, 1926 in New York City with the Columbia Phonograph Company, now the Columbia Recording Corporation. I have some of his old records, which are interesting rather because of their excellent reproduction of Dr. Cabot's voice than for their value in phonocardiography, a characteristic still true of many other such records, though improvements are in progress in the effort to develop this procedure into a practical method of teaching and of recording.
Prospective Evaluation of Cardiac Risk Indices for Patients Undergoing Noncardiac Surgery
Authors: Kenneth Gilbert
Journal: Annals of Internal Medicine (2000)

Background: Prediction of perioperative cardiac complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed to aid prediction, but their performance has not been systematically compared. Objective: To compare four existing methods for predicting perioperative cardiac risk. Design: Prospective cohort study. Setting: Two teaching hospitals in London, Ontario, Canada. Patients: 2035 patients referred for medical consultation before elective or urgent noncardiac surgery. Measurements: Myocardial infarction, unstable angina, acute pulmonary edema, or death. The indices were compared by examining the areas under their respective receiver-operating characteristic (ROC) curves. Results: Cardiac complications occurred in 6.4% of patients. The area under the ROC curve was 0.625 (95% CI, 0.575 to 0.676) for the American Society of Anesthesiologists index, 0.642 (CI, 0.588 to 0.695) for the Goldman index, 0.601 (CI, 0.544 to 0.657) for the modified Detsky index, and 0.654 (0.601 to 0.708) for the Canadian Cardiovascular Society index. These values did not significantly differ. Conclusions: Existing indices for prediction of cardiac complications perform better than chance, but no index is significantly superior. There is room for improvement in our ability to predict such complications.
A postsynaptic location of alpha2 adrenoceptors in vascular smooth muscle: in vivo studies in the conscious rabbit
Authors: C. A HAMILTON, J. L REID
Journal: Cardiovascular Research (1982)

The rise in blood pressure after intravenous administration of a range of alpha-adrenoceptor agonists and the effect of alpha adrenoceptor antagonists was studied in groups of conscious rabbits. Phentolamine was equally effective at blocking the pressor response to the alpha 1 adrenoceptor agonist phenylephrine and the mixed alpha 1/alpha 2 adrenoceptor agonist noradrenaline. Phenoxybenzamine which acts preferentially on alpha 1 adrenoceptors and the more specific alpha 1 adrenoceptor antagonist prazosin were more effective against phenylephrine induced rises in pressure, while yohimbine and alpha yohimbine which preferentially act on alpha 2 adrenoceptors were more effective against noradrenaline. The immediate pressor response to intravenous injections of the alpha 2 adrenoceptor agonists clonidine and guanabenz was blocked more effectively by phentolamine than prazosin when doses which gave a postsynaptic location of both alpha 1 and alpha 2 adrenoceptors both of which mediate vasoconstrictor responses in vascular smooth muscle.
Tl–201 SPECT in Clarifying False Positive FDG PET Findings Caused by Osteoradionecrosis in a Case of Nasopharyngeal Carcinoma
Authors: Chih-Hsiu Wang, Ji-An Liang, Kuo-Yang Yen, Te-Chun Hsieh, Shung-Shung Sun, Yu-Chin Wu, Yu-Yi Lin, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2009)

FDG PET is effective for detecting recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. However, false-positive FDG PET scans caused by osteoradionecrosis (ORN) have been reported. This 42-year-old male NPC patient was referred for FDG PET due to inconclusive CT/nasopharyngoscopic findings 8 years after radiotherapy. Intense FDG uptake in the nasopharyngeal region was seen. To rule out the possibility of a false-positive FDG PET scan, Tl–201 SPECT was subsequently performed, which was negative in the corresponding area. Final histopathological examination confirmed ORN. This case demonstrates that Tl–201 SPECT may help differentiate false positive FDG PET findings caused by ORN from recurrent tumor in NPC patients after radiotherapy.
Pseudomonas Infections of the Foot Following Puncture Wounds
Authors: Paul H. Johanson
Journal: JAMA (1968)

Subacute infections of cartilaginous areas of the foot following puncture wounds in 11 children have persisted in spite of the administration of large doses of many different antibiotics. After an average of three weeks' delay, the failure of the treatment was explained by culture ofPseudomonas aeruginosa. Following appropriate surgical care, the infection has apparently been eliminated in all cases, but most of the children have significant residual skeletal damage. Prior reference to this condition has not been found in the medical literature.
Balancing benefits and harms: the example of non-steroidal anti-inflammatory drugs
Authors: Paul Dieppe, Christopher Bartlett, Peter Davey, Lesley Doyal, Shah Ebrahim
Journal: BMJ (2004)

To provide safe and effective interventions for people, reliable and valid evidence is needed. This is most easily produced by undertaking trials in samples of people who are as homogeneous as possible and applying the results to similar, well defined groups of patients. To be equitable, however, appropriate care needs to be provided for everyone in the diverse community using health services. Therefore, there is a tension between obtaining scientific evidence that is reliable but which can be applied only to a small subset of the population, and distributive justice that requires that all in need are treated equally appropriately.

Drugs have potential harms as well as benefits. Doctors would like to be able to balance any risks against benefits to derive a therapeutic ratio for each patient, but this is difficult. Formal trials can tell a lot about the efficacy of a drug in a specific context, but unless they are huge and pragmatic they tell less about a drug's toxicity. Post-marketing surveillance may uncover more information on toxicity, but the data usually lack sufficient detail to lead to an understanding of the determinants of adverse reactions. Furthermore, extrapolation of the efficacy or toxicity of a drug in one disease or group of patients to those associated with different diseases or groups can be difficult and misleading.

We examined aspects of these problems in the context of one commonly prescribed class of drugs—non-selective, non-steroidal anti-inflammatory agents (NSAIDs)—and their use in the management of joint pain.

We compared the types of patients in whom trials of non-selective NSAIDs are conducted with those who receive the drugs in practice. Then we examined the prevalence and associations of adverse events in these two groups.

### Methods

As NSAIDs are primarily used to treat arthritic pain, we studied trials of these drugs in patients with …
A metabolomic approach for diagnosis of experimental sepsis
Authors: José L. Izquierdo-García, Nicolás Nin, Jesús Ruíz-Cabello, Yeny Rojas, Marta de Paula, Sonia López-Cuenca, Luis Morales, Leticia Martínez-Caro, Pilar Fernández-Segoviano, Andrés Esteban, José A. Lorente
Journal: Intensive Care Medicine (2011)
P1-221: Randomized trial of a 3-fold dose intensification of Ifosfamide, Carboplatin, Etoposide chemotherapy for the treatment of small cell lung cancer
Authors: Serge Leyvraz, Sandro Pampallona, Giovanni Martinelli, Ferdinand Ploner, Solange Peters, Savina Aversa, Paal Brunsvig, Ana Montes, Andrzej Lange, Yilmaz Ugur, Giovanni Rosti
Journal: Journal of Thoracic Oncology (2007)