tbuckley/cabot-search huggingface dataset:
Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG)
Authors: K Paavonen
Journal: Cardiovascular Research (2003)

Objective: To determine whether the amino acid 897 threonine (T) to lysine (K) polymorphism of the KCNH2 (HERG) potassium channel influences channel performance or patient phenotype. Methods: The phenotypic effects of this polymorphism were investigated in vitro by electrophysiological experiments in HEK-293 cells and in vivo by exercise electrocardiography in a group of LQTS patients carrying the same genetically proven KCNQ1 mutation. Results: When expressed in HEK-293 cells, the 897T isoform of the KCNH2 channel exhibited changes in inactivation and deactivation properties, and a smaller current density than the more common 897K isoform. Western blot experiments indicated that the decreased current density associated with 897T was caused by reduced channel expression. During a maximal exercise test in 39 LQT1 patients carrying an identical KCNQ1 mutation (G589D) and showing a prolonged QT interval (>440 ms), QT intervals were longer in patients carrying the 897T allele than in those homozygous for the 897K allele. Conclusions: The K897T variation has an effect on channel function and clinical phenotype. Our data warrant further investigations into the significance of this polymorphism in drug-induced and inherited LQTS.
Adrenal-to-Brain Transplants and Parkinson's Disease
Authors: Erik-Olof Backlund
Journal: JAMA (1987)

<h3>To the Editor.—</h3> In a comment on adrenal-to-brain transplants in the May 22/29 issue of<i>JAMA</i>,<sup>1</sup>the work by our group was mentioned in slightly incorrect terms. First, our pioneer operation was performed in March<i>1982</i>(not 1985), and a second patient underwent operation one year later. These two patients were reported in 1985.<sup>2</sup>Two more patients underwent operation last year and a clinical report appeared recently.<sup>3</sup> Further, the author of the article commented that "none of the patients has demonstrated any benefit." This does not give the true scientific credit to our tentative operations. None of the patients had<i>permanent</i>improvement from the procedure, but a temporary improvement was registered in all of them, albeit in the first two it was of subtle character. In patients 3 and 4, receiving the transplants in the putamen, a fairly pronounced clinical effect was seen, although it was short
Gall-bladder water and electrolyte transport and its regulation.
Authors: J R Wood, J Svanvik
Journal: Gut (1983)

Progress reportGall-bladder water and electrolyte transport and its regulation Diemerbroek' in 1672 appreciated that bile entered the gall bladder to 'acquire greater strength and digestive power'.A study by Rous and McMaster2 in 1921 and later work by Ravdin and his coworkers3 4 provided direct experimental support for the notion that the gall bladder concentrates hepatic bile by selective reabsorption of bile constituents.These early studies have been reviewed in detail by Ivy.5 The nature of water and electrolyte absorption by gall-bladder mucosa has been extensively studied by Diamond and his colleagues whose work has provided an important basis for understanding of transport by this and other more complex epithelia.68Subsequent studies using isotope and Wood and Svanvik
Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon
Authors: S Freier, O Weiss, M Eran, A Flyvbjerg, R Dahan, I Nephesh, T Safra, E Shiloni, I Raz
Journal: Gut (1999)

AIMS To study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon. METHODS Malignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays. RESULTS All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. CONCLUSIONS This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.
Does cimetidine cause weight loss?
Authors: J Garrow
Journal: BMJ (1993)

have such an interest before making the referral.""Does this happen in practice?Occasions arise when doctors can provide privately ser- vices that the NHS cannot fund, but comprehensive guidelines are needed for these because of the ethical issues that they raise.In view of the changing nature of medical practice in Britain the General Medical Council should assess the effectiveness of its current recommendation and consider updating it along the lines of the American model.
Upregulation of Urea Transporter UT-A2 and Water Channels AQP2 and AQP3 in Mice Lacking Urea Transporter UT-B
Authors: Janet D. Klein, Jeff M. Sands, Liman Qian, Xiaodan Wang, Baoxue Yang
Journal: Journal of the American Society of Nephrology (2004)

The UT-B urea transporter is the major urea transporter in red blood cells and kidney descending vasa recta. Humans and mice that lack UT-B have a mild urine-concentrating defect. Whether deletion of UT-B altered the expression of other transporter proteins involved in urinary concentration was tested. Fluorescence-based real-time reverse transcription-PCR and Northern blot analysis showed upregulation of the UT-A2 urea transporter and the aquaporin 2 (AQP2) and AQP3 water channel transcripts but no change in other urea transporters or AQP. Western blot analysis showed that UT-A2 protein abundance in the outer medulla of UT-B null mice increased to 122 +/- 6% of wild-type control. AQP2 protein abundance increased to 177 +/- 32% and 127 +/- 7% in the outer and inner medulla, respectively, of UT-B null versus wild-type mice. The abundance of UT-A1, AQP1, renal outer medullary potassium channel, and NKCC2/BSC1 proteins were not significantly different between UT-B null and wild-type mice. The increases in AQP2 and AQP3 would reduce water loss and improve concentrating ability. The lack of UT-B does not result in a change in expression of urea transporters involved in urea reabsorption from the inner medullary collecting duct (UT-A1 and UT-A3). However, UT-B null mice have a selective increase in UT-A2 protein abundance. This may be an adaptive response to the loss of UT-B, because UT-B and UT-A2 are involved in different intrarenal urea recycling pathways.
A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes
Authors: Lynsey M Cree, David C Samuels, Susana Chuva de Sousa Lopes, Harsha Karur Rajasimha, Passorn Wonnapinij, Jeffrey R Mann, Hans-Henrik M Dahl, Patrick F Chinnery
Journal: Nature Genetics (2008)
A CASE OF QUADRUPLETS.
Authors: FRANK A. STAHL
Journal: JAMA (1895)

A case of quadruplets occurring but once in 350,000 to 400,000 births, where there was no trace of heredity; where labor, with the exception of rupturing the membranes, was normal; where, notwithstanding the plural fetuses, none presented in a manner compromising the delivery of the other. The interesting, theoretical, as well as practical study of such a case as a whole possesses sufficient intrinsic value to warrant even a superficial presentation of the case. The case occurred at home under poor circumstances, unfortunately away from the advantages of a maternité and a couveuse, and was attended by a midwife. I saw the case upon the third day. The husband, Patrick C., is a laborer, aged 32 years, a native of County Mayo, Ireland. His height is 5 feet, 11 inches; weight 190 pounds. Physically he is well developed. There is no trace of multiple pregnancy in his line. The wife,
(35) Poikiloderma congenitale (Thomson-Rothmund syndrome)
Authors: M.J. Cheesbrough, P.D.C. Kinmont
Journal: British Journal of Dermatology (1978)

Journal Article (35) Poikiloderma congenitale (Thomson‐Rothmund syndrome) Get access M.J. Cheesbrough, M.J. Cheesbrough General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar P.D.C. Kinmont P.D.C. Kinmont General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 98, Issue s16, 1 July 1978, Pages 66–67, https://doi.org/10.1111/j.1365-2133.1978.tb13637.x Published: 01 July 1978
Crying in Infants and Children
Authors: R. S. Illingworth
Journal: BMJ (1955)

Considering that crying is universal among children, and that the crying of children occasions so much dis- tress to adults, there is comparatively little in the literature on the subject.In this paper I have attempted to bring together data concerning crying from my own experience and from a wide variety of sources.How soon does a Child Cry?He may cry before birth.There have been numerous reports in the literature about infants crying in utero- the so-called vagitus uterinus.King and Bourgeois (1947) collected 125 cases from the literature from A.D. 1800.According to Parviainen (1949) vagitus uterinus was renowned in fable and legend.He wrote that there are stories of it in ancient Hindu, Babylonian, Assyrian, Greek, and Roman writings.St. Bartho- lomew and Mahomet were said to h4ve cried in utero.One child was said to have cried 14'days before birth.McLane (1933) described a fase which occurred in an operating theatre.The cry was heard by all present, and a superstitious nurse spent -the rest of the time on her knees in prayer.Crotty and Kuehnle (1948), in reviewing the subject, wrote that for a cry to be heard the membranes must have ruptured and air must have entered the uterine cavity.The cry may result from some manipulative procedure, or merely from uterine contractions.In the past vagitus uterinus was asso- ciated with a high foetal mortality, but it is thought (Field, 1943) that this was merely due to panic at what was wrongly thought to be foetal distress, with consequent precipitate efforts to deliver the child.The cause of crying in utero is unknown.How does he Cry ?Charles Darwin was greatly interested in the mani- festations of emotion in man and animals (Darwin, 1889), and went to great trouble to find out how animals in countries abroad expressed pleasure and displeasure.He wrote a very accurate account of the facial changes when a person cries.More recently Collins (1932) reviewed the literature on the subject.Crying is normally involuntary, though some actors, including an occasional politician in a foreign country, appear to be able to produce tears at will.When a small
Pregnancy Potential of Human Oocytes – The Effect of Cryopreservation
Authors: David Levran, Jehoshua Dor, Edwina Rudak, Laslo Nebel, Izhar Ben-Shlomo, Zion Ben-Rafael, Shlomo Mashiach
Journal: New England Journal of Medicine (1990)

In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos?The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos.Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05).The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.
Abstract 1528: Cooperative cross-talk between neuroblastoma subtypes confers resistance to anaplastic lymphoma kinase inhibition
Authors: Andrew M. Chan, Xiaocai Yan, Colin R. Kennedy, Sarah B. Tilkens, Olena Wiedemeier, Hong Guan, Jong-In Park
Journal: Cancer Research (2012)

Abstract Neuroblastoma is a pediatric solid tumor that can be stratified into stroma-rich and stroma-poor histological subgroups. The stromal compartment of neuroblastoma is composed mostly of Schwann cells and they play critical roles in the differentiation, survival and angiogenic responses of tumor cells. In certain neuroblastoma cell lines, the coexistence of neuroblastic N-type and substrate-adherent S-type is frequently observed. One such cell line, SK-N-SH, harbors a F1174L oncogenic mutation in the Anaplastic Lymphoma Kinase (ALK) gene. Treatment of SK-N-SH with an ALK chemical inhibitor, TAE684, resulted in the outgrowth of S-type cells that expressed the Schwann cell marker, S100α6. Nucleotide sequencing analysis of these TAE684-resistant (TR) sublines revealed the presence of the ALK F1174L mutation suggesting their tumor origin, although ALK protein was not detected. Consistent with these findings, TR cells displayed ∼9-fold higher IC50 values than N-type cells. Also, unlike N-type cells, TR cells have readily detectable phosphorylated STAT3 but weaker phosphorylated AKT. Under co-culture conditions, TR cells conferred survival to N-type cells against the apoptotic effect of TAE684. Co-cultivation also greatly enhanced the overall phosphorylation of STAT3 and its transcriptional activity in N-type cells. Finally, conditioned medium from TR clones enhanced cell viability of N-type cells and this effect was Phosphatidylinositol 3-Kinase-dependent. Taken together, these results demonstrate the ability of tumor-derived S-type cells in protecting N-type cells against the apoptotic effect of an ALK kinase inhibitor through upregulating pro-survival signaling. This project was supported by MACC funds, Advancing a Healthier Wisconsin, Wisconsin Breast Cancer Showhouse (O.W.), NIH CA133669 (H.G. and A.M.C.) and the Children's Research Institutes of the Children's Hospital of Wisconsin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1528. doi:1538-7445.AM2012-1528
Delayed‐type hypersensitivity and circulating basophils: A population study
Authors: M. CHAVANCE, B. HERBETH, B. LESOURD
Journal: Allergy (1991)

The factors related to delayed‐type hypersensitivity (DTH) have been investigated in two samples of elderly non‐hospitalized ( n = 375) and hospitalized subjects ( n = 409). Percent basophils was found to be consistently related to the number of positive responses to seven common antigens in the different samples or subsamples considered. The mean number of responses, after adjustment for age, sex and sample was 1.55 below 0.5% basophils, 1.87 between 0.5 and 1.5% and 1.96 over 1.5% ( P &lt; 0.01). No relation was observed between percent basophils and the mean diameter of the positive responses, suggesting that basophils might be related to the early phase of DTH reactions. As previously reported, the number of positive responses was found to be lower in women than in men and to be inversely related to age.
Thymidylate Synthase Expression and Outcome of Patients Receiving Pemetrexed for Advanced Nonsquamous Non–Small-Cell Lung Cancer in a Prospective Blinded Assessment Phase II Clinical Trial
Authors: Marianne C. Nicolson, Dean A. Fennell, David Ferry, Kenneth O'Byrne, Riyaz Shah, Vanessa Potter, Geraldine Skailes, Sunil Upadhyay, Paul Taylor, Valerie André, Tuan S. Nguyen, Scott P. Myrand, Carla Visseren-Grul, Mayukh Das, Keith M. Kerr
Journal: Journal of Thoracic Oncology (2013)

In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level.Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ² analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS.The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control).The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts.
918 HIGH SCD36 PLASMA LEVEL IS ASSOCIATED WITH STEATOSIS AND ITS SEVERITY IN PATIENTS WITH CHRONIC GENOTYPE 1 HEPATITIS C
Authors: S. Petta, A. Handberg, G. Marchesini, C. Camma, V. Di Marco, D. Cabibi, F.S. Macaluso, A. Craxi
Journal: Journal of Hepatology (2012)
Hepatocellular carcinoma on cirrhosis-free liver in a HCV-infected thalassemic
Authors: Andrea Mancuso, Paolo Rigano, Disma Renda, Veronica Di Salvo, Caterina Borgna Pignatti, Francesca Guddo, Antonio Buccellato, Nicola Nicoli, Aurelio Maggio
Journal: American Journal of Hematology (2005)
INTERMEDIATE RISK PATIENTS WITH RENAL INSUFFICIENCY HAVE MORE CALCIFIED CORONARY ARTERY LESIONS, MORE DISTAL LESION DISTRIBUTIONS, AND LONGER/WIDER LESION GEOMETRIES BY LESION SPECIFIC CALCIUM SCORING
Authors: Wassim Mohammed Odeh, Zhen Qian, Parag Joshi, Kunal Bhatt, Reynaria Pitts, Viju Varghese, James Lee, Nancy Flockhart, Szilard Voros, Joseph Miller, Sarah Rinehart
Journal: Journal of the American College of Cardiology (2013)
Montaigne's Essays
Authors: J. Sheather
Journal: BMJ (2010)

Some ideas seem to hover just beyond the horizon of possibility. Try to imagine modern medicine without our idea of “the self,” without the idea that we each possess a unique, authentic, evolving identity—an inner core, unlike all others, the essence of who we most deeply are. Depth psychology, narrative medicine, person centred care, a “good death”: the language of medicine has increasingly aligned itself to the powerful gravitational field of the self. It wasn’t always this way. Our idea of who we are is one of the great works of modernity, and it takes considerable mental cunning to see it as anything other than normal or natural.

In 1580 the French late …
Fanconi's anaemia associated with multicentric Bowen's disease and decreased NK cytotoxicity
Authors: C. LEBBE, L. PINQUIER, M. RYBOJAD, C. CHOMIENNE, S. OCHONISKY, J. M. MICLEA, E. GLUCKMAN, P. MOREL
Journal: British Journal of Dermatology (1993)

Journal Article Fanconi's anaemia associated with multicentric Bowen's disease and decreased NK cytotoxicity Get access C. LEBBÉ, C. LEBBÉ Service de Dermatologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar L. PINQUIER, L. PINQUIER Service de Dermatologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar M. RYBOJAD, M. RYBOJAD Service de Dermatologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar C. CHOMIENNE, C. CHOMIENNE Service de Médecine Nucléaire, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar S. OCHONISKY, S. OCHONISKY Service de Dermatologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar J. M. MICLEA, J. M. MICLEA Services d'Hématologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar E. GLUCKMAN, E. GLUCKMAN Services d'Hématologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar P. MOREL P. MOREL Service de Dermatologie, Hôpital Saint‐Louis, 1 Av. Cl, Vellefaux, 75475, Paris, Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 5, 1 November 1993, Pages 615–618, https://doi.org/10.1111/j.1365-2133.1993.tb00497.x Published: 01 November 1993 Article history Accepted: 22 April 1993 Published: 01 November 1993
222. Enhancement of Intracellular Gene Delivery by the S413-PV Cell Penetrating Peptide
Authors: Miguel Mano, Cristina Teodósio, Artur Paiva, Sérgio Simões, Maria C. Pedroso de Lima
Journal: Molecular Therapy (2005)

Cell penetrating peptides have been shown to translocate across eukaryotic cell membranes through a temperature-insensitive and energy-independent mechanism that does not involve membrane receptors or transporters. The capacity of these peptides to efficiently penetrate cell membranes, and most importantly the ability shared by a number of cell penetrating peptides to accumulate inside the nucleus of cells, render them particularly suited to act as gene delivery vectors.