tbuckley/cabot-search huggingface dataset:
480 FOLLICULAR HELPER T-CELLS POPULATE THE INTRAHEPATIC INFILTRATES OF HCV GENOTYPE-1 CHRONICALLY INFECTED PATIENTS AND PREDICT THE ACHIEVEMENT OF VIROLOGICAL RESPONSE FOLLOWING IFN-BASED TREATMENT
Authors: C. Tripodo, S. Petta, D. Cabibi, C. Cammà, C. Guarnotta, M. Colombo, D. Ferraro, A. Craxì
Journal: Journal of Hepatology (2011)
Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans
Authors: Maple M. Fung, Carie Nguyen, Parag Mehtani, Rany M. Salem, Brandon Perez, Brenda Thomas, Madhusudan Das, Nicholas J. Schork, Sushil K. Mahata, Michael G. Ziegler, Daniel T. O’Connor
Journal: Circulation (2008)

Background— Catecholamines govern stress blood pressure responses. Catecholaminergic responses may be partially genetic and contribute to the complex heritability of hypertension. Methods and Results— To evaluate catecholaminergic responses without systemic counterregulation, we infused graded concentrations of tyramine, an indirect presynaptic norepinephrine releaser, into dorsal hand veins of 49 normotensive men and women of 5 ethnicities. Vascular responses were coupled to common (minor allele frequency &gt;10%) single-nucleotide polymorphisms at adrenergic target loci within presynaptic pathways. Significance was set at P &lt;0.003 after Bonferroni correction. Generalized analysis of molecular variance (GAMOVA) was performed to determine whether genetic admixture contributed to results. Venoconstriction progressed to 47% with increasing concentrations of tyramine (0.129 to 25.8 mmol/L; P &lt;0.001). Family history of hypertension ( P &lt;0.001) and female sex ( P =0.02) predicted blunted tyramine responses. Two genetic loci significantly predicted vascular response: chromogranin B, which encodes a protein that catalyzes catecholamine vesicle formation ( CHGB , exon 4, Glu348Glu; P =0.002), and cytochrome b-561 ( CYB561 , intron 1, C719G; P &lt;0.001), an electron shuttle for catecholamine synthesis. Stepwise regression suggested important effects for the CHGB locus, with polymorphisms for the vacuolar-ATPase β-subunit ( ATP6V1B1 , exon 1, Ile30Thr) and flavin-containing monooxygenase-3 ( FMO3 , exon 3, Lys158Glu, P =0.002). GAMOVA did not show a significant relationship between overall genetic profile and hand-vein constriction ( P =0.29), which indicates that population stratification did not contribute to this phenotype. Conclusions— Locally infused tyramine produced dose-dependent pressor responses, predicted by family history of hypertension, sex, and genetic variants at loci, particularly CHGB , that encode the biosynthesis, storage, and metabolism of catecholamines. Such variants may influence the complex heritability of adrenergic responses and perhaps hypertension.
Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy
Authors: Andrew A. House, Misha Eliasziw, Daniel C. Cattran, David N. Churchill, Matthew J. Oliver, Adrian Fine, George K. Dresser, J. David Spence
Journal: JAMA (2010)

Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B(6), and vitamin B(12)) has been shown to lower the plasma concentration of homocysteine.To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications.A multicenter, randomized, double-blind, placebo-controlled trial (Diabetic Intervention with Vitamins to Improve Nephropathy [DIVINe]) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy.Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B(6) (25 mg/d), and vitamin B(12) (1 mg/d), or matching placebo.Change in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes were dialysis and a composite of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured.The mean (SD) follow-up during the trial was 31.9 (14.4) months. At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m(2) in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m(2) in the placebo group (mean difference, -5.8; 95% confidence interval [CI], -10.6 to -1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04). Plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) micromol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) micromol/L in the placebo group (mean difference, -4.8; 95% CI, -6.1 to -3.7; P < .001, in favor of B vitamins).Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events.isrctn.org Identifier: ISRCTN41332305.
Effects of Calcium Supplementation on Pregnancy-Induced Hypertension
Authors: James M. Roberts
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Bucher et al<sup>1</sup>conclude that calcium supplementation reduces blood pressure during pregnancy and also decreases the incidence of preeclampsia. The authors point out that the reduction in blood pressure resulting in the reduced diagnosis of preeclampsia may "have no effect on the harmful pathologic process." Nonetheless, they conclude that "current, limited evidence supports a policy of offering calcium supplementation to all pregnant women in whom there is a concern about the development of preeclampsia." We would like to take issue with their data selection, conclusions, and, most certainly, their recommendations. The studies in the meta-analysis include extremely heterogeneous patients with different risks for developing preeclampsia. Two of the studies<sup>2,3</sup>include patients already diagnosed with mild preeclampsia or at high risk for preeclampsia based on angiotensin sensitivity testing. These women are quite different from healthy nulliparous patients who comprise the majority of cases. There are further
Relationships of Perfluorooctanoate and Perfluorooctane Sulfonate Serum Concentrations between Mother–Child Pairs in a Population with Perfluorooctanoate Exposure from Drinking Water
Authors: Debapriya Mondal, Maria-Jose Lopez-Espinosa, Ben Armstrong, Cheryl R. Stein, Tony Fletcher
Journal: Environmental Health Perspectives (2012)

There are limited data on the associations between maternal or newborn and child exposure to perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). This study provides an opportunity to assess the association between PFAA concentrations in mother-child pairs in a population exposed to PFOA via drinking water.We aimed to determine the relationship between mother-child PFAA serum concentrations and to examine how the child:mother ratio varies with child's age, child's sex, drinking-water PFOA concentration, reported bottled water use, and mother's breast-feeding intention.We studied 4,943 mother-child pairs (children, 1-19 years of age). The child:mother PFAA ratio was stratified by possible determinants. Results are summarized as geometric mean ratios and correlation coefficients between mother-child pairs, overall and within strata.Child and mother PFOA and PFOS concentrations were correlated (r = 0.82 and 0.26, respectively). Up to about 12 years of age, children had higher serum PFOA concentrations than did their mothers. The highest child:mother PFOA ratio was found among children ≤ 5 years (44% higher than their mothers), which we attribute to in utero exposure and to exposure via breast milk and drinking water. Higher PFOS concentrations in children persisted until at least 19 years of age (42% higher than their mothers). Boys > 5 years of age had significantly higher PFOA and PFOS child:mother ratios than did girls.Concentrations of both PFOA and PFOS tended to be higher in children than in their mothers. This difference persisted until they were about 12 years of age for PFOA and at least 19 years of age for PFOS.
P905 THE RISK OF DELISTING OR DEATH IN LIVER TRANSPLANT CANDIDATES INCREASES FOLLOWING INFECTIONS: RESULTS FROM THE NACSELD CONSORTIUM
Authors: J.G. O'Leary, J.S. Bajaj, F. Wong, P.S. Kamath, S.W. Biggins, H.M. Patton, M.B. Fallon, G. Garcia-Tsao, R.M. Subramanian, B.J. Maliakkal, R. Malik, L.R. Thacher, K.R. Reddy
Journal: Journal of Hepatology (2014)
Palmar Dermatoglyphics In Heart Disease
Authors: E. Franklin Stone
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In the recent article by Takashina and Yorifuji entitled, "Palmar Dermatoglyphics in Heart Disease" (<b>197</b>:689, 1966), authors report distal placement of the palmar axial triradius at a highly significant level in a group of individuals with congenital heart disease as compared to their control groups. We would like to comment on two aspects of their study. First, the authors combine the data from both male and female subjects in making their comparison between groups. This would not be inappropriate if the frequency of distal palmar axial triradii were similar in both males and females. However, from the data presented in Table 2 of their paper, it is clear that the frequency of distal palmar axial triradii in control females is approximately seven times higher than that in control males. In fact, the females in the control group have a higher frequency of distal palmar axial triradii
Peripheral Venoconstriction in Human Congestive Heart Failure
Authors: J. EDWIN WOOD, JULIUS LITTER, ROBERT W. WILKINS
Journal: Circulation (1956)

A method for measuring venous "tone" in the limb segment of man in vivo was used to study the problem of cardiac decompensation. Venoconstriction was present in patients with heart failure and it tended to remit as the patients improved.
Abstract 2218: Systematic identification of combinatorial markers of drug sensitivity in cancer cell lines.
Authors: Adel Tabchy, Nevine Eltonsy, Gordon B. Mills
Journal: Cancer Research (2013)

Abstract Purpose: Translating the cancer genome into highly efficacious targets to guide rational therapeutic combinations is a major emerging challenge. Methods: We established an in silico bioinformatic platform in parallel with a high throughput screening platform evaluating the pharmacological activity of 37 novel targeted agents across 669 highly characterized cell lines representing the genetic and tumor-type heterogeneity of human cancers. Analysis of large scale pharmacological data coupled to massive sequencing data on cell lines was performed to systematically identify combinatorial biomarkers of sensitivity and resistance to cancer therapeutics. Genomic predictors discovered in a 141 cell line training set were validated in an independent non-overlapping test set of 359 cell lines screened on 14 of the compounds. Results: We demonstrate combinations of genomic events that are co-occurring or mutually exclusive and act as co-drivers in various tumors, representing potential targets for combinatorial intervention in cancer. We find that multiple cooperating genomic events predict response to drug intervention independent of tumor lineage. Conclusions: The coupling of scalable in silico and functional high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to prevent the emergence of resistance. Citation Format: Adel Tabchy, Nevine Eltonsy, Gordon B. Mills. Systematic identification of combinatorial markers of drug sensitivity in cancer cell lines. [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 2218. doi:10.1158/1538-7445.AM2013-2218
Changes of Tc-99m HMPAO Brain Distribution in Herpes Encephalitis
Authors: Y LE SCAO, A TURZO, M GUIAS, G LE MENN, M GARRE, P P MORIN
Journal: Clinical Nuclear Medicine (1993)

A right-handed, 38-year-old man with herpes simplex virus encephalopathy (HSVE) underwent Tc-99m HMPAO brain SPECT imaging (associated with CT scan of the brain) at the onset of clinical signs and 6 months later. The symptoms consisted of fever, grand mal seizures, and regressive left hemiparesis. The patient became progressively socially withdrawn, with depressed performances on frontal tests. At the first study, the CT scan was normal, while brain SPECT imaging showed a focal hyperperfusion of the right frontal lobe, which progressed to hypoperfusion in the second study. The second CT scan showed marked atrophy of the right frontal lobe, and was in accordance with EEG findings.
Preoperative Radiation in Treatment of Breast Carcinoma
Authors: Galen M. Tice
Journal: JAMA (1960)

In the period from January, 1936, to June, 1942, 40 patients with breast carcinoma were treated with x-ray (250 kv.) before, rather than after, operation. All were reexamined annually, and in all but four cases contact was maintained until the present time or until death. It is now possible to report that 7 (17.5%) of the 40 patients are living 20 years after the diagnosis of breast carcinoma was established. The diagnoses were confirmed by biopsy in all but four advanced cases. Two case histories given in some detail illustrate the effects of the radiation on the tumor and justify the use of radiation first in order to reduce the danger of disseminating tumor cells during the subsequent surgery. It is believed that modern radiologic techniques may overcome former objections to preoperative irradiation and that this plan deserves more extensive trial.
Heritability of blood pressure
Authors: J H Burn
Journal: BMJ (1978)

own treachery and regicide?Only by making the last of the Plantagenets a monster.Thanks to Shakespeare the mud has stuck, but mud is mud, not kyphoscoliosis, Klumpke's paralysis, Erb's palsy, Sprengel's deformity, cerebral palsy, or even coeliac passion.
UK's “ethical recruitment policy” needs to be strengthened
Authors: Daloni Carlisle
Journal: BMJ (2004)

The Department of Health's code of conduct on overseas recruitment must be strengthened if Britain is to shrug off its international “bad guy” image, the author of a new report said last week.

Research by Professor James Buchan, Queen Margaret University College, Edinburgh, for the Department for International Development, shows a substantial increase in international recruitment to the NHS in recent years, with half of new registrants on the General Medical Council …
The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease
Authors: Ana Cuesta, Laia Pedrola, Teresa Sevilla, Javier García-Planells, María José Chumillas, Fernando Mayordomo, Eric LeGuern, Ignacio Marín, Juan J. Vílchez, Francesc Palau
Journal: Nature Genetics (2001)
Androgen receptors influence the production of pulmonary surfactant in the testicular feminization mouse fetus.
Authors: H C Nielsen
Journal: Journal of Clinical Investigation (1985)

A sexual dimorphism in fetal pulmonary maturation has been described in which the female fetal lung produces surfactant earlier in gestation than the male fetal lung. This is felt to be related to the increased incidence in male newborns of the Respiratory Distress Syndrome. Dihydrotestosterone will delay surfactant production in the female fetus, and a relationship between fetal sexual differentiation and fetal lung maturation has been proposed. We hypothesized that the dimorphism in fetal surfactant production is dependent on androgen receptor function. We measured phosphatidylcholine (PC), saturated phosphatidylcholine (SPC), and sphingomyelin (S) in the amniotic fluid of fetal mice of the mouse model of testicular feminization (Tfm mouse). In this model, male carriers of the X-linked Tfm gene have no functional androgen receptors. The mean amniotic fluid phosphatidylcholine to sphingomyelin ratio (PC/S ratio) was 28% higher in females than in normal males, and the amniotic fluid PC/S ratio of the Tfm male fetuses was the same as the females. The ratio of amniotic fluid saturated phosphatidylcholine to sphingomyelin (SPC/S ratio) was lowest in males, intermediate in females, and highest in Tfm males. A significant relationship between the fetal groups and the amniotic fluid SPC/S ratio was identified by analysis of variance. There were no differences in the whole lung phospholipid content between the three groups. To substantiate the effect of androgen receptors, dihydrotestosterone was injected into pregnant carriers of the Tfm mutation, 2.5 mg/d from day 10 of gestation through the day of sacrifice. The amniotic fluid PC/S ratio was decreased in the female fetuses (consisting of both homozygous normal and heterozygous carriers of the Tfm gene), but not in the Tfm male fetuses. The overall result was no significant difference between the male and female amniotic fluid PC/S ratio while the Tfm amniotic fluid PC/S ratio remained at the level of the untreated females. We conclude that androgens affect fetal lung development via a mechanism dependent on the presence of androgen receptors.
Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium
Authors: Markus Schwaiger, Richard A. Neese, Louis Araujo, William Wyns, Judith A. Wisneski, Heinz Sochor, Stanley Swank, David Kulber, Carl Selin, Michael Phelps, Heinrich R. Schelbert, Michael C. Fishbein, Edward W. Gertz, Herbert Hansen
Journal: Journal of the American College of Cardiology (1989)
Adjuvant Treatment for Resectable Pancreatic Cancer
Authors: Yu Jo Chua, David Cunningham
Journal: Journal of Clinical Oncology (2005)

There are relatively few randomized studies of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic adenocarcinoma. The European Study Group for Pancreatic Cancer 1 (ESPAC1) trial is the largest study of adjuvant treatment to date. The results of ESPAC1 are discussed in the context of other evidence from previous randomized studies, which have also been combined in a meta-analysis. Overall, the existing data show a clear benefit for postoperative adjuvant chemotherapy, which has not been demonstrated for adjuvant chemoradiotherapy. The subgroup of patients with resection margin positive disease did seem to benefit less from adjuvant chemotherapy, and showed a trend towards improved survival with chemoradiotherapy. Adjuvant chemoradiotherapy should be evaluated further in this latter group of patients. The optimal chemotherapy regimen for use as adjuvant treatment is the subject of ongoing trials. Other strategies which should be explored include neoadjuvant treatment and the incorporation of novel targeted agents into management.
Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network
Authors: Céline E. Toutain, Laurent Brouchet, Isabelle Raymond-Letron, Patricia Vicendo, Hortense Bergès, Julie Favre, Marie-José Fouque, Andrée Krust, Anne-Marie Schmitt, Pierre Chambon, Pierre Gourdy, Jean-François Arnal, Françoise Lenfant
Journal: Circulation Research (2008)

Although 17beta-estradiol (E2) is protective in experimental models of myocardial and brain ischemia, its effect on skin ischemia remains unknown. Here, we assessed the protective effect of E2 in a mouse model of skin ischemia, mimicking the surgery of skin flaps. Whereas necrosis appeared in the half portion of the skin flap within 1 week after surgery in ovariectomized mice, it was reduced up to 10-fold when mice were pretreated with E2, at least 3 days before the surgery. The beneficial effect of E2 appeared to be attributable to an increase in skin survival, revealed by measuring viability of ex vivo explants and enhancement of the antiapoptotic Bcl-2 protein expression in vivo. This protective effect on the skin contributed to the protection of the vascular network and facilitated reperfusion, which was found to be accelerated in ovariectomized E2-treated mice, whereas hemorrhages were observed in untreated mice. E2 also increased expression of fibroblast growth factor-2 isoforms in the skin and circulating vascular endothelial growth factor in the serum. Finally, this protective effect of E2 was abolished in estrogen receptor-deficient mice (ERalpha(-/-)) but maintained in chimeric mice reconstituted with ERalpha-deficient bone marrow, indicating dispensable action of E2 in bone marrow-derived cells. This protective effect of E2 was mimicked by treatment with tamoxifen, a selective estrogen receptor modulator. In conclusion, we have demonstrated for the first time that E2 exerts a major preventive effect of skin flap necrosis through a prevention of ischemic-induced skin lesions, including those of the vascular network, which contributes to accelerate the reperfusion of the skin flap.
Long-Term Renal Function in Kidney Donors: A Comparison of Donors and Their Siblings
Authors: SUSAN L. WILLIAMS
Journal: Annals of Internal Medicine (1986)

To assess the effects of unilateral nephrectomy, we evaluated renal function and hypertension in kidney donors who had had nephrectomies 10 years ago or more and siblings who had not had nephrectomies. No statistically significant difference was found between the prevalence of hypertension in donors and siblings. Serum creatinine concentrations were 20% higher in donors and creatinine clearances, 20% lower than corresponding values in siblings. Twenty-four-hour urinary protein excretion increased in all donors after nephrectomy and was more marked in men than women. Of the 38 donors, 12 excreted more than 150 mg/24 h of urinary protein, but only 2 excreted more than 300 mg/24 h. The presence of proteinuria did not correlate with the presence of hypertension, level of renal function, or time since nephrectomy. We conclude that, with the exception of mild proteinuria of unknown clinical significance, unilateral nephrectomy is not associated with adverse effects on kidney function.
Controlled therapeutic trial to determine the optimum dose of antacids in duodenal ulcer.
Authors: N Kumar, J C Vij, A Karol, B S Anand
Journal: Gut (1984)

Antacids are widely used in the management of duodenal ulcer but the optimum dose of antacid required for ulcer healing has not been determined. We therefore studied 107 patients with endoscopically diagnosed duodenal ulcer who were allotted at random to one of the following treatment groups; placebo (group P) and antacid (groups A, B and C). A liquid antacid (Aludrox MH, Wyeth) with neutralising capacity of 2.3 mmol HCl/ml was administered in graded doses of 7.5 ml (Group A), 15 ml (Group B), and 30 ml (Group C), one hour and three hours after each meal, six times a day for four weeks. Patients in group P received 15 ml liquid placebo in a similar fashion. Complete symptomatic relief was obtained in 33% of patients in the placebo group, 54% in antacid group A, 89% in group B, and 92% in group C. Endoscopic assessment at the end of four weeks of treatment gave an ulcer healing rate of 29% in the placebo group, 46% in group A (103.5 mmol antacid/day), 85% in group B (207 mmol/day), and 88% in group C (414 mmol/day). There was no significant difference in the healing rates and pain relief between placebo and antacid group A, while both groups B and C had significantly higher ulcer healing rates and pain relief compared with placebo (p less than 0.001) and antacid group A (p less than 0.01). Drug related unwanted effects were recorded only in group C - 28% of patients suffered from diarrhoea. It is concluded that the optimum antacid requirements for the treatment of duodenal ulcer is 90 ml (acid neutralising capacity, 207 mmol HCl) per day.