tbuckley/cabot-search huggingface dataset:
Reexpression of T-type Ca2+ channel gene and current in post-infarction remodeled rat left ventricle
Authors: B Huang
Journal: Cardiovascular Research (2000)

Objective: T-type Ca2+ currents (ICa-T) are present in neonatal rat myocytes but is not detected in adult ventricular myocytes. The present study was designed to investigate the expression of the T-type Ca2+ channel gene and current in post-infarction remodeled hypertrophied rat left ventricle (LV). Methods: We compared the expression of T-type Ca2+ channel gene α-1G in neonatal rat LV, in adult sham-operated LV and remodeled hypertrophied LV 3 to 4 weeks post-myocardial infarction (MI) using RNase protection assay (RPA). The cDNA fragment of α-1G used in RPA was obtained from poorly conserved region of recently published T-type Ca2+ channel coding sequence of rat by RT-PCR. The fragment was verified by restriction enzyme digestion and sequencing. The presence of ICa-T in LV of sham and post-MI rats was examined using patch-clamp techniques. In the presence of K+-free, Na+-free external solution, ICa-T was separated from ICa-L by different holding potentials (HP). ICa-T was also recorded during depolarization to −40 mV from a HP of −80 mV with NaCl in external solution and INa suppressed by 100 μM tetrodotoxin (TTX). Results: The T-type Ca2+ channel gene α-1G was expressed in neonatal heart, the expression level decreased by 80%, in adult sham heart and was reexpressed in MI (158% increases compared to sham; P<0.01). ICa-T was recorded in 11 of 31 MI cells in presence of K+-free, Na+-free external solution and in 9 of 14 cells when INa was suppressed by TTX. ICa-T was not detected in any of 21 sham cells. ICa-T density was 1.1±0.4 pA/pF. ICa-T was more sensitive to Ni2+ and less sensitive to nisoldipine. Conclusions: T-type Ca2+ channel gene and current are reexpressed in rat post-MI remodeled LV myocytes. Its functional significance in the post-MI remodeling process remains to be defined.
THE MULTIPLICATION OF BACTERIOPHAGE IN VIVO AND ITS PROTECTIVE EFFECT AGAINST AN EXPERIMENTAL INFECTION WITH SHIGELLA DYSENTERIAE
Authors: René J. Dubos, June Hookey Straus, Cynthia Pierce
Journal: The Journal of Experimental Medicine (1943)

1. Anti-Shiga bacteriophage injected into the general circulation can multiply in the brain of mice infected intracerebrally with Shigella dysenteriae. 2. Under proper conditions, the injection of active bacteriophage into the general circulation can protect mice against an otherwise fatal intracerebral infection with Shigella dysenteriae. 3. The protection so induced appears to depend upon the early establishment of a high bacteriophage level in the infected animal.
Genetic Manipulation of Cardiac K <sup>+</sup> Channel Function in Mice
Authors: Jeanne M. Nerbonne, Colin G. Nichols, Thomas L. Schwarz, Denis Escande
Journal: Circulation Research (2001)

In the mammalian myocardium, potassium (K(+)) channels control resting potentials, action potential waveforms, automaticity, and refractory periods and, in most cardiac cells, multiple types of K(+) channels that subserve these functions are expressed. Molecular cloning has revealed the presence of a large number of K(+) channel pore forming (alpha) and accessory (beta) subunits in the heart, and considerable progress has been made recently in defining the relationships between expressed K(+) channel subunits and functional cardiac K(+) channels. To date, more than 20 mouse models with altered K(+) channel expression/functioning have been generated using dominant-negative transgenic and targeted gene deletion approaches. In several instances, the genetic manipulation of K(+) channel subunit expression has revealed the role of specific K(+) channel subunit subfamilies or individual K(+) channel subunit genes in the generation of myocardial K(+) channels. In other cases, however, the phenotypic consequences have been unexpected. This review summarizes what has been learned from the in situ genetic manipulation of cardiac K(+) channel functioning in the mouse, discusses the limitations of the models developed to date, and explores the likely directions of future research.
How to Optimize Physicians’ Communication Skills in Cancer Care: Results of a Randomized Study Assessing the Usefulness of Posttraining Consolidation Workshops
Authors: Darius Razavi, Isabelle Merckaert, Serge Marchal, Yves Libert, Sandrine Conradt, Jacques Boniver, Anne-Marie Etienne, Ovide Fontaine, Pascal Janne, Jean Klastersky, Christine Reynaert, Pierre Scalliet, Jean-Louis Slachmuylder, Nicole Delvaux
Journal: Journal of Clinical Oncology (2003)

Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program.Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire.Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004).Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.
On a Febrile Disorder Communicated from Calves, and Accompanied by an Eczematous Eruption
Authors: T. F. Pearse
Journal: BMJ (1885)

In addition, the word (5) "Insaiiitv " should be kept, and also (7) "General Paralysis," a disease so' strongly marked out by its charac- teristics as to render it incapable of being classified with ordinary mental disease.Concerning Epilepsy, I am doubtful.It is an attendant's term for a certain class of cases ; but, 'considering the fact that it accom- panies all the seven forms mentioned above, in many cases it can scarcely be counted apart from them without makiig the terms overlap.Mania, Melancholia, Exaltation, Dementia, Idiocy, 'and General Paralysis, combined with a free use of adjectives, ought to satisfy the most pedantic scholar, and it is not certain that the otie term "In- sanity " would not be sufficient tor all practical purposes.
Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme
Authors: Ralf Jacob, Klaus-Peter Zimmer, Jacques Schmitz, Hassan Y. Naim
Journal: Journal of Clinical Investigation (2000)

Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive human intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase, the components of the intestinal integral membrane glycoprotein sucrase-isomaltase (SI). Several known phenotypes of CSID result from an altered posttranslational processing of SI. We describe here a novel CSID phenotype, in which pro-SI undergoes an unusual intracellular cleavage that eliminates its transmembrane domain. Biosynthesis of pro-SI in intestinal explants and in cells transfected with the SI cDNA of this phenotype demonstrated a cleavage occurring within the endoplasmic reticulum due to a point mutation that converts a leucine to proline at residue 340 of isomaltase. Cleaved pro-SI is transported to and processed in the Golgi apparatus and is ultimately secreted into the exterior milieu as an active enzyme. To our knowledge this is the first report of a disorder whose pathogenesis results not from protein malfolding or mistargeting, but from the conversion of an integral membrane glycoprotein into a secreted species that is lost from the cell surface.
Colorectal cancer statistics, 2014
Authors: Rebecca Siegel, Carol DeSantis, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2014)

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in men and women in the United States. This article provides an overview of colorectal cancer statistics, including the most current data on incidence, survival, and mortality rates and trends. Incidence data were provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results program and the North American Association of Central Cancer Registries. Mortality data were provided by the National Center for Health Statistics. In 2014, an estimated 71,830 men and 65,000 women will be diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease. Greater than one-third of all deaths (29% in men and 43% in women) will occur in individuals aged 80 years and older. There is substantial variation in tumor location by age. For example, 26% of colorectal cancers in women aged younger than 50 years occur in the proximal colon, compared with 56% of cases in women aged 80 years and older. Incidence and death rates are highest in blacks and lowest in Asians/Pacific Islanders; among males during 2006 through 2010, death rates in blacks (29.4 per 100,000 population) were more than double those in Asians/Pacific Islanders (13.1) and 50% higher than those in non-Hispanic whites (19.2). Overall, incidence rates decreased by approximately 3% per year during the past decade (2001-2010). Notably, the largest drops occurred in adults aged 65 and older. For instance, rates for tumors located in the distal colon decreased by more than 5% per year. In contrast, rates increased during this time period among adults younger than 50 years. Colorectal cancer death rates declined by approximately 2% per year during the 1990s and by approximately 3% per year during the past decade. Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations.
Relationship Between Carotid Intima-Media Thickness and the Presence and Extent of Coronary Stenosis in Type 2 Diabetic Patients With Carotid Atherosclerosis but Without History of Coronary Artery Disease
Authors: Ryuuichi Kasami, Hideaki Kaneto, Naoto Katakami, Satoru Sumitsuji, Keita Yamasaki, Tadashi Kuroda, Kouichi Tachibana, Tetsuyuki Yasuda, Akio Kuroda, Taka-aki Matsuoka, Munehide Matsuhisa, Iichiro Shimomura
Journal: Diabetes Care (2011)

We examined the relationship between the presence and extent of coronary stenosis and carotid intima-media thickness (CIMT) in type 2 diabetic patients without history of coronary artery disease (CAD) but with carotid atherosclerosis.A total of 91 type 2 diabetic patients underwent multi-slice computed tomography coronary angiography.Max-IMT in the ≥ 50% stenosis group by multi-slice computed tomography coronary angiography estimation was significantly greater than the 0-25 and 25-50% stenosis group (2.68 ± 0.77 vs. 1.61 ± 0.49 mm, P < 0.0005, and 2.14 ± 0.81 mm, P < 0.05, respectively), and max-IMT in the 25-50% stenosis group was significantly greater than the 0-25% stenosis group (P < 0.05) after adjustment for age, sex, duration of type 2 diabetes, hypertension, and dyslipidemia. In the analysis for trend through the categories of max-IMT, as max-IMT increased, the percentage of ≥ 50% stenosis increased and the percentage of 0-25% stenosis decreased.Our data suggest that max-IMT might be closely associated with the extent of coronary stenosis in type 2 diabetic patients without history of CAD but with carotid atherosclerosis.
Local regulation of postprandial motor responses in ileal pouches
Authors: A Mularczyk, E Contessini-Avesani, B Cesana, P A Bianchi, G Basilisco
Journal: Gut (1999)

Local mechanisms are involved in the postprandial regulation of ileal tone in healthy subjects, but whether these mechanisms affect the postprandial tonic response of ileal pouches has not yet been investigated.To study the effect of a meal on pouch tone and phasic motor activity in patients with gut continuity or ileostomy and, in the latter group, the effect of a pouch perfusion with chyme or saline.Twenty patients with ileal pouches: 10 with gut continuity and 10 with ileostomy.Pouch tone and the frequency of phasic volume events were recorded with a barostat under fasting and postprandial conditions and after perfusion of the isolated pouch with chyme or saline.The meal increased pouch tone and the frequency of phasic volume events in the patients with gut continuity, but not in those with ileostomy. Pouch perfusion with chyme induced a greater increase in pouch tone than saline.The meal stimulated pouch tone and phasic motor activity. These effects were at least partially related to local pouch stimulation by intraluminal contents.
Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk
Authors: Han W. Kim, Lowie Van Assche, Robert B. Jennings, W. Benjamin Wince, Christoph J. Jensen, Wolfgang G. Rehwald, David C. Wendell, Lubna Bhatti, Deneen M. Spatz, Michele A. Parker, Elizabeth R. Jenista, Igor Klem, Anna Lisa C. Crowley, Enn-Ling Chen, Robert M. Judd, Raymond J. Kim
Journal: Circulation Research (2015)

After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements.
Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice
Authors: Noriaki Okamoto, Risa Chihara, Chiori Shimizu, Sogo Nishimoto, Takeshi Watanabe
Journal: Journal of Clinical Investigation (2007)

We previously demonstrated that artificial lymph nodes (aLNs) could be generated in mice by the implantation of stromal cell-embedded biocompatible scaffolds into their renal subcapsular spaces. T and B cell domains that form in aLNs have immune response functions similar to those of follicles of normal lymphoid tissue. In the present study, we show that the aLNs were transplantable to normal as well as SCID mice, where they efficiently induced secondary immune responses. Antigen-specific secondary responses were strongly induced in aLNs even 4 weeks after their transplantation. The antigen-specific antibody responses in lymphocyte-deficient SCID mice receiving transplanted aLNs were substantial. The cells from the aLNs migrated to the SCID mouse spleen and BM, where they expanded to generate large numbers of antigen-specific antibody-forming cells. Secondary responses were maintained over time after immunization (i.e., antigen challenge), indicating that aLNs can support the development of memory B cells and long-lived plasma cells. Memory CD4(+) T cells were enriched in the aLNs and spleens of aLN-transplanted SCID mice. Our results indicate that aLNs support strong antigen-specific secondary antibody responses in immunodeficient mice and suggest the possibility of future clinical applications.
Pneumatic Dilation and Laparoscopic Heller's Myotomy Equally Effective for Achalasia
Authors: Stuart Jon Spechler
Journal: New England Journal of Medicine (2011)

Primary (idiopathic) achalasia is associated with degeneration of neurons in the wall of the esophagus, especially inhibitory neurons that produce nitric oxide.1 Without inhibitory innervation, the lower esophageal sphincter cannot relax completely during swallowing, and the body of the esophagus cannot contract in a peristaltic fashion. The demonstration of these two abnormalities by means of esophageal manometry establishes the diagnosis of achalasia. The unrelenting contraction of the lower esophageal sphincter creates a barrier that impedes the passage of any swallowed material into the stomach. This results in the typical achalasia symptoms of dysphagia for both liquids and solids and regurgitation. . . .
Multicenter Phase II Study of Neoadjuvant Lapatinib and Trastuzumab With Hormonal Therapy and Without Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: TBCRC 006
Authors: Mothaffar F. Rimawi, Ingrid A. Mayer, Andres Forero, Rita Nanda, Matthew P. Goetz, Angel A. Rodriguez, Anne C. Pavlick, Tao Wang, Susan G. Hilsenbeck, Carolina Gutierrez, Rachel Schiff, C. Kent Osborne, Jenny C. Chang
Journal: Journal of Clinical Oncology (2013)

We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)- amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor (ER) when expressed. In this clinical trial, we sought to translate these findings to patients using targeted therapy without chemotherapy.Women with stages II to III HER2-positive breast cancers were eligible. They received trastuzumab once per week (4 mg/kg loading, then 2 mg/kg) and lapatinib 1000 mg once per day for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone-releasing hormone [LHRH] agonist if premenopausal). Pathologic response was assessed by ER status. Biopsies were obtained at baseline, weeks 2 and 8, and time of surgery.Sixty-six patients were enrolled, and 64 were eligible and evaluable for response. Median tumor size was 6 cm (range, 1.5 to 30 cm). Adverse events were mainly grades 1 to 2 (GI, 63%; skin, 46%). Grade 3 metabolic, GI, and liver (18%; 12 patients) and grade 4 liver toxicities (one patient) were also observed. Overall, in-breast pathologic complete response (pCR; ypT0-is) was 27% (ER positive, 21%; ER negative, 36%). The rate of low-volume residual disease (ypT1a-b) was 22% (ER positive, 33%; ER negative, 4%).In patients with locally advanced HER2-positive breast cancer, our approach of targeted therapy only resulted in a high pCR rate without chemotherapy. Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study.
Cardiac Autonomic Neuropathy Predicts Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients With Diabetic Nephropathy
Authors: Anne Sofie Astrup, Lise Tarnow, Peter Rossing, Birgitte V. Hansen, Jannik Hilsted, Hans-Henrik Parving
Journal: Diabetes Care (2006)

OBJECTIVE—Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS—In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy and a matched group of 191 patients with long-standing type 1 diabetes and normoalbuminuria were followed for 10.1 years (range 0.0–10.3 years). At baseline, CAN was assessed by heart rate variation (HRV) during deep breathing. HRV was evaluated as a predictor of the primary end point: cardiovascular morbidity and mortality. As secondary end points, all-cause mortality and the influence of HRV on progression of diabetic nephropathy (decline in glomerular filtration rate [GFR]) was evaluated. RESULTS—During the follow-up, 79 patients (40%) with nephropathy reached the combined primary end point vs. 19 patients (10%) with normoalbuminuria (log-rank test, P &amp;lt; 0.0001). The unadjusted hazard ratio (HR) for reaching the primary end point when having an abnormal HRV (≤10 bpm) measured at baseline compared with a normal HRV was 7.7 (range 1.9–31.5; P = 0.004) in patients with nephropathy. Similarly in the normoalbuminuric patients, the unadjusted HR was 4.4 (1.4–13.6; P = 0.009). In patients with nephropathy, abnormal HRV was significantly associated with fatal and nonfatal cardiovascular disease after adjustment for cardiovascular risk factors. The adjusted HR for reaching the primary end point in a patient with nephropathy and an abnormal HRV was 6.4 (1.5–26.3, P = 0.010), as compared with a normal HRV. The unadjusted HR for dying when having an abnormal HRV compared with a normal HRV was 3.3 (95% CI 1.0–10.7; P = 0.043) in patients with diabetic nephropathy. After adjustment for confounding factors, the impact of HRV on all-cause mortality in patients with nephropathy was no longer significant (P = 0.293). There was no relationship between abnormal HRV and rate of decline in GFR. CONCLUSIONS—HRV is an independent risk factor for cardiovascular morbidity and mortality in type 1 diabetic patients with nephropathy.