tbuckley/cabot-search huggingface dataset:
Sodium pump distribution is not reversed in the DBA/2FG-pcy, polycystic kidney disease model mouse.
Authors: G Kawa, S Nagao, A Yamamoto, K Omori, Y Komatz, H Takahashi, Y Tashiro
Journal: Journal of the American Society of Nephrology (1994)

Recently, it has been reported that Na,K-ATPase in the renal epithelia of human autosomal dominant polycystic kidney disease and cpk mouse, a murine model of autosomal recessive polycystic kidney disease, mislocates to apical plasma membrane and that mislocated Na,K-ATPase causes the cyst formation. Whether the DBA/2FG-pcy mice, which are presumably a suitable model for autosomal dominant polycystic kidney disease, also exhibit the reversal polarity of Na,K-ATPase localization was examined. Kidneys of newborn DBA/2FG-pcy mice, and those at early and late stages of cyst development were examined by immunohistochemical techniques. At any stage, abnormal distribution of Na,K-ATPase on the apical membranes of tubular epithelial cells could not be detected. It is suggested that cysts can be formed without reversed polarity of Na,K-ATPase distribution in pcy mice.
Lung trauma after suicidal attempt; MDCT with angiography and perfusion and MRI with DWI in diagnostic and following
Authors: Aleksandar Ivkovic, Tamara Milosavljevic, Zoran Radovanovic
Journal: European Respiratory Journal (2013)

Purpose: Lung trauma is a significant source of morbidity and mortality. Purpose is to determine all possible injuries and complications in patients who survive suicide attempt.  Material and methods: We examined 37 patients after suicide attempt. All patients were examined on MDCT within 4 hours after incident. There were 20 female and 17 male patients from 16 to 38 years old. One female patient was examined after 3 separate attempts in period of 2 years. 13 patients finished lethal, 22 went to surgery. From survived patients 11 had another suicide attempt and 6 finished lethal. Four patients died from other causes, connected to trauma (thromboembolism) in period first year after. In 15 cases we performed pulmonary angiography and in 9 patients we performed MDCT perfusion to determine unseen injuries. In 15 patients we performed MRI with DWI.  Results: The time of injury, mechanism of injury, and evidence of associated injury to other systems are all salient features of an adequate clinical history. We obtained Information directly from the patient whenever possible and from other witnesses to the accident if available. We separate findings in blood vessels injuries, airway injuries, bone injuries and soft tissue injuries. Major criteria were presents of lung hematoma, fluid or gas. We followed up all patients with minor injuries. The traumatic mediastinal emphysema occurs along with severe combined injuries. A typical feature is the subcutaneous emphysema as well as crackling sounds and frequently a pneumothorax.  Conclusion: MDCT is golden standard for diagnostic of lung injury. MDCT perfusion and MRI DWI are new methods give us information of unseen injuries.
Inhibition of Mammary Tumorigenesis in Carcinogen-Treated Lewis Rats by Suppression of Prolactin Secretion&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C W Welsch, C K Brown, M Goodrich-Smith, J Van, B Denenberg, T M Anderson, C L Brooks
Journal: JNCI Journal of the National Cancer Institute (1979)

One hundred sixty-eight female Lewis rats were treated intragastrically with 10 mg 7,12-dimethylbenz[a]anthracene at 56 and 63 days of age. Pituitary prolactin secretion was suppressed in one-half of these rats by daily sc administrations of 2-bromoergocryptine mesylate (CB-154; 0.4 mg/100 g body wt) from 29 to 90 days of age (series 1) and from 90 to 140 days of age (series 2). Treatment with CB-154 was initiated prior to the onset of palpable mammary carcinomas. Control rats were given injections of saline. Inguinal mammary glands were excised from 10 control and 10 CB-154-treated rats at the cessation of saline and CB-154 treatments and examined for hyperplastic nodules (HN). The remaining rats were palpated weekly for mammary carcinomas (MC) and killed at 200 days of age. Mean number of HN per rat, mean number of MC per rat, and percent of rats with MC were, respectively: series 1--controls, 0.6, 1.5, and 68; CB-154 treatment, 0.5, 1.1, and 62; series 2--controls, 10.4, 2.0, and 94; CB-154 treatment, 5.1, 1.1, and 56. The number of HN and MC was only slightly reduced in rats when prolactin was suppressed during carcinogen treatment (series 1) but markedly reduced when prolactin was suppressed after carcinogen treatment (series 2). These results provide evidence that prolactin is involved in the early development of mammary dysplasias in the carcinogen-treated female Lewis rat.
Neuropathy and Celiac Disease—Reply
Authors: Sujata Thawani, Jonas F. Ludvigsson
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
A microbial aetiology of acne: what is the evidence?
Authors: B. Shaheen, M. Gonzalez
Journal: British Journal of Dermatology (2011)

A microbial aetiology of acne has been suggested since the beginning of the last century. There is considerable evidence, circumstantial at best, which suggests that micro-organisms, particularly Propionibacterium acnes, are important in the pathogenesis of acne vulgaris. However, it is still unclear whether P. acnes is actually a causal agent in the development of noninflamed or inflamed acne lesions. Based on a review of the microbiological data on normal and acne-affected skin, we propose that P. acnes neither initiates comedogenesis nor has a role in the initiation of inflammation in inflamed acne lesions.
Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.
Authors: S A Stalcup, L M Pang, J S Lipset, C E Odya, T L Goodfriend, R B Mellins
Journal: Circulation Research (1978)

Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.
Clonal Evolution: Multiregion Sequencing of Esophageal Adenocarcinoma Before and After Chemotherapy
Authors: Siddhartha Devarakonda, Ramaswamy Govindan
Journal: Cancer Discovery (2015)

Abstract Summary: It is possible to decipher the clonal architecture of a tumor and the sequence in which cancer clones acquire genomic alterations through multiregion sequencing (M-seq). Serial evaluation of tumor specimens through M-seq can provide valuable information on the molecular basis of resistance to therapy. Cancer Discov; 5(8); 796–8. ©2015 AACR. See related article by Murugaesu et al., p. 821.
High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.
Authors: D L Trump, K H Havlin, E M Messing, K B Cummings, P H Lange, V C Jordan
Journal: Journal of Clinical Oncology (1989)

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.
Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience.
Authors: A S Pappo, J Fontanesi, X Luo, B N Rao, D M Parham, C Hurwitz, L Avery, C B Pratt
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P &lt; .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.
Derivation of genetic interaction networks from quantitative phenotype data.
Authors: Becky L Drees, Vesteinn Thorsson, Gregory W Carter, Alexander W Rives, Marisa Z Raymond, Iliana Avila-Campillo, Paul Shannon, Timothy Galitski
Journal: Genome biology (2005)

We have generalized the derivation of genetic-interaction networks from quantitative phenotype data. Familiar and unfamiliar modes of genetic interaction were identified and defined. A network was derived from agar-invasion phenotypes of mutant yeast. Mutations showed specific modes of genetic interaction with specific biological processes. Mutations formed cliques of significant mutual information in their large-scale patterns of genetic interaction. These local and global interaction patterns reflect the effects of gene perturbations on biological processes and pathways.
Is transthoracic core needle biopsy under CT scan a good deal for benign diseases' diagnosis?
Authors: Clara Fontaine-Delaruelle, Gilbert Ferretti, Delphine Gamondes, Eric Pradat, Pierre-Jean Souquet, Sébastien Couraud
Journal: European Respiratory Journal (2014)

BACKGROUND: Transthoracic core needle biopsy under CT-Scan (TTNB) is frequently used for lung malignancies diagnosis. However, there is little data about its interest in the diagnosis of non-malignant diseases. This work aims to determine TTNBs diagnostic performance in this setting and whether some factors may influence diagnostic accuracy.  METHOD: All TTNBs performed in three university centers of thoracic radiology between 2006 and 2012 were analyzed. Medical charts were then reviewed in order to record the final diagnosis retained (either by the TTNB, either by other exam or follow-up) by the physicians. Only TTNBs with a benign final diagnosis were included in this study while TTNBs with either no final diagnosis, either a malignant diagnosis were excluded. This study was declared to French ethic committee. Chi-square test was used for proportion comparisons.  RESULTS: On the 980 TTNBs performed, 62 met the study criteria (61 patients). Final diagnosis were infectious (50%), inflammatory (23%), benign tumors (19%), and non-specific benign diseases (8%). Final diagnosis was concordant with initial diagnosis by TTNB in 68%. Sensibility and specificity for TTNB in this setting were 64% and 83%. Factors associated with a higher diagnostic accuracy were: radiologists9 training (84% of diagnostic concordance if radiologist did more than 100 TTNBs during the study period vs 42%, pl0.001); targets9 location in lower lobe (82% vs 50% in upper/median p =0.016); and needle diameter (69% for 16/18G vs 33% for 19/22G p=0.033).  CONCLUSION: TTNB has moderate performance to diagnose accurately benign diseases but may be helpful if previous exams failed to find the correct diagnose.
Vinorelbine Is an Effective and Safe Drug for AIDS-Related Kaposi’s Sarcoma: Results of a Phase II Study
Authors: Guglielmo Nasti, Domenico Errante, Renato Talamini, Giuliano Rizzardini, Marco Fasan, Giuseppe Landonio, Claudia Zeroli, Guido Chichino, Ezio Nigra, Emanuela Vaccher, Umberto Tirelli
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi’s sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m 2 every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.
Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen–positive chronic hepatitis B
Authors: Maureen M. Jonas, Mei‐Hwei Chang, Etienne Sokal, Kathleen B. Schwarz, Deirdre Kelly, Kyung Mo Kim, Simon C. Ling, Philip Rosenthal, Dumitru Oraseanu, Laurie Reynolds, Alexandra Thiry, Peter Ackerman
Journal: Hepatology (2015)

This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide‐naïve children (2 to &lt;18 years) with hepatitis B envelope antigen (HBeAg)‐positive chronic hepatitis B (CHB). Blinded treatment was administered for a minimum of 48 weeks. After week 48, patients with HBeAg seroconversion continued blinded treatment; those without switched to open‐label entecavir. The primary endpoint was HBeAg seroconversion and HBV DNA &lt;50 IU/mL at week 48. A total of 180 patients were randomized (2:1) and treated. Baseline median age was 12 years, with approximately 50% of children ages &gt;12 to &lt;18, and 25% each ages ≥2 to ≤6 and &gt;6 to ≤12. Rates for the primary endpoint at week 48 were significantly higher with entecavir than placebo (24.2% [29 of 120] vs. 3.3% [2 of 60]; P = 0.0008). Furthermore, higher response rates were observed with entecavir compared with placebo for the key week 48 secondary endpoints: HBV DNA &lt;50 IU/mL (49.2% [59 of 120] vs. 3.3% [2 of 60]; P &lt; 0.0001); alanine aminotransferase normalization (67.5% [81 of 120] vs. 23.3% [14 of 60]; P &lt; 0.0001); and HBeAg seroconversion (24.2% [29 of 120] vs. 10.0% [6 of 60]; P = 0.0210). Among entecavir‐randomized patients, there was an increase in all efficacy endpoints between weeks 48 and 96, including an increase from 49% to 64% in virological suppression. The cumulative probability of emergent entecavir resistance through years 1 and 2 of entecavir was 0.6% and 2.6%, respectively. Entecavir was well tolerated with no observed differences in adverse events or changes in growth compared with placebo. Conclusion : In childhood CHB, entecavir demonstrated superior antiviral efficacy to placebo with a favorable safety profile. These results support the use of entecavir as a therapeutic option in children and adolescents with CHB. (H epatology 2016;63:377–387)
Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of 6% Miltefosine Solution, a Topical Chemotherapy in Cutaneous Metastases From Breast Cancer
Authors: R. Leonard, J. Hardy, G. van Tienhoven, S. Houston, P. Simmonds, M. David, J. Mansi
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare 6% miltefosine solution (Miltex; Asta Medica, Frankfurt, Germany), a new topical cytostatic drug, with placebo as palliative treatment for cutaneous metastases from breast cancer. PATIENTS AND METHODS: In a double-blind, placebo-controlled, multicenter phase III study, a total of 52 patients with inoperable progressive skin lesions from histologically or cytologically confirmed breast cancer, not manageable by radiotherapy or systemic treatment, with superficial or flat skin lesions (estimated depth of invasion ≤ 1 cm) were randomized to receive either 6% miltefosine solution or placebo. The solution was applied at the dose of 2 drops/10 cm 2 , once daily during the first week and twice daily thereafter until treatment failure. RESULTS: Treatment groups were well balanced for patient characteristics at study entry except for a small difference in age. Time to treatment failure (TTF), the primary parameter of this study, showed miltefosine solution to be significantly superior to placebo (P = .007); the median TTF in the miltefosine solution group was nearly three times longer than that in the placebo group (56 days v 21 days). The rate of response based on intention to treat patients was 33.3% for miltefosine solution compared with 3.7% for placebo (P = .006). Cutaneous reactions were seen mainly in the miltefosine group, with the type and frequency similar to those observed in previous studies. CONCLUSION: 6% Miltefosine solution is confirmed as an effective palliative treatment option for cutaneous metastases from breast cancer. Skin reactions, when present, are well tolerated and only occasionally require cessation of treatment.
Abstract 3642: Local Therapeutic Angiogenesis Is Limited by Microvascular Clearance
Authors: Kha Le, Chao-Wei Hwang, A. Rami Tzafriri, Mark Lovich, Elazer Edelman
Journal: Circulation (2008)

Local growth factor (GF) delivery is an attractive mode of vascular regenerative therapy for ischemic tissues. Yet, local release of proangiogenic GFs does not produce a sustained angiogenic response in clinical trials. We hypothesize that angiogenic therapies are self-regulated by dynamically altering tissue transport characteristics. Induced neocapillaries increase drug clearance rates, limiting tissue drug levels and induced vessel growth. We examined the interdependence of FGF distribution and angiogenesis in the rabbit heart in vivo (Fig ). 35 S-FGF1 penetrated 0.6 mm into the myocardium within 48 hr of release from epicardial controlled release patches. Drug release remained constant and angiogenesis was achieved but peaked at day 8 and regressed by day 31, as neocapillary clearance induced rapid increase of GF washout. An ex-vivo perfused heart model supported this interpretation. FGF2 distributions followed linear diffusion with low diffusivity (0.02 μm 2 /s) and low tissue penetration in the absence of coronary flow. Flow restoration enhanced clearance, contracting FGF2 penetration −46%. Findings were explained by a diffusion-clearance model, with a clearance rate constant K = 1.15×10 −4 sec −1 . The validated model of myocardial GF transport was coupled to a model angiogenic response to provide an integrated computational framework for evaluating local angiogenic therapy (insert). Induced angiogenesis is a double-edged sword. Early release of angiogenic compounds stimulates neo-vascularization but the very efficacy of these compounds enhances their clearance and abrogates their pharmacologic benefit.