tbuckley/cabot-search huggingface dataset:
Induction of high-affinity interleukin 1 receptor on human peripheral blood lymphocytes by glucocorticoid hormones.
Authors: T Akahoshi, J J Oppenheim, K Matsushima
Journal: The Journal of Experimental Medicine (1988)

The in vitro effect of glucocorticoids (GCs) on IL-1-R expression of human PBMCs was investigated. Both physiological and pharmacological concentration ranges of GC increased the specific binding of 125I-labeled human rIL-1 alpha to PBMCs. This enhancement was specific for GC, since other steroid hormones, such as progesterone, 17 beta-estradiol, and testosterone failed to elevate the binding of 125I-IL-1 alpha to PBMCs. The effect was time dependent with maximal effect occurring 6 h after treatment and dose dependent with half-maximal effect elicited by 100 nM prednisolone. Scatchard plot analysis indicated that 125I-IL-1 alpha binding increased from approximately 100 IL-1-R per cell to 2 X 10(3) receptors per cell without a major change in affinity (Kd = 2.6 X 10(-10) M). The subpopulation of PBMCs induced by GC to express higher levels of IL-1-R consisted predominantly of B lymphocytes, but not T lymphocytes, large granular lymphocytes, or monocytes. GCs also induced the expression of IL-1-R on some other cell types, including normal human dermal fibroblasts and the human large granular lymphocyte cell line YT. Since cycloheximide and actinomycin D inhibited the induction of IL-1-R by GC, synthesis of both new RNA and protein seems to be required for IL-1-R induction. This study presents the first evidence of upregulation of the receptors for IL-1 by GC, and may account for the reported enhancement of in vitro and in vivo humoral immune responses by GCs.
Selenoproteins and Cancer Prevention
Authors: Cindy D. Davis, Petra A. Tsuji, John A. Milner
Journal: Annual Review of Nutrition (2012)

The discovery of multiple selenoproteins has raised tantalizing questions about their role in maintaining normal cellular function. Unfortunately, many of these remain inadequately investigated. While they have a role in maintaining redox balance, other functions are becoming increasingly recognized. As the roles of these selenoproteins are further characterized, a better understanding of the true physiological significance of this trace element will arise. This knowledge will be essential in defining optimum intakes to achieve cellular homeostasis in order to optimize health, including a reduction in cancer, for diverse populations. Human variation in the response to selenium likely reflects significant interactions between the type and amounts of selenium consumed with the genome and a host of environmental factors including the totality of the diet, as discussed in this review.
Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: A multicenter controlled trial
Authors: G V Gregorio, P Jara, L Hierro, C Diaz, A de la Vega, A Vegnente, R Iorio, F Bortolotti, C Crivellaro, L Zancan, H Daniels, B Portmann, G Mieli-Vergani
Journal: Hepatology (1996)

The comparative efficacy of prednisolone followed by interferon alfa (IFN-α) versus IFN-α alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 %] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-α (n = 34); placebo followed by IFN-α (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-α was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 %) had a baseline aspartate aminotransferase (AST) level ≤ 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 %]) or placebo [12 of 30 (40 %)] as against controls (4 of 31 [13 %], P&lt; .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of ≤ 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-α, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-α.
RESPONSE: Re: A Structured Review of Studies on Health-Related Quality of Life and Economic Evaluation in Pediatric Acute Lymphoblastic Leukemia
Authors: A. Simon Pickard, Leigh-Ann Topfer, David Feeny
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: A comprehensive review was made of the literature on the health-related quality of life (HRQL) and economic outcomes of children with acute lymphoblastic leukemia (ALL), the most common of all cancers in childhood. Objectives: The primary objectives of the review were to locate and describe measures of HRQL used in pediatrics and in pediatric oncology that might be applicable to ALL, to summarize studies that have applied HRQL measures to ALL, to identify and summarize economic evaluations of the costs and consequences of care for pediatric ALL, and to identify areas requiring further research. Data sources: To identify the HRQL literature in pediatric ALL, searches were run on the major biomedical and social science bibliographic databases. Search terms included a variety of MeSH and other thesaurus terms, text words, names of HRQL instruments, and the names of key authors in the field. The economic literature searches included most of the same databases, with the addition of the National Health Service Economic Evaluation Database and EconLit. Searches on specific authors and instruments and hand searches were also conducted. Study selection: Only English language studies published from 1975 through 2000 were included. Data extraction: Standardized data extraction forms were used to
'Aggressive keloid': a severe variant of familial keloid scarring
Authors: A. Bayat, G. Arscott, W. E R Ollier, M. W J Ferguson, D A. McGrouther
Journal: Journal of the Royal Society of Medicine (2003)

of gastrointestinal symptoms, but the manifestations could have been limited by the steroid she was taking.Although femoral hernias usually contain omentum or small bowel, occasionally they contain appendix, caecum, testicle, ovary, a Meckel's diverticulum or a caecal diverticulum. 2revious workers have described necrotizing fasciitis of the abdominal wall secondary to a strangulated femoral hernia containing a perforated sigmoid diverticulum in the presence of a rectosigmoid cancer, though this involved the left femoral canal. 3Necrotizing fasciitis has also been described in the abdominal wall over the right iliac fossa secondary to perforation of a sigmoid diverticulum. 4We have not found any previous report of a perforated sigmoid diverticulum presenting with cellulitis and abscess formation in the right thigh.
Human pulmonary infection with Corynebacterium equi
Authors: T Egawa, H Hara, I Kawase, T Masuno, S Asari, M Sakurai, S Kishimoto
Journal: European Respiratory Journal (1990)

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.
WHO records slight blip in downward trend in Ebola incidence
Authors: A. Gulland
Journal: BMJ (2015)

A slight increase in the number of new cases of Ebola virus disease in February has caused only a small blip on the downward curve of the graph since the epidemic peaked at the beginning of December.

Weekly incidence peaked in the week ending 3 December 2014, when there were 1210 new confirmed, suspected, and probable cases. By contrast, in the week to 4 March the World Health Organization reported only 240 confirmed, suspected, and probable cases, of which 132 were confirmed. So WHO’s dramatic warning given in October that the number of new cases could reach 10 000 a week by December was never realised.

The roots of the current epidemic …
NITROGEN BALANCE ON RICE DIET 1
Authors: Ernst Peschel, Ruth Lohmann Peschel
Journal: Journal of Clinical Investigation (1950)

The nitrogen excretion in the urine of 52 pa- tients with hypertensive vascular disease or ne- phritis who followed the rice diet for one to 14 days, averaged, according to Kempner (1), 4.83 Gm. daily.In 46 patients who followed it for 15 to 30 days, the average was 3.6 Gm., in 26 patients on the diet for one to two months, 2.93 Gm. and in 32 patients on the diet for a period longer than two months, the average was 2.26 Gm.These were all hospital patients.Schwartz and Merlis (2) determined the nitro- gen excretion of five physically healthy persons and of one patient with multiple sclerosis who had followed the rice diet for eight days, and of one pa- tient with severe hypertension who had been on the diet for 90 days.The nitrogen excretion in the urine of these six people after they had been on the diet three to eight days averaged 4.90 Gm. daily: 5.15 Gm. on the third day, 4.86 Gm. on the sixth, and 4.68 Gm. on the eighth day.The patient who followed the diet for 90 days had a urinary nitro- gen excretion of 3.81 Gm. on the 90th day.The average nitrogen output in the stool after three to eight days was 1.17 Gm., after 84 to 90 days 1.49 Gm.The caloric intake in each case was 2289 cal- ories; the nitrogen intake, according to analysis, was 2.63 Gm. per day.Schwartz and Merlis found that under these circumstances all their patients were in negative nitrogen balance.The average nitrogen deficit after eight days was 3.22 Gm., the nitrogen deficit after 90 days was 2.67 Gm.N per day.Currens and his associates (3) reported on nitro- gen balance tests in two hypertensive patients who were on the rice diet.The first patient, during the first week on the diet, showed a negative nitrogen balance of 5 Gm. per day; the second, after three months, showed a negative balance of 1 Gm. per day.We have examined the nitrogen balance in 11 patients with hypertensive vascular disease after
Randomized Phase III Trial of Pegylated Liposomal Doxorubicin Versus Vinorelbine or Mitomycin C Plus Vinblastine in Women With Taxane-Refractory Advanced Breast Cancer
Authors: Alan M. Keller, Robert G. Mennel, Vassilis A. Georgoulias, Jean-Marc Nabholtz, Aura Erazo, Anna Lluch, Charles L. Vogel, Manfred Kaufmann, Gunther von Minckwitz, I. Craig Henderson, Lillian Mellars, Leila Alland, Craig Tendler
Journal: Journal of Clinical Oncology (2004)

Purpose To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m 2 every 28 days); or comparator-vinorelbine (30 mg/m 2 weekly) or mitomycin C (10 mg/m 2 day 1 and every 28 days) plus vinblastine (5 mg/m 2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.
West Nile infections are occurring early in North America
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

The United States is seeing West Nile virus infections earlier than usual. The Centers for Disease Control and Prevention (CDC) had reported two cases in humans—:one in Arizona and one in New Mexico—:and avian, animal, or mosquito infections in 17 states by 1 June. Last year more than 260 people died from the disease in the United States.

ProMedmail.org, a service of the International Society for Infectious Diseases, said West Nile virus was now widespread throughout the United States and …
Peripheral vasoconstriction after open-heart surgery
Authors: H. R. Matthews, J. B. Meade, C. C. Evans
Journal: Thorax (1974)

<b>Matthews, H. R., Meade, J. B. and Evans, C. C. (1974).</b><i>Thorax</i>, <b>29</b>, 338-342. <b>Peripheral vasoconstriction after open-heart surgery.</b> Great toe temperatures have been recorded serially after open-heart surgery on 148 patients in order to study the change from a peripherally vasoconstricted to a peripherally vasodilated state. The results in 81 `normals9 show a remarkably consistent warm-up pattern which is independent of the duration or nature of operation and of many other potential variables. The reproducibility of this event has enabled us to construct a nomogram which predicts the limits of time within which a patient should warm up if he is recovering normally from operation. In our unit patients should reach a toe temperature of 34°C within 6·5 hours of return to the intensive care unit if they are breathing spontaneously and within 8 hours if they are on intermittent positive-pressure ventilation, time limits at lower temperatures also being defined by the nomogram. It is anticipated that the recognition of the normal postoperative warm-up pattern will facilitate the early detection and effective treatment of circulatory insufficiency after open-heart surgery.
A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder
Authors: E. Sherwood Brown, Jackie Peterson Todd, Lisa T. Hu, Joy M. Schmitz, Thomas J. Carmody, Alyson Nakamura, Prabha Sunderajan, A. John Rush, Bryon Adinoff, Mary Ellen Bret, Traci Holmes, Alexander Lo
Journal: American Journal of Psychiatry (2015)

Objective: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. Method: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology–Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. Results: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. Conclusions: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.
ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth
Authors: An-Wen Liu, Jing Cai, Xiang-Li Zhao, Ting-Hui Jiang, Tian-Feng He, Hua-Qun Fu, Ming-Hua Zhu, Shu-Hui Zhang
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC). Experimental Design: MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways. Results: MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression–related signaling pathways including JNK, NFκB, and toll-like receptors were repressed by MAP4K4 downregulation. Conclusions: MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance. Clin Cancer Res; 17(4); 1–11. ©2010 AACR.
Intussusception and metastatic colon cancer in an adult with cystic fibrosis
Authors: Francis J Gilchrist, Andrew M Jones, Rowland J Bright-Thomas
Journal: Journal of the Royal Society of Medicine (2012)

Cystic fibrosis (CF) is a true multi-system disease and as life expectancy continues to increase, the spectra of symptoms and diagnoses seen in patients is ever expanding. Some of the conditions that are now seen in CF are specific to the underlying disease process, others are side-effects of long term medications and some are simply related to patients older age. Cancers of the digestive tract were previously extremely rare in patients with CF as they were unlikely to live to an age at which they would present. Over recent years they have been seen more frequently and research has shown that their incidence is higher in patients with CF when compared to the general population.1 In contrast, it has been known for some time that intussusception is more common in children with CF with the peak incidence at 3–12 months of age.2 More recently, in association with patients increased life expectancy, there have been a number of reports of intussusception in older children and adults with CF.3–7 Most of these reports have found the lead point to be inspisated faeces and none have identified a malignant lead point. We present the case of a 35-year-old woman with CF who presented with a sigmoid intussusception caused by 2 malignant polyps. At the time of diagnosis, metastases were identified in 2 local lymph nodes and the liver. As well as being the first reported case of intussusception in a patient with CF in which a malignant lead point has been identified, the case highlights a number of other important clinical, psychological and social issues.
MITF-siRNA Formulation Is a Safe and Effective Therapy for Human Melasma
Authors: Xiang Yi, Guang Zhao, Hongjie Zhang, Di Guan, Rusong Meng, Yingyu Zhang, Qingqi Yang, Henming Jia, Kejun Dou, Chui Liu, Fangyuan Que, James Q Yin
Journal: Molecular Therapy (2010)

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor–siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma. It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor–siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.