tbuckley/cabot-search huggingface dataset:
Detection of Preinvasive Cancer of the Cervix and the Subsequent Reduction in Invasive Cancer
Authors: R. Bergstrom, H. O. Adami, L. Gustafsson, J. Ponten, P. Sparen
Journal: JNCI Journal of the National Cancer Institute (1993)

Cytologic screening and follow-up can reduce the incidence of cervical cancer by detection and removal of precursor lesions. It is unknown, however, whether differences in histopathologic criteria for these precursor lesions affect the benefit of screening. These criteria may be difficult to study, but they are likely to be reflected in reported incidence of in situ cancer in small areas of Sweden. Our purpose was to test the hypothesis that the benefit of screening can be predicted by histopathologic criteria as reflected in the reported incidence of cancer in situ. Incidence data were from the Swedish National Cancer Registry. Regression models showing the relationship between in situ and invasive cancer were formulated and estimated. Each county (total, 24) was a unit of measurement, and adjustment was made for the incidence of invasive cancer before screening. During population-based screening in Sweden, the incidence of cancer in situ varied about fourfold among the 24 counties, which indicates that the criteria used to diagnose cancer in situ differed markedly. No statistically significant ( P <.O5) associations were found between the incidence of cancer in situ in 1965, 1970, or 1975 and the reduction in invasive cancer 5, 10, or 15 years later. According to the best-fitting model, detection of 100 extra cases of cancer in situ per 100000 women per year in 1975 resulted in a reduction of 1.0 (95% confidence interval [CI] = −1.6–3.7) cases of invasive cancer 10 years later. The corresponding best model estimate implied a reduction of 4.6 cases (95% CI = 1.5–7.7) in a model restricted to cancer in situ in patients aged 20–50 years (when organized screening took place), invasive cancer in patients aged 30–60 years, and cancer in situ measured in 1970. The absent, or at most weak, association between detection of cancer in situ and subsequent reduction in invasive cancer indicates that relaxed histopathologic criteria for cancer in situ may result in extensive, unnecessary treatment of lesions that would regress spontaneously. Further studies are urgently needed to enable identification of neoplasms likely to progress to invasive, fatal disease. [J Natl Cancer Inst 85: 1050–1057, 1993]
Reply: Comorbidities and Chronic Obstructive Pulmonary Disease: Is There a Place for Lung Fibrosis?
Authors: Jørgen Vestbo, Marc Decramer
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

We thank Dr. Oba for his interest in and comments on the revised document of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1). We acknowledge that there are limits to the evidence base for roflumilast, but find that there is sufficient evidence for improvement in lung function and reduction of exacerbations, as stated in the document. However, as the evidence is weaker than for other drug classes, and because of the less favorable side effect profile, we do not recommend roflumilast as a firstchoice therapy but rather as one of several alternative choices. The GOLD document also lists all the adverse effects of roflumilast mentioned by Dr. Oba. We are somewhat less encouraged by the effects of theophylline than Dr. Oba, but do list theophylline as another possible treatment, and to a broader range of patients. We also thank Dr. West for pointing out the limitations of using FEV1 alone and not considering the underlying pathophysiology leading to chronic bronchitis and/or emphysema—there is a significant proportion of patients with both. However, as we have no treatments aimed specifically at either of these disorders, we do not think a global document gains from “splitting” rather than “lumping” for management. We disagree with the statement that only subjects with reversible airway obstruction (at least measured as FEV1 reversibility) will benefit from bronchodilator treatment, and we therefore recommend a treatment trial with bronchodilators in patients with symptoms. As in medicine in general, this needs to be followed up, and patients who do not feel any benefit should of course not continue for symptomatic purposes alone. We believe that on a global scale, exposures other than smoking matter for the development of persistent airflow limitation, and we do not see any reason to highlight smoking here. And is chronic obstructive pulmonary disease (COPD) treatable? Yes, as treatment includes symptom management; not least, nonpharmacological treatment, such as pulmonary rehabilitation, has a major impact on symptoms and quality of life. Dr. Tzouvelekis and colleagues turn our attention to combined pulmonary fibrosis and emphysema. We also find the topic very interesting but find that our current knowledge on this entity does not warrant specific focus on combined pulmonary fibrosis and emphysema in the executive summary of a global COPD document. We hope that current and future research will enable us to better understand and manage this subgroup of patients with COPD.
Loss of Phosphatase and Tensin Homolog or Phosphoinositol-3 Kinase Activation and Response to Trastuzumab or Lapatinib in Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancers
Authors: Bhuvanesh Dave, Ilenia Migliaccio, M. Carolina Gutierrez, Meng-Fen Wu, Gary C. Chamness, Helen Wong, Archana Narasanna, Anindita Chakrabarty, Susan G. Hilsenbeck, Jian Huang, Mothaffar Rimawi, Rachel Schiff, Carlos Arteaga, C. Kent Osborne, Jenny C. Chang
Journal: Journal of Clinical Oncology (2010)

Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and lapatinib, an epidermal growth factor receptor/HER2 tyrosine kinase inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit.We evaluated the effect of trastuzumab or lapatinib in three HER2-overexpressing cell lines. We confirmed the in vitro observations in two neoadjuvant clinical trials in patients with HER2 overexpression; 35 patients received trastuzumab as a single agent for the first 3 weeks, then docetaxel every 3 weeks for 12 weeks (trastuzumab regimen), whereas 49 patients received lapatinib as a single agent for 6 weeks, followed by trastuzumab/docetaxel for 12 weeks before primary surgery (lapatinib regimen). Apoptosis, Ki67, p-MAPK, p-AKT, and PTEN were assessed by immunohistochemistry. Genomic DNA was sequenced for PIK3CA mutations.Under low PTEN conditions, in vitro data indicate that lapatinib alone and in combination with trastuzumab was effective in decreasing p-MAPK and p-AKT levels, whereas trastuzumab was ineffective. In the clinical trials, we confirmed that low PTEN or activating mutation in PIK3CA conferred resistance to the trastuzumab regimen (P = .015), whereas low PTEN tumors were associated with a high pathologic complete response rate (P = .007).Activation of PI3 kinase pathway is associated with trastuzumab resistance, whereas low PTEN predicted for response to lapatinib. These observations support clinical trials with the combination of both agents.
Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: A randomized controlled pilot study
Authors: Marije W. Kroon, Bas S. Wind, Johan F. Beek, J.P. Wietze van der Veen, Ludmila Nieuweboer-Krobotová, Jan D. Bos, Albert Wolkerstorfer
Journal: Journal of the American Academy of Dermatology (2011)
How do neuronal and muscle-mechanical properties contribute to the performance of the “delta lognormal” model?
Authors: C.C.A.M. Gielen
Journal: Behavioral and Brain Sciences (1997)

Plamondon &amp; Alimi's model will gain substantially in credibility when it is able to come up with predictions for new (rather than old) experimental results that discriminate between various models. Moreover, the present model is nothing more than a descriptive “black box,” not an explanation for motor performance. A link to the contribution of various neuronal mechanisms involved in motor control and of muscle properties to the performance of the model is crucial.
A clinical–biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status
Authors: E. Bria, G. De Manzoni, S. Beghelli, A. Tomezzoli, S. Barbi, C. Di Gregorio, M. Scardoni, E. Amato, M. Frizziero, I. Sperduti, V. Corbo, M. Brunelli, S. Bersani, G. Tortora, A. Scarpa
Journal: Annals of Oncology (2012)
1305 POSITIVE ANTI-GP210 ANTIBODIES IS A RISK FACTOR FOR POOR BIOCHEMICAL RESPONSE TO URSODEOXYCHOLIC ACID TREATMENT IN JAPANESE PATIENTS WITH PRIMARY BILIARY CIRRHOSIS
Authors: M. Nakamura, M. Ito, K. Yamamoto, M. Zeniya, H. Ohira, E. Hashimoto, M. Honda, S. Kaneko, Y. Ueno, K. Kikuchi, S. Onji, S. Shimoda, H. Takikawa, A. Tanaka, A. Komori, H. Yatsuhashi, H. Kondo, K. Harada, S. Onishi, H. Tsubouchi, Y. Nakanuma, H. Ishibashi
Journal: Journal of Hepatology (2011)
Epidermal naevus syndrome
Authors: M.K. ATTIA, A.M. ABDEL-AZIZ
Journal: British Journal of Dermatology (1976)

Journal Article Epidermal naevus syndrome Get access M.K. ATTIA, M.K. ATTIA Department of Dermatology, Maadi Armed Forces Hospital, Cairo, Egypt Search for other works by this author on: Oxford Academic Google Scholar A.M. ABDEL‐AZIZ A.M. ABDEL‐AZIZ Department of Dermatology and Venereology, Al‐Azhar University, Cairo, Egypt Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue 6, 1 December 1976, Pages 647–648, https://doi.org/10.1111/j.1365-2133.1976.tb07039.x Published: 01 December 1976
Ten year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance
Authors: C Mazzeo
Journal: Gut (2003)

Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy.Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects.For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses.In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.
Substance P recognition by a subset of human T lymphocytes.
Authors: D G Payan, D R Brewster, A Missirian-Bastian, E J Goetzl
Journal: Journal of Clinical Investigation (1984)

The interaction of substance P with human blood T-lymphocytes, which stimulates T-lymphocyte proliferation, was quantified by both flow cytometric and direct binding assays. Fluorescence-detection flow cytometry recorded the binding of dichlorotriazinylamino-fluorescein-labeled substance P to 21 +/- 10% (mean +/- SD, n = 6) and 35 +/- 8% (n = 2) of human blood T-lymphocytes before and after stimulation with 10 micrograms/ml of phytohemagglutinin, respectively. The suppressor-cytotoxic (leu 2a) and helper-inducer (leu 3a) subsets identified by phycoerythrin-labeled monoclonal antibodies contained substance P-reactive T-lymphocytes at respective mean frequencies of 10 and 18%. [3H]substance P bound rapidly and reversibly to a mean of 7035 +/- 2850 sites/T-lymphocyte, which exhibited a dissociation constant (KD) of 1.85 +/- 0.70 X 10(-7) M (mean +/- SD, n = 5). [D-Pro2,D-Phe7,D-Trp9]substance P inhibited the binding of dichlorotriazinylamino-fluorescein-labeled substance P and [3H]substance P to T-lymphocytes at concentrations that suppressed the proliferative response to substance P. Substance P, eledoisin, and substance K (alpha-neurokinin), which all share with substance P the carboxy-terminal substituent -Gly-Leu-Met-NH2, were more potent than substance P in inhibiting the binding of [3H]substance P to T-lymphocytes, suggesting the importance of this sequence in the interaction. Purified human blood B-lymphocytes, monocytes, polymorphonuclear leukocytes, and platelets, and cultured Hut 78 cutaneous lymphoma T-cells, Jurkat cells, Molt-4 lymphoblasts, and HL-60 and U-937 monocyte-like cells all showed only minimal specific binding of [3H]substance P. The recognition of substance P by T-lymphocytes provides one mechanism for selective modulation of immunity by sensory nerves.
Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial
Authors: Theonest K Mutabingwa, Devota Anthony, Archie Heller, Rachel Hallett, Jalal Ahmed, Chris Drakeley, Brian M Greenwood, Christopher JM Whitty
Journal: The Lancet (2005)
Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells
Authors: Robert E. Schwartz, Morayma Reyes, Lisa Koodie, Yuehua Jiang, Mark Blackstad, Troy Lund, Todd Lenvik, Sandra Johnson, Wei-Shou Hu, Catherine M. Verfaillie
Journal: Journal of Clinical Investigation (2002)

We have derived from normal human, mouse, and rat postnatal bone marrow primitive, multipotent adult progenitor cells (MAPCs) that can differentiate into most mesodermal cells and neuroectodermal cells in vitro and into all embryonic lineages in vivo. Here, we show that MAPCs can also differentiate into hepatocyte-like cells in vitro. Human, mouse, and rat MAPCs, cultured on Matrigel with FGF-4 and HGF, differentiated into epithelioid cells that expressed hepatocyte nuclear factor-3β (HNF-3β), GATA4, cytokeratin 19 (CK19), transthyretin, and α-fetoprotein by day 7, and expressed CK18, HNF-4, and HNF-1α on days 14–28. Virtually all human, as well as a majority of rodent cells stained positive for albumin and CK18 on day 21; 5% (rodent) to 25% (human) cells were binucleated by day 21. These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored glycogen. MAPCs, which can be expanded in vitro and maintained in an undifferentiated state for more than 100 population doublings, can thus differentiate into cells with morphological, phenotypic, and functional characteristics of hepatocytes. MAPCs may therefore be an ideal cell for in vivo therapies for liver disorders or for use in bioartificial liver devices.
The Actions of Secretagogues on Oxygen Uptake by Isolated Mammalian Parietal Cells
Authors: Andrew H. Soll
Journal: Journal of Clinical Investigation (1978)

The action of histamine, carbamylcholine, and gastrin on oxygen uptake by cells isolated from canine fundic mucosa was studied in vitro. Viable mucosal cells were prepared by exposure of separated mucosa sequentially to collagenase and EDTA. Oxygen consumption, determined by polarography, was chosen as an index of physiological response of mucosal cells to secretagogues.
Second line treatment for severe acute childhood asthma
Authors: M South
Journal: Thorax (2003)

The choice of treatment for a child with severe acute asthma unresponsive to high dose inhaled bronchodilators and oral or intravenous corticosteroids is still the subject of debate. Although both salbutamol and aminophylline have been around for a long time and have been the subject of many studies, it is still not possible unreservedly to recommend one of these agents over the other as second line treatment.
Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer
Authors: K. Mimori, Y. Tanaka, K. Yoshinaga, T. Masuda, K. Yamashita, M. Okamoto, H. Inoue, M. Mori
Journal: Annals of Oncology (2004)

By using array comparative genomic hybridization (CGH), the increased copy number of CYP24 (which encodes vitamin D 24-hydroxylase) at 20q13.2 was previously reported, leading to the identification of CYP24 as a candidate oncogene in breast cancer. CYP24 leads to abrogate growth control mediated by vitamin D.We examined CYP24 expression as well as VDR (vitamin D receptor) gene expression in 42 esophageal cancer cases using semi-quantitative RT-PCR assay. We induced CYP24 in seven esophageal cancer cell lines using 25-hydroxyvitamin D3 [25(OH)D3] and compared cell growth rate, measured using the 3-(4, 5-dimethylthiazol-2-y)-2, 5-diphenyltetrazolium bromide (MTT) assay system.The overall survival rate was significantly higher in 25 cases of lower CYP24 expression than 17 cases of higher CYP24 expression (P <0.05); on the other hand, 23 cases of low VDR expression had a poorer prognosis than 19 cases of high VDR expression. Moreover, we disclosed that the inverse correlation between CYP24 and VDR expression is significant in esophageal cancer cases (P <0.05). Furthermore, the cell growth evaluated by MTT assay was greatly increased in CYP24-induced and VDR-diminished cells than non-responding cells by 25(OH)D3 activity (P <0.01).Overexpression of the candidate oncogene CYP24 is inversely correlated to vitamin D receptor expression, and may play an important role in determination of the malignant potential of esophageal cancer.
Mucosal gastrin concentration, molecular forms of gastrin, number and ultrastructure of G-cells in patients with duodenal ulcer.
Authors: W Creutzfeldt, R Arnold, C Creutzfeldt, N S Track
Journal: Gut (1976)

The mean antral immunoreactive gastrin (IRG) concentration of 38 duodenal ulcer (DU) patients was significantly higher (35-9+/-5-2 mug/g) than that of 21 controls (15-9+/-2-6 mug/g). Also the mean IRG concentration in the proximal duodenal mucosa of 15 DU patients (3-2+/-0-8 mug/g) was higher (but not significantly) than that of 10 controls (1-8+/-0-5 mug/g). The number of G-cells in the antral mucosa of 58 DU patients and in the duodenal mucosa of 29 DU patients was not larger than that of controls. The distribution of immunoreactivity in gastrin components has been investigated in the antral and duodenal mucosa of six DU patients and six controls. In the antral mucosa the mean percentage of G-17 was 93-3% in DU patients and 92-0% in controls. G-34 amounted to 4-0% in DU patients and to 5-0% in controls. The G-34 percentage in the duodenal mucosa was higher (however not significantly) in the DU patients than in the controls (50-1% versus 35-8%). Ultrastructurally, the antral G-cells of DU patients had a significantly lower density index of their secretory granules suggesting higher functional activity. It is concluded that the exaggerated serum IRG response of DU patients to different stimuli is not a consequence of an increased G-cell mass.
Protective effect of Th22 cells and intrahepatic IL-22 in drug induced hepatocellular injury
Authors: Rongtao Lai, Xiaogang Xiang, Ruidong Mo, Rebecca Bao, Peng Wang, Simin Guo, Gangde Zhao, Honglian Gui, Hui Wang, Shisan Bao, Qing Xie
Journal: Journal of Hepatology (2015)
Biology and pathophysiology of the amyloid precursor protein
Authors: Hui Zheng, Edward H Koo
Journal: Molecular Neurodegeneration (2011)

The amyloid precursor protein (APP) plays a central role in the pathophysiology of Alzheimer's disease in large part due to the sequential proteolytic cleavages that result in the generation of β-amyloid peptides (Aβ). Not surprisingly, the biological properties of APP have also been the subject of great interest and intense investigations. Since our 2006 review, the body of literature on APP continues to expand, thereby offering further insights into the biochemical, cellular and functional properties of this interesting molecule. Sophisticated mouse models have been created to allow in vivo examination of cell type-specific functions of APP together with the many functional domains. This review provides an overview and update on our current understanding of the pathobiology of APP.
Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response
Authors: Tao Peng, Liming Hao, Joseph A. Madri, Xiao Su, Jack A. Elias, Gregory L. Stahl, Stephen Squinto, Yi Wang
Journal: Journal of Clinical Investigation (2005)

The role of complement component C5 in asthma remains controversial. Here we examined the contribution of C5 at 3 critical checkpoints during the course of disease. Using an mAb specific for C5, we were able to evaluate the contribution of C5 during (a) the initiation of airway inflammation, (b) the maintenance of airway hyperresponsiveness (AHR), and (c) sustainment of an ongoing airway response to allergen provocation. Our results indicate that C5 is probably activated intrapulmonarily after infections or exposures to allergen and C5 inhibition has profound effects at all 3 critical checkpoints. In contrast to an earlier report, C5-deficient mice with established airway inflammation did not have elevated AHR to nonspecific stimuli. In the presence of airway inflammation, C5a serves as a direct link between the innate immune system and the development of AHR by engaging directly with its receptors expressed in airways. Through their powerful chemotactic and cell activation properties, both C5a and C5b-9 regulate the downstream inflammatory cascade, which results in a massive migration of inflammatory cells into the bronchial airway lumen and triggers the release of multiple harmful inflammatory mediators. This study suggests that targeting C5 is a potential clinical approach for treating patients with asthma.