tbuckley/cabot-search huggingface dataset:
Serum Glutamate Levels Correlate with Gleason Score and Glutamate Blockade Decreases Proliferation, Migration, and Invasion and Induces Apoptosis in Prostate Cancer Cells
Authors: Shahriar Koochekpour, Sunipa Majumdar, Gissou Azabdaftari, Kristopher Attwood, Ray Scioneaux, Dhatchayini Subramani, Charles Manhardt, Giovanni D. Lorusso, Stacey S. Willard, Hillary Thompson, Mojgan Shourideh, Katayoon Rezaei, Oliver Sartor, James L. Mohler, Robert L. Vessella
Journal: Clinical Cancer Research (2012)

During glutaminolysis, glutamine is catabolized to glutamate and incorporated into citric acid cycle and lipogenesis. Serum glutamate levels were measured in patients with primary prostate cancer or metastatic castrate-resistant prostate cancer (mCRPCa) to establish clinical relevance. The effect of glutamate deprivation or blockade by metabotropic glutamate receptor 1 (GRM1) antagonists was investigated on prostate cancer cells' growth, migration, and invasion to establish biologic relevance.Serum glutamate levels were measured in normal men (n = 60) and patients with primary prostate cancer (n = 197) or mCRPCa (n = 109). GRM1 expression in prostatic tissues was examined using immunohistochemistry (IHC). Cell growth, migration, and invasion were determined using cell cytotoxicity and modified Boyden chamber assays, respectively. Apoptosis was detected using immunoblotting against cleaved caspases, PARP, and γ-H2AX.Univariate and multivariate analyses showed significantly higher serum glutamate levels in Gleason score ≥ 8 than in the Gleason score ≤ 7 and in African Americans than in the Caucasian Americans. African Americans with mCRPCa had significantly higher serum glutamate levels than those with primary prostate cancer or benign prostate. However, in Caucasian Americans, serum glutamate levels were similar in normal research subjects and patients with mCRPC. IHC showed weak or no expression of GRM1 in luminal acinar epithelial cells of normal or hyperplastic glands but high expression in primary or metastatic prostate cancer tissues. Glutamate deprivation or blockade decreased prostate cancer cells' proliferation, migration, and invasion and led to apoptotic cell death.Glutamate expression is mechanistically associated with and may provide a biomarker of prostate cancer aggressiveness.
Prevalence of Kaposi Sarcoma–Associated Herpesvirus Infection in Homosexual Men at Beginning of and During the HIV Epidemic
Authors: Dennis H Osmond, Susan Buchbinder, Amber Cheng, Alison Graves, Eric Vittinghoff, Cynthia K Cossen, Bagher Forghani, Jeffrey N Martin
Journal: JAMA (2002)

ContextSome studies have inferred that an epidemic of Kaposi sarcoma–associated herpesvirus (KSHV) infection in homosexual men in the United States occurred concurrently with that of human immunodeficiency virus (HIV), but there have been no direct measurements of KSHV prevalence at the beginning of the HIV epidemic.ObjectivesTo determine the prevalence of KSHV infection in homosexual men in San Francisco, Calif, at the beginning of the HIV epidemic in 1978 and 1979 and to examine changes in prevalence of KSHV at time points from 1978 through 1996 in light of changes in sexual behavior.Design, Setting, and ParticipantsAnalysis of a clinic-based sample (n = 398) derived from the San Francisco City Clinic Cohort (ages 18-66 years) (n = 2666 for analyses herein) and from population-based samples from the San Francisco Men's Health Study (MHS) (ages 25-54 years) (n = 825 and 252) and the San Francisco Young Men's Health Study (YMHS) (ages 18-29 years) (n = 428-976, and 557); behavioral studies were longitudinal and KSHV prevalence studies were cross-sectional.Main Outcome MeasuresAntibodies against KSHV and HIV; sexual behaviors.ResultsThe prevalence of KSHV infection in 1978 and 1979 was 26.5% of 235 (a random sample) overall (weighted for HIV infection) vs 6.9% (128/1842) for HIV in the San Francisco City Clinic Cohort sample. The prevalence of KSHV infection remained essentially unchanged between an MHS sample of 252 in 1984 and 1985 (29.6%) and a YMHS sample of 557 in 1995 and 1996 (26.4%), while HIV prevalence dropped from 49.5% of 825 in 1984 and 1985 (MHS) to 17.6% of 428 in 1992 and 1993 (YMHS). The proportion of men practicing unprotected receptive anal intercourse with 1 or more partners declined from 54% to 11% during the 1984 through 1993 period (MHS) with similar though slightly higher values in the YMHS in 1992 and 1993; whereas for unprotected oral intercourse it ranged between 60% and 90% in the 1984 through 1996 period (MHS and YMHS).ConclusionsInfection with KSHV was already highly prevalent in homosexual men when the HIV epidemic began in San Francisco, and its prevalence has been maintained at a nearly constant level. Any declines in the incidence of Kaposi sarcoma do not appear to be caused by a decline in KSHV transmission.
Immunoglobulin (Ig) mu, kappa transgenic mice express transgenic idiotype on endogenously rearranged IgM and IgA molecules by secretion of chimeric molecules.
Authors: Q Vos, R J Hodes
Journal: The Journal of Experimental Medicine (1992)

The sera of C57BL/6 mice transgenic for a mu a allotype heavy (H) chain and kappa light chain gene contained endogenous nontransgene immunoglobulin (IgM) (mu b allotype) and IgA molecules which carried the idiotype expressed by the transgenically encoded IgM (mu a) molecule. Serological analysis demonstrated that the presence of the transgenic idiotype on endogenous IgM and IgA was caused by the secretion of chimeric molecules that carried both chains encoded by the mu a transgene and products of endogenously rearranged Ig mu b or alpha genes. These and other results suggest that allelic exclusion of Ig gene rearrangement in mu, kappa transgenic mice is not absolute, that B cells can secrete Igs composed of more than a single (H) chain type, and that endogenous isotype switching does not result in a complete silencing of transgene expression.
Smaller Brain Size Associated With Unawareness of Illness in Patients With Schizophrenia
Authors: L A Flashman, T W McAllister, N C Andreasen, A J Saykin
Journal: American Journal of Psychiatry (2000)

Although several neuropsychological studies have supported the notion of frontal and parietal lobe involvement in unawareness of illness in schizophrenia, neuroanatomic differences have not been examined.Thirty patients with schizophrenia spectrum disorder were rated by means of a structured interview assessing awareness of illness and performance on clinical rating scales. With 13 healthy comparison subjects, they underwent neuropsychological assessment and a scan using three-dimensional, spoiled gradient recall acquisition volumetric magnetic resonance imaging.Patients who were relatively unaware of their illness had smaller brain and intracranial volumes (brain tissue plus CSF) than either aware patients or normal comparison subjects, who did not differ significantly from each other.These findings suggest that unawareness of illness is an important phenomenological feature with neurological correlates that is seen in at least one subgroup of patients with schizophrenia.
Molecular Genetics and Epidemiology of Prostate Carcinoma
Authors: Emiel Ruijter, Christina van de Kaa, Gary Miller, Dirk Ruiter, Frans Debruyne, Jack Schalken
Journal: Endocrine Reviews (1999)

I. Introduction A. Prostate carcinoma epidemiology: mortality rates, incidence, and prevalence B. Familial clustering of prostate carcinoma C. Scope of the review II. Somatic Genetic Alterations in Prostate Carcinoma A. Alterations in DNA methylation B. The androgen signaling cascade C. Vitamin D and prostate carcinoma D. Oncogenes E. TSGs F. Metastasis suppressor genes (MSGs) G. Telomerase activity III. Etiology of Familial Clustering of Prostate Carcinoma IV. Human Papillomavirus and Prostate Carcinoma V. Morphological Diversity of Prostate Carcinoma VI. Concluding Remarks
Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma
Authors: R. Buhl, M. Solèr, J. Matz, R. Townley, J. O'Brien, O. Noga, K. Champain, H. Fox, J. Thirlwell, G. Della Cioppa
Journal: European Respiratory Journal (2002)

The ability of omalizumab, an anti-immnoglobulin‐E agent, to maintain long‐term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24‐week double-blind extension to a 28‐week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 µg·day −1 ) than in the placebo group (43 µg·day −1 ). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.
Multiple functions of CXCL12 in a syngeneic model of breast cancer
Authors: Sharon A Williams, Yuka Harata-Lee, Iain Comerford, Robin L Anderson, Mark J Smyth, Shaun R McColl
Journal: Molecular Cancer (2010)

Abstract Background A growing body of work implicates chemokines, in particular CXCL12 and its receptors, in the progression and site-specific metastasis of various cancers, including breast cancer. Various agents have been used to block the CXCL12-CXCR4 interaction as a means of inhibiting cancer metastasis. However, as a potent chemotactic factor for leukocytes, CXCL12 also has the potential to enhance anti-cancer immunity. To further elucidate its role in breast cancer progression, CXCL12 and its antagonist CXCL12 (P2G) were overexpressed in the syngeneic 4T1.2 mouse model of breast carcinoma. Results While expression of CXCL12 (P2G) significantly inhibited metastasis, expression of wild-type CXCL12 potently inhibited both metastasis and primary tumor growth. The effects of wild-type CXCL12 were attributed to an immune response characterized by the induction of CD8 + T cell activity, enhanced cell-mediated cytotoxicity, increased numbers of CD11c + cells in the tumor-draining lymph nodes and reduced accumulation of myeloid-derived suppressor cells in the spleen. Conclusions This study highlights the need to consider carefully therapeutic strategies that block CXCL12 signaling. Therapies that boost CXCL12 levels at the primary tumor site may prove more effective in the treatment of metastatic breast cancer.
Evidence that histidine is an essential amino acid in normal and chronically uremic man.
Authors: J D Kopple, M E Swendseid
Journal: Journal of Clinical Investigation (1975)

The requirement for dietary histidine was investigated in four normal and three chronically uremic men. Subjects lived in a metabolic unit where they were fed three isonitrogenous diets in the following order: a 40-g protein diet (28 plus or minus SD 8 days), a semi-synthetic amino acid diet deficient in histidine (35 plus or minus 2 days), and an amino acid diet which contained histidine (31 plus or minus 5 days). With ingestion of the histidine-deficient diet, nitrogen balance gradually became negative, and serum albumin decreased in six subjects. Plasma histidine fell by 82 plus or minus 6 per cent; muscle histidine decreased by 62 plus or minus 19 per cent; the hematocrit fell by 25 plus or minus 9 per cent; and serum iron rose. Subjects felt unwell, and in five cases a skin lesion consisting of fine scales, dry skin, and mild erythema developed. After administration of the histidine-repletion diet, nitrogen balance became positive in six subjects; serum albumin increased in five cases; plasma and muscle histidine rose; serum iron fell abruptly; a reticulocytosis ensued; and the hematocrit rose. The clinical symptoms and skin lesions disappeared. These observations indicate that histidine is an essential amino acid in normal and chronically uremic man. The absence of dietary histidine is associated with failure of normal erythropoiesis.
Supportive Care Considerations for Older Adults With Cancer
Authors: Arash Naeim, Matti Aapro, Rashmi Subbarao, Lodovico Balducci
Journal: Journal of Clinical Oncology (2014)

The treatment of cancer presents specific concerns that are unique to the growing demographic of elderly patients. Because the incidence of cancer is strongly correlated with aging, the expansion of supportive care and other age-appropriate therapies will be of great importance as the population of elderly patients with cancer increases in the coming years. Elderly patients are especially likely to experience febrile neutropenia, complications from chemotherapy-induced nausea, anemia, osteoporosis (especially in patients diagnosed with breast or prostate cancer), depression, insomnia, and fatigue. These issues are often complicated by other chronic conditions related to age, such as diabetes and cardiac disease. For many patients, symptoms may be addressed both through lifestyle management and pharmaceutical approaches. Therefore, the key to improving quality of life for the elderly patient with cancer is an awareness of their specific needs and a familiarity with emergent treatment options.
Measurement of PIP3 Levels Reveals an Unexpected Role for p110β in Early Adaptive Responses to p110α-Specific Inhibitors in Luminal Breast Cancer
Authors: Carlotta Costa, Hiromichi Ebi, Miriam Martini, Sean A. Beausoleil, Anthony C. Faber, Charles T. Jakubik, Alan Huang, Youzhen Wang, Madhuri Nishtala, Ben Hall, Klarisa Rikova, Jean Zhao, Emilio Hirsch, Cyril H. Benes, Jeffrey A. Engelman
Journal: Cancer Cell (2014)
Convergent adaptation of human lactase persistence in Africa and Europe
Authors: Sarah A Tishkoff, Floyd A Reed, Alessia Ranciaro, Benjamin F Voight, Courtney C Babbitt, Jesse S Silverman, Kweli Powell, Holly M Mortensen, Jibril B Hirbo, Maha Osman, Muntaser Ibrahim, Sabah A Omar, Godfrey Lema, Thomas B Nyambo, Jilur Ghori, Suzannah Bumpstead, Jonathan K Pritchard, Gregory A Wray, Panos Deloukas
Journal: Nature Genetics (2006)
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma
Authors: Carl Persson, Lena Uller
Journal: European Respiratory Journal (2014)

reagent.Their findings further suggest that for the paucibacillary type of samples, such as CSF, less sample reagent might be necessary.These findings need to be confirmed independently and should be combined with testing of the tuberculocidal effect at lower sample-to-sample-reagent ratios before they can be recommended for clinical use.We hope that other groups will follow the example of R.F.Luo and co-workers and evaluate different protocols for different sample types, so that Xpert testing on nonrespiratory samples can be optimised.
Atrial natriuretic peptide levels in the sleep apnoea/hypopnoea syndrome.
Authors: T W Mackay, M F Fitzpatrick, S Freestone, M R Lee, N J Douglas
Journal: Thorax (1994)

BACKGROUND--Patients with the sleep apnoea/hypopnoea syndrome have increased salt and water excretion at night which has been reported to be associated with an increase in plasma levels of atrial natriuretic peptide (ANP). A study was performed to determine whether any rise in plasma ANP levels was related to nocturnal hypoxaemia. METHODS--Nine patients with sleep apnoea/hypopnoea syndrome were studied on two nights, one breathing air and the other 28% oxygen, the order being randomised. Venous levels of ANP, aldosterone, and renin activity were measured. RESULTS--No decrease in plasma ANP levels on oxygen was seen, and, indeed, there was no evidence of an overnight increase in ANP levels. CONCLUSION--Oxygen therapy does not diminish nocturnal plasma ANP levels in patients with sleep apnoea/hypopnoea syndrome.
Emergence of novel strain of Vibrio cholerae with epidemic potential in southern and eastern India
Authors: T. Ramamurthy, Surabhi Garg, Rakhi Sharma, S.K. Bhattacharya, G. Balakrish Nair, Toshio Shimada, Tae Takeda, Tadahiro Karasawa, Hisao Kurazano, Amit Pal, Yoshifumi Takeda
Journal: The Lancet (1993)
The Need for Lymph Node Dissection in Nonmetastatic Breast Cancer
Authors: Catherine Pesce, Monica Morrow
Journal: Annual Review of Medicine (2012)

Determining whether cancer has spread to locoregional lymph nodes is a critical step in the initial staging of breast cancer patients. Although axillary dissection reliably identifies nodal metastases and prevents the recurrence of cancer in the axilla, there is a significant incidence of long-term side effects, notably lymphedema, and the procedure is of no therapeutic benefit in women without axillary metastases. With the advent of sentinel lymph node biopsy, the axilla can be accurately staged in patients with T1–T3, clinically node-negative breast cancers while avoiding the morbidity of axillary lymph node dissection if the nodes do not contain cancer. Recent clinical trials suggest that for women with metastases to 1 or 2 sentinel nodes, the radiation and systemic therapy that are part of modern multimodality breast cancer treatment can replace axillary dissection when breast-conserving therapy is undertaken. For those with greater disease burden or those undergoing mastectomy, axillary dissection remains standard management.
Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics
Authors: Peter H. Stone, Shigeru Saito, Saeko Takahashi, Yasuhiro Makita, Shigeru Nakamura, Tomohiro Kawasaki, Akihiko Takahashi, Takaaki Katsuki, Sunao Nakamura, Atsuo Namiki, Atsushi Hirohata, Toshiyuki Matsumura, Seiji Yamazaki, Hiroyoshi Yokoi, Shinji Tanaka, Satoru Otsuji, Fuminobu Yoshimachi, Junko Honye, Dawn Harwood, Martha Reitman, Ahmet U. Coskun, Michail I. Papafaklis, Charles L. Feldman
Journal: Circulation (2012)

Background— Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. Methods and Results— Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. Conclusions— Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. Clinical Trial Registration— URL: http:www.//clinicaltrials.gov . Unique Identifier: NCT01316159.
Jean Margaret Euphemie Dickinson
Authors: J. D. J. Dickinson
Journal: BMJ (2014)

Jean Margaret Euphemie Dickinson was part of a medical family. Her father, William Robinson Dickinson, was a general practitioner in Wombwell, Yorkshire. Her brother James and sister Mary both worked as GPs. Born in Barnsley, Jean started at Sheffield medical school, where her older siblings qualified. At boarding school she had received little science education, and so she failed her first MB examination. She then moved to study in Dublin, where her grandparents lived, and she qualified at the College of Surgeons there. …
O169 RIFAXIMIN VERSUS LACTULOSE IN THE TREATMENT OF MINIMAL HEPATIC ENCEPHALOPATHY IN PATIENTS WITH CIRRHOSIS: A PROSPECTIVE, RANDOMIZED, ACTIVE-COMPARATOR, NON-INFERIORITY TRIAL
Authors: O. Goyal, S.S. Sidhu, R.A. Parker, J. Prasad, H. Kishore, A. Sood, V. Mehta, R.S. Chhina
Journal: Journal of Hepatology (2014)
Induction and mode of action of suppressor cells generated against human gamma globulin. II. Effects of colchicine.
Authors: D E Parks, D A Shaller, W O Weigle
Journal: The Journal of Experimental Medicine (1979)

The ability of colchicine (Col) to interfere with suppressor cells specific for the soluble protein antigen human gamma globulin (HGG) has been examined. This interference may be the mechanism of the adjuvanticity promoted by Col. When injected into A/J mice at the appropriate time and concentration, both Col and cyclophosphamide promoted an adjuvant increase in the plaque-forming cell response to 100 micrograms of immunogenic, aggregated HGG. Col abrogated both the induction of suppressor cells when injected with 3 h of tolerization with deaggregated (DHGG) and the expression of previously induced suppressor cells when injected with the antigenic challenge. Interference with the generation and expression of antigen-specific suppressor cells had no detectable effects on the immunologic unresponsive state to HGG. Col did not interfere with the induction of tolerance at a dose (1 mg/kg) that abolished the generation of suppressor cells. Furthermore, the absence of colchicine-sensitive-suppressor cells during the establishment of tolerance had no observable effect on the duration of unresponsivness in either helper T- or B-lymphocyte populations. Finally, Col was not able to terminate the unresponsive state established by DHGG even when responsive splenic B cells could be demonstrated in tolerant animals. These data indicate that suppressor cells are not required for the establishment and maintenance of the unresponsive state to this antigen.