tbuckley/cabot-search huggingface dataset:
Cigarette Smoking Is Associated With Advanced Renal Cell Carcinoma
Authors: Matvey Tsivian, Daniel M. Moreira, Jorge R. Caso, Vladimir Mouraviev, Thomas J. Polascik
Journal: Journal of Clinical Oncology (2011)

Purpose Cigarette smoking is a recognized risk factor for renal cell carcinoma (RCC), but little data are available on the association between smoking and RCC biology. We investigated the association between cigarette smoking and RCC stage in a large contemporary multiethnic surgical cohort. Patients and Methods We retrospectively reviewed the demographic, clinical, and pathologic data of patients undergoing surgery for RCC between 2000 and 2009. Advanced RCC was defined as metastatic disease, pathologic stage ≥ T3, and/or lymph node involvement. Self-reported smoking history included smoking status, duration, intensity, cumulative exposure, and cessation. Patient and tumor characteristics were compared between the groups in univariate and multivariate analyses. Results Of the 845 eligible patients, 19.4% and 29.1% were current and former smokers, respectively, and 207 patients (24.5%) had advanced disease. In both univariate and multivariate analyses, smoking was consistently associated with advanced RCC, and cessation reversed the risk. Current and former smokers had 1.5- and 1.6-fold increased odds of advanced disease, respectively. Heavier smoking (longer duration and exposure) was associated with increased risk of advanced RCC, whereas durable cessation reduced the odds of advanced disease. Conclusion Cigarette smoking is an independent risk factor for advanced RCC. Heavier smoking increases the likelihood of advanced disease. Durable smoking cessation attenuated the risk of advanced disease. Given that cigarette smoking is among the few modifiable risk factors for RCC, our results reinforce the importance of smoking cessation and encourage further investigation of the association between smoking and RCC biology.
A CASE OF CONJOINED TWINS
Authors: M. Witkin
Journal: BMJ (1929)

CONJOINED TWINS.[Ts Bm 1117 different things, it m-ay be that gimilar factors are at.woAk in dysenteric infections, and nay explain the absence of lasting agglutination in somine acute cases and its per- sistence in those people who caxL give no history of dysentery-. CONCLUS1ONTS.1. Agglutinins to B. dysenteriawe were present in 6.29 per cent. of 524 serums taken from individuals only one of whom gave a history of dysentery, thirty years plrevinusly.2. The series consisted of an equal number af nmales and; females.The males showed 6.1 per cent.positive and tlhe females 6.48 per cent.The highest titres were fownd in specimens from males.3. The males reacted most frequently to Senine's bacillus" but the highest titres were to Types V, W, and Z of the Flexner group.The females reacted most frequently to Type V Flexmer.4. The presence of these " normal agglutiniins " ay interfere with serological.diagnosis, as they sometimes come witliii-rthe range of the standards laid dowmn as indicative of active inifection; besides, i-r active infetions aggIntinins may niot atways reach these suggested standards.5.There is sufficient evidenece to suggest that these so-called.normal agglttiuiiis are the ontcomne of .sutbfimintalor miiild infection with homologouts or associated micro- organi.sms,and that the term " normal 2 wien applied to this reaction is a mrsn6mer, and shokld be avoided.My thanks are due to Dr. F. M. Rowlanid of Licbfield for revising the mnanuscript.
Schizophrenic: forever young?
Authors: Benedetta Frida Baldi, Christine Hoyer, Nicolas Le Novère
Journal: Genome Medicine (2010)

Schizophrenia is a multifactorial complex disease with a large impact on society. Many hypotheses have been proposed over the years to explain its causes, and genomics and functional genomic approaches may shed light on the reason behind these controversies and discrepancies. We give an overview of several approaches that have been used to identify the genetic causes and molecular phenotypes of the disease. We focus on a recent microarray analysis by Torkamani and colleagues on the evolution of regulatory networks in normal and schizophrenic brains. Combining the conclusion of that study with the prevalent hypotheses of schizophrenia, we suggest that the schizophrenic brain might resemble a juvenile brain.
Reflex Effects of Stimulation of Carotid Sinus and Aortic Baroreceptors on Hindlimb Vascular Resistance in Dogs
Authors: Roger A. L. Dampney, Michael G. Taylor, Elspeth M. McLachian
Journal: Circulation Research (1971)

Two series of experiments were performed on anesthetized dogs whose hindlimbs were perfused at constant flow and the blood pressures in the femoral artery, aortic arch, and carotid sinus recorded. The reflex changes in hindlimb vascular resistance were determined in response to changes in pressure in the aortie arch in the first series, and in the carotid sinus in the second. In each series, when one baroreceptor area was stimulated, the other area was eliminated-in the first series, by perfusing the carotid sinuses at constant pressure, and in the second, by vagotomy. The quantitative relationships between hindlimb vascular resistance and pressure at each of the two baroreceptor sites were determined over the low frequency range (0.001-0.1 Hz). The average estimated steady-state gain of the carotid sinus baroreceptor system was 2.22±0.19 ( SE ) and that of the aortic baroreceptor system 1.06±0.13. The time courses of response for both systems were similar but the aortic baroreceptors were about half as sensitive as the carotid sinus baroreceptors over the entire frequency range.
Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity
Authors: Emilie Mamessier, Aude Sylvain, Marie-Laure Thibult, Gilles Houvenaeghel, Jocelyne Jacquemier, Rémy Castellano, Anthony Gonçalves, Pascale André, François Romagné, Gilles Thibault, Patrice Viens, Daniel Birnbaum, François Bertucci, Alessandro Moretta, Daniel Olive
Journal: Journal of Clinical Investigation (2011)

NK cells are a major component of the antitumor immune response and are involved in controlling tumor progression and metastases in animal models. Here, we show that dysfunction of these cells accompanies human breast tumor progression. We characterized human peripheral blood NK (p-NK) cells and malignant mammary tumor-infiltrating NK (Ti-NK) cells from patients with noninvasive and invasive breast cancers. NK cells isolated from the peripheral blood of healthy donors and normal breast tissue were used as controls. With disease progression, we found that expression of activating NK cell receptors (such as NKp30, NKG2D, DNAM-1, and CD16) decreased while expression of inhibitory receptors (such as NKG2A) increased and that this correlated with decreased NK cell function, most notably cytotoxicity. Importantly, Ti-NK cells had more pronounced impairment of their cytotoxic potential than p-NK cells. We also identified several stroma-derived factors, including TGF-β1, involved in tumor-induced reduction of normal NK cell function. Our data therefore show that breast tumor progression involves NK cell dysfunction and that breast tumors model their environment to evade NK cell antitumor immunity. This highlights the importance of developing future therapies able to restore NK cell cytotoxicity to limit/prevent tumor escape from antitumor immunity.
Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.
Authors: D Caillot, O Casasnovas, A Bernard, J F Couaillier, C Durand, B Cuisenier, E Solary, F Piard, T Petrella, A Bonnin, G Couillault, M Dumas, H Guy
Journal: Journal of Clinical Oncology (1997)

PURPOSE The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. PATIENTS AND METHODS Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. RESULTS The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value &lt; 9 g/L were associated with better outcome. CONCLUSION In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.
In vivo osmoregulation of Na/myo-inositol cotransporter mRNA in rat kidney medulla.
Authors: A Yamauchi, T Nakanishi, Y Takamitsu, M Sugita, E Imai, T Noguchi, Y Fujiwara, T Kamada, N Ueda
Journal: Journal of the American Society of Nephrology (1994)

myo-Inositol, a major compatible osmolyte in renal medulla, is accumulated in kidney-derived epithelial cells cultured in hypertonic media via Na/myoinositol cotransporter (SMIT). The altered medium osmolality of Madin-Darby canine kidney cells leads to changes in the transcription of the SMIT gene and mRNA abundance. To investigate whether SMIT is regulated by tonicity in vivo, renal medullary myoinositol and SMIT mRNA was measured in rats in hydrated and dehydrated states. Rats were divided into two groups: (1) hydrated rats, free access to 3% sucrose water; (2) dehydrated rats, 3 days of water deprivation. Urine sodium, potassium, urea, and osmolality in dehydrated rats were significantly higher than in hydrated rats. Renal medullary sodium, urea, and myo-inositol in dehydrated rats were significantly higher than in hydrated rats. Northern analysis revealed that there was a message hybridized to SMIT cDNA in the cortex and outer and inner medulla of the kidney. Compared with hydrated rats, SMIT mRNA in dehydrated rats was 2.6-fold higher in the outer medulla and 2.5-fold higher in the inner medulla. These results indicate that there is osmoregulatory SMIT in the outer and inner medulla of the kidney and that myo-inositol accumulation in this region is probably due to the increased expression of the SMIT gene.
Platelet Sequestration in Man. I. Methods*
Authors: Richard H. Aster, James H. Jandl
Journal: Journal of Clinical Investigation (1964)

MethodsPreparation and labeling of platelet concentrates with Cr`for transfusion.Platelet-rich plasma was prepared using plastic equipment throughout the procedure.'Chromium"-labeled "EDTA platelets" were prepared according to the method of Aas and Gardner (2) except that no surface-active agent was used.In some experiments platelets were labeled in isotonic NaCl rather than plasma, or the procedure was carried out at room temperature rather than at 40 C.These changes were found not to affect the platelet survival pattern.Chromium"-labeled "citrate platelets" were prepared as follows.A freshly made solution containing 0.085 M trisodium citrate, 0.065 M citric acid, and 2% dextrose was sterilized by Seitz filtration.After 90 to 95 ml was injected into an empty blood pack,' 500 ml of blood was collected from the donor.The first 10 ml of blood to enter the collection tubing was discarded before mixing blood with the anticoagulant.2The pH of the collected blood was about 6.5; the final whole blood concentration
Induction of hsp70-Mediated Th17 Autoimmunity Can Be Exploited as Immunotherapy for Metastatic Prostate Cancer
Authors: Timothy Kottke, Luis Sanchez-Perez, Rosa Maria Diaz, Jill Thompson, Heung Chong, Kevin Harrington, Stuart K. Calderwood, Jose Pulido, Nick Georgopoulos, Peter Selby, Alan Melcher, Richard Vile
Journal: Cancer Research (2007)

Abstract A close connectivity between autoimmune and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoimmune disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70. We show here that, in the prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8-dependent progressive autoimmune reactivity, associated with IL-17 expression. This autoimmune response was also able to induce the rejection of established prostate tumors, but not other histologic types of tumors, growing elsewhere in the animal. These data show that the intimate connectivity between autoimmune and tumor rejection responses extends beyond the classic melanoma paradigm and may be clinically valuable for the treatment of established metastatic disease of the prostate. [Cancer Res 2007;67(24):11970–9]
The AC133 Epitope, but not the CD133 Protein, Is Lost upon Cancer Stem Cell Differentiation
Authors: Kristel Kemper, Martin R. Sprick, Martijn de Bree, Alessandro Scopelliti, Louis Vermeulen, Maarten Hoek, Jurrit Zeilstra, Steven T. Pals, Huseyin Mehmet, Giorgio Stassi, Jan Paul Medema
Journal: Cancer Research (2010)

Colon cancer stem cells (CSC) can be identified with AC133, an antibody that detects an epitope on CD133. However, recent evidence suggests that expression of CD133 is not restricted to CSCs, but is also expressed on differentiated tumor cells. Intriguingly, we observed that detection of the AC133 epitope on the cell surface decreased upon differentiation of CSC in a manner that correlated with loss of clonogenicity. However, this event did not coincide with a change in CD133 promoter activity, mRNA, splice variant, protein expression, or even cell surface expression of CD133. In contrast, we noted that with CSC differentiation, a change occured in CD133 glycosylation. Thus, AC133 may detect a glycosylated epitope, or differential glycosylation may cause CD133 to be retained inside the cell. We found that AC133 could effectively detect CD133 glycosylation mutants or bacterially expressed unglycosylated CD133. Moreover, cell surface biotinylation experiments revealed that differentially glycosylated CD133 could be detected on the membrane of differentiated tumor cells. Taken together, our results argue that CD133 is a cell surface molecule that is expressed on both CSC and differentiated tumor cells, but is probably differentially folded as a result of differential glycosylation to mask specific epitopes. In summary, we conclude that AC133 can be used to detect cancer stem cells, but that results from the use of this antibody should be interpreted with caution.
Nursing downgraded by surreptitious political change
Authors: Mark Aitken
Journal: Journal of the Royal Society of Medicine (2007)

Shields and Watson1 (JRSM 2007;100:70-74) voiced their fears for the decline of nursing as a profession from the perspective of its poor academic standing. Clearly nursing requires the lateral thinking of an academic power base if it is not to be dismembered by the present government's weapons of self-destruction, which are currently targeted on the whole of the NHS. Whether the possession of higher scholastic qualifications should be a prerequisite for entry into the nursing profession is quite another matter.

Several decades of surreptitious political change have downgraded much of the nursing environment and the quality of staff. Why did the nursing and medical fraternity condone these changes? What happened to the Ward Sister—the Consultant's most important partner—and her brood of nurses that constituted the ward's family? That team structure used to be the linchpin of a focused, caring inpatient service. Now it is fragmented. Ward Sisters come and go. Nurses go off sick. Consultants mumble to themselves, looking in vain for a familiar face amongst the doctors and nurses wandering about the wards.

Who accepted the compartmentalised unisex ward? Fine if bed occupancy is less than 80% and sufficient toileting facilities are available for both sexes: a nightmare when occupancy is regularly greater that 95%. Patient dignity, privacy, sensitivity and choice are only cherry picked by the politicians when it brings a smile to the faceless NHS bean counters.

By all means let's encourage academic high flyers into nursing as well as medicine, but preferably those with a vocation driven by compassion that can blossom into charisma. Let's distance ourselves from the current plague of pseudo-doctors and pseudo-nurses whose brains are filled with dogma-driven tick boxes.
Molecular Pathways: Blockade of the PRLR Signaling Pathway as a Novel Antihormonal Approach for the Treatment of Breast and Prostate Cancer
Authors: Jason S. Damiano, Ernesto Wasserman
Journal: Clinical Cancer Research (2013)

The prolactin (PRL)-prolactin receptor (PRLR) signaling complex has been implicated in the pathology of breast and prostate carcinoma. A multitude of pro-oncogenic intracellular signaling pathways are activated by PRL in breast and prostate epithelial cells, leading to enhanced cellular proliferation, survival, and tumorigenesis in numerous model systems. Emerging evidence suggests that targeting the PRL-PRLR axis in human cancer may represent an unexploited avenue for therapeutic intervention and, given the extensive cross-talk between PRLR and other signal transduction pathways, a potential means through which other anticancer agents could be rendered more efficacious in the clinic. LFA102 is a potent anti-PRLR neutralizing antibody that efficiently abrogates the function of this receptor in vivo, mediating significant antitumor effects in preclinical models. The clean safety profile of this antibody in animals and in the clinical experiences to date suggests that blocking the PRLR signaling pathway in human tumors may have few significant toxicologic consequences and may be a promising approach to treating cancer. A phase I trial in patients with breast and prostate cancer is underway to better understand the clinical utility of LFA102 and the contribution of PRL to the maintenance and progression of human cancer.
Expression of Transforming Growth Factor β Isoforms and Their Receptors in Malignant Fibrous Histiocytoma of Soft Tissues
Authors: Tetsuji Yamamoto, Toshihiro Akisue, Takashi Marui, Ikuo Fujita, Keiji Matsumoto, Toshiaki Hitora, Teruya Kawamoto, Keiko Nagira, Tetsuya Nakatani, Masahiro Kurosaka
Journal: Clinical Cancer Research (2004)

Transforming growth factor beta (TGF-beta) is a multifunctional growth factor that variably affects proliferation, differentiation, and extracellular matrix formation. Little information is currently available on the TGF-beta expression in malignant fibrous histiocytoma (MFH). The aims of the present study were to investigate the expression of TGF-beta isoforms and their receptors in human MFH specimens.The expression of TGF isoforms, and TGF-beta receptors (TGF-beta R1 and -beta R2) were immunohistochemically evaluated in 43 paraffin-embedded MFH specimens. Furthermore, the correlation of the TGF-beta and receptor expression with tumor proliferative activity assessed by MIB-1 indices was analyzed.Positive immunoreactivity for TGF-beta1, -beta2, and -beta 3 was identified in tumor cells of 42, 40, and 38 of the 43 MFHs, respectively. In each TGF-beta isoform immunostaining, the specimens were divided into two groups based on the number of positive tumor cells: those with low (<25%) and those with high (>==25%) immunoreactivity. There were no statistically significant differences in the MIB-1 indices between the two groups. Positive immunoreactivity for TGF-beta R1 and -beta R2 was identified in tumor cells of 36 and 24 of the MFHs, respectively. The specimens were divided into two groups based on their receptor expression patterns: those with both TGF-beta R1- and -beta R2-positive immunoreactivity (n = 23), and those with both or either TGF-beta R1- and -beta R2-negative immunoreactivity (n = 20). The MIB-1 indices in the both-TGF-beta R1- and -beta R2-positive group were significantly higher than those in the other group (P = 0.0102). There was no significant difference in pulmonary metastasis ratios between the two groups.These findings strongly suggest an association of the TGF-beta ligand/receptor system with a significantly higher MIB-1 index in human MFHs. Investigation of the TGF-beta R1 and -beta R2 coexpression might be useful in predicting tumor behavior of MFHs.
Endothelin-Induced Increased Aldosterone Activity Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein
Authors: Apurv Khanna, Jan Simoni, Donald E. Wesson
Journal: Journal of the American Society of Nephrology (2005)

The hypothesis that increased dietary protein augments distal nephron acidification through endothelin-mediated increased aldosterone activity was tested. Munich-Wistar rats were studied after 3 wk of diets with 50% high protein (HiPro) and 20% control (CON) casein-provided protein, the latter comparable to standard diet. HiPro versus CON rats had higher distal nephron H+ secretion by in vivo microperfusion as shown previously. Perfusion with inhibitors of Na+/H+ exchange (EIPA, 10(-5) M), H+-ATPase (bafilomycin, 10(-7) M), and H+-K+-ATPase (Sch 28080 [10(-5) M] and ouabain [10(-3) M]) support that higher Na+/H+ exchange and higher H+-ATPase but not higher H+-K+-ATPase activity mediated increased H+ secretion in HiPro rats. Oral bosentan, an endothelin A/B receptor antagonist, decreased distal nephron H+ secretion in HiPro rats as a result of reduced Na+/H+ exchange and H+-ATPase activity as shown previously by the authors' laboratory. HiPro versus CON rats had higher plasma aldosterone (60.9 +/- 5.9 versus 42.2 +/- 4.4 pg/ml; P < 0.024) and higher urine aldosterone excretion (21.9 +/- 3.9 versus 10.5 +/- 2.8 ng/d; P < 0.04) in the absence but not presence of bosentan, consistent with endothelin-mediated increased aldosterone secretion. HiPro rats that did versus did not ingest the aldosterone antagonist spironolactone had lower distal nephron H+ secretion (29.2 +/- 3.3 versus 42.1 +/- 3.8 pmol/mm per min; P < 0.05) as a result of lower H+-ATPase activity without differences in Na+/H+ exchange or H+-K+-ATPase activity. The data support that dietary protein provided as casein increases distal nephron acidification through endothelin-stimulated Na+/H+ exchange and endothelin-stimulated aldosterone secretion that increases H+-ATPase activity.