tbuckley/cabot-search huggingface dataset:
Variable Clinical Presentations of Nasal and Waldeyer Ring Natural Killer/T-Cell Lymphoma
Authors: Ye-Xiong Li, Qing-Feng Liu, Hui Fang, Shu-Nan Qi, Hua Wang, Wei-Hu Wang, Yong-Wen Song, Jiade Lu, Jing Jin, Shu-Lian Wang, Yue-Ping Liu, Ning Lu, Xin-Fan Liu, Zi-Hao Yu
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the clinical characteristics, prognosis, and treatment outcome for patients with nasal natural killer (NK)/T-cell lymphoma (N-NKTL) and Waldeyer ring NK/T-cell lymphoma (WR-NKTL). Experimental Design: A total of 145 patients with N-NKTL and 95 patients with WR-NKTL were compared. Results: Compared with N-NKTL, WR-NKTL exhibited distinct differences in clinical features with a propensity for nodal involvement, more advanced stages, low elevated lactate dehydrogenase, intermediate chemosensitivity, and a favorable prognosis. Compared with patients with WR-NKTL, patients with N-NKTL were associated with a lower overall response (54% versus 89%) and higher persistent or progressive disease after initial chemotherapy (46% versus 11%; P = 0.000). The 5-year overall survival and progression-free survival rates were 67% and 56% for N-NKTL and 65% and 47% for WR-NKTL, respectively. Patients with stage II WR-NKTL showed favorable prognosis compared with those with stage II N-NKTL. Compared with radiotherapy alone, patients with early-stage WR-NKTL that received radiotherapy and chemotherapy showed a superior progression-free survival and improved overall survival. In contrast, the addition of chemotherapy to radiotherapy did not provide any survival benefit for patients with early-stage N-NKTL. Conclusions: N-NKTL and WR-NKTL represent heterogeneous groups with variable clinical features, responses, prognosis, and treatment options.
Effect of dietary fat saturation on plasma lipoproteins and high density lipoprotein metabolism of the rhesus monkey.
Authors: K S Chong, R J Nicolosi, R F Rodger, D A Arrigo, R W Yuan, J J MacKey, S Georas, P N Herbert
Journal: Journal of Clinical Investigation (1987)

Rhesus monkeys were fed corn or coconut oil-based diets for 3-6 mo to determine effects on the composition of all lipoprotein classes and on the metabolism of high density lipoproteins (HDL). Major findings included the following. Coconut oil feeding increased concentrations of all classes of plasma lipoproteins without altering lipoprotein size, suggesting an increase in particle number. The percentage of saturated fatty acids in the cholesteryl esters (CE) of low density lipoproteins (LDL) and HDL reached 40% with coconut oil feeding. This value probably constitutes a minimum estimate of the CE which were of intracellular rather than intraplasmic origin. The CE in LDL and HDL were nearly identical suggesting virtually complete equilibration by the core lipid transfer reaction. The CE in very low density lipoproteins, in contrast, were significantly more saturated than those in LDL and HDL irrespective of diet. Lower HDL levels on the corn oil diet were associated with higher fractional catabolic rates for both apolipoprotein A-I (0.42 vs. 0.31 d-1) and apolipoprotein A-II (0.45 vs. 0.30 d-1).
Patients’ Revisions of Their Beliefs About the Need for Hospitalization
Authors: W Gardner, C W Lidz, S K Hoge, J Monahan, M M Eisenberg, N S Bennett, E P Mulvey, L H Roth
Journal: American Journal of Psychiatry (1999)

An influential rationale for involuntary hospitalization is that prospective patients who refuse hospitalization at the time it is offered are likely to change their belief about the necessity of hospitalization after receiving hospital treatment. The authors examine how patients changed their evaluations of psychiatric hospitalization following hospital treatment.The authors studied 433 patients who were interviewed about their hospitalization within 2 days of their admission to a psychiatric hospital; 267 of these patients were reinterviewed 4-8 weeks following discharge.When reinterviewed at follow-up, 33 (52%) of 64 patients who said at admission that they did not need hospitalization said that, in retrospect, they believed they had needed it. Only 9 (5%) of 198 patients who said at admission that they needed hospitalization shifted to saying that they had not needed it.Many of the patients who initially judged that they did not need hospitalization revised their belief after hospital discharge and reported that they had needed hospital treatment. However, perceptions of coercion were stable from admission to follow-up, and patients' attitudes toward hospitalization did not become more positive. Coerced patients did not appear to be grateful for the experience of hospitalization, even if they later concluded that they had needed it.
PCP4 regulates Purkinje cell excitability and cardiac rhythmicity
Authors: Eugene E. Kim, Akshay Shekhar, Jia Lu, Xianming Lin, Fang-Yu Liu, Jie Zhang, Mario Delmar, Glenn I. Fishman
Journal: Journal of Clinical Investigation (2014)

Cardiac Purkinje cells are important triggers of ventricular arrhythmias associated with heritable and acquired syndromes; however, the mechanisms responsible for this proarrhythmic behavior are incompletely understood. Here, through transcriptional profiling of genetically labeled cardiomyocytes, we identified expression of Purkinje cell protein-4 (Pcp4), a putative regulator of calmodulin and Ca2+/calmodulin-dependent kinase II (CaMKII) signaling, exclusively within the His-Purkinje network. Using Pcp4-null mice and acquired cardiomyopathy models, we determined that reduced expression of PCP4 is associated with CaMKII activation, abnormal electrophysiology, dysregulated intracellular calcium handling, and proarrhythmic behavior in isolated Purkinje cells. Pcp4-null mice also displayed profound autonomic dysregulation and arrhythmic behavior in vivo. Together, these results demonstrate that PCP4 regulates cardiac excitability through both Purkinje cell-autonomous and central mechanisms and identify this modulator of CaMKII signaling as a potential arrhythmia-susceptibility candidate.
BTEB2, a Krüppel-Like Transcription Factor, Regulates Expression of the SMemb/Nonmuscle Myosin Heavy Chain B (SMemb/NMHC-B) Gene
Authors: Noboru Watanabe, Masahiko Kurabayashi, Yukio Shimomura, Keiko Kawai-Kowase, Yo-ichi Hoshino, Ichiro Manabe, Masafumi Watanabe, Masanori Aikawa, Makoto Kuro-o, Toru Suzuki, Yoshio Yazaki, Ryozo Nagai
Journal: Circulation Research (1999)

We have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at −105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle cell (SMC) line. In this study, we attempted to isolate cDNA clones encoding for the transcription factors that control the expression of the SMemb gene through binding to this cis -regulatory element. We screened a λgt11 cDNA library prepared from C2/2 cells, a rabbit-derived SMC line, by using a radiolabeled concatenated oligonucleotide containing SE1 as a probe. Sequence analysis revealed that one of the cDNA clones corresponds to the rabbit homologue of basic transcriptional element binding protein-2 (BTEB2), which has previously been identified as one of the Krüppel-like transcription factor. Gel mobility shift assays and antibody supershift analyses with nuclear extracts from C2/2 cells indicate that BTEB2 is a major component of nuclear factor:SE1 complexes. Furthermore, a glutathione S -transferase-BTEB2 fusion protein binds to the SE1 in a sequence-specific manner. In support of the functionality of BTEB2 binding, basal promoter activity and BTEB2-induced transcriptional activation were markedly attenuated by the disruption of the SE1. In adult rabbit tissues, BTEB2 mRNA was most highly expressed in intestine, urinary bladder, and uterus. BTEB2 mRNA levels were downregulated in rabbit aorta during normal development. Moreover, immunohistochemical analysis indicated a marked induction of BTEB2 protein in the neointimal SMC after balloon injury in rat aorta. These results suggest that BTEB2 mediates the transcriptional regulation of the SMemb/NMHC-B gene and possibly plays a role in regulating gene expression during phenotypic modulation of vascular SMC.
Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation
Authors: Jacques P. Zappulla, Patrice Dubreuil, Sabine Desbois, Sébastien Létard, Nadine Ben Hamouda, Marc Daëron, Georges Delsol, Michel Arock, Roland S. Liblau
Journal: The Journal of Experimental Medicine (2005)

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for &amp;gt;24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis.
MANPOWER STUDIES WITH SPECIAL REFERENCE TO PSYCHIATRISTS
Authors: DANIEL BLAIN, HOWARD POTTER, HARRY SOLOMON
Journal: American Journal of Psychiatry (1960)

In summary, may I state that, with the help of a number of foundations which have contributed a total of approximately $27,000, the first year has proved to be largely a matter of exploration rather than definition. A large number of interesting contacts with leading professional groups have been made. A tremendous amount of interest has been developed in the study. Many suggestions have come toward modifying it in one direction or another, perhaps most important has been the suggestion that since this is such an enormously important project, it must be done well or not done at all. The activities of the consultants have been extremely helpful. It has been of particular interest to note that the highly successful National Manpower Council working with Dr. Ginzberg and his associates also came to the end of their first year remarking that, in spite of careful planning, the first year had turned out to be largely exploratory. Of great interest was Dr. Ginzberg's remark that no definitive plan for approaching manpower studies had yet been developed. The conclusion after 8 months of effort with a small staff is that the time is now come to enter into an intensive effort over a number of months, mainly to design a series of studies and operations which will, in time, enable progress to be made in this problem. Accordingly, a staff of competent technicians in research design, psychiatric and sociological personnel with clinical and teaching experience will work with the national consultants to produce such a program as may receive financial support over such a period of time as necessary for this important subject.
End-Tidal Carbon Monoxide Corrected for Lung Volume Is Elevated in Patients with Cystic Fibrosis
Authors: Suzanne W. Terheggen-Lagro, Marielle W. Bink, Hendrik J. Vreman, Cornelis K. van der Ent
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Several factors influence levels of end-tidal carbon monoxide (ETCO). We studied determinants of ETCO corrected for inhaled CO (ETCOc) levels in healthy control subjects and compared ETCOc levels and determinants between healthy control subjects and patients with cystic fibrosis (CF). Thirty healthy control subjects (mean ± SD age, 23 ± 6 years) and twenty clinically stable patients with CF, aged 13.5 ± 3.5 years were included. ETCO was measured with the CO-STAT End-Tidal Breath Analyzer (Natus Medical, Inc., San Carlos, CA), and determinants included lung volume (measured with the multiple-breath helium wash-in method), CO-diffusion capacity, and different expiratory flow rates. In healthy control subjects we found a significant correlation between ETCOc and lung volume (r = 0.64, p < 0.05) and with CO-diffusion capacity uncorrected for VA (r = 0.48, p = 0.02). There was no expiratory flow rate dependency in either group. Patients with CF showed no difference in ETCOc levels compared with control subjects (mean 1.2 ± 0.4 ppm vs. 1.3 ± 0.4 ppm, p = 0.32), but patients with CF had lower total lung capacity–helium than healthy control subjects. ETCOc corrected for lung volume was significantly higher in patients with CF compared with control subjects (p < 0.001). We hypothesize that a possible increase in breath CO caused by airway inflammation might be masked by differences in lung volumes between control subjects and patients with CF.
Renal Pressor System in Hypertension
Authors: LEONARD T. SKEGGS, JOSEPH R. KAHN
Journal: Circulation (1958)

Hypertensin has been found in the circulating arterial blood in dogs with experimental renal hypertension and in human beings with essential hypertension. Two different chemical forms of the material have been obtained in purified form and their chemical constitution determined. The decapetide hypertensin I is the initial product of the action of renin on its substrate. This material is transformed to the vasoconstrictor octapeptide hypertensin II by a chloride activated enzyme of the plasma.
PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR
Authors: Hongbing Zhang, Natalia Bajraszewski, Erxi Wu, Hongwei Wang, Annie P. Moseman, Sandra L. Dabora, James D. Griffin, David J. Kwiatkowski
Journal: Journal of Clinical Investigation (2007)

The receptor tyrosine kinase/PI3K/Akt/mammalian target of rapamycin (RTK/PI3K/Akt/mTOR) pathway is frequently altered in tumors. Inactivating mutations of either the TSC1 or the TSC2 tumor-suppressor genes cause tuberous sclerosis complex (TSC), a benign tumor syndrome in which there is both hyperactivation of mTOR and inhibition of RTK/PI3K/Akt signaling, partially due to reduced PDGFR expression. We report here that activation of PI3K or Akt, or deletion of phosphatase and tensin homolog (PTEN) in mouse embryonic fibroblasts (MEFs) also suppresses PDGFR expression. This was a direct effect of mTOR activation, since rapamycin restored PDGFR expression and PDGF-sensitive Akt activation in Tsc1–/– and Tsc2–/– cells. Akt activation in response to EGF in Tsc2–/– cells was also reduced. Furthermore, Akt activation in response to each of EGF, IGF, and PMA was reduced in cells lacking both PDGFRα and PDGFRβ, implying a role for PDGFR in transmission of growth signals downstream of these stimuli. Consistent with the reduction in PI3K/Akt signaling, in a nude mouse model both Tsc1–/– and Tsc2–/– cells had reduced tumorigenic potential in comparison to control cells, which was enhanced by expression of either active Akt or PDGFRβ. In conclusion, PDGFR is a major target of negative feedback regulation in cells with activated mTOR, which limits the growth potential of TSC tumors.
Management of acute stroke in the elderly: preliminary results of a controlled trial.
Authors: W M Garraway, A J Akhtar, R J Prescott, L Hockey
Journal: BMJ (1980)

A randomised controlled trial compared the management of elderly patients with acute stroke in a stroke unit and medical units. A significantly higher proportion of patients discharged from the stroke unit (78 of the 155 admitted) were assessed as independent compared with patients discharged from medical units (49 of the 152 admitted). The intensive use of treatment that might have been implied by creating a stroke unit did not occur, although almost all the patients admitted to the unit received occupational therapy while only 47% of the patients admitted to medical units received occupational therapy. The delay before starting treatment was significantly shorter in the stroke unit. Results of this trial show that the stroke unit improved the natural history of stroke by increasing the proportion of patients who were returned to functional independence.
Abortions and Acute Identity Crisis in Nurses
Authors: WALTER F. CHAR, JOHN F. McDERMOTT
Journal: American Journal of Psychiatry (1972)

About a month after Hawaii became the first state in the U.S. to make abortion a personal matter to be decided between a woman and her physician, 2 hospitals, in efforts to obtain psychiatric consultation for their nurses who were upset by abortion work, contacted the authors. 2 nurses in a small hospital which had been doing abortions were also interviewed by 1 of the authors. All the nurses interviewed suffered from strong emotional reactions, including anxiety and depression. The strong reactions were unexpected by some of the nurses, although many of them had approved of the new abortion law before it went into operation. Other problems included overidentification with the aborted fetus, hostility toward most of the abortion patients, and acute identity crisis regarding nursing role and function (e.g., conflict between training to save life and job to terminate it, resentment of physician). Resolution of the problems made use of abreaction and the psychiatrists as positive therapeutic figures. The nurses reestablished a more positive identification with their patients and regained objectivity about abortions. The authors recommend that adequate time and effort should be spent helping nurses prepare for their role when an institution begins to perform unrestricted abortions.
Effect of glycated proteins on the matrix of glomerular epithelial cells.
Authors: A K Singh, W Mo, G Dunea, J A Arruda
Journal: Journal of the American Society of Nephrology (1998)

In this study, cultured glomerular epithelial cells (GEC) were exposed to a diabetic milieu containing glycated proteins to determine whether such proteins cause metabolic alterations that may lead to defects seen in the extracellular matrix in diabetic nephropathy. Cultured glomerular epithelial cells were cloned and maintained in RPMI media containing 10% fetal bovine serum (FBS). The medium was changed to RPMI-1% glycated FBS (experimental) or RPMI-1% control FBS, and cells were incubated for 1 or 4 d. Mitogenicity was tested by 3H-thymidine uptake. The media were collected and analyzed for collagenase activity by a quantitative fluorescence assay and by zymography. The cell layers were processed for matrix antigen (collagen I, glomerular basement membrane antigens, laminin, and fibronectin) and for the proteins of the tight junction (cadherin, desmosomal protein) by quantitative immunoperoxidase and immunofluorescence. Cell lysates were tested for cadherin and desmosomal protein by immunoblotting. Cells were also grown on 0.2-microM filter membranes to test for permeability to 3H-inulin and 125I-albumin. Glycated FBS resulted in a 1.8-fold increase in 3H-thymidine uptake in subconfluent layers accompanied by an increase in cell number. The treatment caused accumulation of laminin (18% above control, P < 0.05) and basement membrane antigens (33% above control, P < 0.05). Collagen I and fibronectin were unchanged. Exposing cells to glycated FBS changed the distribution of cadherin from a linear to a diffuse pattern associated with a decrease in cadherin observed on immunoblots. The media of glycated FBS-treated cells contained 45% lower collagenase activity (72-, 92-, and 150-kD species). Permeability to inulin increased by 550% and to albumin by 320% in glycated FBS-treated monolayers compared with controls. It is concluded that glycated proteins increased the accumulation of matrix proteins in the GEC, associated with a concomitant depression in collagenase activity. There were qualitative and quantitative changes in the tight junction protein cadherin. These matrix changes resulted in a functional defect in the permselective properties of the GEC tight junctions and manifested as increased leakage of inulin and albumin. Thus, the GEC are metabolically sensitive to the presence of glycated proteins, and this could play a role in the pathogenesis of diabetic nephropathy.
Possible involvement of pregnane X receptor–enhanced CYP24 expression in drug-induced osteomalacia
Authors: Jean Marc Pascussi, Agnes Robert, Minh Nguyen, Odile Walrant-Debray, Michèle Garabedian, Pascal Martin, Thierry Pineau, Jean Saric, Fréderic Navarro, Patrick Maurel, Marie Josè Vilarem
Journal: Journal of Clinical Investigation (2005)

Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D3-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16α-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16α-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D3. Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between –326 and –142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D–responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D3 hormonal activity and calcium homeostasis through the activation of PXR.
Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study
Authors: Damien Portevin, Felicien Moukambi, Petra Clowes, Asli Bauer, Mkunde Chachage, Nyanda E Ntinginya, Elirehema Mfinanga, Khadija Said, Frederick Haraka, Andrea Rachow, Elmar Saathoff, Maximilian Mpina, Levan Jugheli, Fred Lwilla, Ben J Marais, Michael Hoelscher, Claudia Daubenberger, Klaus Reither, Christof Geldmacher
Journal: The Lancet Infectious Diseases (2014)