tbuckley/cabot-search huggingface dataset:
Gamma interferon induces different keratinocyte cellular patterns of expression of HLA-DR and DQ and intercellular adhesion molecule-I (ICAM-I) antigens
Authors: C.E.M. GRIFFITHS, J.J. VOORHEES, B.J. NICKOLOFF
Journal: British Journal of Dermatology (1989)

With indirect immunofluorescence techniques we demonstrated that recombinant gamma-interferon induced the expression of the class II antigens HLA-DR and HLA-DQ as well as intercellular adhesion molecule-1 (ICAM-1) on normal, cultured human keratinocytes grown in low-calcium, serum-free medium. Each antigen displayed a distinctive cellular staining pattern. HLA-DR was strongly localized to perinuclear zones with intense cell surface expression; HLA-DQ displayed a perinuclear accentuation, but with minimal cell surface staining, and ICAM-1 was strongly expressed in a diffuse cytoplasmic pattern with intense cell surface expression. Keratinocytes grown in medium supplemented with 10% fetal calf serum underwent differentiation, with a diminished expression of all three antigens as compared to those grown in low-calcium, serum-free medium. These results confirm that gamma interferon can differentially regulate HLA-DR nd HLA-DQ expression; that there are probably different biochemical metabolic pathways by which these three molecules are expressed on keratinocytes, and that the expression is also a function of the degree of keratinocyte differentiation. The strong cell surface expression of ICAM-1 is suggested to be of major importance as the recognition molecule, by which T cells bind to gamma interferon exposed keratinocytes, and suggests and integral role for this molecule in epidermal lymphocyte trafficking.
Triple Intrathecal Therapy Alone With Omission of Cranial Radiation in Children With Acute Lymphoblastic Leukemia
Authors: Hsi-Che Liu, Ting-Chi Yeh, Jen-Yin Hou, Kuan-Hao Chen, Ting-Huan Huang, Ching-Yi Chang, Der-Cherng Liang
Journal: Journal of Clinical Oncology (2014)

Purpose To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Patients and Methods Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. Results Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μL with blasts in a nontraumatic sample) nor CNS-3 (≥ 5 WBCs/μL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates ± SE were 84.2% ± 3.0% and 90.6% ± 2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4% ± 1.0%. Conclusion Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.
THYMUS-DEPENDENT LYMPHOCYTES IN TISSUE SECTIONS OF REJECTING RAT RENAL ALLOGRAFTS
Authors: C. M. Balch, C. B. Wilson, S. Lee, J. D. Feldman
Journal: The Journal of Experimental Medicine (1973)

Lewis kidneys were grafted into BN recipients and examined at daily intervals up to 6 days after grafting with immunofluorescent reagents. A horse antiserum specific for T lymphocytes revealed an increasing number of T lymphocytes in the cellular infiltrates of rejecting allografts. These were detectable 1 day after grafting, reached a maximum 3 days later, and were relatively diminished at 6 days. In control isografts and nonimmunological inflammations of kidney, a small number of dispersed T lymphocytes was seen. A rabbit antirat thymocyte antiserum, given to allografted BN rats, prolonged survival of the grafts and decreased the cellular infiltrate and the number of T lymphocytes in the infiltrates. We conclude that in graft rejection there is a flow of T lymphocytes into areas of tissue damage and these T lymphocytes are immunologically reactive to graft antigens.
STUDIES ON THE PNEUMONIC EXUDATE
Authors: Frederick T. Lord, Robert N. Nye
Journal: The Journal of Experimental Medicine (1921)

The purulent sputum obtained during life and the exudate at autopsy from the later stages of lobar pneumonia commonly erode the surface of Löoffler's blood serum. Cellular material obtained from the pneumonic lung in an early stage of lobar pneumonia failed to erode the surface until washed with normal saline solution. Mixtures of washed pneumonic cellular material and normal human serum fail to erode Löffler's blood serum when the amount of cellular material is less than one part of cells to approximately three parts of serum. Erosion occurs when the cellular material exceeds this amount in the ratio.
Distribution of Blood Flow within the Skin of the Rabbit with Particular Reference to Hair Growth
Authors: Geoffrey D. Thorburn, Brian H. Casey, Geoffrey S. Molyneux
Journal: Circulation Research (1966)

Previous work using a Kr 85 clearance technique demonstrated the existence in rabbit thigh skin of a bimodal distribution of blood flow which was consistent with the presence of two distinct vascular compartments with markedly different flow rates. These observations on the rabbit thigh have been extended to compare flow patterns during the inactive phase of the hair growth cycle and during active hair growth. Resting areas and hair-growing areas of rabbit skin have been examined histologically and the vascular pattern has been demonstrated after perfusion of the vessels with India ink. The results provide an anatomical basis for the two-compartment model derived from analysis of the clearance curves. The mean rate of blood flow for the fast compartment during the inactive phase was 29.7 ml/100 g tissue/min and 4.3 ml/100 g tissue/min for the slow compartment; these did not change significantly with active hair growth. However the relative size of the fast compartment altered markedly with active hair growth, the relative size of the fast compartment increasing from 21 to 67% of the tissue mass. The mean cutaneous blood flow was more than doubled during the active phase. Histological studies demonstrated a marked increase in the size of the follicles during the active phase and a concomitant increase in the extent of the vascular bed around the follicles. This would indicate that the fast compartment represents the follicular tissue and its associated blood supply; its flow rate was a measure of nutrient blood flow to the hair follicle. The flow rate of the slow compartment was then a measure of nutrient blood flow in the rest of the skin. These conclusions were supported by observations in areas of skin with sparse hair growth. The effect of body heating and cooling on cutaneous blood flow distribution was also noted.
Safety and activity of the anti-CD79B antibody–drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study
Authors: Maria Corinna A Palanca-Wessels, Myron Czuczman, Gilles Salles, Sarit Assouline, Laurie H Sehn, Ian Flinn, Manish R Patel, Randeep Sangha, Anton Hagenbeek, Ranjana Advani, Herve Tilly, Olivier Casasnovas, Oliver W Press, Sreeni Yalamanchili, Robert Kahn, Randall C Dere, Dan Lu, Surai Jones, Cheryl Jones, Yu-Waye Chu, Franck Morschhauser
Journal: The Lancet Oncology (2015)
Pathogenesis of Human Cystic Renal Disease
Authors: K D Gardner
Journal: Annual Review of Medicine (1988)

Cystic diseases of the kidney are common, often progressive disorders. The best of several alternative hypotheses to explain their development cites tubular dilation and compression of adjacent tissue. The initiating event may involve focal proliferation of epithelial cells and a consequent increase in the resistance to flow along affected tubules. Decompression of cysts has re-emerged as a potentially beneficial approach to therapy in selected cases of renal cystic disease.
A Randomized Clinical Trial of a Brief Hypnosis Intervention to Control Side Effects in Breast Surgery Patients
Authors: G. H. Montgomery, D. H. Bovbjerg, J. B. Schnur, D. David, A. Goldfarb, C. R. Weltz, C. Schechter, J. Graff-Zivin, K. Tatrow, D. D. Price, J. H. Silverstein
Journal: JNCI Journal of the National Cancer Institute (2007)

Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective. We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening (attention control). Patients were not blinded to group assignment. Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog scale (0–100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional costs and time in the operating room were assessed via chart review. Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 μg; difference = 32.63; 95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference = 6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means = 6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; difference = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95% CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to 31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time. Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue, discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the use of hypnosis with breast cancer surgery patients.
Complex Regulation of Signal Transducers and Activators of Transcription 3 Activation in Normal and Malignant Keratinocytes
Authors: Marlene R. D. Quadros, Francesca Peruzzi, Csaba Kari, Ulrich Rodeck
Journal: Cancer Research (2004)

Abstract Previous work implicated activation of the signal transducer and activator of transcription (STAT)3 downstream of the epidermal growth factor receptor (EGFR) in the malignant phenotype of squamous carcinoma cells (SCC). Here, we show that EGFR-dependent STAT3 activation is restricted to malignant keratinocytes. Specifically, constitutive and epidermal growth factor-induced phosphorylation of STAT3 on Y705 was observed only in SCC but not in either immortalized (HaCaT) or normal keratinocyte strains. Furthermore, STAT3 activation as determined by DNA binding assays was restricted to SCC and dependent on EGFR activation. Forced expression of EGFR in immortalized keratinocytes (HaCaT cells) was associated with enhanced EGFR activation but not STAT3-Y705 phosphorylation. EGFR-dependent activation of mitogen-activated protein kinase (MAPK) kinase 1 negatively regulated STAT3-Y705 phosphorylation in normal and malignant keratinocytes. Together, these results underscore that EGFR activation is required but not sufficient for STAT3 activation to occur in malignant keratinocytes. They also highlight complex regulation of STAT3 phosphorylation through EGFR activation including negative regulation via the MAPK kinase/MAPK signaling pathway.
Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells
Authors: Joanne N. Davis, Michael T. McCabe, Simon W. Hayward, John M. Park, Mark L. Day
Journal: Cancer Research (2005)

Abstract The loss of the retinoblastoma tumor suppressor gene (RB) is common in many human cancers, including prostate. We previously reported that engineered deletion of RB in prostate epithelial cells results in sustained cell growth in serum-free media, a predisposition to develop hyperplasia and dysplasia in prostate tissue recombinant grafts, and sensitization to hormonal carcinogenesis. Examining the molecular consequence of RB loss in this system, we show that cyclooxygenase-2 (COX-2) is significantly up-regulated following RB deletion in prostate tissue recombinants. To study the effect of RB deletion on COX-2 regulation, we generated wild-type (PrE) and Rb−/− (Rb−/−PrE) prostate epithelial cell lines rescued by tissue recombination. We show elevated COX-2 mRNA and protein expression in Rb−/−PrE cell lines with increased prostaglandin synthesis. We also find that loss of Rb leads to deregulated E2F activity, with increased expression of E2F target genes, and that exogenous expression of E2F1 results in elevated COX-2 mRNA and protein levels. COX-2 promoter studies reveal that E2F1 transcriptionally activates COX-2, which is dependent on the transactivation and DNA-binding domains of E2F1. Further analysis revealed that the E2F1 target gene, c-myb, is elevated in Rb−/−PrE cells and E2F1-overexpressing cells, whereas ectopic overexpression of c-myb activates the COX-2 promoter in prostate epithelial cells. Additionally, cotransfection with E2F1 and a dominant-negative c-myb inhibited E2F1 activation of the COX-2 promoter. Taken together, these results suggest activation of a transcriptional cascade by which E2F1 regulates COX-2 expression through the c-myb oncogene. This study reports a novel finding describing that deregulation of the Rb/E2F complex results in increased COX-2 expression and activity.
A three‐signal model of <scp>T</scp>‐cell lymphoma pathogenesis
Authors: Ryan A. Wilcox
Journal: American Journal of Hematology (2015)

T-cell lymphoma pathogenesis and classification have, until recently, remained enigmatic. Recently performed whole-exome sequencing and gene-expression profiling studies have significant implications for their classification and treatment. Recurrent genetic modifications in antigen ("signal 1"), costimulatory ("signal 2"), or cytokine receptors ("signal 3"), and the tyrosine kinases and other signaling proteins they activate, have emerged as important therapeutic targets in these lymphomas. Many of these genetic modifications do not function in a cell-autonomous manner, but require the provision of ligand(s) by constituents of the tumor microenvironment, further supporting the long-appreciated view that these lymphomas are dependent upon and driven by their microenvironment. Therefore, the seemingly disparate fields of genomics and immunology are converging. A unifying "3 signal model" for T-cell lymphoma pathogenesis that integrates these findings will be presented, and its therapeutic implications briefly reviewed.
A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d
Authors: Yuval Sagiv, Li Bai, Datsen G. Wei, Reuven Agami, Paul B. Savage, Luc Teyton, Albert Bendelac
Journal: The Journal of Experimental Medicine (2007)

Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)–resident lipid transfer protein involved in the biosynthesis and lipid loading of apolipoprotein B. MTP was recently suggested to directly regulate the biosynthesis of the MHC I–like, lipid antigen presenting molecule CD1d, based on coprecipitation experiments and lipid loading assays. However, we found that the major impact of MTP deficiency occurred distal to the ER and Golgi compartments. Thus, although the rates of CD1d biosynthesis, glycosylation maturation, and internalization from the cell surface were preserved, the late but essential stage of recycling from lysosome to plasma membrane was profoundly impaired. Likewise, functional experiments indicated defects of CD1d-mediated lipid presentation in the lysosome but not in the secretory pathway. These intriguing findings suggest a novel, unexpected role of MTP at a late stage of CD1d trafficking in the lysosomal compartment.
Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells.
Authors: I Anegón, M C Cuturi, G Trinchieri, B Perussia
Journal: The Journal of Experimental Medicine (1988)

We report evidence that FcR(CD16) on human NK cells are signal-transducing molecules that, upon ligand binding, induce transcription of genes encoding surface activation molecules [IL-2-R(CD25)] and cytokines (IFN-gamma and TNF) relevant to NK cell biology and functions. Homogeneous NK and T cell populations purified from short-term bulk cultures of PBMC with irradiated B lymphoblastoid cell lines were cultured in the presence of FcR ligands (particulate immune complexes or immobilized anti-CD16 antibodies) alone or with rIL-2. Upon 18 h of stimulation, NK cells express Tac, TfR, and 4F2 antigens and produce IFN-gamma and TNF; both effects are synergistically enhanced in the presence of rIL-2, which is itself ineffective. Treatment of NK cells with FcR(CD16) ligands induces accumulation of mRNA for IFN-gamma and TNF and, to a lesser extent, IL-2-R with fast kinetics also in the absence of de novo protein synthesis. rIL-2 and FcR(CD16) ligands synergize to induce mRNA accumulation. mRNA accumulation and transcription of TNF and IFN-gamma genes induced by FcR(CD16) ligands are greater than those induced by rIL-2, and the reverse is true for IL-2-R. The two stimuli do not synergize at the transcriptional level. These observations indicate that the mechanisms through which FcR(CD16) ligands and rIL-2 induce NK cell activation are, in part, distinct. Both operate at the transcriptional level, although other mechanisms are probably induced by the FcR ligand stimulus per se or in combination with other lymphokines and synergize at a post-transcriptional or translational level to enhance NK cell activation.
Association of hGrb10 Genetic Variations With Type 2 Diabetes in Caucasian Subjects
Authors: Rosa Di Paola, Ester Ciociola, Watip Boonyasrisawat, David S Nolan, Jill Duffy, Giuseppe Miscio, Carmela Cisternino, Grazia Fini, Vittorio Tassi, Alessandro Doria, Vincenzo Trischitta
Journal: Diabetes Care (2006)

The genes contributing to type 2 diabetes are mostly unknown (1). Grb10 is an adapter protein that, in target tissues (2,3), interacts with the insulin receptor (3–9), thus affecting downstream signaling (10–12) and insulin action (2,7,10–16). We tested the hypothesis that variants in the Grb10 gene modulate the risk for type 2 diabetes, one of the most frequent outcomes of insulin resistance.

Resequencing of coding and immediately flanking sequences of hGrb10 (17,18) identified six single nucleotide polymorphisms (SNPs), five of which had a minor allele frequency >5%. Based on their physical location and their mutual linkage disequilibrium, these five SNPs (i.e., rs1800504, rs2715128, rs2072235, rs4947710, and …
Early Detection of Microcirculatory Impairment in Diabetic Patients With Foot at Risk
Authors: Stefan Zimny, Frauke Dessel, Marianne Ehren, Martin Pfohl, Helmut Schatz
Journal: Diabetes Care (2001)

To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk.This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound.In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046).Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.
Dementia and ethics: the views of informal carers
Authors: J. C Hughes, T. Hope, S. Reader, D. Rice
Journal: Journal of the Royal Society of Medicine (2002)

There has been little work on the ethical issues facing non-professionals who care for relatives or others with dementia. A qualitative pilot study was conducted in ten such individuals, eight of them women, caring for persons drawn mainly from one general practice. The interviews indicated that many of the dilemmas faced by carers are ethical and that the issues differ from those faced by professionals. Ethical issues are sometimes the most troublesome matter for carers. Unlike issues for professionals, they arise from a personal context and are shaped by long-term relationships.
Disputing Psychiatry's Redefinition
Authors: Norman A. Clemens, William Bebchuk, Bernard D. Beitman, Barton J. Blinder, Glen O. Gabbard, Marcia Kraft Goin, Michael C. Hughes, Jerald Kay, Robert A. Kimmich, Susan G. Lazar, David Reiss, Eva M. Szigethy, Allan Tasman
Journal: American Journal of Psychiatry (1997)