tbuckley/cabot-search huggingface dataset:
Brian James Darby
Authors: Henry Halliday, Brian Dean
Journal: BMJ (2004)

An immunologist who initiated our understanding of autoimmune diseases Deborah Doniach was part of a groundbreaking team that showed that Hashimoto's disease of the thyroid was caused by autoimmunity.Hitherto it was thought that antibodies in blood were specifically targeted against external agents, mainly bacteria and viruses.The discovery led to the wider concept of organ-specific autoimmunity, later found to be a major causal factor in other endocrine disorders.Doniach postulated that Addison's disease, thyrotoxicosis, myxoedema, pernicious anaemia, and hypoparathyroidism might have the same aetiology, as diabetes mellitus was common in all of them.The eldest of three daughters of a Ukrainian concert pianist and a bohemian Norwegian teacher of therapeutic dance, Doniach was charming and cultivated, and a talented musician.Her father, a passionate Zionist who had changed his name from Joseph Niswitzki to Arieh Abileah, eventually became professor of music at the Jerusalem Conservatory.Deborah was educated at the Lycée Molière in Paris and studied medicine at the Sorbonne, interrupting her studies in 1934 to marry Israel "Sonny" Doniach, whom she had first met in Palestine when she was 15; they spent 75 years together.Moving to London, she enrolled at the Royal Free Hospital Medical School.She spent three years as house physician, surgeon, and junior medical officer in the London County Council service, followed by four years as assistant lecturer in chemical pathology at the Middlesex Hospital.In 1951 she moved to the Royal Free, returning to the Middlesex as an endocrinologist two years later.She spent the rest of her career there, becoming one of the first immunopathologists and rising to the rank of professor in 1974.Doniach discovered that patients with thyroiditis-Hashimoto's disease-had raised
Activated Monocytes Induce Smooth Muscle Cell Death
Authors: Puvi N. Seshiah, Dean J. Kereiakes, Sanjay S. Vasudevan, Neuza Lopes, Baogen Y. Su, Nicholas A. Flavahan, Pascal J. Goldschmidt-Clermont
Journal: Circulation (2002)

Plaque disruption is the inciting event for coronary thrombosis and acute coronary syndromes. Multiple factors influence plaque rupture, including the loss of vascular smooth muscle cells (VSMCs). We hypothesized that monocytes/macrophages (MMs) activated by macrophage colony-stimulating factor (M-CSF) are responsible for VSMC death.VSMC apoptosis was markedly increased in the presence of both M-CSF and MMs (58.8+/-3.3%) compared with VSMCs plus M-CSF without MMs (15.7+/-1.5%, P< or =0.00005), VSMCs plus MMs without M-CSF (22.7+/-3.7%, P< or =0.0001), or control VSMCs alone (13.2+/-2.1%, P< or =0.0001). MM cell contact was required for M-CSF-stimulated killing of VSMCs, and MMs displayed an M-CSF concentration-dependent killing effect. Abciximab binds Mac-1 (CD11b/CD18) on MMs. When added to VSMCs exposed to MMs and M-CSF, abciximab (7 microg/mL) significantly reduced VSMC apoptosis (19.1+/-2.2%, P< or =0.0003). Therapeutic doses of tirofiban (0.35 microg/mL) and eptifibatide (5 microg/mL), which inhibit platelet glycoprotein (GP) IIb/IIIa but not Mac-1, did not block activated MM-induced VSMC apoptosis (65.0+/-3.4% and 51.3+/-2.5%, respectively). A recombinant anti-CD-18 antibody had an effect similar to that of abciximab (16.5+/-0.4%).These data suggest that monocytes and physiological concentrations of M-CSF trigger VSMC apoptosis. Abciximab and specific inhibitors of the Mac-1 receptor can antagonize this process.
Poisoning in children.
Authors: J R Sibert
Journal: BMJ (1973)

three infants were delivered vaginally, of which 10 were in poor condition (oneminute Apgar score of five or less and re- quiring intubation).In all 10 there was usually more than one abnormal feature in the fetal heart record.Specific features were variable decelerations (10/10), baseline tachycardia (7/10), and loss of beat-to-beat variation (7/10).In three cases the cord was found to be prolapsed.A pH estimation was made at the start of the second stage in three cases, the values being 7-31, 7-29, and 7.10 respectively.In cases of breech delivery where other high-risk factors will not usually apply, com- pression of the umbilical cord is the most likely cause of asphyxia.There is now con- siderable evidence demonstrating significant changes in the fetal heart rate when this occurs.Our own data suggest that cord problems are readily detected in breech de- liveries by continuous monitoring of the fetal heart and we believe that, because of its continuous nature, this will play a greater role in the management of the breech than fetal blood sampling.-Weare, etc.,
Involvement of protein kinase C in superoxide anion-induced activation of nuclear factor-κB in human endothelial cells
Authors: N Ogata
Journal: Cardiovascular Research (2000)

Nuclear factor-kappa B (NF-kappa B) plays an important role in the regulation of redox-sensitive genes which are related to the pathogenesis of various vascular diseases. Although oxygen free-radicals are known to activate NF-kappa B, the signaling pathway of oxygen free radical-induced NF-kappa B activation remains largely unclear. Thus, this study was performed to examine the possible involvement of protein kinase C (PKC) in the oxygen free radical-induced NF-kappa B activation in human umbilical vein endothelial cells (HUVECs).Superoxide anion was generated by xanthine and xanthine oxidase. An electrophoretic mobility shift assay (EMSA) was performed using a kappa B-motif oligonucleotide and nuclear extracts from HUVECs. Immunoblot analysis using an antibody against I kappa B alpha, phosphorylated by I kappa B alpha kinase, or myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylated by protein kinase C was carried out. An NF-kappa B luciferase reporter gene assay was also performed.The treatment of the cells with superoxide anion for 60 min increased the NF-kappa B/DNA binding activity. Immunoblot analysis showed that superoxide anion induced phosphorylation of I kappa B alpha within 10 min. Furthermore, phosphorylation of MARCKS occurred more rapidly than phosphorylation of I kappa B alpha. Pretreatment of the cells with calphostin C (100-400 nmol/l) and chelerythrine chloride (5-10 mumol/l), inhibitors of PKC, abolished the superoxide anion-induced NF-kappa B activation. Down-regulation of endogenous PKC by long-term exposure to phorbol 12-myristate 13-acetate decreased the superoxide anion-induced NF-kappa B activation to a basal level. Superoxide anion induced the luciferase reporter gene and this induction was completely inhibited by calphostin C (200 nmol/l) and 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron).These results suggest that PKC is involved in the activation of NF-kappa B by superoxide anion in human endothelial cells.
Molecular therapy for peritoneal dissemination of xenotransplanted human MKN-45 gastric cancer cells with adenovirus mediated Bax gene transfer
Authors: Y Tsunemitsu, S Kagawa, N Tokunaga, S Otani, T Umeoka, J A Roth, B Fang, N Tanaka, T Fujiwara
Journal: Gut (2004)

<b>Background:</b> Gene therapy is an innovative therapeutic approach for cancer. An adenoviral vector expressing the tumour suppressor <i>p53</i> gene (Ad/p53) is currently under clinical evaluation for various cancers. We recently developed a binary adenoviral vector system that can express the strong proapoptotic gene <i>Bax</i> (Ad/PGK-GV16+Ad/GT-Bax: Ad/Bax). <b>Aims:</b> To evaluate the potential of <i>Bax</i> gene therapy for gastric cancer, we assessed its antitumour effect in comparison with that of <i>p53</i>. <b>Methods:</b> The human gastric cancer cell lines MKN-1, MKN-7, MKN-28, and MKN-45 were treated with Ad/Bax or Ad/p53, and cell viability, transgene expression, and caspase activation were assessed in vitro. To compare the antitumour effects of Ad/Bax and Ad/p53 treatment in vivo, subcutaneous tumours and peritoneal dissemination of MKN-45 cells were generated in nude mice. Each mouse underwent intratumoral or intraperitoneal administration of viruses and the growth of implanted tumours was observed after treatment. <b>Results:</b> Treatment with Ad/Bax and Ad/p53 resulted in marked Bax and p53 protein expression and effective apoptosis induction in MKN-1, MKN-7, and MKN-28 cells in vitro. In contrast, MKN-45 cells showed resistance to Ad/p53 and only treatment with Ad/Bax resulted in activation of caspase 3 expression and massive apoptosis. Ad/Bax treatment was more effective in suppressing both subcutaneous and peritoneally disseminated MKN-45 tumours compared with Ad/p53 treatment. <b>Conclusion:</b> Ad/Bax treatment significantly inhibited the growth of even p53 resistant gastric cancer in vitro and in vivo. Therefore, adenovirus mediated <i>Bax</i> gene transfer may be useful in gene therapy for gastric cancers.
Interferon enhances prostacyclin production by cultured vascular endothelial cells.
Authors: A Eldor, R Fridman, I Vlodavsky, E Hy-Am, Z Fuks, A Panet
Journal: Journal of Clinical Investigation (1984)

The effects of interferon (IFN) on the arachidonate metabolism and physiological functions of cultured endothelial cells and blood platelets have been examined. Cultured bovine aortic endothelial cells were found to be sensitive to the antiviral and antiproliferative activities of human leukocyte (alpha) IFN and to increase their capacity to synthesize prostacyclin (PGI2) upon exposure to IFN. Several observations indicate that IFN stimulates PGI2 synthesis at the level of the enzymes phospholipase A2 and cyclooxygenase: (a) PGI2 production was dependent upon the supply of exogenous arachidonic acid or the liberation of endogenous cellular arachidonate by ionophore A23187, but was not observed when IFN-treated cells were exposed to the endoperoxide prostaglandin H2. (b) IFN had no effect on the spontaneous release of PGI2 into the culture medium during the incubation period (24-72 h). (c) The stimulatory effect of IFN on PGI2 production was inhibited by both glucocorticoids and indomethacin. The effect of IFN on platelet prostaglandin metabolism was also investigated. Incubation of platelet-rich plasma with IFN had no effect on platelet aggregation and thromboxane A2 production. The biological significance of the findings presented in this paper may be considered in view of the protective role of PGI2 in the vessel wall and the fact that infection with certain viruses induces endothelial damage both in man and experimental animal models.
Effect of increased peritubule protein concentration on proximal tubule reabsorption in the presence and absence of extracellular volume expansion.
Authors: C E Ott, J A Haas, J L Cuche, F G Knox
Journal: Journal of Clinical Investigation (1975)

The effect of increased peritubule capillary oncotic pressure on sodium reabsorption by the proximal tubule of the dog was investistigated after extracellular volume expansion (ECVE) with Ringer's solution or during continued hydropenia. Control measurements were made after ECVE or during hydropenia and again during renal arterial infusion with hyperoncotic albumin solution. Absolute reabsorption by the proximal tubule was calculated from fractional reabsorption and single nephron filtration rates as determined by micropuncture. Direct measurements of efferent arteriole protein were used to determine efferent arteriolar oncotic pressure. Albumin infused into the renal artery after ECVE significantly increased efferent oncotic pressure by 17.6 plus or minus 5.3 mm Hg. Fractional and absolute reabsorption by the proximal tubule increased from 20 plus or minus 6 to 37 plus or minus 5% and from 22 plus or minus 6 to 36 plus or minus 7 nl/min, respectively. During hydropenia, the albumin infusion significantly increased efferent oncotic pressure by 15.0 plus or minus 4.4 mm Hg. However, in contrast to the effect seen during ECVE, neither fractional nor absolute reabsorption was changed, delta equals 0.3 plus or minus 1.5% and 3 plus or minus 5 nl/min, respectively. Single nephron filtration rates were not significantly different between the groups and were unchanged by the albumin infusion. Peritubule capillary hydrostatic pressures, measured with a null-servo device, were not changed by the albumin infusion in either group. Renal interstitial hydrostatic pressure, measured from chronically implanted polyethylene capsules, was decreased significantly from 7.2 plus or minus 0.9 to 3.4 plus or minus 0.6 mm Hg in the hydropenic group and from 0.6 plus or minus 0.6 to 4.8 plus or minus 0.7 mm Hg in the Ringer's expanded group. In the hydropenic group, the increase in efferent oncotic pressure was nearly compensated for by changes in interstitial forces so that the calculated net force for capillary uptake was almost unchanged, 17.8 mm Hg before vs. 21.4 mm Hg during the albumin infusion. The increased efferent oncotic pressure in the Ringer's expanded group was not compensated, so that the calculated net force for uptake was increased, 11.9 mm Hg before to 22.2 mm Hg during the albumin infusion. Thus, while the increase in efferent oncotic pressure during albumin infusion was not significantly different between the groups, absolute and fractional reabsorptions were increased only in the animals in which the extracellular volume was expanded. The results suggest that ECVE alters the effect of increased peritubule oncotic pressure on sodium reabsorption by the proximal tubule.
Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C.
Authors: J Zemmour, P Parham
Journal: The Journal of Experimental Medicine (1992)

The HLA-C locus remains an enigma. The serological polymorphism is poorly defined, HLA-C molecules are expressed at the cell surface at about 10% the levels of HLA-A and -B, and their importance for antigen presentation to either CD8-bearing T cells or natural killer cells is unclear. Our understanding of HLA-C polymorphism has also lagged behind that of HLA-A and -B. We have applied the polymerase chain reaction to the characterization of cDNA encoding HLA-C antigens. Combining the recent results with previously characterized HLA-C alleles gives a data base of 26 sequences, which was used to analyze the nature of HLA-C polymorphism and compare it to the variation seen in HLA-A and -B. The sequences form 10 families of alleles that correlate well with the patterns of serological crossreactivity, including the C blanks, and all major HLA-C allelic families appear to have been sampled. The families further divide into two groups of HLA-C alleles defined on the basis of linked substitutions in the 3' exons. In comparison with HLA-A and -B, HLA-C alleles are more closely related to each other, there being less variation in residues of the antigen recognition site and more variation at other positions. In particular, the helix of the alpha 1 domain of HLA-C molecules is unusually conserved. Despite the reduced diversity in the antigen recognition site, it is evident that HLA-C genes have been the target of past selection for polymorphism. Within the antigen recognition site, it is the alpha 1 domain that is most diagnostic of HLA-C, whereas the alpha 2 domain is similar to that of HLA-B, the locus to which HLA-C is most closely related. In particular, conserved motifs in the alpha 1 helix and the conserved glycine at the base of the B pocket (position 45) provide a combination of features that is uniquely found in HLA-C molecules. We hypothesize that these features restrict the peptides bound by HLA-C molecules and in this manner reduce the efficiency of HLA-C assembly and expression at the cell surface. The overall picture HLA-C polymorphism obtained from this sampling of HLA-C alleles is unlikely to change as further alleles are characterized.
Serum Creatinine, Height, and Weight Do Not Predict Glomerular Filtration Rate in Children with IDDM
Authors: Wayne R Waz, Teresa Quattrin, Leonard G Feld
Journal: Diabetes Care (1993)

To assess the validity of two equations: K x height/serum creatinine (KL/Cr; K = 0.55 for females 1-18 yr of age and 0.7 for males 12-18 yr of age) and (140 - age) x weight/72 x creatinine (x0.85 for women; Cockroft-Gault) in estimating glomerular filtration rate in children and adolescents with IDDM.From the records of the Children's Hospital Diabetes Clinic, we selected 70 patients with GFR determined by 99mTc-labeled DTPA plasma clearance, stable renal function, and simultaneous measurements of height, weight, blood pressure, HbA1c, and plasma creatinine. We compared DTPA-GFR with estimated GFR from KL/Cr and Cockroft-Gault equations for three groups: all patients, patients with DTPA-GFR < or = 140 ml.min-1 x 1.73 m-2, and patients with DTPA-GFR > 140 ml.min-1 x 1.73 m-2.For all patients, mean values for DTPA-GFR = 147 (95% confidence interval, 139-155), for KL/Cr = 118 (110-125), and for Cockroft-Gault = 84 ml.min-1 x 1.73 m-2 (78-90). For patients with DTPA-GFR < or = 140, DTPA-GFR = 123 (117-128), KL/Cr = 110 (100-119), and Cockroft-Gault = 92 (82-102). For patients with DTPA-GFR > 140, DTPA-GFR = 167 (158-177), KL/Cr = 125 (114-136), and Cockroft-Gault = 77 (71-84). Linear regression analysis showed significant (P < 0.05) relationships for KL/Cr only in patients with DTPA-GFR < or = 140 (r = 0.29), for Cockroft-Gault in all patients (r = -0.46), and for patients with DTPA-GFR < or = 140 (r = -0.31). Determination of a revised K for use in KL/Cr from individual calculations of K (DTPA-GFR x Cr/L) yielded an average value of 0.70 (SD = 0.11). With the use of K = 0.7, the mean KL/Cr value for patients with DTPA-GFR < or = 140 ml.min-1 x 1.73 m-2 was 125 +/- 27 (95% confidence interval, 115-135), compared with a DTPA-GFR value of 123 +/- 14 (95% confidence interval, 117-128).KL/Cr and Cockroft-Gault do not accurately estimate DTPA plasma clearance. We recommend the use of K equal to 0.70 when estimating GFR in children and adolescents with IDDM and DTPA-GFR < or = 140 using KL/Cr and do not recommend the use of the KL/Cr (for patients with DTPA-GFR > 140) or the Cockroft-Gault equation in this population.
18F-FDG Imaging of a Rare Cutaneous Infection by Mycobacterium avium Complex
Authors: Zhemin Huang, Chun Qiu, Yihui Guan
Journal: Clinical Nuclear Medicine (2014)

A 17-year-old male patient was admitted into our hospital with granulomatous eruption (primarily on the lower extremities), diarrhea, fever, and weight loss for 6 months. F-FDG PET/CT scan was performed to rule out the possibility of malignant metastasis or paraneoplastic syndromes. F-FDG PET/CT scan showed multiple bone and skin lesions with significantly intense FDG uptakes and lymph nodes with moderate FDG uptake. A biopsy of the skin lesions was performed, and the tissue was sent for a broad-range polymerase chain reaction amplification, which showed that the pathogenic organism was Mycobacterium avium complex.
Acute alterations in diastolic left ventricular chamber distensibility: mechanistic differences between hypoxemia and ischemia in isolated perfused rabbit and rat hearts.
Authors: L F Wexler, E O Weinberg, J S Ingwall, C S Apstein
Journal: Circulation Research (1986)

Changes in diastolic chamber distensibility (DCD) during hypoxemia and ischemia were studied in isolated-buffer-perfused rabbit hearts. Two minutes of hypoxemia (low PO2 coronary flow) resulted in a shift of the diastolic pressure-volume curve to the left, i.e., distensibility was decreased (hypoxemic contracture). In contrast, 2 minutes of ischemia (zero coronary flow) resulted in an initial shift of the diastolic pressure-volume curve to the right indicating increased distensibility, which was followed by a later (30 minutes) shift to the left (ischemic contracture). Two minutes of ischemia superimposed on hypoxemia caused complete reversal of contracture. A quick stretch and release applied to the myocardium reversed late ischemic contracture but did not effect early hypoxemic contracture. The role of intracellular pH in modulating changes in DCD during hypoxia and ischemia was studied using phosphorus-31 nuclear magnetic resonance spectroscopy of isolated-buffer-perfused rat hearts that demonstrated changes in DCD similar to rabbit hearts during hypoxemia and ischemia. Intracellular pH decreased from 7.03 +/- 0.02 to 6.87 +/- 0.03 (p less than .01) during 2 minutes of ischemia but did not change significantly during 4 minutes of hypoxemia. When 2 minutes of ischemia were superimposed on hypoxemia, pH decreased from 6.99 +/- 0.01 during hypoxemia to 6.88 +/- 0.02 after 2 minutes of ischemia (p less than .01), concomitant with the complete reversal of hypoxemic contracture. These results suggest different mechanisms for late ischemic and early hypoxemic contracture and also suggest an explanation for the opposite initial changes in DCD seen after brief periods of ischemia and hypoxemia. The early development of contracture during hypoxemia and rapid redevelopment of diastolic tension after quick stretching are consistent with the hypothesis that hypoxemic contracture results from persistent Ca++-activated diastolic tension secondary to impaired calcium resequestration by the sarcoplasmic reticulum. In contrast, the late development of contracture during global ischemia and reversal by quick stretching is compatible with rigor bond formation. The initial increase in distensibility during early ischemia and the reversal of hypoxemic contracture by a brief period of superimposed ischemia probably is the result of two factors present during ischemia but not during hypoxemia: the collapse of the coronary vasculature and loss of the "erectile" effect and, the rapid development of intracellular acidosis, which has been shown to affect myofibrillar calcium sensitivity, and this may lead to a decrease in Ca++ activated diastolic tension.
TEE-guided anticoagulation in patients undergoing electrical cardioversion of atrial fibrillation: results from the ACUTE registry
Authors: R.A. Grimm, D.A. Agler, S.E. Vaughn, M. Thamilarasan, M.K. Chung, G. Scalia, R.D. Murray, J.D. Thomas, A.L. Klein
Journal: Journal of the American College of Cardiology (1998)
Breathing the Fire: Fighting to Report—and Survive—the War in Iraq
Authors: Akhila Kosaraju
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Specific Lymphocyte Sensitization in Cancer: Is There a Common Antigen in Human Malignant Neoplasia?
Authors: E. A. Caspary, E. J. Field
Journal: BMJ (1971)

From human cancer tissue a basic protein can be extracted by the method which yields encephalitogenic factor when applied to human brain. This tumour basic protein (obtained from several different neoplasms) acts as an antigen in the cytopherometric test for malignant neoplasia and in general gives higher results than does brain basic protein. The reverse is true when degenerative disease of the nervous system is studied. The basic protein extractable from brain and from tumours thus has some degree of specificity probably referable to its amino-acid sequence.