tbuckley/cabot-search huggingface dataset:
Quantitative evaluation of antibody-dependent lymphocyte-mediated lysis of human red cells
Authors: Roger J. Kurlander, Wendell F. Rosse, Euripides Ferreira
Journal: American Journal of Hematology (1979)

Abstract The ability of lymphocytes to lyse human red cells coated with anti‐D antibody was assessed by measuring 51 Cr release from labeled red cells incubated with peripheral blood leukocyte suspensions from 12 normal donors. Mixed mononuclear cell suspensions (containing monocytes and lymphocytes) from all donors produced lysis of sensitized red cells. Treatment with carbonyl iron reduced monocyte concentration to less than 1.2% in all donors, as measured by morphologic criteria, esterase staining and ingestion of latex particles. Lysis of red cells following monocyte depletion was markedly reduced in 8 of the 12 donors. Despite depletion of monocytes, unchanged or increased lysis was noticed with the leukocytes of the remaining 4 donors. This lysis was due to lymphocytes, not to residual monocytes. If target red cells were treated with papain or trypsin prior to sensitization, marked lysis occurred with lymphocytes of all donors, including those which did not lyse unmodified red cells. Direct cytolysis of sensitized red cells during contact with small lymphocytes was recorded using microcinematography, which confirmed the role of lymphocytes in mediating lysis. Lymphocyte‐mediated lysis of red cells increased with mounting levels of antibody sensitization regardless of prior treatment with papain. Papain increased antibody coating per red cell, yet lysis per molecule of antibody bound was also increased. Lysis was inhibited by IgG1 and IgG3 in the fluid phase but not by IgG2 or IgG4. At an equivalent level of antibody sensitization lysis was augmented by concurrent coating of the red cells with C3b, C3d and/or C4b, though these components could not produce lysis in the absence of antibody coating.
High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1–specific CTL response
Authors: Frederic Toulza, Adrian Heaps, Yuetsu Tanaka, Graham P. Taylor, Charles R. M. Bangham
Journal: Blood (2007)

Evidence from population genetics, gene expression microarrays, and assays of ex vivo T-cell function indicates that the cytotoxic T lymphocyte (CTL) response to human T-lymphotropic virus type 1 (HTLV-1) controls the level of HTLV-1 expression and the proviral load. The rate at which CTLs kill autologous HTLV-1-infected lymphocytes differs significantly among infected people, but the reasons for such variation are unknown. Here, we demonstrate a strong negative cor-relation between the frequency of CD4(+)FoxP3(+) Tax(-) regulatory T cells (T(regs)) in the circulation and the rate of CTL-mediated lysis of autologous HTLV-1-infected cells ex vivo. We propose that the frequency of CD4(+)FoxP3(+) Tax(-) T(regs) is one of the chief determinants of the efficiency of T cell-mediated immune control of HTLV-1.
A child with upper abdominal pain and pancreatitis
Authors: R Talukdar, D Chaudhuri, P Vora, S Khanna, N Saikia, S Mazumder, A Kumar
Journal: Gut (2007)

An 11-year-old male child presented at the emergency department with history of rapid onset upper abdominal pain of 8 h duration. The pain was associated with nausea and vomiting, and there was radiation of pain …
On the Operation (Alexander-Adams) of Shortening the round Ligaments for Uterine Displacements, with Three Cases
Authors: W. L. Reid
Journal: BMJ (1884)

958l-w .^Nov'. 1 1884.Dr. MCVAIL,; in reply, said that, at thatadvanced hourDf the moeti.g, he would say ouly a very few words.He in no sense, at ,that meeting, sought to controvert the view that, under certain-circim- stances, the strong expiratory act of coughing might give rise to emjhysematous dilatation of the cells, and he would therefore pass over all that had beensaid by speakers on that point.Also he had dis- tinctly guarded himself from any remarks on the nutritional causes of emphysema, as time had not permitted the extended explanation of teir share in the production of emphysema, that was dsirable.As, however, nearly all the speakers had alluded to this side of the question, he would say that he was convinced that.-nutritional,or trophic emphysema, apart altogether from bronehitis, was exceedinly .emmon.He found that young men, who came to the dispensary of the Western Infirmary of Glasgow, were peculiarly subject to it: young menfrom ship-building yards, and other public works, in Glasgow, wht had begun, at a very early age, to drink whisky on pay-nights, and who, at a very little over the age of twenty yeas, had, in many cases, already lost as much as a quarter, or a third, of their breath-re- serve space, and whose arteries al4o were becoming zigzagged from
457 ROLE OF 18FDG PET-CT IN PATIENTS LISTED FOR LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA
Authors: T. Decaens, E. Itti, A. Laurent, A. Luciani, J. Tran Van Nhieu, M. Hurtova, M. Meignan, A. Mallat, D. Cherqui, C. Duvoux
Journal: Journal of Hepatology (2009)
Reviewers chosen by authors
Authors: A. Tonks
Journal: BMJ (1995)

We are always looking for ways of improving our processes of peer review, and over the next few months we will be exploring the option of using reviewers nominated by authors. We therefore ask all researchers to suggest two or three potential reviewers for papers they submit for publication. The reviewers can come from anywhere in the world, and we especially welcome reviewers from outside Britain.

This policy could improve the quality of peer review in two important ways. Firstly, authors are often better placed than editors to know whom to approach for a considered, balanced, and credible opinion in their field of …
Symmetrical Peripheral Gangrene in Myocardial Infarction
Authors: S. J. Caserta, Robert Metz, Michael Anton
Journal: New England Journal of Medicine (1956)

SYMMETRICAL peripheral gangrene is not a commonplace event, and yet the initiating factors may vary considerably. Frequently, it complicates severe cases of frostbite, ergotism and ball-valve thrombus with mitral stenosis. It is rarely secondary to congenital cardiac defect,1 pneumonia,2 myocardial infarction,3 4 5 paroxysmal ventricular tachycardia6 and severe congestive heart failure.7 The present case is one of acute myocardial infarction followed by symmetrical peripheral gangrene.Case ReportA 58-year-old housewife entered the hospital complaining of severe substernal pain radiating to both axillas. The pain, sudden in onset, initially was felt the preceding night while she was in bed. It had persisted unabated . . .
Interaction of the Tumor Metastasis Suppressor Nonmetastatic Protein 23 Homologue H1 and Estrogen Receptor α Alters Estrogen-Responsive Gene Expression
Authors: Carol D. Curtis, Varsha S. Likhite, Ian X. McLeod, John R. Yates, Ann M. Nardulli
Journal: Cancer Research (2007)

Abstract Metastasis of cancer cells from the primary tumor is associated with poor prognosis and decreased overall survival. One protein implicated in inhibiting metastasis is the tumor metastasis suppressor nonmetastatic protein 23 homologue 1 (NM23-H1). NM23-H1 is a multifunctional protein, which, in addition to limiting metastasis, has DNase and histidine protein kinase activities. We have identified new functions for NM23-H1 in influencing estrogen receptor α (ERα)–mediated gene expression. Using a battery of molecular and biochemical techniques, we show that NM23-H1 interacts with ERα and increases the ERα–estrogen response element (ERE) interaction. When NM23-H1 expression is increased in U2 osteosarcoma and MDA-MB-231 breast cancer cells, transcription of a transiently transfected, estrogen-responsive reporter plasmid is decreased. More importantly, when endogenous NM23-H1 expression is knocked down in MCF-7 human breast cancer cells using small interfering RNA, estrogen responsiveness of the progesterone receptor (PR), Bcl-2, cathepsin D, and cyclin D1 genes, but not the pS2 gene, is enhanced. Furthermore, NM23-H1 associates with the region of the PR gene containing the +90 activator protein 1 site, but not with the ERE-containing region of the pS2 gene, indicating that NM23-H1 mediates gene-specific effects by association with endogenous chromatin. Our studies suggest that the capacity of NM23-H1 to limit the expression of estrogen-responsive genes such as cathepsin D and Bcl-2, which are involved in cell migration, apoptosis, and angiogenesis, may help to explain the metastasis-suppressive effects of this protein. The complementary abilities of ERα and NM23-H1 together to influence gene expression, cell migration, and apoptosis could be key factors in helping to determine tumor cell fate. [Cancer Res 2007;67(21):10600–7]
REDUCED MORBIDITY FROM SKELETAL METASTASES IN BREAST CANCER PATIENTS DURING LONG-TERM BISPHOSPHONATE (APD) TREATMENT
Authors: A.Th. van Holten-Verzantvoort, O.L.M. Bijvoet, J. Hermans, H.I.J. Harinck, J.W.F. Elte, L.V.A.M. Beex, F.J. Cleton, H.M. Kroon, P. Vermey, J.P. Neijt, G. Blijham
Journal: The Lancet (1987)
Cigarette Smoking Impairs Human Pulmonary Immunity to <i>Mycobacterium tuberculosis</i>
Authors: Seónadh M. O’Leary, Michelle M. Coleman, Wui Mei Chew, Colette Morrow, Anne Marie McLaughlin, Laura E. Gleeson, Mary P. O’Sullivan, Joseph Keane
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Cigarette smoking is linked to important aspects of tuberculosis, such as susceptibility to infection, disease reactivation, mortality, transmission, and persistent infectiousness. The mechanistic basis for this remains poorly understood.To compare the functional impairment seen in human alveolar macrophages (AM) from nonsmokers, smokers, and ex-smokers after infection with Mycobacterium tuberculosis (Mtb).AM were acquired at bronchoscopy, and number and viability from smoking donors were compared with nonsmoking donors. AM were challenged in vitro with Mtb and intracellular bacterial viability was measured. Cytokine secretion was measured 24 hours postinfection by ELISA. Previously we determined the frequency of CD4(+)FoxP3(+) T cells in the presence or absence of allogeneic AM, and data were reanalyzed to separate the patient subjects according to smoking status.There were significantly more AM from smokers compared with nonsmokers or ex-smokers (P < 0.01). AM from smokers could not control intracellular Mtb growth. Nonsmokers' AM generated significantly more tumor necrosis factor (TNF)-α, IFN-γ, and IL-1β after Mtb infection compared with uninfected AM (P < 0.05). However, Mtb-infected AM from smokers did not secrete significantly more TNF-α, IFN-γ, and IL-1β compared with uninfected smokers' AM. AM taken from ex-smokers also failed to secrete significantly increased TNF-α, IFN-γ, and IL-1β after Mtb infection. Both smokers' and nonsmokers' AM induced FoxP3(+) T regulatory cell phenotype responses in allogeneic admixed T cells (>4.8 fold; P < 0.05). Even after Mtb infection, AM continued to drive this regulatory phenotype.In smokers, the pulmonary compartment has a number of macrophage-specific immune impairments that provide some mechanistic explanations whereby cigarette smoking renders a patient susceptible to tuberculosis infection and disease.
Evaluation of Exercise Capacity Using Submaximal Exercise at a Constant Work Rate in Patients With Cardiovascular Disease
Authors: Akira Koike, Takashi Yajima, Hiromasa Adachi, Noritaka Shimizu, Hiroshi Kano, Keiichi Sugimoto, Akihiro Niwa, Fumiaki Marumo, Michiaki Hiroe
Journal: Circulation (1995)

Background Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient’s daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (V̇ o 2 ) kinetics, we measured the time constant of V̇ o 2 both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects. Methods and Results A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. V̇ o 2 was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of V̇ o 2 during the onset of 50-W exercise was 61.4±15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of V̇ o 2 were slower) than that in normal subjects (48.8±10.4 seconds, P =.008). The time constant of V̇ o 2 during the onset of exercise was significantly negatively correlated with peak V̇ o 2 ( r =−.67) and maximal work rate ( r =−.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak V̇ o 2 ( r =−.63) and maximum work rate ( r =−.54). Conclusions The time constant of V̇ o 2 during and after recovery from 50 W of constant work rate exercise, which does not require the subject’s maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease.
Abstract 4566A: Effect of the anti-histaminic cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms
Authors: Cheng-Da Hsu, Yu-Min Feng, Syue-Yi Chen, Jing-Wen Feng
Journal: Cancer Research (2014)

Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide; however, current chemotherapeutic drugs for hepatocellular carcinoma (HCC) are either poorly effective or expensive. The majority of patients can't have good outcomes by taking these drugs. Currently, we had a breakthrough finding in a case report of two patients with advanced HCC. We found one had complete remission of liver tumors, one had decrease of their alpha-fetoprotein levels and that both their lung metastasis had complete remission after the concomitant use of thalidomide and cyproheptadine. In light of a previous study that cyproheptadine affects the cell cycle and impedes leukemia cell growth by suppressing the action of transcription factor of cyclin D, we assume that cyproheptadine is the key factor in this treatment. Therefore, the purpose of this study was to investigate whether cyproheptadine inhibits HCC cell growth by impeding cancer cell cycle and to explore the molecular mechanisms of cyproheptadine-induced cell cycle arrest. First, we confirmed that cyproheptadine had inhibition effect on two HCC cell lines, HepG2 and Huh-7, by cell viability assay. Besides, to explore how cyproheptadine affects HCC cell cycle we analyzed DNA content by flow cytometry and found cell cycle arrest at the G1 to S transition in HepG2 cells and at the S to G2 transition in Huh-7 cells. Finally, we investigated the mechanism of cyproheptadine-induced cell cycle arrest using western blot analysis. Interestingly, our results showed that cyproheptadine promoted P38 activation by phosphorylation than subsequently stabilized P16 and caucused hypophosphorylation of Rb in HepG2 cells. On the other hand, cyproheptadine not only promoted P38 activation but also activated ATM/Chk2 pathway to stabilize P21 in Huh-7 cells. These novel results demonstrated that cyproheptadine suppressed HCC cells through the Non-classical P38 MAP Kinase Functions: Cell Cycle Checkpoints and ATM/Chk2 pathway, and provided a potential treatment option in HCC. Citation Format: Cheng-Da Hsu, Yu-Min Feng, Syue-Yi Chen, Jing-Wen Feng. Effect of the anti-histaminic cyproheptadine on cell cycle of hepatocellular carcinoma cells and its mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4566A. doi:10.1158/1538-7445.AM2014-4566A
A Psychiatric Odyssey
Authors: Paul G. Myerson
Journal: JAMA (1971)

As Dr. Masserman states in his opening sentence, this is a curious book. But it is also a fascinating, intriguing, frank, provocative, and occasionally irritating one. The author, a brilliant, erudite, extremely active psychiatrist, psychoanalyst, researcher, and administrator, has played a prominent part in the psychiatric scene during the past 30 years. In this volume, the 49th either written or edited by him, he opens to public view various intimate memorabilia—letters, case histories, book reviews, reports to the courts, casual comments, and recapitulations of his philosophy and of his clinical approach. The reader, particularly if he has any acquaintance with dramatis personae, will find himself absorbed by the author's openness; will be admiring and perhaps envious of his keen intelligence, humor, and courage; will be alternately amused and aghast when he tilts with his protagonists; and will be inevitably left breathless by his amazing energy. Dr. Masserman does not suffer
Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats
Authors: Masayoshi Kobune, Yutaka Kohgo, Junji Kato, Etsu Miyazaki, Yoshiro Niitsu
Journal: Hepatology (1994)

To explore a mechanism of interleukin (IL)-6-induced hypoferremia in rats, iron metabolism was investigated both in vivo and in vitro. Recombinant IL-6 was intraperitoneally administered to male Wistar rats and the serial change of parameters related to iron metabolism was examined. After administration of IL-6, plasma IL-6 concentration increased rapidly, reached its maximum in 1 hr and thereafter decreased quickly. Plasma IL-6 3 hr after IL-6 injection (50 micrograms/kg) was 3 units/ml, which is a concentration capable of inducing hepatic 125I-labeled transferrin uptake in vitro using isolated hepatocytes. Plasma iron concentration and transferrin saturation had decreased to approximately one third of the initial level within 3 hr and then recovered. Total iron binding capacity remained unchanged for 6 hr, then began to decrease. Red blood cell count and hemoglobin concentration showed no remarkable changes during this period. By ferrokinetic study with plasma that contained iron 59-labeled transferrin, the plasma iron disappearance half time, calculated from the disappearance curve, was significantly shortened from 55 min to 22 min by IL-6 treatment (p < 0.01). The ferritin concentration in the liver was increased significantly after the administration of IL-6 (p < 0.001), but transiently decreased in the spleen. The plasma ferritin showed a gradual increase during the 6-hr period after IL-6 injection. The uptake of 125I-labeled diferric transferrin by isolated hepatocytes was increased by IL-6 treatment and this increment was inhibited by addition of 100-fold excess unlabeled transferrin. On the other hand, no significant increment of 125I-labeled diferric transferrin uptake was observed in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitation of coronary venous adenosine in patients: limitations evaluated by radioimmunoassay
Authors: C. W HAMM, W. KUPPER, R. BREDEHORST, H. HILZ, W. BLEIFELD
Journal: Cardiovascular Research (1988)

Experimental studies have shown that adenosine is rapidly released in response to myocardial ischaemia. To evaluate whether coronary venous adenosine release is a metabolic characteristic of myocardial ischaemia in patients, adenosine concentrations were measured by a highly sensitive and specific radioimmunoassay. In three patients with normal coronary arteries and in seven with obstructive coronary artery disease coronary venous adenosine content was measured at rest and during atrial pacing. When whole blood or plasma were extracted immediately with perchloric acid the adenosine content was found to be lower than that previously reported. Recovery studies showed that the importance of time and temperature at low adenosine concentrations had been underestimated in preceding studies. In patients with coronary artery disease coronary venous adenosine concentration increased from 106.3(48.8) nmol·litre−1 to 114.9(57.0) nmol·litre−1 (NS) during pacing and was 130.4(63.3) nmol·litre−1 (NS) 2 min after pacing. Even in the presence of lactate production enhanced adenosine release was not consistently evidenced. Furthermore, venous adenosine content did not increase in five patients undergoing coronary artery occlusion during angioplasty of the left anterior descending coronary artery. The extremely short half life of coronary venous adenosine appears to preclude its use as an index of myocardial ischaemia in patients.
Blurred vision: targeting a diagnosis
Authors: C. P. Buscombe, S. Lin, N. J. Wilson-Holt
Journal: BMJ (2013)

A 68 year old woman with a longstanding history of non-specific inflammatory arthritis (which had been extensively investigated) was referred to the ophthalmologist with a three month history of flashing lights and blurred vision. Her regular drugs included meloxicam, omeprazole, amitriptyline, and 400 mg hydroxychloroquine, which she had been taking daily for 15 years. She was of normal body weight.

Ophthalmological assessment showed a reduced visual acuity at 6/18 in the right eye and 6/12 in the left eye, with mild depression in colour vision on Ishihara plate testing. Early cataracts were present, and fundal examination identified bilateral changes in epithelial retinal pigment at both posterior poles.Visual field testing showed bilateral annular scotomas.

She was referred for further investigations, including colour fundus photography, which show bilateral disturbance of retinal pigments at both maculas giving a “bull’s eye” appearance (fig 1⇓)



Fig 1 Colour fundal photography of both eyes at presentation





### 1 What is the likely underlying diagnosis?

#### Short answer

The central visual field loss suggests macular disease, and fundus photography shows characteristic “bull’s eye” retinopathy. Because this patient is being treated with hydroxychloroquine, this finding is strongly suggestive of a toxic retinopathy secondary to this drug.

#### Long answer

Hydroxychloroquine is commonly used to treat inflammatory and …
Effect of cytochrome P450 induction on phosphorus metabolites and proton relaxation times measured byin vivo31P-magnetic resonance spectroscopy and1H-magnetic resonance relaxometry in human liver
Authors: W Block, C Reichel, F Traber, T Skodra, R Lamerichs, B Kreft, U Spengler, T Sauerbruch, H Schild
Journal: Hepatology (1997)

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.