tbuckley/cabot-search huggingface dataset:
Two homozygous cases of erythrocyte pyruvate kinase (PK) deficiency in Japan: PK sendai and PK shinshu
Authors: Kenzaburo Tani, Hisaichi Fujii, Keisuke Takahashi, Hiromi Ogura, Hitoshi Kanno, Kiyoshi Hayasaka, Kuniaki Narisawa, Tatsutoshi Nakahata, Taro Akabane, Takayuki Morisaki, Hisashi Tsutsumi, Shiro Miwa
Journal: American Journal of Hematology (1988)

Abstract Two new erythrocyte pyruvate kinase (PK) variants with severe nonspherocytic hemolytic anemia are presented. These cases are both considered to be homozygous because of the consanguineous marriages in their parents. Their erythrocyte PK's were characterized by the recommended methods of the International Committee for Standardization in Haematology (ICSH). These two variants have been named PK Sendai and PK Shinshu. PK Sendai showed a high K 0.5S (phosphoenolpyruvate), was remarkably inhibited by ATP, and was thermolabile, while PK Shinshu demonstrated remarkably low enzyme activity and required a high level of fructose 1,6‐diphsphate for activation.
Clonal expansion in follicular lymphoma occurs subsequent to antigenic selection.
Authors: A D Zelenetz, T T Chen, R Levy
Journal: The Journal of Experimental Medicine (1992)

The genesis of human follicular lymphoma (FL) is a multistep process. The initial event is thought to be the chromosomal translocation t(14;18)(q32;q21) juxtaposing the bcl-2 proto-oncogene with the immunoglobulin (Ig) H chain locus joining segment (JH) as an error of D-J or V-D joining in the pre-B cell. However, FL is recognized clinically as a tumor of surface Ig (sIg)-positive B cells with morphologic and phenotypic similarities to the centrocyte of the secondary immune response. Thus, additional steps must be involved in the clonal expansion of the FL tumor cell beyond the activation of bcl-2 as a consequence of the t(14;18) translocation. Like the normal centrocyte, somatic mutations accumulate in the variable (V) genes of FL tumor B cells. To determine if clonal expansion of FL occurs before or after the development of the malignant follicle, we sought to examine the evolution of the FL V gene from its unmutated germline (GL) counterpart. To obtain the GL gene we first cloned the productively rearranged V gene of patient MT FL and obtained the clone rMTF. A hybridization probe derived from the 2.1-kb region upstream of the V gene in clone rMTF identified a single band in Southern blot hybridization of GL DNA. This probe was used to screen a size-selected library, and candidate GL V genes were isolated. Two identical clones, MTGL1 and 2, proved to have upstream regions (USRs) that were colinear with the USR of the rMTF. Thus, the MTGL clones represent the unmutated GL V genes, which were productively rearranged in the MT FL. Comparison of the GL V gene sequence to a consensus of MT FL V gene sequences revealed 42 mutations, demonstrating that malignant clonal expansion occurred subsequent to the activation of somatic mutation, presumably in the malignant follicle. Furthermore, the individual FL V gene sequences segregated into two distinct patterns of mutation. The major population represented 71% of the clones, and the minor population 29%. To investigate possible mechanisms for the parallel selection of distinct tumor cell populations, we analyzed the pattern of silent and replacement mutations within the V gene sequences. We found that in the framework regions (FRs) of both populations there were significantly fewer replacement changes than expected, suggesting that negative selective pressure was maintaining the structural integrity of the sIg. In contrast, the complementarity determining regions (CDRs), which make up the antigen binding domain of Ig, had an excess of replacement changes, suggesting positive selection for altered ligand binding.
Abstract 5106: Induction of reactive oxygen species-dependent mitotic arrest and apoptosis by sulforaphane in human bladder cancer 5637 cells
Authors: Yung Hyun Choi
Journal: Cancer Research (2014)

Abstract The present study was undertaken to determine whether sulforaphane-derived reactive oxygen species (ROS) might cause growth arrest and apoptosis in human bladder cancer 5637 cells. Our results show that the reduced viability of 5637 cells by sulforaphane is due to mitotic arrest, but not the G2 phase. The sulforaphane-induced mitotic arrest correlated with an induction of cyclin B1 and phosphorylation of Cdk1, as well as a concomitant increased complex between cyclin B1 and Cdk1. Sulforaphane-induced apoptosis was associated with the activation of caspase-8 and -9, the initiators caspases of the extrinsic and intrinsic apoptotic pathways, respectively, and activation of effector caspase-3 and cleavage of PAPR. However, blockage of caspase activation inhibited apoptosis and abrogated growth inhibition in sulforaphane-treated 5637 cells. This study further investigated the roles of ROS with respect to mitotic arrest and the apoptotic effect of sulforaphane, and the maximum level of ROS accumulation was observed at 30 min after sulforaphane treatment. However, a ROS scavenger, N-acetyl L-cysteine, notably attenuated sulforaphane-mediated apoptosis as well as mitotic arrest. Overall, these results suggest that sulforaphane induces mitotic arrest and apoptosis of 5637 cells via a ROS-dependent pathway. Citation Format: Yung Hyun Choi. Induction of reactive oxygen species-dependent mitotic arrest and apoptosis by sulforaphane in human bladder cancer 5637 cells. [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 5106. doi:10.1158/1538-7445.AM2014-5106
Malaria. Laboratory diagnosis.
Authors: C C Draper
Journal: BMJ (1971)

Transfusion MalariaAccidentally induced malaria as a result of blood transfusion is not uncommon in several countries and may become more frequent as the demand for blood increases.The available though incomplete records covering the period 1950-68 and based on data gathered in 35 countries gave the figure of 655 cases, of which over one half were due to P. malariae, with P. vivax, P. falciparum, and P. olale in the decreasing order of fre- quency.:'There is a definite relationship between the incidence of imported malaria and the number of cases due to blood transfusion."3In the United Kingdom only eight cases of transfusion malaria have been described over the past 30 years, but probably such occurrences were more common in this country and elsewhere and not diagnosed or not reported."4Prevention of transfusion malaria depends on the elimination as a whole-blood donor of anyone who ever had malaria in the past or who has ever been exposed to malaria during a specified period prior to blood transfusion.This type of screening is quite effective when strictly applied.Detection of malaria infection in a suspected donor is notoriously difficult.Microscopic examination of a blood film is of little value, since asymptomatic parasitaemia is usually very scanty.Nevertheless, methods of indirect diagnosis of malaria by the use of immunofluorescence tests offer the best possibilities for rou- tine screening of latent malaria infections. Laboratory Diagnosis
Measuring Splanchnic Oxygenation by Gastric Tonometry
Authors: Robert Schlichtig
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Maynard and colleagues<sup>1</sup>used gastric tonometry to assess splanchnic oxygenation.<sup>2</sup>They found gastric intramucosal pH (pHim), calculated from tonometer PCO<sub>2</sub>and arterial HCO<sub>3</sub>- by the Henderson-Hasselbalch equation, to be the most reliable predictor of outcome. They further suggested that adequacy of splanchnic oxygenation may be the responsible discriminant between survivors and nonsurvivors. We agree that gastric Pco<sub>2</sub>, the directly measured variable, is a valid measure of gastric oxygenation when interpreted properly, and that it represents a major advance in intensive care unit monitoring. We would also argue that calculated pHim, viewed in isolation, is not. The physiological principle underlying tonometry is that ischemic tissue produces "metabolic acid" (lactate?) that neutralizes tissue bicarbonate. For each millimole per liter of HCO<sub>3</sub>- neutralized, tissue Pco<sub>2</sub>increases by 1÷0.0306 (the latter number is the solubility coefficient of CO<sub>2</sub>), or 33 mm Hg;
Arterial Malformations which Cause Compression of the Trachea or Esophagus
Authors: ROBERT E. GROSS
Journal: Circulation (1955)

In recent years observations have shown that there are certain arterial malformations in the superior mediastinum which bring about significant compression of either the trachea or esophagus, or both of these structures. If the arterial derangements are of such a nature that symptoms are produced by obstruction of the esophagus and particularly by the impairment of the tracheal airway, it is of prime importance to recognize the underlying vascular malformation because surgical approach to the problem has a great deal to offer either by division of an offending vessel or by displacement of an artery in such a manner that more room is provided for the esophagus and trachea. Roentgenographic examination of the esophagus and trachea with contrast media usually gives a fairly clear impression of the arterial derangement and leads to accurate diagnosis. Visualization of the aortic pathways by angiocardiography or by retrograde aortography is seldom necessary. At operation, all these anomalies can be exposed through a left anterolateral transpleural approach to the superior mediastinum. Most of the thymus gland can be dissected off and discarded, allowing good visualization of the region. Emphasis must be placed upon the fact that constrictions of the esophagus or trachea are not caused solely by vessels or ligaments, but that constriction is likewise produced by fibrous bands or sheaths which accompany these vessels and ligaments. Hence, it is important, not only to divide or displace the appropriate vessel or ligament, but also to cut any strands or bands of tissue which accompany these structures and which form a part of a constricting mechanism. In a series of cases in which surgical therapy has been undertaken for alleviating compression of the esophagus or trachea for the various vascular anomalies under consideration, it has been shown that the risks of surgery can be kept relatively low and that the benefits which accrue from such treatment are real and well worth seeking.
A clinical approach to the use of methotrexate for sarcoidosis
Authors: R. P Baughman, E. E Lower
Journal: Thorax (1999)

The management of patients with sarcoidosis has been the subject of many papers in this1 and other journals.2-5 The large number of papers are, in part, because of the difficulty in defining who should be treated for this disease and with what. The most commonly used pharmaceutical class for sarcoidosis has been corticosteroids, both topically and systemically.6 The use of systemic steroids for sarcoidosis was the subject of a trial by the British Thoracic Society1 which concluded that there were some patients who required no treatment and some who would need immediate treatment because of the severity of the disease. In between was a group of patients with persistent disease who appeared to benefit from treatment with corticosteroids. One of the points made was that some patients needed treatment for long periods of time.

The term “chronic sarcoidosis” has been used by Dr Geraint James to describe patients with disease for more than two years.7He noted that some features of sarcoidosis such as lupus pernio and neurological disease were associated with a low rate of remission, while other features such as erythema nodosum were associated with a high resolution rate by two years. Several other manifestations of the disease have been associated with chronic disease: bone cysts, cor pulmonale, pulmonary fibrosis,8 and nephrolithiasis.9 Based on the type and duration of symptoms one can classify patients as acute or chronic.10A third group is also evident—namely, those who are refractory to corticosteroid therapy. This includes some neurosarcoidosis patients, patients who develop organ failure, and those who die despite corticosteroid treatment.11 12 Treatment for sarcoidosis is often dependent on the patient’s own manifestation. A patient with anterior uveitis may be a candidate for topical steroids alone, but a patient with neurological disease …
Knock-in of Oncogenic <i>Kras</i> Does Not Transform Mouse Somatic Cells But Triggers a Transcriptional Response that Classifies Human Cancers
Authors: Sabrina Arena, Claudio Isella, Miriam Martini, Ario de Marco, Enzo Medico, Alberto Bardelli
Journal: Cancer Research (2007)

KRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the Kras G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. On the contrary, mouse cells in which we overexpressed the corresponding Kras cDNA were readily transformed. The levels of Kras activation in knock-in cells were comparable with those present in human cancer cells carrying the corresponding mutation. Kras-mutated cells were compared with their wild-type counterparts by gene expression profiling, leading to the definition of a "mutated Kras-KI signature" of 345 genes. This signature was capable of classifying mouse and human cancers according to their KRAS mutational status, with an accuracy similar to or better than published Ras signatures. The isogenic cells that we have developed recapitulate the oncogenic activation of KRAS occurring in cancer and represent new models for studying Kras-mediated transformation. Our results have implications for the identification of human tumors in which the oncogenic KRAS transcriptional response is activated and suggest new strategies to build mouse models of tumor progression.
Carcinogenic potential of benzene and toluene when evaluated using cyclin-dependent kinase activation and p53-DNA binding.
Authors: C Dees, M Askari, D Henley
Journal: Environmental Health Perspectives (1996)

Benzene is carcinogenic, whereas toluene is thought to have little carcinogenic potential. Benzene and toluene were found to activate cyclin-dependent kinase 2 in rat liver epithelial (RLE) and HL60 cells. pRb105 was hyperphosphorylated in RLE cells treated with either solvent. Kinase activation and subsequent hyperphosphorylation of pRb105 and p53 by benzene or toluene may be responsible for their growth promotional effects, but it does not account for increased potential of benzene to induce cancer. Therefore, we examined the ability of these solvents to increase p53-DNA site-specific binding in RLE cells. Benzene increased p53-DNA site-specific DNA binding in RLE cells compared to control levels or the effects of toluene. Increased p53-DNA site-specific binding by benzene may be caused by damage to cellular DNA. If so, although both solvents appear to have promotional activity, the increased potential of benzene to damage DNA may be responsible to the difference in the ability of benzene to cause cancer.
The Beta1c Globulin in Childhood Nephrotic Syndrome
Authors: Samuel P. Gotoff, Francis X. Fellers, Gordon F. Vawter, Charles A. Janeway, Fred S. Rosen
Journal: New England Journal of Medicine (1965)

INVESTIGATIONS of serum complement in clinical and experimental renal disease have suggested an immune mechanism in certain forms of nephritis. In the two laboratory models for glomerulonephritis, nephrotoxic nephritis and foreign protein nephritis, serum complement titers have been shown to fall at the time the renal lesions develop.1 , 2 Observations of complement in human nephritis date back to 1915, when Gunn3 found low levels in acute glomerulonephritis. Subsequently, other investigators have confirmed these findings and reported diminished complement titers in subacute glomerulonephritis, in systemic lupus erythematosus and in some cases of the nephrotic syndrome. In contrast, complement titers were normal in . . .
Predictive perceptions, predictive actions, and beyond
Authors: Romi Nijhawan
Journal: Behavioral and Brain Sciences (2008)

Abstract Challenges to visual prediction as an organizing concept come from three main sources: (1) from observations arising from the results of experiments employing unpredictable motion, (2) from the assertions that motor processes compensate for all neural delays, and (3) from multiple interpretations specific to the flash-lag effect. One clarification that has emerged is that visual prediction is a process that either complements or reflects non-visual (e.g., motor) prediction.
Termination of Malignant Ventricular Arrhythmias with an Implanted Automatic Defibrillator in Human Beings
Authors: M. Mirowski, Philip R. Reid, Morton M. Mower, Levi Watkins, Vincent L. Gott, James F. Schauble, Alois Langer, M. S. Heilman, Steve A. Kolenik, Robert E. Fischell, Myron L. Weisfeldt
Journal: New England Journal of Medicine (1980)

THE development of a clinically applicable, automatic, implantable defibrillator has been described previously.1 This electronic device is designed to monitor cardiac electrical activity, to recognize ventricular fibrillation and ventricular tachyarrhythmias with a sinusoidal wave form, and then to deliver corrective defibrillatory discharges. It is intended to protect patients at particularly high risk of sudden death whenever and wherever they are stricken by these lethal arrhythmias.After extensive preclinical testing, 2 a pilot study of this new technique was recently initiated at The Johns Hopkins Hospital. This article decribes the first three patients in whom the automatic defibrillator was implanted to manage . . .
IDIOSYNCRASY TO SALYRGAN
Authors: S. K. Sundaram
Journal: JAMA (1934)

To the Editor:—  Dr. L. J. Wolf's communication inThe Journal, April 7, page 1177, describing two cases of fatal idiosyncrasy to salyrgan, has prompted me to refer to a third case which I had the misfortune to be responsible for. Early last year I had to treat a boy about 10 years of age who had rheumatic mitral stenosis and regurgitation. Edema developed. It was spreading and would not yield to ordinary diuretics and digitalis. The urine contained only a trace of albumin and there were no casts in the deposit. I gave him 0.5 cc. of salyrgan diluted with 10 cc. of double distilled water intravenously. The father of the boy reported to me next day that within less than five minutes of my departure after giving the injection the boy complained of sudden pain in the chest and collapsed. The boy had had no salyrgan before.  Prior
Do metabolic factors add to the effect of overweight on hand osteoarthritis? The Rotterdam Study
Authors: S Dahaghin, S M A Bierma-Zeinstra, B W Koes, J M W Hazes, H A P Pols
Journal: Annals of the Rheumatic Diseases (2007)

As hand joints are non-weight bearing, the association between overweight and hand osteoarthritis (HOA) is critical to understanding how overweight may associate with osteoarthritis (OA) apart from axial load. Overweight might be associated with the occurrence of OA through other metabolic factors.To evaluate the role of overweight in HOA, cross-sectional data of a population-based study were used (> or =55 years, n = 3585). The role of diabetes, hypertension and total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio on HOA, and whether they play an intermediate role in the association of overweight/HOA was investigated. Furthermore, the prevalence of HOA in the concurrent presence of overweight and other metabolic factors was evaluated.Independently of other metabolic factors, overweight (body mass index (BMI) >27.4 kg/m(2)) showed a significant association with HOA (OR 1.4, 95% CI 1.2 to 1.7). The association between diabetes and HOA was only present in people aged 55-62 years (OR 1.9, 95% CI 1.0 to 3.8), but was absent in the total population or in other age groups. The association of hypertension with HOA was weak, and disappeared after adjustment for BMI. The total/HDL cholesterol ratio showed no significant association with HOA. The concurrent presence of overweight, diabetes and hypertension resulted in an even higher prevalence of HOA (OR 2.3, 95% CI 1.3 to 3.9) compared with subjects with none of these characteristics; this prevalence increased further in the younger age group (OR 3.2, 95% CI 1.1 to 8.8).No intermediate effect of metabolic factors on the association of overweight with HOA was found. An increase in the prevalence of HOA, however, seems to be present when overweight occurs together with hypertension and diabetes especially at a relatively young age.
Accuracy of Precordial Percussion and Palpation-Reply
Authors: Paul S. Heckerling, Stanley L. Wiener, Mark S. Kushner
Journal: JAMA (1994)

<h3>In Reply.</h3> — We agree with Dr Spodick that our concordance estimate for percussion was based on a small number of observations. The concordance κ for percussion was 0.57, representing moderate interobserver agreement.<sup>1</sup>However, the 95% confidence interval for κ ranged from 0.18 (slight agreement) to 0.96 (almost perfect agreement).<sup>1</sup>Further studies with larger numbers of observations will be necessary to estimate κ more precisely. In separate observations on 60 hospitalized patients, we compared the precordial percussion results of two medical residents with those of one of the investigators on each patient. A total of nine different residents were involved in measuring cardiac size during the observational period. We found that the percussion results of all three examiners generally agreed to within 0.2 to 0.7 cm (S.L.W., unpublished data, December 1993). Nevertheless, as suggested by Spodick, additional studies with multiple observers will be required to assess the generalizability
WHO in 2002: Faltering steps towards partnerships
Authors: G. Yamey
Journal: BMJ (2002)

Public-private partnerships for health have been a defining feature of Gro Brundtland's term as director general of WHO. How is WHO performing in its role as a partner? 

WHO must “reach out to others,” said Gro Brundtland in her first speech after her election as director general of the organisation.1 This statement heralded a new era of partnerships between WHO and other health agencies, the private sector, and civil society (box 1).2 In this article, I examine how WHO is performing in these alliances, with a particular focus on Roll Back Malaria.

#### Summary points

Gro Brundtland's election as director general heralded a new era of partnerships between WHO and other health agencies, the private sector, and civil society

WHO has found it hard to let go of its traditional role as being “in charge” of global health activities

The Roll Back Malaria partnership has been plagued by a lack of clear governance and ineffectiveness at country level

WHO could play an important role in helping countries coordinate new global health initiatives with health systems strengthening

The organisation needs to articulate a clear policy on working in partnerships, including proper safeguards in its interactions with the private sector

Malaria causes about 3000 deaths a day, over 90% of which are in sub-Saharan Africa.3 It is both a disease of poverty and a cause of poverty (fig 1), slowing economic growth by 1.3% per year in endemic areas.3 Roll Back Malaria (RBM) was launched in 1998 as Brundtland's “pathfinder” project,4 bringing together the biggest players in health with the aim of halving the malaria death rate by 2010.



Fig 1 
Global burden of malaria



It has had two major successes. Firstly, it brought together more than 90 multilateral, bilateral, non-governmental, and private organisations. Secondly, it has raised the profile of …