tbuckley/cabot-search huggingface dataset:
COMPLEMENT FIXATION IN DISEASED TISSUES
Authors: Peter M. Burkholder
Journal: The Journal of Experimental Medicine (1961)

An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease.
Diuresis Related to Cold Exposure
Authors: K. M. Shakir
Journal: JAMA (1985)

<h3>To the Editor.—</h3> We read with great interest the observations of Blume et al relating hyperosmolality and serum arginine vasopressin (AVP) levels to high-altitude exposure of trained mountaineers. The lack of ambient or core temperature data opens to question the conclusion that altitude is the sole cause of these changes. A cold exposure-associated diuresis in humans has been reported in the literature.<sup>2,3</sup>Radomski and Boutelier<sup>4</sup>found that repeated cold exposure in warmly dressed humans would blunt this cold-associated diuresis. Segar and Moore<sup>3</sup>measured serum AVP levels in human subjects placed in cold and warm chambers and concluded that serum AVP levels increased with heat exposure and decreased with cold exposure. The elevation of serum AVP levels was associated with diuresis in these subjects. The combined effect of altitude and cold exposure should be considered in subjects with unchanged serum AVP concentration and hyperosmolal serum, as found by
Issues around early diagnosis of Alzheimer's disease
Authors: P. J. Gordon, S. F. Gordon
Journal: BMJ (2011)

<h3>Abstract</h3> <h3>Background</h3> In 2017, the World Health Organization declared the snakebite envenomation as a neglected tropical disease. Annually, snakebite envenomation causes approximately 400,000 permanent disabilities and 95,000 deaths worldwide. People with the greatest risk of envenomation lack access to adequate health care, including treatment with antivenom. We developed an analysis of accessibility to antivenom in Brazil in order to verify the impacts on mortality. <h3>Methods and Findings</h3> Information about number of accidents, deaths, antivenom, medical assistance, and species, were retrieved from the Brazilian Health Informatics Department (DATASUS) from 2010 to 2015 and analyzed using geostatistics to evaluate the association between snakebite accidents and mortality. An Spatial analysis using Global Moran’s I was performed in order to verify the presence of spatiality as an independent variable to the distribution of the accidents. In addition, we also tested three different analysis of regression using Ordinary Least Square (OLS), Spatial Error, and Geographically Weighed Regression (GWR), together with the information obtained from the DATASUS and sociodemographic indicators, to verify the spatial-temporal distribution of envenomation cases and time to reach the healthcare centers. The regression presenting the lowest Akaike Criterion Information (AIC), highest adjusted R<sup>2</sup>, and variables with p &lt; 0.05 was selected to represent our model. Lastly, the accessibility index was performed using 2-step floating catchment area based on the amount of hospital beds and inhabitants. This study revealed 141,039 cases of snakebites, 598 deaths, and mortality rate of 3.13 per 1,000,000 inhabitants. Moreover, GWR presented the best fit (AIC = 55477.56; adjusted R<sup>2</sup> = 0.55) and showed that illiteracy, income, percentage of urban population, percentage of antivenom, accessibility index for hospital beds with antivenom, proportion of cases with more than 3 hours to reach healthcare are correlated with the mortality rate by snakebite (p &lt; 0.05). <h3>Conclusion</h3> This study identified regions affected by snakebite and how the accessibility to antivenom treatment plays an important role in the mortality in Brazil. Public interventions can located to those most vulnerable regions in order to improve the accident outcome.
Death Following Physical Stress
Authors: Zenonas Danilevicius
Journal: JAMA (1978)

Strenuous physical activity, such as shoveling snow, long has been suspected to be a contributing factor in a number of sudden cardiac deaths.  Vuori et al 1 now provide support for this suspicion. They examined the circumstances surrounding 2,606 sudden deaths, and by reviewing the case histories and autopsy reports, they tried to establish correlation of the fatal event with the type and intensity of physical activity.  The authors defined sudden death as one occurring through natural causes while the patient was not restricted to home, hospital, or institution and when, during the preceding 24 hours, he was able to function in his normal surroundings and activities.  According to Vuori et al, a full 73% of all sudden deaths examined were caused by acute or chronic ischemic heart disease. At least one third of all these cardiac sudden deaths were associated with physical or psychological stress. Sudden deaths in connection
Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model
Authors: Barry J. Kappel, Javier Pinilla-Ibarz, Adam A. Kochman, Jeffrey M. Eng, Vanessa M. Hubbard, Ingrid Leiner, Eric G. Pamer, Glen Heller, Marcel R. M. van den Brink, David A. Scheinberg
Journal: Blood (2005)
Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease
Authors: G. Acocella, L. Bonollo, M. Garimoldi, M. Mainardi, L. T. Tenconi, F. B. Nicolis
Journal: Gut (1972)

The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.
Abolition of Prescription Charges
Authors: S. E. Sutton
Journal: BMJ (1964)

of facilities for routine screening of healthy women by cervical cytology at regular inter- vals.This matter vitally concerns clinical pathologists, and in most departments of clinical pathology there is already a service in exfoliative cytology for patients referred from many specialties, of which gynaecology is one."It is the opinion of the Council that any service in cervical cytology for healthy women should be regarded as preventive medicine and should be organized in collaboration with the hospital laboratory service, with which it should have the closest integration.The Council believe that cytological examinations and the training of technicians for this work must be in the hands of consultant pathologists.They believe it to be necessary to stress once more that a large proportion of hospital laboratories are already short of staff and accommodation, and it is clear that the implementation of the recommendations now being made about exfoliative cytology can only make matters worse.The appointment of extra staff and the provision of increased accommodation in hospital laboratories, which were already necessary, may now be expected to become even more urgent requirements."The Council wish to place these views on record, for they believe it to be vitally impor-
Abstract 3292: The exploration of novel strategy for treatment of pancreactic cancer using genetically engineered mice
Authors: Motohisa Tada, Hideaki Ijichi, Koji Miyabayashi, Dai Mohri, Yoshinari Asaoka, Tsuneo Ikenoue, Keisuke Tateishi, Rintarou Mikata, Takeshi Ishihara, Fumihiko Kanai, Fumio Imazeki, Harold L. Moses, Masao Omata, Osamu Yokosuka
Journal: Cancer Research (2011)

Abstract (Background and Aim) Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease in human. Previously, we have reported a genetically engineered mouse PDAC progression model which has pancreatic-specific transforming growth factor-beta receptor type II knockout in the context of Kras activation (Ijichi H, et al 2006). This model shows PDAC with 100 % penetrance and recapitulates the signature of human PDAC well. Using this model, we explored novel treatment for PDAC. (Materials and Methods) For single agent treatment, mice were treated orally 6 times per week with vehicle (0.5 % carboxymethyl cellulose, CMC), sunitinib, axitinib, 5 kinds of anigiotensin II receptor blockers (ARBs), such as candesartan, telmisartan, losartan, valsartan, or olmesartan, respectively from the 3 wk of age. For combined agent experiment, mice were treated orally with vehicle (0.5 % CMC), axitinib or candesartan from the 3 wk of age and also treated with saline or gemcitabine, i.p. twice a week, from the 4 wk of age. Treatment continued until the mice became distressed, and then they were dissected. In vivo anti-tumor effect and survival time were assessed. Immunostaining of tumor tissue for caspase 3, Ki67, CD31, and VEGF was performed. (Results)Median survival time of single use of axtinib and sunitinib group was statistically longer and that of candesartan and telmisartan group was tended to be longer than that of control group. Axtinib, sunitinib, candesartan, and telmisartan group showed significant anti-tumor effect in vivo. In the combined treatment experiment, using gemcitabine showed statistically significant longer survival and more anti-tumor effect than that of single agent treatment group. Axitinib and sunitinib group showed significantly higher caspase 3 score and lower Ki67 score than that of control, however, candesartan and telimisartan group showed no change of these scores, compared to control. Microvessel density of axtinib, sunitinib, candesartan, and telmisartan group was significantly lower than that of control and other ARBs. VEGF expression of candesartan and telmisartan group was significantly lower than that of control and other ARBs. (Conclusion)Targeting angiogenesis with multikinase inhibitor or ARB in addition to gemcitabine may be a promising therapeutics for PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3292. doi:10.1158/1538-7445.AM2011-3292
Tumor necrosis factor transactivates ErbB2 in breast cancer cells.
Authors: MA Rivas, M Tkach, CJ Proietti, C Rosemblit, W Beguelin, V Sundblad, MC Díaz Flaqué, EH Charreau, PV Elizalde, R Schillaci
Journal: Cancer Research (2009)

Abstract Abstract #4056 We have previously shown that TNFα induces proliferation of the murine mammary adenocarcinoma C4HD through activation of the PI-3K/Akt signaling pathway that converges on the transcriptional activation of NF-κB. Since C4HD tumor overexpresses ErbB2 and given that this tyrosine kinase plays a critical role in C4HD cell proliferation, we wondered whether interactions between TNFα and ErbB2 could be taking place. Our findings revealed that treatment of C4HD cells with the ErbB2 inhibitor AG825 blocked TNFα-induced proliferation. Similar results were obtained using the human ErbB2-overexpressing cell line SK-BR-3. Then, we studied the effect of TNFα on ErbB2 phosphorylation in C4HD and SK-BR-3 cells. We found that TNFα increased total ErbB2 tyrosine phosphorylation in C4HD and SK-BR-3 cells, as well as on the specific residues tyrosines 927 and 1172 in murine cells and on its human homologues 877 and 1222. These effects where not caused by the release of ErbBs ligands from the cell membrane by TNFα, since treatment with the metalloprotease inhibitor GM6001 did not affect TNFα-induced ErbB2 phosphorylation. We then studied if c-Src was involved in the above effect given that it is known to directly phosphorylate ErbB2 in the Tyr 877 residue. We found that addition of PP2, a Src family inhibitor, completely inhibited phosphorylation of Tyr 927/877 ErbB2, and that to a lesser degree it inhibited Tyr 1172/1222 ErbB2 in both cell types. We also performed an in vitro cold phosphorylation assay where we observed that c-Src immunoprecipitated from C4HD cells treated with TNFα was able to phosphorylate ErbB2 on Tyr 927 residue. Taken together, these results indicate that TNFα induces phosphorylation of ErbB2 at Tyr877/927 residue and that c-Src is the tyrosine kinase involved in this effect. In addition, we observed that upon TNFα stimulation, ErbB2 associated with ErbB3 leading to PI-3K/Akt pathway activation. Treatment of cells with AG825 inhibited Akt and NF-κB activation by TNFα, as evidenced by western blots of phospho proteins and reporter gene studies, respectively. The above data for the first time identify TNFα as a cytokine able to transactivate ErbB2, disclosing c-Src involvement in such effect. Also we demonstrated that TNFα ability to activate Akt and NF-κB transcriptional activation is dependent on ErbB2 phosphorylation in breast cancer cells that overexpress ErbB2. Interestingly, TNFα appears as a new player in ErbB2-overexpressing breast tumors, and its eventual worth as a prognostic factor in anti ErbB2 therapy is yet to be determined. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4056.
Quantitative intravenous myocardial contrast echocardiography predicts recovery of left ventricular function after revascularization in chronic coronary artery disease
Authors: Shota Fukuda, Takeshi Hozumi, Takashi Muro, Hiroyuki Watanabe, Eiichi Hyodo, Minoru Yoshiyama, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2003)
Problems in Prescription Order Communications
Authors: William S. Apple
Journal: JAMA (1963)

THE PRESCRIPTION ORDER is the focal point of the physician-patient-pharmacist relationship. In 1962, more than 700 million prescription orders carried communications from physicians to pharmacists. The basic safeguard for the patient of having one practitioner prescribe and another dispense was recognized by law as early as 1240 AD. With the separation of professional functions, a new responsibility was created which must be shared jointly by the prescribing physician and the dispensing pharmacist. The need for absolute precision in prescription order communications—written or oral—is made obvious to all medical and pharmacy students. Later, in practice, the volume and tempo of these communications increase so substantially that unless practitioners are constantly on the alert, situations tend to develop which can be hazardous for the patient. The many anecdotes concerning the physician's handwriting reflect a certain public awareness of the communications problem, and the increase in criminal actions and civil damage suits is
Diabetes Cure — Is the Glass Half Full?
Authors: Jonathan S. Bromberg, Derek LeRoith
Journal: New England Journal of Medicine (2006)

Nearly 80 years after the first clinical use of insulin, many important advances in the treatment of type 1 diabetes mellitus continue to be made. In this issue of the Journal, Shapiro et al.1 report on a multinational, prospective trial to disseminate the complicated knowledge and techniques required to prepare and transplant human islets and to evaluate the ability to provide a durable cure for a highly selected group of patients with type 1 diabetes.It is important to realize how far this field has come in the past few years (Figure 1). Before 2000, the preceding two decades of . . .
Some critical issues and concerns related to research advances on toxicology of chemical mixtures.
Authors: R S Yang
Journal: Environmental Health Perspectives (1998)

This paper addresses some of the issues and concerns on research advances on the toxicology of chemical mixtures. Emphases will be selectively given to the following questions and answers: Can mechanistic studies be conducted on chemical mixtures? The fact that any studies, including mechanistic studies, of single chemicals are really the study of the parent chemical plus its metabolites underscores the relevance of mechanistic studies on chemical mixtures. Can predictions be made on the health effects of chemical mixtures? Some successes are already evident in the literature on simpler chemical mixtures. For more complex mixtures, it is possible and we propose an approach here. What can we learn from other disciplines (the importance of interdisciplinary collaboration)? Two aspects, the knowledge and methodologies available in clinical pharmacology and the latest advances in structure-oriented lumping in chemical engineering, are discussed in detail. Unrepeatable results: The possibility of magnification of biologic variability because of low-level exposures to chemical mixtures is suggested with special reference to some known examples, including the controversial study on synergistic interactions of endocrine disruptors. Is the driving force for scientific investigations on chemical mixtures the legislative and regulatory atmosphere? Two laws with chemical mixtures specifically in the language are quoted and discussed. Their implications regarding research funding and activities are described. What are the pitfalls of applying for research funding on investigating chemical mixtures? The dilemma at least one investigator faces in pursuing research funding is elaborated. The questions and issues listed above are not all inclusive, but they represent some of the aspects that need to be brought into the open in the scientific community for discussion and/or debate. Thus, the primary objective of this paper is to provide some momentum for the beginning of a fruitful and stimulating discussion.
Promotion of neuronal differentiation of neural progenitor cells by using EGFR antibody functionalized collagen scaffolds for spinal cord injury repair
Authors: Xiaoran Li, Zhifeng Xiao, Jin Han, Lei Chen, Hanshan Xiao, Fukai Ma, Xianglin Hou, Xing Li, Jie Sun, Wenyong Ding, Yannan Zhao, Bing Chen, Jianwu Dai
Journal: Biomaterials (2013)
Obesogens: An Environmental Link to Obesity
Authors: Wendee Holtcamp
Journal: Environmental Health Perspectives (2012)

Focus FocusObesity is rising steadily around the world.Convincing evidence suggests that diet and activity level are not the only factors in this trend-chemical "obesogens" may alter human metabolism and predispose some people to gain weight.Fetal and early-life exposures to certain obesogens may alter some individuals' metabolism and fat-cell makeup for life.Other obesogenic effects are linked to adulthood exposures.O besity has risen steadily in the United States over the past 150 years, 1 with a marked uptick in recent decades. 2 In the United States today more than 35% of adults 3 and nearly 17% of children aged 2-19 years are obese. 4Obesity plagues people not just in the United States but worldwide, including, increasingly, developing countries. 5Even animals-pets, laboratory animals, and urban rats-have experienced increases in average body weight over the past several decades, 6 trends not necessarily explained by diet and exercise.In the words of Robert H. Lustig, a professor of clinical pediatrics at the University of California, San Francisco, "[E]ven those at the lower end of the BMI [body mass index] curve are gaining weight.Whatever is happening is happening to everyone, suggesting an environmental trigger." 7Many in the medical and exercise physiology communities remain wedded to poor diet and lack of exercise as the sole causes of obesity.However, researchers are gathering convincing evidence of chemical "obesogens"-dietary, pharmaceutical, and industrial compounds that may alter metabolic processes and predispose some people to gain weight. 8,9e idea that chemicals in the environment could be contributing to the obesity epidemic is often credited to an article by Paula Baillie-Hamilton, published in the Journal of Alternative and Complementary Medicine in 2002. 10Her article presented evidence from earlier toxicologic studies published as far back as the 1970s in which low-dose chemical exposures were associated with weight gain in experimental animals.At the time, however, the original researchers did not focus on the implications of the observed weight gains.
The Upright Posture and Renal Blood Flow
Authors: Joseph J. Kaufman
Journal: JAMA (1966)

To the Editor:—  The article Postural Augmentation of Plasma Renin Activity by Cohen, Rovner, and Conn ( 197 :973, 1966) is an important exposition of the relationship of postural changes to the vagaries of renovascular hypertension. Their work would support our observations and those of other workers who have related changes occurring in the upright position to the production or exacerbation of hypertension of renal origin ( JAMA  187 :977, 1964). In this article and another on the subject ( Surgery  53 : 736, 1963) we have emphasized the association of renal ptosis to diminished renal blood flow both in the presence of stenosing lesions of the renal artery and in subjects whose vessels are otherwise normal.  Some patients who have fibromuscular dysplasia of the renal artery may be normotensive in the recumbent position and hypertensive in upright postures. We have postulated that when the patient assumed an upright position, the kidney descended and
Development of pituitary adenoma in women with hyperprolactinaemia
Authors: J. P Sheehan, D. A Sisam
Journal: BMJ (1984)

increase we would need 20 million patients with 20 million controls.'Again this ignores all the additional practical problems of post- marketing surveillance.3The salutary lesson with postmarketing surveillance is that 10 000 patients are too few to detect rare adverse reactions.Professor Rawlins, like many others, chose the number arbitrarily.That postmarketing studies "are likely to be worthwhile only if they enrol 10 times the number of patients in premarketing trials" is no argument."The Grand Old Duke of York, he had 10 000 men" and he found, like we will in postmarketing sur- veillance, that they do not achieve what is expected of them.