tbuckley/cabot-search huggingface dataset:
THE AFTER-TREATMENT OF CASES OF ABDOMINAL SECTION.Read in the Section of Obstetrics and Diseases of Women, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May 1891.
Authors: CHARLES P. NOBLE
Journal: JAMA (1891)

According to Oliver Wendell Holmes, to successfully treat an individual one should begin with the grandfather. The same principle applies to the successful after-treatment of cases of abdominal section. Whenever possible, careful preparatory treatment should be carried out. Nutrition should be improved, when depraved; the enunctories should be made active, especially the bowels and skin. Operation should be rapid, careful and thorough. Diseased, and especially suppurating, structures should receive most careful attention, and unless vital, organs be completely removed. Asepsis in clean operations, and irrigation and drainage in dirty operations, are essentials. Under such conditions, unless operation has been made a last resort, or the vital organs of the individual are seriously crippled, proper after-treatment of cases of abdominal section will insure a successful result quite uniformly. That which is accomplished by after-treatment in cases of abdominal section is principally of a negative character. The object is to protect the
The pro-inflammatory effect of HMGB1, a mediator of inflammation in arthritis, is dependent on the redox status of the protein
Authors: Lars Ottosson, Peter Lundbäck, Hulda Hreggvidsdottir, Huan Yang, Kevin J Tracey, Daniel J Antoine, Helena Erlandsson-Harris, Ulf Andersson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> High mobility group box protein 1 (HMGB1) is a nuclear protein involved in chromatin architecture and is present in all cells. HMGB1 also functions as a prototype alarmin and is released passively during necrotic cell death, as well as actively secreted from certain immunocompetent cells. Levels of HMGB1 are highly elevated in synovial tissue of rheumatoid arthritis patients, and the protein is an important mediator of different inflammatory processes. Blocking the inflammatory effect of HMGB1 with antibodies or specific inhibitors ameliorates disease in different experimental arthritis models. In this study, the authors wanted to investigate if the redox status of HMGB1 is important for the pro-inflammatory effect of the protein. We also investigated if the presence of the redox sensitive cysteine is necessary for binding of HMGB1 to its receptor TLR4/MD2. <h3>Methods</h3> To determine the redox status of HMGB1, meaning the three cysteines present in the molecule, the authors used tryptic digestion followed by liquid chromatography electrospray tandem mass spectrometry. To investigate the pro-inflammatory effect of HMGB1 and HMGB1-mutants, primary human and murine macrophages and macrophage-like RAW 264.7-cells were stimulated with HMGB1 and cytokine production was measured by ELISA. Binding studies of HMGB1 to its receptor TLR4/MD2, and investigation of the importance of redox status, was performed by Surface-Plasmon Resonance analysis. <h3>Results</h3> The authors could determine that, in order for HMGB1 to have a pro-inflammatory effect, the redox sensitive cysteine at position 106 (C106) needs to be in a reduced thiol state and the cysteines at position 23 and 45 have to form a disulfide bridge. Oxidation of C106 or lack of a disulfide bridge between C23 and C45 then causes HMGB1 to lose its pro-inflammatory effect. In Surface-Plasmon Resonance experiments the authors could demonstrate that a substitution of C106 for an alanine or a serine inhibited the binding of HMGB1 to its receptor TLR4/MD2. <h3>Conclusion</h3> The pro-inflammatory effect of HMGB1 is dependent on the redox status of all three present cysteines. The reduced C106 is necessary for the binding of HMGB1 to its receptor TLR4/MD2 explaining the lack of cytokine inducing effect of HMGB1 where C106 has been substituted for another amino acid or if the cysteine has been oxidised. The knowledge of the importance of the redox status of HMGB1 can promote the development of therapies targeted at only blocking HMGB1 when it is in its pro-inflammatory form.
Abstract 1692: Expression of argininosuccinate synthetase protein and correlation with response to the novel therapeutic pegylated arginine deiminase (ADI-PEG20) in osteosarcoma
Authors: Rebecca Sowers, John Bomalaski, Richard Gorlick
Journal: Cancer Research (2012)

Abstract The amino acid arginine is involved in protein synthesis and tumor metabolism and is essential for the growth of human cancer cells. Pegylated arginine deiminase (ADI-PEG20) is a novel therapy that lowers extracellular arginine levels and has shown evidence of clinical response and low toxicity in patients with tumors lacking argininosuccinate synthetase (ASS1) protein expression, including melanoma and hepatocellular carcinoma. Recently it has been shown that ASS1 expression was deficient in 63% (39/62) of Japanese osteosarcoma patient samples, and reduced ASS1 was associated with pulmonary metastases. In addition, they showed that ASS1 deficient, but not ASS1 expressing, osteosarcoma cells lines did not grow in arginine-deficient media, and recommended evaluation of arginine depletion with ADI-PEG20 in osteosarcoma. Because ADI-PEG20 efficacy appears to correlate with ASS1 protein expression, a cohort of osteosarcoma tissue sections (n=171) was stained immunohistochemically to determine the presence or absence of ASS1 protein. Sixty-four percent (n=109) indicated negligible or no staining for ASS1 protein suggesting further that osteosarcoma might be a candidate for ADI-PEG20 sensitivity. Western blots were performed on patient-derived osteosarcoma cell lines (n=18) to determine levels of ASS1 protein expression prior to treatment with ADI-PEG20. Of the 18 cell lines studied, four cell lines had noticeably diminished ASS1 protein expression. The remaining 13 cell lines exhibited varying amounts of ASS1 protein expression with five of these cell lines appearing strongly positive indicating possible overexpression of ASS1 protein. Cytotoxicity assays were performed on a subset of cell lines representing both elevated and decreased ASS1 protein expression to determine the in vitro effectiveness of ADI-PEG20 in patient-derived osteosarcoma cell lines and its correlation with ASS1 protein expression. Some of the ASS1 deficient cell lines showed decreased cell viability in response to arginine depletion with ADI-PEG 20. These findings suggest that arginine depletion with ADI-PEG 20 may be a potential targeted treatment for osteosarcoma patients deficient in ASS1 expression. In addition, further preclinical studies are ongoing, including xenograft models, to understand better the mechanism of this agent in osteosarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1692. doi:1538-7445.AM2012-1692
The Public Health Model for Mental Health Care for the Elderly
Authors: Ira R. Katz
Journal: JAMA (2000)

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
Osteoblastic intracellular pH and calcium in metabolic and respiratory acidosis
Authors: Yaacov Ori, Soo Gil Lee, Nancy S. Krieger, David A. Bushinsky
Journal: Kidney International (1995)

In vitro metabolic acidosis (Met) induces greater bone mineral resorption than respiratory acidosis (Resp). Met, but not Resp, inhibits osteoblasts which control many aspects of osteoclastic function. To determine whether at a similar decrement in extracellular pH, Met and Resp would induce different changes in intracellular pH (pHi) and/or intracellular calcium concentration ([Ca2+]i) of osteoblasts, we measured pHi and [Ca2+]i in an osteoblast-like rat osteosarcoma cell line (UMR-106). Cells were grown to confluence on glass slides and loaded with either 1.5 microM BCECF, for pHi, or 1.5 microM Fura-2, for [Ca2+]i, in control (Ctl; pH approximately 7.40, PCo2 approximately 40, [HCO3-] approximately 24) medium. The fluorescence ratio at excitation wavelengths of 502 and 440 nm was measured for pHi and at 340 and 380 nm for [Ca2+]i. Following a baseline scan in Ctl medium, cells were transferred to either Met (pH approximately 7.10, PCo2 approximately 40, [HCO3-] approximately 12), Resp (pH approximately 7.10, PCo2 approximately 80, [HCO3-] approximately 24) or Ctl conditions. Medium pH, PCo2 and [HCO3-] were held constant over the course of the experiment. Compared to Ctl, pHi was lower in Met (P < 0.001) and even lower in Resp (P < 0.001 vs. Met and vs. Ctl). These changes were maintained over the period of observation. Compared to Ctl, [Ca2+]i was higher in Met (P < 0.001) and even higher in Resp (P < 0.001 vs. Met and vs. Ctl) within 20 to 100 seconds. However, after 100 seconds [Ca2+]i was not different in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
THE EFFECT OF THE INTESTINAL FLORA ON THE GROWTH RATE OF MICE, AND ON THEIR SUSCEPTIBILITY TO EXPERIMENTAL INFECTIONS
Authors: René J. Dubos, Russell W. Schaedler
Journal: The Journal of Experimental Medicine (1960)

Mice delivered by Caesarian section were used to develop a new mouse colony which has been maintained in an environment protected from contact with common mouse pathogens, but not in the germ-free state. These mice, designated as NCS, were compared with animals of the same sex and age coming from the parent colony maintained under ordinary conditions. The NCS mice grew more rapidly than ordinary mice on complete diets; moreover, they continued to gain weight-although at a slower rate-when fed deficient diets which caused ordinary mice to stop growing, or to lose weight. The NCS mice proved much more susceptible than ordinary mice to certain experimental bacterial infections. In contrast, they were much more resistant than ordinary mice to the lethal effect of large doses of endotoxins. However, they responded to injection of minute amounts of these endotoxins by a marked increase in susceptibility to staphylococcal infection. Bacteriological studies revealed striking qualitative differences between the intestinal flora of NCS and ordinary mice. When NCS mice were contaminated-either by contact or by feeding-with a strain of Escherichia coli recovered from the intestine of ordinary mice, they acquired the characteristics of the latter animals with regard to weight gain on various diets, and to response to bacterial pathogens and endotoxins. NCS mice have been found well suited to the study of several nutritional, bacteriological, and immunological problems and it appears that their production on a large scale will not present unsurmountable difficulties.
Historical importance of outpatients.
Authors: H G Calwell
Journal: BMJ (1978)

disease.The latter disease may be more common than what was conveniently known as Friedlander's pneumonia, due to infection with K edwardsii or K atla7itae, and must be considered in all severe cases of pneumonia.For this reason and for the very wide anti- bacterial spectrum, I would advocate that gentamicin and erythromycin be regarded as the drug combination of choice in the face of fulminating pneumonia, particularly one which is not responding to treatment with a penicillin or tetracycline.The combination of gentamicin and erythromycin not only has the virtue that it will cover almost the whole range of bacterial infections, excluding tuberculosis, but also includes cover for at least some Bacteroides species, which, admittedly, are very rare causes of pneumonia, and will be effective against Mybcoplasrna pneunioniiae infection, though this is rarely the cause of life-threatening disease.The recently suggested alternative' of tetracycline and rifampicin might not have the same wide spectrum cover against Gram- negative bacteria.
The Chemistry of Heart Failure
Authors: A. C. Corcoran
Journal: JAMA (1961)

This is one of the few books that I have read with complete interest, enthusiasm, and satisfaction. It is beautifully produced. It is also a remarkably clear exposition of a recondite and important subject written for the medical student, clinician, and cardiologist and holding an appeal also for the chemist and physicist. The authors note that they have little confidence in chemical theories which make no attempt to account for morphological or physiological events in the contractile process. Accordingly, they develop provocative and stimulating concepts of molecular mechanisms of congestive heart failure, fibrillation, and digitalis action. I do not feel competent to challenge these and regard them as interesting concepts for the authors' later work, and, provisionally, as acceptable bases for treatment and teaching. This is a fascinating little volume, and all concerned with its publication are to be congratulated.
Abstract 5261: Role of anterior gradient protein-2 in prostate cancer bone metastasis
Authors: Diptiman Chanda, Anandi Sawant, Tatyana Isayeva, Selvarangan Ponnazhagan
Journal: Cancer Research (2011)

Abstract Skeletal metastasis is common in late stage prostate cancer, which leads to significant decline in the quality of life and mortality. In a recent study, we identified over-expression of anterior gradient protein (AGR2) in the PC3, bone metastatic prostate cancer cells following in vitro growth in bone marrow-conditioned medium. AGR2 is a secreted protein and originally reported for its role in the formation of forebrain and mucus-secreting cement gland in the frog Xenopus laevis. Role of AGR2 in carcinogenesis and metastasis is recently being investigated and reports indicate it is over-expressed in various adenocarcinomas and linked to poor survival. But no study has elucidated the role of AGR2 in bone metastasis. When AGR2 expression was compared between human prostate cancer cell lines obtained from bone (PC3), lymph node (LnCap) and brain (Du145) by RT-PCR and Western blot, highest level of AGR2 was observed in PC3 cells. To further confirm, PC3 cells expressing firefly luciferase were injected in athymic nude mice via intra-cardiac route and cells were retrieved from bone, adrenal, lung and heart 3 weeks later following organ dissemination. RT-PCR analysis indicated highest AGR2 expression in PC3 cells isolated from bone microenvironment, suggesting that AGR2 may have a potential role in prostate cancer bone metastasis. To correlate the relevance of this finding in humans, AGR2 immunohistochemistry was performed on human primary and metastatic prostate cancer tissue sections. Preliminary results indicate higher AGR2 expression in metastasized bone sections compared to primary prostate cancers. Additionally, AGR2 was stably silenced in the PC3 cells utilizing a short hairpin RNA and growth kinetics of the cell line was tested in vivo following intra-cardiac injection in a preclinical mouse model. 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 5261. doi:10.1158/1538-7445.AM2011-5261
A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome
Authors: Hidenori Ohnishi, Rie Miyata, Tomonori Suzuki, Touichiro Nose, Kazuo Kubota, Zenichiro Kato, Hideo Kaneko, Naomi Kondo
Journal: Journal of Allergy and Clinical Immunology (2011)
Confidential medical records and epidemiological research.
Authors: E. G. Knox
Journal: BMJ (1992)

Communicable Disease Surveillance Centre gives a far better epidemiological overview of food poisoning in England and Wales than does the Office of Population Censuses and Surveys, whose statistics are mainly based on formal notifications from general practitioners.Laboratories can, however, report only on the specimens they receive.What effects the health service reforms will have on the provision of data for epidemiological purposes remain to be seen.The relation between consultants in communicable disease control and their local laboratories needs to be formalised to enable the consultant to collate all local epidemiological information and to avoid problems of confidentiality.Consideration should be given to a system whereby the consultants in communicable disease control receive reports on communicable diseases from all sources and are respon- sible not only for initiating the appropriate public health response but also for effecting the "formal notification" to the Office of Population Censuses and Surveys, thereby securing more complete and accurate national surveillance data.The Review of Law on Infectious Disease Control has suggested that for diseases for which early public health intervention is required better methods of notification should exist.'The Liverpool Sanitary Act 1846 required the medical officer of health to "point out the most efficacious means for checking and preventing the spread of epidemic disease."'While awaiting new legislation consultants in communicable disease control can fulfil this function and, by informing clinical colleagues of the benefits of timely communication, can improve the notification of infectious diseases.
Prognostic Implications of Epidermal Growth Factor Receptor and KRAS Gene Mutations and Epidermal Growth Factor Receptor Gene Copy Numbers in Patients with Surgically Resectable Non-small Cell Lung Cancer in Taiwan
Authors: Hui-Ping Liu, Hong-Dar Isaac Wu, John Wen-Cheng Chang, Yi-Cheng Wu, Hsin-Yi Yang, Ya-Ting Chen, Wen-You Hsieh, Ying-Tsong Chen, Yi-Rong Chen, Shiu-Feng Huang
Journal: Journal of Thoracic Oncology (2010)
US drug regulator rejects accusations that it unfairly targets Indian generic firms
Authors: S. Bagcchi
Journal: BMJ (2014)

The US drugs regulator has defended its actions against Indian generic drug manufacturers who flout safety and quality standards. The regulator said that product safety was its top priority and that it would take any action deemed necessary to protect consumers.

Margaret Hamburg, the US Food and Drug Administration’s commissioner, was in India for a 10 day visit from 10 February. She angered some Indian officials, who claimed that the FDA was unduly targeting Indian companies for substandard practices.

India supplies about 40% of the generic and over-the-counter drugs consumed in the United States, making it the second largest supplier (after Canada). But Indian drug manufacturers accounted for half of the warning letters issued by the FDA in 2013.

In January the FDA banned the import of drugs made at two further facilities run by the Indian generics manufacturer Ranbaxy Laboratories after finding problems with the manufacturing …
Hepatocellular response to chemical stress in CD-1 mice: Induction of early genes andγ-glutamylcysteine synthetase
Authors: Neil R. Kitteringham, Helen Powell, Yuri N. Clement, Charlotte C. Dodd, Justice N. Tettey, Munir Pirmohamed, Dennis A. Smith, Lesley I. McLellan, Kevin B. Park
Journal: Hepatology (2000)

Exposure of cells to toxic chemical species can result in reduced glutathione (GSH) depletion, generation of free radicals, and/or binding to critical cell determinants. Chemical stress is usually followed by a concerted cellular response aimed at restoring homeostasis, although the precise initial stimulus for the response is unclear. We have focused on one component of this stress response, the up-regulation of γ-glutamylcysteine synthetase (γ-GCS) and the preceding molecular events involved in its regulation in an in vivo mouse model. Male CD-1 mice received buthionine sulphoximine (BSO; 7.2 mmol/kg), diethyl maleate (DEM; 4.2 mmol/kg), paracetamol (APAP; 3.5 and 1.0 mmol/kg), or carbon tetrachloride (CCl 4 ; 1.0 and 0.2 mmol/kg). Biochemical (serum transaminase and hepatic GSH levels) and molecular ( c-jun and c-fos messenger RNA [mRNA] levels and activator protein 1 [AP-1] DNA binding activity) parameters were measured, as well as the consequent effects on γ-GCS levels and activity. All compounds produced GSH depletion, but only the higher doses of APAP and CCl 4 caused liver damage. DEM, APAP, and CCl 4 increased c-jun and c-fos mRNA levels, together with an increase in AP-1 binding; BSO failed to induce AP-1 despite an increase in c-fos . Interestingly, the effects on γ-GCS varied markedly according to the compound: BSO and DEM increased γ-GCS enzyme activity, although only DEM, but not BSO, resulted in an increase in γ-GCS h mRNA and protein. In contrast, APAP and CCl 4 both increased γ-GCS h mRNA and protein; however, there was a marked dose-dependent decrease in γ-GCS activity. These data indicate that the effect of chemical stress on the liver is compound specific and is not merely dependent on depletion of GSH.
Poly(ester amine)-mediated, Aerosol-delivered Akt1 Small Interfering RNA Suppresses Lung Tumorigenesis
Authors: Cheng-Xiong Xu, Dhananjay Jere, Hua Jin, Seung-Hee Chang, Youn-Sun Chung, Ji-Young Shin, Ji-Eun Kim, Sung-Jin Park, Yong-Hoon Lee, Chan-Hee Chae, Kee Ho Lee, George R. Beck, Chong-Su Cho, Myung-Haing Cho
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for the development of novel therapeutic options. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.Objectives: To demonstrate the feasibility and emphasize the importance of noninvasive aerosol delivery of Akt1 small interfering RNA (siRNA) as an effective and selective option for lung cancer treatment.Methods: Nanosized poly(ester amine) polymer was synthesized and used as a gene carrier. An aerosol of poly(ester amine)/Akt1 siRNA complex was delivered into K-rasLA1 and urethane-induced lung cancer models through a nose-only inhalation system. The effects of Akt1 siRNA on lung cancer progression and Akt-related signals were evaluated.Measurements and Main Results: The aerosol-delivered Akt1 siRNA suppressed lung tumor progression significantly through inhibiting Akt-related signals and cell cycle.Conclusions: The use of poly(ester amine) serves as an effective carrier, and aerosol delivery of Akt1 siRNA may be a promising approach for lung cancer treatment and prevention.