tbuckley/cabot-search huggingface dataset:
Nuclear transfer to prevent maternal transmission of mitochondrial DNA disease
Authors: J. Poulton, P. Oakeshott
Journal: BMJ (2012)

Would be a major advance, but safe alternatives exist for most affected families 

Two new techniques to prevent diseases of maternally transmitted mitochondrial DNA—maternal spindle transfer and pronuclear transfer—have prompted a public consultation by the Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom.1 2 3 After the announcement of the consultation, much of the comment in the press focused on “three parent embryos” as if they were a novelty.4 They are not, and such red herrings serve only to cloud the debate.

About one in 400 people have a maternally inherited pathogenic mutation of mitochondrial DNA. Mutations may cause no symptoms or may present at any age with problems such as developmental regression, deafness, blindness, neuropathy, diabetes, or cardiomyopathy. Mitochondrial DNA is maternally inherited because mitochondria are located in the cytoplasm, and the sperm contributes almost no cytoplasm to the fertilised egg. Many of these diseases are heteroplasmic—that is, mitochondria with mutant and normal DNA coexist in the same patient; low doses of mutant DNA cause mild symptoms and high doses cause severe symptoms. If heteroplasmic women transmit high doses of mutant mitochondrial DNA to their children,5 these children are severely affected. Homoplasmic women, whose mitochondria all have identical DNA, transmit 100% mutant …
Memorable patients: Doing as they are told
Authors: O. Fleming
Journal: BMJ (1998)

We all worry about patients' compliance. However, this is not the hazard. Occasionally advice can be taken too literally.

A young woman brought her baby to see me on account of nappy rash. The baby did not look ill and I asked the mother to undress her. I was horrified by the sight of a baby seemingly consisting of skin and bones. The only time I had seen anything like it was an illustration of …
Long-Term Effect of a First Pregnancy on the Secretion of Prolactin
Authors: Victoria C. Musey, Delwood C. Collins, Paul I. Musey, D. Martino-Saltzman, John R.K. Preedy
Journal: New England Journal of Medicine (1987)

An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post-stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross-sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years.On the theory that early pregnancy may protect women against breast cancer by a long-term depression of prolactin secretion, basal and perphenazine-stimulated release of prolactin, as well as basal and GnRH- stimulated release of LH and FSH were assayed in women before and after their 1st full term pregnancy, and in groups of parous and nulliparous women. The study groups were 15 women aged 18-23 and 9 women aged 29- 40. All hormone samples were taken at 0800 in the early follicular phase on women who had never taken oral contraceptives, or in the cross section survey, women who had not been exposed for at least 6 months. There were no significant differences in LH or FSH basal or stimulated levels for 100 minutes after GnRH. In contrast after term pregnancy both basal and stimulated prolactin levels were significantly lower than comparable levels in nulliparous controls. Parous women returned for their second prolactin assay from 5-11 months after delivery. The cross-section basal prolactin levels were done from 12-150 months after delivery, with no evidence of an effect of age, parity or elapsed time. These results are appropriate for a protective factor against breast cancer, and prolactin is known to stimulate breast neoplasm in rodents.
Blood Test for Variant Creutzfeldt-Jakob Disease—Reply
Authors: Graham S. Jackson, Jesse Burk-Rafel, Simon Mead, John Collinge
Journal: JAMA Neurology (2014)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
In the absence of the low density lipoprotein receptor, human apolipoprotein C1 overexpression in transgenic mice inhibits the hepatic uptake of very low density lipoproteins via a receptor-associated protein-sensitive pathway.
Authors: M C Jong, V E Dahlmans, P J van Gorp, K W van Dijk, M L Breuer, M H Hofker, L M Havekes
Journal: Journal of Clinical Investigation (1996)

To study the role of apoC1 in lipoprotein metabolism, we have generated transgenic mice expressing the human APOC1 gene. On a sucrose-rich diet, male transgenic mice with high APOC1 expression in the liver showed elevated levels of serum cholesterol and triglyceride compared with control mice (5.7+/-0.7 and 3.3+/-2.1 vs. 2.7+/-0.1 and 0.4+/-0.1 mmol/liter, respectively). These elevated levels were mainly confined to the VLDL fraction. Female APOC1 transgenic mice showed less pronounced elevated serum lipid levels. In vivo VLDL turnover studies revealed that, in hyperlipidemic APOC1 transgenic mice, VLDL particles are cleared less efficiently from the circulation as compared with control mice. No differences were observed in the hepatic production and extrahepatic lipolysis of VLDL-triglyceride. Also, VLDL isolated from control and APOC1 transgenic mice were found to be equally good substrates for bovine lipoprotein lipase in vitro. These data indicate that the hyperlipidemia in APOC1 transgenic mice results primarily from impaired hepatic VLDL particle clearance, rather than a defect in the hydrolysis of VLDL-triglyceride. To investigate which hepatic receptor is involved in the apoC1-mediated inhibition of VLDL clearance, APOC1 transgenic mice were bred with an LDL receptor-deficient (LDLR(-/-)) background. In addition, control, LDLR(-/-), and LDLR(-/-)/APOC1 mice were transfected with adenovirus carrying the gene for the receptor-associated protein (Ad-RAP). Both serum cholesterol and triglyceride levels were strongly elevated in LDLR(-/-)/APOC1 mice compared with LDLR(-/-) mice (52+/-19 and 36+/-19 vs. 8.4+/-0.9 and 0.5+/-0.2 mmol/liter, respectively), indicating that apoC1 inhibits the alternative VLDL clearance pathway via the remnant receptor. Transfection of LDLR(-/-) mice with Ad-RAP strongly increased serum cholesterol and triglyceride levels, but to a lesser extent than those found in LDLR(-/-)/APOC1 mice (39+/-8 and 17+/-8 vs. 52+/-19 and 36+/-19 mmol/liter, respectively). However, in LDLR(-/-)/APOC1 mice the transfection with Ad-RAP did not further increase serum cholesterol and triglyceride levels (52+/-19 and 36+/-19 vs. 60+/-10 and 38+/-7 mmol/liter, respectively). From these studies we conclude that, in the absence of the LDLR, apoC1 inhibits the hepatic uptake of VLDL via a RAP-sensitive pathway.
Middle-Ear Problems in Childhood
Authors: George Heller
Journal: JAMA (1966)

To the Editor:—  Doctor Davison's article ( 196 :834, 1966) concerning middle-ear problems in childhood describes beautifully the absurd dichotomy that exists between the otologist and the practicing pediatrician in the matter of the therapy of acute otitis media. For example, the simple matter of examination of the child is reported as being impossible without mummification and the aid of two assistants. If this were true, the practicing pediatrician would never be able to care for this problem because it would be a physical and economic impossibility to make home visits along with two assistants. In 1940 ( J Pediat  17 :322, 1940) I described a very simple method of examining the small child and I can assure Dr. Davison that no pediatrician feels the need of such terrifying maneuvers as he insists are necessary.  Other items in his article seem to be at variance from scientific necessity or even common sense.
Professional Standards Review Organizations
Authors: Stephen M. Davidson
Journal: JAMA (1973)

Certain weaknesses in the evaluation methods utilized by the authors of "Professional Standards Review Organizations" undermine the validity of the program effectiveness results cited by them to the extent that program success has not been demonstrated. These weaknesses are grouped into three categories: (1) failure to account for causal factors other than the Hospital Admission and Surveillance Program (HASP), (2) weaknesses in the HASP evaluation time period selection, and (3) weaknesses in the measurement criteria.
Endogenous catecholamines are not necessary for ischaemic preconditioning in the isolated perfused rat heart
Authors: E. O Weselcouch, A. J Baird, P. G Sleph, S. Dzwonczyk, H. N Murray, G. J Grover
Journal: Cardiovascular Research (1995)

Journal Article Endogenous catecholamines are not necessary for ischaemic preconditioning in the isolated perfused rat heart Get access Edward O Weselcouch, Edward O Weselcouch Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Anne J Baird, Anne J Baird Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul G Sleph, Paul G Sleph Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven Dzwonczyk, Steven Dzwonczyk Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Holt N Murray, Holt N Murray Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary J Grover Gary J Grover * Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, F1.4803, Princeton, NJ 08543-4000, USA *Correspondence to Dr Grover. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 1, January 1995, Pages 126–132, https://doi.org/10.1016/S0008-6363(96)88557-9 Published: 01 January 1995 Article history Received: 01 June 1994 Accepted: 28 September 1994 Published: 01 January 1995
Abstract 5375: Enhanced permeability of nanoscale chemotherapeutic agents for the treatment of breast cancer
Authors: Oliver Molina, Eugena Yu, Sarah Abdulabbas, Steve Lopez
Journal: Cancer Research (2014)

Abstract Nanotechnology is becoming increasingly successful in advancing site-specific drug delivery to cancer tissues. The ability to deliver drugs more effectively to a region of interest translates into less harmful side effects and more beneficial therapeutic action. This technology is currently in use in treating a number of human cancers. Certain therapeutic limitations are encountered, such as short circulation life, poor drug permeability, and drug resistance. These limitations can be addressed with the use of nanoscale particles that allow for controlled release of the drug. This presentation will educate the audience about approaches to treating cancer using new technologies. Objectives The main objective of this strategy is to minimize the side effects associated with chemotherapy, while enhancing the overall efficacy of the treatment of breast cancer, and other cancers. - Tackle drug limitations by combining nanotechnology and chemotherapeutic methods that have been shown to increase therapeutic efficacy - Measure the effects of this combinatorial strategy using a mouse model bearing human breast tumors - Assemble the drug into a nanoscale shell in order to form a polymeric nanoparticle capable of providing controlled drug release. - Create leaky vasculature in the vicinity of tumor tissue without affecting normal tissue Methods 1st Method: Synthesis of a nanoparticle which encapsulates two chemotherapeutic agents, Paclitaxel and Cisplatin. The nanoparticle formed is a lipid-polymer hybrid whose main components are as follows: a core encapsulating the two drugs; a biocompatible shell to promote drug retention inside the core; and a polymer stealth layer outside the lipid shell to enhance nanoparticle stability and systemic circulation lifetime. 2nd Method: The tumor will be starved by limiting vascular growth using the drug, Endostatin. In addition, the permeability of the vasculature surrounding the tumor will be made more permeable for drug uptake by using a permability enhancing agent, iRGD. Note: This abstract was not presented at the meeting. Citation Format: Oliver Molina, Eugena Yu, Sarah Abdulabbas, Steve Lopez. Enhanced permeability of nanoscale chemotherapeutic agents for the treatment of breast cancer. [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 5375. doi:10.1158/1538-7445.AM2014-5375
Abstract 4072: Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+prostate cancer stem cells.
Authors: Gamze Goksel, Ayhan Bilir, Ruchan Uslu, Hakan Akbulut, Ummu Guven, Gulperi Oktem
Journal: Cancer Research (2013)

Abstract Tumor mass contains a complex and heterogeneous phenotypic population including a rare group of cancer cells that are capable of serving cancer- initiating cells or cancer stem cells (CSCs). Established cancer cell lines contain CSCs, which can be propagated, to form in vitro 3D tumor spheroids. Spheroids reflect differentiation properties of CSCs in serum contained medium and more accurately reflect the complex in vitro microenvironment than simple two-dimensional monolayer. Aberrant activation of Wnt signaling is strongly implicated in the progression of cancer and controls CSCs properties. In this study we hypothesize that when cells maintained as spheroids the structure of CSCs could be show differentiation between CSCs and non- CSCs counterpart. It is possible to determine target molecules for CSCs eradication and specify a clue in therapeutic strategies of cancer. With this aim, CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with remained heterogeneous cancer cells bulk population. Wnt1, Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expression analysis was applied and protein expression levels of Wnt1, Fzd and Axin were shown by immunohistochemistry. Results show that Wnt1 expression significantly higher in non cancer stem cells compared to CSCs. Nevertheless Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expressions were higher in CSCs group than the other population. Increased Wnt1 immunoreactivity was demonstrated in the non-cancer stem cells. It is possible to assume that intracellular signaling of Wnt pathway and related molecules in the nucleus and/or cytoplasm might play an important role independent of Wnt ligand. This unexpected expression could be important for CSCs behavior and targeting of this pathway could have therapeutic value in cancer. Citation Format: Gamze Goksel, Ayhan Bilir, Ruchan Uslu, Hakan Akbulut, Ummu Guven, Gulperi Oktem. Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4072. doi:10.1158/1538-7445.AM2013-4072
ATHEROMA AND OTHER LESIONS PRODUCED IN RABBITS BY CHOLESTEROL FEEDING
Authors: C. H. Bailey
Journal: The Journal of Experimental Medicine (1916)

The feeding of egg yolk or pure cholesterol to rabbits produces an abundant deposit of anisotropic fat in various organs. From this deposit characteristic lesions secondarily result in certain organs. Prominent among these lesions is an atheroma of the aorta very similar in the gross and histologically to the human lesion. Lesions of other vessels are also produced, conspicuous among which are those of the branches of the pulmonary artery. There is a large deposit of anisotropic fat in the liver which produces a cirrhosis. Enlargement of the adrenals occurs, probably due to the storage of an excessive amount of anisotropic fat. In a certain proportion of rabbits conspicuous lesions are produced in the kidneys consisting of nodular deposits of anisotropic fat in the medullary portion, the fat being contained for the most part in endothelial cells and fibroblasts in the interstitial tissue. Later softening occurs in these areas as in the aorta; the cells break down; there is an abundant deposit of cholesterol crystals, some calcification, and a proliferation of connective tissue. Scars frequently extend outward from these lesions through the cortex, but the nodular deposits of anisotropic fat are never seen in the cortex. It is impossible to determine definitely from these experiments whether or not these deposits are dependent on preexisting interstitial lesions.
Defense against free radicals has therapeutic implications
Authors: K. Simmons
Journal: JAMA (1984)

Like aspirin,  oxygen were being introduced as a new drug, it would probably fail to pass the stringent guidelines imposed by the Food and Drug Administration, says Joe M. McCord, PhD, who goes on to explain:  minimum effective dose is too close to a dangerous, toxic dose. But there are defenses, and these offer promise of new therapeutic approaches to myocardial infarction (MI) and for preventing ischemic damage during organ transplantation.  Ninety-eight percent of molecular oxygen is completely reduced to water in the process of respiration, says McCord, who is professor and chair of the Department of Biochemistry, University of South Alabama College of Medicine, Mobile. The other 2%, he says, turns into potentially toxic free radicals—molecules with heightened chemical reactivity because of the single, unpaired electron in their outer shell.   bottom line here is that if you do anything less than the complete, full reduction of
Professors speak out against advertising directly to consumers
Authors: Jeanne Lenzer
Journal: BMJ (2005)

The drug industry's “onslaught of advertising to promote prescription drugs… does not promote public health” and “increases costs and unnecessary prescriptions,” more than 200 US medical school professors said last week. In the United States the industry spends $4bn (£2.3bn; €3.3bn) a year on direct to consumer advertising.

The professors signed a petition organised by Commercial Alert, an Oregon based nonprofit organisation that seeks to “protect communities from commercialism.” The …
Prognostic Influences and Radiation Therapy According to Pattern of Disease
Authors: M. Vera Peters
Journal: JAMA (1973)

Developments during the past decade have helped to solve some clinical mysteries and have allowed a more thoughtful approach in the treatment of Hodgkin's disease. Better information is now available on established prognostic influences, and new prognostic influences have been revealed. Certain specific patterns of disease have emerged from recent studies in clinical presentation. These were made possible by more complete clinical assessment of patients at the time of diagnosis than was done previously. The purpose of this communication is to review prognostic influences, applying them to our own experiences when possible, and to show the evolution of recognized patterns of disease. The favorable and unfavorable features of each clinical pattern of Hodgkin's disease will be discussed. Finally, a treatment plan will be proposed according to the pattern and extent of disease. <h3>Population Studied.—</h3> The major prognostic influences will be shown in an analysis of 1,131 successive, previously untreated patients
STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE
Authors: P. Andreini, M. L. Drasher, N. A. Mitchison
Journal: The Journal of Experimental Medicine (1955)

A study was made of variation in weight of the host lymph nodes, spleen, and thymus, after implantation of transplantable tumors in susceptible and See PDF for Structure non-susceptible hosts. The lymph nodes and spleens of non-susceptible hosts increased in weight during the period when the organs were participating in the immunological response, though an increase also took place in susceptible hosts. Variations in protein nitrogen and pentose- and desoxypentosenucleic acid of the draining lymph nodes of non-susceptible mice were also studied. The protein nitrogen content increased with the weight of the nodes. Increase in the PNA/DNA ratio occurred while the lymph node cells were engaged in production of antibody. Increase in the PNA/DNA ratio was interpreted as an increase in PNA per cell, and therefore of the rate of protein synthesis.
986 INTRAHEPATIC CHOLESTATIS OF PREGNANCY: A “IN VIVO” MODEL OF THE HEPATIC CLEARANCE OF ADIPONECTIN
Authors: G. Soardo, L. Driul, A. Carnelutti, L. Domenis, D. Cappello, D. De Silvestri, D. Marchesoni, L.A. Sechi, D. Donnini
Journal: Journal of Hepatology (2010)