tbuckley/cabot-search huggingface dataset:
Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation.
Authors: W M Holleran, M Q Man, W N Gao, G K Menon, P M Elias, K R Feingold
Journal: Journal of Clinical Investigation (1991)

Stratum corneum lipids comprise an approximately equimolar mixture of sphingolipids, cholesterol, and free fatty acids, arranged as intercellular membrane bilayers that are presumed to mediate the epidermal permeability barrier. Prior studies have shown that alterations in epidermal barrier function lead to a rapid increase in cholesterol and fatty acid synthesis which parallels the early stages of the repair process. Despite an abundance of indirect evidence for their role in the barrier, the importance of sphingolipids has yet to be demonstrated directly. Whereas sphingolipid synthesis also increases during barrier repair, this response is delayed in comparison to cholesterol and fatty acid synthesis (Holleran, W.M., et al. 1991. J. Lipid Res. 32:1151-1158). To further delineate the role of sphingolipids in barrier homeostasis, we assessed the impact of inhibition of sphingolipid synthesis on epidermal barrier recovery. A single topical application of beta-chloro-L-alanine (beta-CA), an irreversible inhibitor of serine-palmitoyl transferase (SPT), applied to acetone-treated skin of hairless mice resulted in: (a) greater than 75% inhibition of SPT activity at 30 min (P less than 0.001); (b) a global decrease in sphingolipid synthesis between 1 and 3 h (P less than 0.02); (c) reduction of epidermal sphingolipid content at 18 h (P less than 0.01); (d) delayed reaccumulation of histochemical staining for sphingolipids in the stratum corneum; and (e) reduced numbers and contents of lamellar bodies in the stratum granulosum. Finally, despite its immediate, marked diminution of sphingolipid synthesis, beta-CA slowed barrier recovery only at late time points (greater than 6 h) after acetone treatment. This inhibition was overridden by coapplications of ceramides (the distal SPT product), indicating that the delay in repair was not due to non-specific toxicity. These studies demonstrate a distinctive role for epidermal sphingolipids in permeability barrier homeostasis.
Access to JAMA
Authors: Catherine D. DeAngelis
Journal: JAMA (2004)

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
Anencephalic Newborns as Organ Donors
Authors: Michael H. Shapiro
Journal: JAMA (1988)

To the Editor.—  In a recent commentary about using anencephalic infants as organ donors, Arras and Shinnar 1 focus primarily on two issues: whether such infants should be considered  dead and whether they should be considered nonpersons. In the first case, they would clearly be available as donors. In the second case matters are less clear, but nonperson status at least helps the case for donation.  Their review of these issues was informative but, as the authors know, there are other problems relevant to whether anencephalic newborns should be used as organ donors. They include the following. (1) Whether life-support measures should be instituted (contrary to most current practices) so that the infant's organs can remain useable until a recipient is found. Life support would then be ended and organs transplanted only on confirmation of brain death. 2 (Such confirmation may be difficult to obtain, as the authors note.)
Paget's disease of bone, osteogenesis imperfecta, and fibrous dysplasia.
Authors: R Smith
Journal: BMJ (1977)

These disorders are seen both by physicians and by orthopaedic surgeons, and each may have a different view of them. The physician may be interested in Paget's disease because of its biochemical changes and the possibility of altering them, where as the orthopaedic surgeon may regard it as a common disorder of bone that makes surgery difficult. The physician finds interest in osteogenesis imperfecta because it is an inherited metabolic disorder; the surgeon because of the deformities and surgical problems it produces. Fibrous dysplasia means to the physician the rare multisystemic polyostotic disease with pigmentation and sexual precocity (Albright's syndrome); the orthopaedic surgeon thinks of the commoner monostotic form apparently limited to bone. The most recent advances have been in the first two disorders; to understand them it is helpful to have some idea of collagen chemistry.
Dog bites recognized as public health problem
Authors: R. Voelker
Journal: JAMA (1997)

IT'S TIME to take some teeth out of a largely unrecognized yet preventable public health problem. Every year in the United States, almost 2% of the population is bitten by a dog. The Centers for Disease Control and Prevention (CDC) in Atlanta, Ga, estimates that of those 4.5 million bites, almost 800 000 are serious enough to require medical attention. In extreme cases, about 18 people die from dog bites every year (<i>Pediatrics</i>. 1996;97:891-895 and<i>Injury Prev</i>. 1996;2:52-54). In many instances, the bite is the result of a pet owner not fully understanding the responsibility involved in owning a dog. Some dog owners disregard leash laws; others may not think twice before leaving infants or young children alone with a dog. Sometimes, parents allow their children to freely approach an unfamiliar dog on the street. "We have to educate dog owners on their responsibilities," says Westwood, Kan, consultant Wayne Hunthausen,
Hirschsprung's Disease and Allied Disorders,
Authors: E R HOWARD
Journal: Gut (2001)

Hirschsprung's Disease and Allied Disorders, 2nd Edn . Edited by AM Holschneider, P Puri (Pp 503; illustrated). The Netherlands: Harwood Academic Publishers, 2000. ISBN 90-5702-263-x.

Hirschsprung's disease, or congenital intestinal aganglionosis, was named after Harald Hirschsprung, a Danish paediatrician who gave the first description of the condition in 1886. At first the massive dilatation of the colon was believed to be caused by an abnormality within the dilated colon itself and the condition was therefore called “congenital megacolon”. Sir Frederick Treves (1898) performed the first curative operation. While operating on a six year old girl he noted that although there was massive dilatation of the proximal colon, the lower sigmoid colon and rectum were narrow. He performed an abdominoperineal resection of the distal colon and rectum with anastomosis of the proximal colon to the anal margin. The patient was known to survive at least until 67 years of age.

The true cause …
A woman with sudden headache followed by collapse
Authors: D. A Jones, F. Walker, N. R Chopra, W. Serino, F. Huwez
Journal: BMJ (2009)

A 41 year old woman was admitted with sudden onset of severe headache followed by collapse and decreased consciousness. She had a history of frequent migraines but was not taking regular drugs. She was a non-smoker with no history of recreational drug use. On admission her Glasgow coma scale was 7/15 (E1 V1 M5). Her pupils were unequal but reactive. Examination of her peripheral nervous system showed increased tone in all four limbs with brisk reflexes. Plantar reflexes were equivocal. Her blood pressure was 150/80 mm Hg, pulse was regular at 44 beats/min, and oxygen saturation was 99% on 10 l/min. Cardiovascular examination was normal. A respiratory examination was normal. The patient was intubated. Computed tomography of the head excluded intracranial haemorrhage. A lumbar puncture was performed, and cerebrospinal fluid was sent for analysis; it showed white blood cell count 0×106/l (reference range 0-5 (all lymphocytes, no neutrophils)), red blood cell count 23×106/l (0-10), protein 0.3 g/l (0.2-0.4), glucose 3.8 mmol/l (3.3-4.4 or about two thirds of the blood glucose concentration), and no xanthochromia. Magnetic resonance imaging (MRI) of the brain was performed one week later (fig 1⇓). Transoesophageal echocardiography was performed three weeks later (fig 2⇓). Fig 1 Magnetic resonance imaging of the brain Fig 2 Transoesophageal echocardiogram with contrast ### Short answers
Oscillations of conduction, action potential duration, and refractoriness. A mechanism for spontaneous termination of reentrant tachycardias.
Authors: L H Frame, M B Simson
Journal: Circulation (1988)

The mechanism of cycle length oscillation and its role in spontaneous termination of reentry was studied in an in vitro preparation of canine atrial tissue surrounding the tricuspid orifice. Reentry occurred around a fixed path with incomplete recovery of excitability. Among 18 experiments, there was complete concordance between the occurrence of spontaneous cycle length oscillation and spontaneous terminations; both were observed in 10 experiments and neither in the other eight (p less than 0.001). Local changes in conduction during oscillations resulted from the dependence of both conduction velocity and action potential duration on the preceding local diastolic interval. Interval-dependent changes in action potential duration contributed to the oscillation by altering the next diastolic interval. Because of changes in action potential duration, changes in cycle length were poorly correlated with changes in diastolic interval and, therefore, with local conduction velocity. Complex oscillations resulted from variations in conduction time at multiple sites in the circuit. Oscillations caused most spontaneous terminations. The critical event was an exceptionally long diastolic interval preceding the next-to-last cycle that accelerated local conduction (which tended to shorten the last cycle) and prolonged action potential duration and refractoriness at the site of block. Ninety-two of 99 recordings of spontaneous termination showed evidence of oscillation of conduction and refractoriness causing block.
Vasopressin V <sub>2</sub> -Receptor Blockade With Tolvaptan in Patients With Chronic Heart Failure
Authors: Mihai Gheorghiade, Imran Niazi, John Ouyang, Frank Czerwiec, Jun-ichi Kambayashi, Manuela Zampino, Cesare Orlandi
Journal: Circulation (2003)

In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V2-receptor antagonist in patients with chronic heart failure (CHF).This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of -0.79+/-0.99, -0.96+/-0.93, and -0.84+/-0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of +0.32+/-0.46 kg in the placebo group (P<0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9+/-0.6, 4.2+/-0.9, 4.6+/-0.4, and 2.3+/-0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively; P<0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed.In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients.
Cranes at Dusk
Authors: Tony Miksanek
Journal: JAMA (1985)

<i>Cranes at Dusk</i>is a novel dealing with the transformation of Japanese society in 1945. Although the book specifically recounts the metamorphosis of the Japanese people at the end of World War II, as they adapt to internal turmoils and outside influences, the novel is also a captivating account of the pain, uncertainty, and conflict associated with any process of growth or change. The events of 1945 are seen through the eyes of a 10-year-old Japanese girl, Saya, who, like the author of the book, is the daughter of a Shinto priest in the old imperial city of Kyoto. Saya's adventures and her personal relationships, especially with her parents, mirror those of all Japan. Saya's mother, who represents the old Japan, is portrayed as traditional, aesthetic, and almost blindly loyal. Saya's father provides a poignant contrast with his calculating mind, malleability, and universalism. He represents the new Japan, or at
Genetic Syndromes of Severe Insulin Resistance
Authors: Robert K. Semple, David B. Savage, Elaine K. Cochran, Phillip Gorden, Stephen O'Rahilly
Journal: Endocrine Reviews (2011)

Insulin resistance is among the most prevalent endocrine derangements in the world, and it is closely associated with major diseases of global reach including diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease, and ovulatory dysfunction. It is most commonly found in those with obesity but may also occur in an unusually severe form in rare patients with monogenic defects. Such patients may loosely be grouped into those with primary disorders of insulin signaling and those with defects in adipose tissue development or function (lipodystrophy). The severe insulin resistance of both subgroups puts patients at risk of accelerated complications and poses severe challenges in clinical management. However, the clinical disorders produced by different genetic defects are often biochemically and clinically distinct and are associated with distinct risks of complications. This means that optimal management of affected patients should take into account the specific natural history of each condition. In clinical practice, they are often underdiagnosed, however, with low rates of identification of the underlying genetic defect, a problem compounded by confusing and overlapping nomenclature and classification. We now review recent developments in understanding of genetic forms of severe insulin resistance and/or lipodystrophy and suggest a revised classification based on growing knowledge of the underlying pathophysiology.
A Developmental Twin Study of Church Attendance and Alcohol and Nicotine Consumption: A Model for Analyzing the Changing Impact of Genes and Environment
Authors: Kenneth S. Kendler, John Myers
Journal: American Journal of Psychiatry (2009)

Objective: Church attendance is one of the most consistent predictors of alcohol and nicotine consumption. The authors sought to clarify changes in the role of genetic and environmental factors in influencing church attendance and the interrelationship between church attendance and alcohol and nicotine use from early adolescence into adulthood. Method: The authors used data from two interview waves 6 years apart of 1,796 male twins from a population-based register, in which respondents were asked about current and past church attendance and psychoactive drug use. Structural twin models were fitted and tested using the Mx software program. Results: As twins developed from childhood through adulthood, the influence of shared environmental factors on church attendance declined dramatically while genetic factors increased. In early and late adolescence, the negative correlations between church attendance and alcohol and nicotine consumption resulted largely from shared environmental factors. In adulthood, the inverse relationship between church attendance and substance use became stronger and arose largely from genetic factors. Conclusions: As individuals mature, they increasingly shape their own social environment in large part as a result of their genetically influenced temperament. When individuals are younger and living at home, frequent church attendance reflects a range of familial and social-environmental influences that reduce levels of substance use. In adulthood, by contrast, high levels of church attendance largely index genetically influenced temperamental factors that are protective against substance use. Using genetically informative designs such as twin studies, it is possible to show that the causes of the relationship between social risk factors and substance use can change dramatically over development.
ONE-STEP GROWTH CURVE OF WESTERN EQUINE ENCEPHALOMYELITIS VIRUS ON CHICKEN EMBRYO CELLS GROWN IN VITRO AND ANALYSIS OF VIRUS YIELDS FROM SINGLE CELLS
Authors: R. Dulbecco, Marguerite Vogt
Journal: The Journal of Experimental Medicine (1954)

The rate of adsorption of WEE virus onto chicken embryo cells in vitro was determined both on a cell layer and on a cell suspension. One-step growth curves were determined in cell suspensions and on cell layers. The latent period varied between 2 and 3(1/2) hours; it was shorter on cell layers and decreased with higher multiplicity of infection. The shortest period is probably the real latent period. The growth curves of the virus showed an initial exponential rise and reached a maximal constant value after 6 to 8 hours. The maximum virus yield per cell varied between 200 and 1000 on the cell layer, and between 100 and 200 in suspended cells. The yield of single infected cells was determined. An analysis of the distributions of the individual yields obtained after various periods of virus growth led to two main conclusions: (1) that virus is released from the same cell over a long period of time; (2) that one phase of the intracellular virus growth is exponential.
Hyperglucagonemia and Its Suppression
Authors: Philip Raskin, Roger H. Unger
Journal: New England Journal of Medicine (1978)

The role of glucagon in diabetes was studied in four patients with juvenile-type diabetes during continuous insulin infusion and a diet containing 150 g per day of carbohydrate. During insulin alone, plasma glucagon, measured at two-hour intervals, averaged 182±34 pg per milliliter, glucose 269±11 mg per deciliter, glucose excretion 52±8 g per 24 hours, ketone excretion 1.3±0.3 mmol per 24 hours, and urea nitrogen 12±2 g per 24 hours (mean ± S.E.M.). Somatostatin (2 mg per day) lowered glucagon to 60±13 pg per milliliter, glucose to 111 ±17 mg per deciliter, glucose excretion to 1 ±0.7 g per 24 hours, ketone excretion to 0.5±0.2 mmol per 24 hours and urea nitrogen excretion to 8±2 g per 24 hours. Replacement of glucagon raised glucagon to 272±30 pg per milliliter, glucose to 202±20 mg per deciliter, glucose excretion to 14±7 g per 24 hours, ketone excretion to 0.8 mmol per 24 hours and urea nitrogen excretion to 11±2 g per 24 hours. In a subsequent study, similar improvement occurred on a diet of 30 g of carbohydrate daily, when absorption of dietary glucose was negligible. Hyperglucagonemia has an important role in diabetes; its correction reduces diabetic abnormalities to or toward normal. (N Engl J Med 299:433–436, 1978)
Abstract 1404: Mitochondrial-targeted nitroxide JP4-039 ameliorates irradiation-induced delay in bone wound healing and inhibits orthotopic tumor growth
Authors: Jean-Claude Rwigema, Abhay Gokhale, Michael Epperly, Julie Glowackie, Hong Wang, Tracy Dixon, Ken Patrene, Peter Wipf, Joel S. Greenberger
Journal: Cancer Research (2010)

Abstract In the case of a nuclear explosion, combined injuries will result from radiation dispersal resulting in burns and cellular damage as well as a concussion wave resulting in traumatic bone fractures. Currently no available drugs are available to protect against both irradiation damage and traumatic bone damage. A new mitochondrial targeted small molecule hemigramicidin S nitroxide JP4-039 has been developed and shown to protect against total body irradiation. JP4-039 was tested to determine its effects on irradiation-induced delay of osseous wound healing. A model for osseous would healing was used where the right hind legs of C57BL/6NHsd female mice were irradiated to doses 0 to 30 Gy 24 hours prior to drilling tibial wounds. JP4-039 (10 mg/kg) was injected either 10 min before or after irradiation. Mice were sacrificed weekly after wounding; tibiae were removed and radiographed for measurement of hole diameter. The left non-irradiated leg served as a control for the irradiated right leg. To determine whether JP4-039 might enhance tumor growth while stimulating bone growth, we injected Lewis lung carcinoma cells subcutaneously above the knee in both legs. The tumor on the right leg was within the 10Gy irradiation field. Tumor growth was monitored daily with calipers. Tukey's test was used to assess statistical significance between control and treated groups. Mice treated with JP4-039 before bone drilling showed significant improvement in osseous wound healing at 14 days and 21 days after drilling (0.55 ± 0.3 and 0.47 ± 0.04 mm, respectively), compared with 0.84 ± 0.05 and 0.64 ± 0.05 mm, respectively for control, untreated mice (p&amp;lt;0.05). Mice treated with JP4-039 prior to 20 Gy irradiation showed improved bone healing compared with controls at 21 days; Mice treated with JP4-039 after 20Gy showed improved bone healing at 21 and 28 days(p&amp;lt;0.05). Mice bearing orthotopic tumors treated with JP4-039 prior to irradiation and bone drilling showed significantly less increase in tumor volume compared with control group in both irradiated and non-irradiated legs (p &amp;lt; 0.05). Thus, treatment with JP4-039 enhanced osseous bone healing when administered before wounding. Furthermore, JP4-039 enhanced healing when administered before or after irradiation. Finally, JP4-039 inhibited tumor growth and may have useful applications in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1404.