tbuckley/cabot-search huggingface dataset:
Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia.
Authors: R V Considine, M R Nyce, L E Allen, L M Morales, S Triester, J Serrano, J Colberg, S Lanza-Jacoby, J F Caro
Journal: Journal of Clinical Investigation (1995)

We tested the hypothesis that liver protein kinase C (PKC) is increased in non-insulin-dependent diabetes mellitus (NIDDM). To this end we examined the distribution of PKC isozymes in liver biopsies from obese individuals with and without NIDDM and in lean controls. PKC isozymes alpha, beta, epsilon and zeta were detected by immunoblotting in both the cytosol and membrane fractions. Isozymes gamma and delta were not detected. There was a significant increase in immunodetectable PKC-alpha (twofold), -epsilon (threefold), and -zeta (twofold) in the membrane fraction isolated from obese subjects with NIDDM compared with the lean controls. In obese subjects without NIDDM, the amount of membrane PKC isozymes was not different from the other two groups. We next sought an animal model where this observation could be studied further. The Zucker diabetic fatty rat offered such a model system. Immunodetectable membrane PKC-alpha, -beta, -epsilon, and -zeta were significantly increased when compared with both the lean and obese controls. The increase in immunodetectable PKC protein correlated with a 40% elevation in the activity of PKC at the membrane. Normalization of circulating glucose in the rat model by either insulin or phlorizin treatment did not result in a reduction in membrane PKC isozyme protein or kinase activity. Further, phlorizin treatment did not improve insulin receptor autophosphorylation nor did the treatment lower liver diacylglycerol. We conclude that liver PKC is increased in NIDDM, a change that is not secondary to hyperglycemia. It is possible that PKC-mediated phosphorylation of some component in the insulin signaling cascade contributes to the insulin resistance observed in NIDDM.
The Inspection of International Cruise Ships
Authors: Leonard C. Marcus
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The "Blue Sheet," the summary for Health Information for International Travel, published biweekly by Centers for Disease Control (CDC), has provided information on inspection of international cruise ships, indicating which of these vessels pass or fail the CDC sanitation standards. As part of the "economy" drive by the current administration, the CDC plans to discontinue this inspection service. The results of the last inspection were published in the "Blue Sheet" of May 9, 1986. Twenty-eight (41.8%) of 67 vessels failed inspection. I think the decision to discontinue the inspection service by the Public Health Service is unwise and in the long term will be costly. According to data from the CDC, outbreaks of foodand water-borne diseases are not unusual aboard ship and have included outbreaks of typhoid fever, viral gastroenteritis, shigellosis, and<i>Vibrio parahemolyticus</i>infection (CDC Water-Related Disease Outbreaks Surveillance, annual summary 1983, issued September 1984). The
Energy Expenditure With Indoor Exercise Equipment
Authors: Thomas Yannios
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The article by Dr Zeni and colleagues<sup>1</sup>concerning energy expenditure and rating of perceived exertion (RPE) using different exercise machines was somewhat misleading and potentially counterproductive to promoting fitness in the general population. In the "Comment" section, the authors stated, "If exercise intensity is established by perceived effort, treadmill walking/running will result in the greatest energy expenditure and cardiorespiratory stimulus." Although this statement was certainly consistent with the study results, the study design was biased toward favoring one form of exercise over the others. The participants in this study, while fairly fit, were nevertheless untrained exercisers. The authors never revealed how these participants became fit before the study, but the implication of the "habituation" process is that they were not proficient in the technical sports represented by most of the exercise machines used. This was a crucial flaw in study design. The impression conveyed by the
Liver transplantation using Donation after Cardiac Death donors
Authors: Diethard Monbaliu, Jacques Pirenne, David Talbot
Journal: Journal of Hepatology (2011)

The success of solid organ transplantation has brought about burgeoning waiting lists with insufficient donation rates and substantial waiting list mortality. All countries have strived to expand donor numbers beyond the standard Donation after Brain Death (DBD). This has lead to the utilization of Donation after Cardiac Death (DCD) donors, also frequently referred to as Non-Heart Beating Donors (NHBD). Organs from these donors inevitably sustain warm ischaemic damage which varies in its extent and affects early graft function as well as graft survival. As a consequence, ‘non-vital’ organs such as renal transplants have increased rapidly from DCD donors but more ‘vital’ organ transplants such as the liver have lagged behind. However, an increasing proportion of liver transplants are now derived from DCD donors.This article covers this expansion, current results, pitfalls, and steps taken to minimize complications and to improve outcome, and future developments that are likely to occur.
Growing Old the Outpatient Way
Authors: L. WILLIAM EARLEY, OTTO VON MERING
Journal: American Journal of Psychiatry (1969)

The authors describe a group of patients in an outpatient clinic who present many diffuse illness symptoms and who pass from one physician to another over a long period of time without noticeable progress. By so doing, such patients manage to create a secondary world in which they play out a great number of problems they have projected.
French doctor accused of euthanasia could face life sentence
Authors: H. Mooney
Journal: BMJ (2011)

A French doctor accused of eight counts of euthanasia has been suspended from practising medicine by the French government last week.

Nicolas Bonnemaison is suspected of administering lethal injections to at least eight terminally ill patients and has been charged with the “poisoning of vulnerable people.” If convicted he could face life imprisonment.

The case of the doctor, who until August had been working in the accident and emergency department of Bayonne Hospital near Pau in the French Pyrenees, has reignited the debate on whether to legalise euthanasia in France. Dr Bonnemaison was told by the French health and employment …
Abstract 322: Dual targeting of the PI3K/mTOR pathways by PF-04691502 or PF-05212384 exhibits therapeutic effects against the metastatic disease progression in the Ovcar 3 disseminated model.
Authors: Zhengming Yan, Douglas Fang, Brett Simmons, Jing Yuan, Julie Kan, Cathy C. Zhang
Journal: Cancer Research (2013)

Abstract Ovarian cancer has the highest mortality rate of all gynecological cancers primarily due to the high incidence of metastatic spread prior to diagnosis. Understanding the biology of this malignancy and developing models that reflect the patient disease phenotype will create better pre-clinical opportunities for testing targeted therapy. We used the Ovcar 3 cell line to establish a metastasis model through serial in vivo passage. The dual PI3K/mTOR inhibitors PF-04691502 and PF-05212384 were then investigated in this model for their therapeutic effect against metastatic disease progression. Notably, the stromal environment and tumor initiating subpopulation play critical roles on the Ovcar 3MET disease invasiveness and progression. Based on the molecular profile, these invasive Ovcar 3MET cells exhibited a more EMT phenotype when compared to parental cells. Impairing PI3K/mTOR pathway with the dual PI3K/mTOR inhibitors resulted in significant anti-metastatic activity and increased survival in the Ovcar 3MET model. Serum CA125 level, which is a validated clinical marker, correlated with anatomic measurement of tumor burdens via BLI and mouse survival time in these studies, providing means for longitudinal monitoring of disease progression and response to therapy. In addition, using ex vivo tumorsphere analysis under serum-free condition, both PF-04691502 and PF-05212384 demonstrated robust activity against the self-renewal ability of Ovcar 3 tumor cells. In summary, this translational tumor model may serve as a valuable tool for testing targeted therapies such as PI3K/mTOR inhibitors for their ability to impact progression of metastatic ovarian disease. Citation Format: Zhengming Yan, Douglas Fang, Brett Simmons, Jing Yuan, Julie Kan, Cathy C. Zhang. Dual targeting of the PI3K/mTOR pathways by PF-04691502 or PF-05212384 exhibits therapeutic effects against the metastatic disease progression in the Ovcar 3 disseminated model. [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 322. doi:10.1158/1538-7445.AM2013-322
Evaluation of the efficacy and tolerability of oral terbinafine (DaskilR) in patients with seborrhoeic dermatitis. A multicentre, randomized, investigator-blinded, placebo-controlled trial
Authors: E. Scaparro, G. Quadri, G. Virno, C. Orifici, M. Milani
Journal: British Journal of Dermatology (2001)

Previous uncontrolled trials have suggested that oral terbinafine, an antimycotic allylamine compound, could be useful in the treatment of seborrhoeic dermatitis.To investigate in a placebo-controlled trial the clinical efficacy of oral terbinafine (Daskil(R), Mipharm, Milan, Italy) in patients with moderate to severe seborrhoeic dermatitis.Sixty outpatients (mean +/- SD age 37 +/- 11 years; 32 men and 28 women) with moderate to severe seborrhoeic dermatitis were enrolled in a multicentre, randomized, placebo-controlled, investigator-blinded, parallel-group, 12-week study. After a 2-week wash-out period, enrolled patients were randomized to treatment with oral terbinafine 250 mg daily (n = 30) or placebo (moisturizing ointment) (n = 30) applied twice daily for 4 weeks (weeks 0-4). Patients were followed up for an additional 8 weeks after completion of treatment and were clinically evaluated at weeks 0, 2, 4 and 12 by an investigator unaware of the patient's type of treatment. The primary end-point of the study was clinical evaluation of erythema, scaling and itching, each scored on a 0-3 scale. A global clinical score, representing the sum of each evaluated symptom, was also calculated.Demographic and clinical data were equally balanced between the placebo and terbinafine groups. All enrolled patients concluded the study. At baseline, the mean +/- SD global clinical score was 7.4 +/- 1.3 in the placebo group and 7.7 +/- 1.0 in the terbinafine-treated group. At weeks 4 and 12 the mean +/- SD global clinical score in the placebo group was 5.9 +/- 1.7 and 6.3 +/- 1.2, respectively, which was not significantly different from baseline. As compared with baseline values and the placebo group, terbinafine treatment significantly (P < 0.0001, Tukey-Kramer test) reduced the mean +/- SD global clinical score (to 1.0 +/- 1.1 at week 4, and 1.2 +/- 1.4 at week 12), as well as the individual erythema, scaling and itching scores. No serious adverse events were recorded during the study in either group.This is the first controlled trial that has shown oral terbinafine to be effective in the treatment of moderate to severe seborrhoeic dermatitis. Clinical improvement following 4 weeks treatment with terbinafine was maintained 8 weeks after completing treatment.
SPECIFIC FRACTIONATION OF A POPULATION OF ANTIDEXTRAN MOLECULES WITH COMBINING SITES OF VARIOUS SIZES
Authors: Stuart F. Schlossman, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1962)

Two human antidextran sera were each fractionated into two populations of antibody by specific absorption of the antidextran on an insoluble dextran (sephadex), washing away non-specific protein, eluting the first fraction of antibody with isomaltose or isomaltotriose, and the second fraction with isomaltohexaose. The differences in behavior of the purified antibody fractions alone, or reconstituted in serum, in quantitative inhibition studies with the isomaltose series of oligosaccharides, or in quantitative precipitin studies with NRC dextrans of graded molecular weight, could be ascribed to differences in the sizes of their combining sites. It was shown that the antibody fractions eluted with isomaltose or isomaltotriose were made up largely of antibodies inhibited readily by the smaller oligosaccharides and therefore having a higher proportion of molecules with smaller-sized combining sites; whereas those fractions eluted with isomaltohexaose contained primarily antibodies readily inhibitable only with the larger oligosaccharides, and hence were considered to have a higher proportion of larger-sized combining sites. The purified antibody fractions were shown to be only fast gamma globulin,—to possess the same mobility in immunoelectrophoresis; in addition the antibody fractions from one individual in double diffusion in agar gave lines which fused with one another, with gamma globulin Fr. II, and with a purified antidextran solution containing the entire population of antidextran antibodies. Evidence was also presented which indicated little or no change in the populations of antibody molecules produced in these two individuals for a period as long as 10 years following immunization. It is felt that these data offer substantial support for the hypothesis that the antidextran produced in a single individual consists of a heterogeneous population of antibody molecules with antibody-combining sites of various sizes.
Regression of Pituitary Prolactinoma With Bromocriptine Administration
Authors: Christos Velentzas
Journal: JAMA (1981)

IT HAS been demonstrated that treatment with bromocriptine mesylate can reduce the size of pituitary prolactinomas.<sup>1,2</sup>The actual mechanism by which this is achieved remains obscure, although bromocriptine has been shown to reduce the mitotic rate of the tumor in rats.<sup>3</sup>In man, bromocriptine, an ergot derivative and dopamine agonist, has a potent inhibitory action on prolactin secretion and, in patients with hyperprolactinemia, it lowers serum prolactin levels and restores gonadal function.<sup>1</sup> We treated a patient with a sizeable pituitary prolactinoma with bromocriptine alone. A remarkable reduction of the tumor size was achieved in addition to the reversal of the biochemical features. <h3>Report of a Case</h3> A 20-year-old man was referred to us for further investigation of hypogonadism and occasional diplopia, which occurred on his looking to the left. His medical history revealed that he had not yet reached puberty and libido was absent. Otherwise, his medical
Repetitive hyperpnoea causes peripheral airway obstruction and eosinophilia
Authors: M.S. Davis, A.N. Freed
Journal: European Respiratory Journal (1999)

Hyperpnoea of canine peripheral airways with dry air results in airway obstruction, mucosal damage, and inflammation. The purpose of this study was to evaluate the effect of repeated dry air challenge (DAC) on airway obstruction, reactivity and the development of airway inflammation in dogs. Canine peripheral airways received DAC (delivered under general anaesthesia through a bronchoscope) every 48 h for two weeks. Peripheral airway resistance and reactivity were measured prior to each DAC. After the final DAC, bronchoalveolar lavage fluid (BALF) cells and soluble mediators from challenged and control airways were measured. Repeated bronchoscopy had no effect on airway mechanics. Repeated DAC produced cumulative increases in peripheral airway resistance and peak obstructive response to DAC. The response to hypocapnia was also increased in airways receiving repeated DAC. However, when the response to agonists was expressed as a change from baseline, consistent significant increases were not observed. Repeated bronchoscopy produced insignificant changes in BALF cells and eicosanoid mediators. Repeated DAC produced marked eosinophilic inflammation and increased prostaglandins D2, E2, and F2alpha, as well as leukotrienes C4-E4. In conclusion, repeated dry air challenge in dogs in vivo causes persistent airway obstruction and inflammation not unlike that found in human asthma.
The liver in protoporphyria
Authors: Joseph R. Bloomer
Journal: Hepatology (1988)

In 1961, Magnus and coworkers (1) reported the case of a 35-year-old man who for 27 years had had intense itching and swelling of his skin after exposure to sunlight.Urinary excretion of porphyrins and porphyrin precursors was normal, but the red blood cells and stool contained increased amounts of protoporphyrin.The authors proposed the name erythropoietic protoporphyria for this "hitherto undescribed erythropoietic condition."tLancet is a widely distributed journal, and several gastroenterologists/hepatologists probably saw the title of the article.Some may have even read the summary, only to breathe a sigh of relief that this was not a type of porphyria which would enter into the differential diagnosis of obscure abdominal pain.Moreover, the liver was not the site of the metabolic disturbance, and the disorder would be classified as erythropoietic and not hepatic.Dark clouds soon began to appear on the horizon, however.In 1963, Porter and Lowe (2) reported a 6-yearold male with clinical and biochemical features of protoporphyria who also had hepatosplenomegaly and abnormal liver biochemistries.At the time of splenectomy, he was found to have a cirrhotic liver.Two years later, Cripps and Scheuer (3) described the histological findings in liver biopsy specimens from five patients with protoporphyria.Four of the biopsies showed focal deposits of pigment containing protoporphyrin, and portal fibrosis was present in two.The rain finally came in 1968, when Barnes and coworkers (4) described a 42year-old man with a long history of photosensitivity who developed jaundice and hepatomegaly, followed by a rapid downhill course and death (4).Postmortem examination indicated that the patient had protoporphyria. DESCRIPTION OF LIVER DISEASEThe incidence and prevalence of protoporphyria have not been precisely determined for any population group.It appears to be a relatively common type of porphyria, perhaps second only to porphyria cutanea tarda in frequency.It occurs in all racial groups and has no sex predominance.
Is it time for a new kind of hospital physician?
Authors: R. M. Temple, V. Kirthi, L. J. Patterson
Journal: BMJ (2012)

The changing demography requires current models of inpatient care to evolve 

Today’s consultant physician manages inpatients who are older and have more comorbidities and a greater complexity of acute illness than in the past. Since the inception of the NHS in 1948, life expectancy in the United Kingdom has increased by 18% and 16.7% for men and women, respectively.1 Half of those aged over 60 years have at least one chronic illness, and this proportion will increase over the next 20 years as the population aged over 85 doubles.2 These demographic shifts place increasing strain on a service that is required to deliver £20bn (€24bn; $32bn) of efficiency savings by 2014.

In a linked article (doi:10.1136/bmj.e652), Wachter and Bell describe the transformation of the organisation of hospital care in the United States and UK over the past 15 years.3 Although changes in US and UK hospital care have been shaped by the structure and culture of the respective healthcare systems, common drivers of change include increasing costs, a need to provide quality care, and restricted resident (US) and junior doctor (UK) hours. The result in both systems is strikingly similar; a new cadre of generalist physicians who are equipped to meet the complex acute care needs and changing demographics of patients newly admitted to hospital has emerged. …
Controversial immunologist faces court case
Authors: X. Bosch
Journal: BMJ (2002)

Spanish immunologist Antonio Arnaiz-Villena, the author of a paper on the genetic origins of Palestinians, has been suspended without pay from the Hospital Doce de Octubre in Madrid, where he heads the department of immunology and molecular biology, after being charged with embezzlement of funds.

Dr Arnaiz-Villena, president of Spain's National Commission of Immunology, was the author of a polemical paper on the genetic origins of Palestinians that was retracted and deleted from records last autumn. In it he said that some Palestinians lived in concentration camps.

The embezzlement charges refer to Dr Arnaiz's “purchase of products not used in his department's healthcare activities; purchase of hospital products used in healthcare activities but in quantities much greater than needed; falsification of statistical data apparently to justify purchases; …
Persistent Urogenital Membrane Sinus as a Clinical Entity
Authors: Robert E. L. Nesbitt
Journal: JAMA (1968)

Persistence of the urogenital membrane has been recently encountered in two young adult females who otherwise had normal external and internal genital development. The anomaly interfered with normal coital function, although not precluding a pregnancy. Since the entity can cause distressing clinical problems in the adult, there is need for early and periodic gynecological screening, beginning with the careful inspection of the external genitalia of all newborn infants.
Novel Molecular Signaling and Classification of Human Clinically Nonfunctional Pituitary Adenomas Identified by Gene Expression Profiling and Proteomic Analyses
Authors: Carlos S. Moreno, Chheng-Orn Evans, Xianquan Zhan, Mammerhi Okor, Dominic M. Desiderio, Nelson M. Oyesiku
Journal: Cancer Research (2005)

Abstract Pituitary adenomas comprise 10% of intracranial tumors and occur in about 20% of the population. They cause significant morbidity by compression of regional structures or the inappropriate expression of pituitary hormones. Their molecular pathogenesis is unclear, and the current classification of clinically nonfunctional tumors does not reflect any molecular distinctions between the subtypes. To further elucidate the molecular changes that contribute to the development of these tumors and reclassify them according to the molecular basis, we investigated 11 nonfunctional pituitary adenomas and eight normal pituitary glands, using 33 oligonucleotide GeneChip microarrays. We validated microarray results with the reverse transcription real-time quantitative PCR, using a larger number of nonfunctional adenomas. We also used proteomic analysis to examine protein expression in these nonfunctional adenomas. Microarray analysis identified significant increases in the expression of 115 genes and decreases in 169 genes, whereas proteomic analysis identified 21 up-regulated and 29 down-regulated proteins. We observed changes in expression of SFRP1, TLE2, PITX2, NOTCH3, and DLK1, suggesting that the developmental Wnt and Notch pathways are activated and important for the progression of nonfunctional pituitary adenomas. We further analyzed gene expression profiles of all nonfunctional pituitary subtypes to each other and identified genes that were affected uniquely in each subtype. These results show distinct gene and protein expression patterns in adenomas, provide new insight into the pathogenesis and molecular classification of nonfunctional pituitary adenomas, and suggest that therapeutic targeting of the Notch pathway could be effective for these tumors.