tbuckley/cabot-search huggingface dataset:
Pericytes in the microvasculature
Authors: K. K. Hirschi, P. A. D'Amore
Journal: Cardiovascular Research (1996)

Pericytes, also known as Rouget cells or mural cells, are associated abluminally with all vascular capillaries and post-capillary venules. Differences in pericyte morphology and distribution among vascular beds suggest tissue-specific functions. Based on their location and their complement of muscle cytoskeletal proteins, pericytes have been proposed to play a role in the regulation of blood flow. In vitro studies demonstrating the contractile ability of pericytes support this concept. Pericytes have also been suggested to be oligopotential and have been reported to differentiate into adipocytes, osteoblasts and phagocytes. The mechanisms involved in vessel formation have yet to be elucidated but observations indicate that the primordial endothelium can recruit undifferentiated mesenchymal cells and direct their differentiation into pericytes in microvessels, and smooth muscle cells in large vessels. Communication between endothelial cells and pericytes, or their precursors, may take many forms. Soluble factors such as platelet-derived growth factor and transforming growth factors-beta are likely to be involved. In addition, physical contact mediated by cell adhesion molecules, integrins and gap junctions appear to contribute to the control of vascular growth and function. Development of culture methods has allowed some functions of pericytes to be directly examined. Co-culture of pericytes with endothelial cells leads to the activation of transforming growth factor-beta, which in turn influences the growth and differentiation of the vascular cells. Finally, the pericyte has been implicated in the development of a variety of pathologies including hypertension, multiple sclerosis, diabetic microangiopathy and tumor vascularization.
Circulatory Adjustments to the Hypoxemia of Congenital Heart Disease of the Cyanotic Type
Authors: HOWARD B. BURCHELL, BOWEN E. TAYLOR, JULIAN R. B. KNUTSON, EARL H. WOOD
Journal: Circulation (1950)

In a limited number of subjects having hypoxemia related to congenital malformations of the heart, no evidence was obtained of a correlation between the degree of hypoxemia or the extent of the polycythemia and the systemic blood flow. The circulatory response to exercise was characterized by a greater increase in the arteriovenous oxygen difference than in the systemic blood flow. A syncopal reaction in one patient was preceded by a greatly increased systemic blood flow and a small arteriovenous oxygen difference.
Attenuation of virus-induced myocardial injury by inhibition of the angiotensin II type 1 receptor signal and decreased nuclear factor-kappa B activation in knockout mice
Authors: Kanjo Yamamoto, Tetsuo Shioi, Koji Uchiyama, Tadashi Miyamoto, Shigetake Sasayama, Akira Matsumori
Journal: Journal of the American College of Cardiology (2003)
A Lecture on Polymyositis: Delivered at the National Hospital for the Paralysed and Epileptic
Authors: W. R. Gowers
Journal: BMJ (1899)

GENTLEMEN,-I desire to direct your attention to-day Tare disease, which is important because it is malady and, though uncommon, has close ,others which are more common and more familiar.is disease that has been termed "polymyositis."It in the simultaneous inflammation of many of some nerves-an inflammation that is symmetrical distribution.I am not sure that it has yet obtained in English descriptive medical literature or in the teaching on which you chiefly depend for your knowledge; but the case I have to show you is an extremely well-marked example of the affection in a severe degree, and fore serve to impress on you its most features.Let me first remind you of some facts relating neuritis, with which this affection is closely allied, indeed, forms part of it; the nerves suffer in association the muscles, although, it would seem, less widely.all, no doubt, acquainted with multiple neuritis," tively new to our nomenclature, but doubtless, parison, old in undiscerned familiarity.Its causes been always with us, and their effects cannot absent.The names we apply are not entirely We call it"polyneuritis," "multiple neuritis," "peripheial neuritis."These terms, however, also cable to other affections.We meet with many nerves of quite different characterThe designation"peripheral neuritis" has also wise used, and it describes three features of inflammation nerves-the fact that the affection is chiefly localised peripheral extremities; the fact that it affects peripheral extremities of the limbs; and it has also ployed as a designation of affections of the nerve trunks distinction from central disease.No term which is the chief characteristic of the disease, symmetry.The motor nerves may be most conspicuously involved, or the sensory nerves may be primarily ,excited to spontaneous sensations or to hyperiesthesia-or they maybe impaired so as Io produce diminished:sensi- bility, but in all cases the symptoms are bilaterally sym- metrical.The symmetry is not always absolute; may be affected somewhat earlier, or in rather than the other; but the correspondence of the affection two sides, whether it be in the arms or legs, dominant feature.The two seldom present conspicuous ferences, either in the area involved or in the symptoms, and the correspondence is often precise.
Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida.
Authors: L J Guillette, T S Gross, G R Masson, J M Matter, H F Percival, A R Woodward
Journal: Environmental Health Perspectives (1994)

The reproductive development of alligators from a contaminated and a control lake in central Florida was examined. Lake Apopka is adjacent to an EPA Superfund site, listed due to an extensive spill of dicofol and DDT or its metabolites. These compounds can act as estrogens. Contaminants in the lake also have been derived from extensive agricultural activities around the lake that continue today and a sewage treatment facility associated with the city of Winter Garden, Florida. We examined the hypothesis that an estrogenic contaminant has caused the current failure in recruitment of alligators on Lake Apopka. Supporting data include the following: At 6 months of age, female alligators from Lake Apopka had plasma estradiol-17 beta concentrations almost two times greater than normal females from the control lake, Lake Woodruff. The Apopka females exhibited abnormal ovarian morphology with large numbers of polyovular follicles and polynuclear oocytes. Male juvenile alligators had significantly depressed plasma testosterone concentrations comparable to levels observed in normal Lake Woodruff females but more than three times lower than normal Lake Woodruff males. Additionally, males from Lake Apopka had poorly organized testes and abnormally small phalli. The differences between lakes and sexes in plasma hormone concentrations of juvenile alligators remain even after stimulation with luteinizing hormone. Our data suggest that the gonads of juveniles from Lake Apopka have been permanently modified in ovo, so that normal steroidogenesis is not possible, and thus normal sexual maturation is unlikely.
Public mental health: the time is ripe for translation of evidence into practice
Authors: Kristian Wahlbeck
Journal: World Psychiatry (2015)

Public mental health deals with mental health promotion, prevention of mental disorders and suicide, reducing mental health inequalities, and governance and organization of mental health service provision. The full impact of mental health is largely unrecognized within the public health sphere, despite the increasing burden of disease attributable to mental and behavioral disorders. Modern public mental health policies aim at improving psychosocial health by addressing determinants of mental health in all public policy areas. Stigmatization of mental disorders is a widespread phenomenon that constitutes a barrier for help-seeking and for the development of health care services, and is thus a core issue in public mental health actions. Lately, there has been heightened interest in the promotion of positive mental health and wellbeing. Effective programmes have been developed for promoting mental health in everyday settings such as families, schools and workplaces. New evidence indicates that many mental disorders and suicides are preventable by public mental health interventions. Available evidence favours the population approach over high-risk approaches. Public mental health emphasizes the role of primary care in the provision of mental health services to the population. The convincing evidence base for population-based mental health interventions asks for actions for putting evidence into practice.
Plasma Cell Granuloma Or Myeloma
Authors: Sheldon F. Markel
Journal: JAMA (1972)

To the Editor.—  In the X-RAY SEMINAR case, Osteoblastic Lesions of Unusual Nature (219:377, 1972) several findings cast some doubt on the diagnosis of multiple myeloma, osteosclerotic variant. The presence of multiple, discrete, purely osteosclerotic lesions, absence of dysproteinemia despite extensive disease, and the histopathologic finding of a mixture of plasma cells and lymphoid elements which Vickery noted as being an atypical picture for multiple myeloma seem to point to another diagnosis—plasma cell granuloma.1,2  There are few unequivocal cases of untreated myeloma with sclerotic bone lesions, unless complicated by fracture or amyloidosis. The histological features of plasma cell granuloma are the infiltrates of uniformly mature plasma cells with occasional Russell bodies; intermingling of other chronically inflammatory cells, mainly lymphocytes, which tend to occur in aggregates and may be missed in small biopsy specimens; and a background of fibrous tissue. Plasma cell granuloma will not recur if completely excised,
Can Glargine Reduce the Number of Lung Infections in Patients With Cystic Fibrosis–Related Diabetes?
Authors: Adriana Franzese, Maria Immacolata Spagnuolo, Angela Sepe, Giuliana Valerio, Enza Mozzillo, Valeria Raia
Journal: Diabetes Care (2005)

Incidence and prevalence of cystic fibrosis–related diabetes (CFRD) are rapidly increasing in recent years, according to the gradual increase in median survival age, which is now around 30 years (1). CFRD, with or without fasting hyperglycemia, may be chronic or intermittent, the latter in physically stressed patients. It is possible that the prediabetic state may have adverse effects on clinical status, nutrition, and lung function in patients with cystic fibrosis (2). As a matter of fact, impairment of lung function seems to appear up to 2–4 years before the clinical onset of diabetes. Insulin therapy was able to improve lung function in CFRD patients (3). Glargine is a recent long-acting insulin analog, which is …
Oncoprotein hides tumor
Authors: Kendall Powell
Journal: The Journal of Experimental Medicine (2005)

An oncogenic fusion protein hijacks a transcription factor, and uses it to help its tumor avoid immune detection, according to a study by Nabarro and colleagues on page 1399. This is the first description of an oncoprotein that can both transform cells and shut down the immune response.The protein, PAX3-FKHR, results from a reciprocal chromosomal translocation in a rare form of a childhood muscle cancer, alveolar rhabdomyosarcoma (ARMS). Through the combined action of the PAX3 DNA-binding domain and the FKHR transcriptional activation domain, the oncoprotein binds and strongly activates PAX3 target genes such as IGF2. This activity confers rapid and invasive tumor growth.






Figure 

PAX3-FKHR induction (top) turns on STAT3 and helps tumors to hide.




Now, this group finds that expression of PAX3-FKHR also significantly dampens immune activation, in part by reducing surface levels of class I MHC on transfected cells. A microarray screen revealed that expression of the fusion protein repressed numerous genes, 40% of which are known targets of STAT1 and/or STAT3, including class I MHC and the cytokine IL-10. Recent studies have shown that overactive STAT3 contributes to tumor immune evasion by stifling inflammation and preventing crosstalk between innate and adaptive immune systems.

STAT3 also acts as a transcriptional coactivator with FKHR. The group now show that PAX3-FKHR also binds to STAT3, but not to STATs 2,4, and 6. Media from cells expressing the fusion protein contained at least one inhibitory cytokine, IL-10, and prevented dendritic cell (DC) activation. Mouse xenografts expressing PAX3-FKHR had decreased inflammatory responses because the numbers of both activated DCs and infiltrating neutrophils and macrophages were reduced.

This inhibition of DC activation and immune cell recruitment might help the tumor establish an immunoinhibitory environment in which to hide. Determining which target genes help the PAX3-FKHRSTAT3 complex to create this environment will require further experiments.
Oxygen Consumption in Infants and Children during Cardiac Catheterization under Different Sedation Regimens
Authors: DAVID E. FIXLER, TED CARRELL, RICHARD BROWNE, KATHRYN WILLIS, WILLIAM W. MILLER
Journal: Circulation (1974)

We measured oxygen consumption in 426 infants and children during cardiac catheterization using an open circuit, flow-through technique. Since this method does not require the cooperation of the patient, determinations were readily made in 170 infants. The purpose of this study was to determine those factors which significantly influence oxygen consumption and to determine the potential errors incurred in using predictive equations for estimating oxygen consumption. The type of sedation or anesthesia given was found to be one of the most important variables influencing oxygen consumption; therefore patients were classified into five anesthetic groups. Stepwise regression analysis revealed that each group had a distinctive set of hemodynamic or physical factors which significantly affected oxygen consumption; hence each group required a different predictive equation. Body size in terms of surface area or weight was the only significant variable common to all five patient groups. Using the predictive equations the estimated values differed from measured values by more than 20 percent in approximately one-fifth of the cases. These data indicate that frequently oxygen consumption cannot be accurately estimated from predictive equations. Therefore if blood flow is to be accurately determined by the Fick method in infants and children, oxygen consumption should be measured during the catheterization procedure.
Is the NHS guilty of ageism by not giving free personal care for some older people in England?
Authors: P. V Knight
Journal: BMJ (2001)

professionals, to replace the current inefficient and fragmented records systems.Milestones for implementation of the falls standard are longer than those for some other parts of the framework as evidence is emerging about how best to organise this key component of services.Achieving organised services for the prevention and management of falls will be a great advance in the care of older people.An inclusive approach was used throughout the development of the national service framework.The success of the approach is one reason why the framework has been so well received; it provides a historic opportunity for transforming health and social care for older people in England.
Review: Teriparatide reduces fractures in postmenopausal women with osteoporosis
Authors: Bruce E. Johnson
Journal: Annals of Internal Medicine (2012)

Source Citation Han SL, Wan SL. Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials. Int J Clin Pract. 2012;66:199-209. 22257045
THE EFFECT OF ANTIHISTAMINIC DRUGS ON CONVULSIVE SEIZURES
Authors: JOHN A. CHURCHILL
Journal: JAMA (1949)

Certain antihistaminic drugs are analeptics and produce convulsions in animals. Although the dose required is about a hundred times that used clinically,<sup>1</sup>1 case is on record in which fits were produced.<sup>2</sup>In a study of the effect of several antihistaminic agents on epileptic seizures, we have found that attacks could be evoked in some persons by doses even smaller than those generally used clinically. This observation deserves the consideration of physicians who are prescribing these drugs. The study was undertaken to see if the common action of myanesin®<sup>3</sup>(3-ortho-toloxy-1,2-propanediol), and diphenhydramine (benadryl®)<sup>4</sup>on parkinsonian tremor also applied to an action on convulsive manifestations. We had observed<sup>5</sup>from electroencephalographic records that the first drug abolished petit mal discharges but increased the discharges from focal lesions of the cerebral cortex. A similar study was therefore made of the action of diphenhydramine and tripelennamine (pyribenzamine®) on seizure
Tarun Kumar Mehrotra
Authors: I Tiwari
Journal: BMJ (2004)

General practitioner Chelmsford, Essex (b Bihar, India, 1936; q Darbhanga 1962; MS), died from a brain tumour on 19 November 2003.​2003.




Figure 1




After training in general surgery in India, Tarun Mehrotra moved to the United Kingdom in 1969. He worked as a senior house officer and surgical registrar in several UK hospitals, but decided to become a general practitioner in 1980. He established a singlehanded practice at Chelmsford in 1983. Because of his illness, he was not able to work for a year. He leaves a wife, Saroj; two children; and a grandson.
Abstract 2320: Oncogenic K-ras and loss of Smad4 mediate invasion by activating a NF-kappaB/EGFR axis that induces expression of MMP9/uPA in human pancreas progenitor cells.
Authors: Alakesh Bera, Shujie Zhao, Lin Cao, James W. Freeman
Journal: Cancer Research (2013)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an extremely fatal and highly metastatic in nature. Several pathways and mutations contribute to the development and pathogenesis of PDAC. Activating K-ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of PDAC. To further study the role of these two mutations in the pathogenesis of PDAC, immortalized human pancreas nestin postive cells (HPNE) were genetically modified by expressing oncogenic K-ras (GD12) and /or by shRNA knock down of Smad4. Present studies show that these two mutations caused increase in expression of EGFR and erbB2 growth factor receptors and increased expression and nuclear translocation of NF-κB. The increase in EGFR expression and nuclear translocation of NF-κB was associated with development of an invasive phenotype as measured by matrigel assays. Our data also demonstrated that MMP9 and uPA were substantially up regulated in HPNE cells that express K-ras or along with loss of Smad4 activities. MMP-9 and uPA are two extracellular matrix (ECM)-degrading proteinases known to play important roles in driving invasion and metastasis. Zymography studies confirm the expression and enzymatic activities of uPA and MMP-9 in the progenitor cells. The mechanism underlying this uPA/MMP9 induction is linked with NF-κB activation. Immuno-fluorescence, Western blot and chromatin immuno-precipitation (ChIP) analysis confirm the nuclear translocation of NF-κB RelA (p65) sub-unit, by induction of K-ras. Following signaling cascade, EGFR activated by the K-ras mediated NF-κB nuclear localization and further activation induced by loss of Smad4. Our results also suggest that the EGFR pathway as a critical mediator connecting Ras to NF-κB in proteolytic enzyme secretion as well as cancer invasion. In conclusion, the present study reveals a new insight in pancreatic progenitor cell invasion which includes signal transduction of K-ras activity and Smad4 inactivation in regulation of NF-κB/EGFR axis to induce expression of uPA and MMP9. Therefore, induction of K-ras and loss of Smad4 could play important roles in PDAC invasion through NF-κB/EGFR activation and subsequent induced expression of MMP9 and uPA, and might be suitable molecular candidates for the development of new therapeutic strategies for pancreatic cancer. Citation Format: Alakesh Bera, Shujie Zhao, Lin Cao, James W. Freeman. Oncogenic K-ras and loss of Smad4 mediate invasion by activating a NF-kappaB/EGFR axis that induces expression of MMP9/uPA in human pancreas progenitor 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 2320. doi:10.1158/1538-7445.AM2013-2320
A NEW BONE CUTTING FORCEPS.
Authors: ALLEN DEVILBISS
Journal: JAMA (1896)

When operating on the skull, after the first opening is made, if with a trephine, it need not be more than ⅜ of an inch in diameter to admit the lower jaw of the forceps. A slot ⅛ of an inch wide, and as long as necessary, can be cut out, and its direction changed so as to follow the line of fracture, or cut out a piece of any size or shape. Three sides of a small or large piece, leaving the tissue attached, may be cut, breaking back the portion left, thus making a trap-door operation of a piece so small that we would be compelled to cut away with any other forceps now used. The jaws move parallel with each other. The lower one is small enough to enter the opening in the upper one, carrying the piece cut off out, and leaving the edge smooth and
A longer view
Authors: C. Douglas
Journal: BMJ (1997)

From the water's edge to the first ridge a densely forested slope averages one in three. There is no path, only an irregular open strip a few metres across and shoulder deep with clinging fern like vegetation. The air is still: moist and oppressively hot. Flies in their black thousands swarm and buzz, too multitudinous to swipe away. Under a searing sun we plod on.

Onwards and upwards, one step at a time. Suddenly, discomfort turns to something worse. In a little clearing a couple of paces ahead a poisonous snake almost a metre long is coiled, tawny and zigzagged, its small bright eyes …