tbuckley/cabot-search huggingface dataset:
Peri-Arthritis of the Shoulder: Studies of Vegetative Function
Authors: E. B. Hansen
Journal: Annals of the Rheumatic Diseases (1952)

Definition.-A diagnosis of peri-arthritis of the shoulder is made when a patient exhibits pain in the region of the shoulder and limited mobility of the joint, apparently of spontaneous onset or following slight injury.The x-ray appearances may show either nothing abnormal or calcific deposits in the capsule or periarticular tissue.This syndrome is not a disease sui generis, since the underlying pathological changes may no doubt affect either ,the joint capsule or the peri-articular tissue.Peri-arthritis of the shoulder, therefore, is a collective term for a number of different lesions of the shoulder, the only common features being pain and limitation of movement in the shoulder joint.A common term may be used for the time being because the clinical features, regardless of the site ofthe morbid changes, which can hardly be determined without biopsy, are more or less uniform.Previous Suggestions regarding the Causes of Peri-Arthritis of the Shoulder Since Duplay (1872) described the syndrome as humeroscapular peri-arthritis, a number of papers have dealt with this lesion.Nevertheless, the actual cause or causes of the disease are obscure, as it is not yet definitely known why the morbid changes arise.The methods used to elucidate these matters comprise (a) direct studies of the shoulder joint and peri-articular tissue at operation, by microscopical examination of biopsy specimens, and (b) clinical studies.In the latter connection it is most interesting to report the papers dealing with the common occurrence of peri-arthritis of the shoulder as a complication of certain other diseases with a constancy which makes it reasonable to presume a pathogenetic relationship.(a) Biopsy Studies.-Neviaser(1945), studying biopsy specimens, found inflammatory changes in the subacromial bursa in seven out of ten cases, tenosynovitis in the long head of the biceps in ten cases, and the capsule adherent to the humeral head in all cases.Microscopical examination of the capsule failed to reveal any definite morbid changes in the synovial cells, but practically all cases exhibited chronic inflammation in the sub- synovial layers, characterized by fibrotic and degenerative processes in the connective tissue and in a few cases by calcification.Culture of the bacteria was negative.Owing to the constant capsular changes, Neviaser interpreted the lesion not as peri-arthritis, but as a thickening and contraction of the capsule which became adherent to the head of the humerus; he therefore suggested the term adhesive capsulitis.
Physical conditioning and membrane receptors for cardioregulatory hormones
Authors: R S. WILLIAMS
Journal: Cardiovascular Research (1980)

To seek possible mechanisms for the relative bradycardia induced by physical conditioning we studied the effects of an eight-week swimming programme upon cardiac beta-adrenergic and muscarinic-cholinergic receptors in rats. A training effect was documented by an increase in the ratio of heart wet weight to body weight in the conditioned animals compared with sedentary controls. Cardiac beta-adrenergic receptors as assessed in crude membrane fractions by the binding of (-) (3H) dihydroalprenolol did not differ significantly in either number or affinity in conditioned hearts (30 +/- 2 fmol.mg-1 protein; KD = 1.4 +/- 0.1 nmol.litre-1) compared with sedentary hearts (33 +/- 2 fmol.mg-1; KD = 1.5 +/- 2 nmol.litre-1). Likewise cardiac muscarinic-cholinergic receptors as assessed by the binding of (3H) quinuclidinyl benzilate to crude cardiac membranes did not differ significantly in either number or affinity in conditioned hearts (116 +/- 6 fmol.mg-1 protein; KD = 0.17 +/- 0.03 nmol.litre-1) compared with sedentary hearts (125 +/- 11 fmol.mg-1; KD = 0.19 +/- 0.03 nmol.litre-1). We conclude that the bradycardia of physical training is probably mediated by mechanisms other than alterations in cardiac beta-adrenergic or muscarinic-cholinergic receptors.
Variants in the hepatocyte nuclear factor-1alpha and -4alpha genes in Finnish and Chinese subjects with late-onset type 2 diabetes.
Authors: J Rissanen, H Wang, R Miettinen, P Kärkkäinen, P Kekäläinen, L Mykkänen, J Kuusisto, P Karhapää, L Niskanen, M Uusitupa, M Laakso
Journal: Diabetes Care (2000)

OBJECTIVE: To determine the role of the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in the etiology of late-onset type 2 diabetes in Finnish and Chinese subjects. RESEARCH DESIGN AND METHODS: The whole coding regions of the genes encoding for HNF-1alpha and HNF-4alpha, including approximately 800 bp of the HNF-1alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptide 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-strand conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism analysis in additional samples of 100 Finnish diabetic patients and 82 Finnish control subjects and in 58 Chinese diabetic patients and 51 Chinese control subjects. RESULTS: No previously reported gene defects were detected, but one novel functionally silent GCC--&amp;gt;GCG variant (nucleotide 73, exon 10) was observed in the HNF-4alpha gene in a Chinese diabetic patient. Interestingly, the Ala98Val substitution of the HNF-1alpha gene occurred at a significantly higher frequency in 140 Finnish diabetic patients compared with 82 control subjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucose tolerance tests in subjects with normal (n = 295) or impaired (n = 38) glucose tolerance. CONCLUSIONS: Variants in the HNF-1alpha and HNF-4alpha genes are unlikely to play a major role in the pathogenesis of late-onset type 2 diabetes in Finnish and Chinese subjects. However, the association of the Ala98Val variant of the HNF-1alpha gene with type 2 diabetes in Finnish subjects may indicate a diabetogenic locus close to the HNF-1alpha gene.
Pulmonary hypertension and fenfluramine.
Authors: M S Wheeley
Journal: BMJ (1981)

oedema, many factors make it unreliable, such as diffcrences in body position, levcl of inspiration, tube-to-object distancc, current and voltage, and the existence of prior lung disease.Furthermore, we have noticcd that the x-ray appearances may lag behind the clinical state of the patient, as judged by respiratory function, by as much as 36 hours during both the development and the resolution of pulmonary oedema.A more accurate diagnosis may be made by using lung functions such as the alvcolar-to-arterial oxygen-tension gradient or the shunt fraction, which would bc easy to measurc wvith a pulmonary artcry catheter in place.
The Role of Antibodies in HIV Vaccines
Authors: John R. Mascola, David C. Montefiori
Journal: Annual Review of Immunology (2010)

Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of host cells or that limit early events of viral dissemination. Such antibodies must target the surface envelope glycoproteins of HIV-1, which are highly variable in sequence and structure. The first subunit vaccines to enter clinical trails were safe and immunogenic but unable to elicit antibodies that neutralized most circulating strains of HIV-1. However, potent virus neutralizing antibodies (NAbs) can develop during the course of HIV-1 infection, and this is the type of antibody response that researchers seek to generate with a vaccine. Thus, current vaccine design efforts have focused on a more detailed understanding of these broadly neutralizing antibodies and their epitopes to inform the design of improved vaccines.
Phosphodiesterase 1A Modulates Cystogenesis in Zebrafish
Authors: Caroline R. Sussman, Christopher J. Ward, Amanda C. Leightner, Jordan L. Smith, Reema Agarwal, Peter C. Harris, Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2014)

Substantial evidence indicates the importance of elevated cAMP in polycystic kidney disease (PKD). Accumulation of cAMP in cystic tissues may be, in part, caused by enhanced adenylyl cyclase activity, but inhibition of cAMP degradation by phosphodiesterases (PDE) likely has an important role, because cAMP is inactivated much faster than it is synthesized. PDE1 is the only PDE family activated by Ca(2+), which is reduced in PKD cells. To assess the contribution of the PDE1A subfamily to renal cyst formation, we examined the expression and function of PDE1A in zebrafish. We identified two splice isoforms with alternative starts corresponding to human PDE1A1 and PDE1A4. Expression of the two isoforms varied in embryos and adult tissues, and both isoforms hydrolyzed cAMP with Ca(2+)/calmodulin dependence. Depletion of PDE1A in zebrafish embryos using splice- and translation-blocking morpholinos (MOs) caused pronephric cysts, hydrocephalus, and body curvature. Human PDE1A RNA and the PKA inhibitors, H89 and Rp-cAMPS, partially rescued phenotypes of pde1a morphants. Additionally, MO depletion of PDE1A aggravated phenotypes in pkd2 morphants, causing more severe body curvature, and human PDE1A RNA partially rescued pkd2 morphant phenotypes, pronephric cysts, hydrocephalus, and body curvature. Together, these data indicate the integral role of PDE1A and cAMP signaling in renal development and cystogenesis, imply that PDE1A activity is altered downstream of polycystin-2, and suggest that PDE1A is a viable drug target for PKD.
Experiences of hospital care and treatment seeking for pain from sickle cell disease: qualitative study
Authors: K. Maxwell, A. Streetly, D. Bevan
Journal: BMJ (1999)

To investigate how sociocultural factors influence the management of pain from sickle cell disease by comparing the experiences of those who usually manage their pain at home with the experiences of those who are more frequently admitted to hospital for management of their pain.Qualitative analysis of semistructured individual interviews and focus group discussions.57 participants with genotype SS or S/beta-thal (44 participants) or SC (9 participants); the status of 4 participants was unknown. 40 participants took part in focus groups, 6 took part in both focus groups and interviews, and 9 were interviewed only. Participants were allocated to focus groups according to ethnic origin, sex, and the number of times that they had been admitted to the hospital for the management of painful crises during the previous year.The relation between patients with sickle cell disease and hospital services is one of several major, nonclinical dimensions that shape experiences of pain management and behavior for seeking health care. Participants' experiences of hospital care show a range of interrelated themes that are common to most participants across variables of sex, ethnicity, and which hospital was attended. Themes identified included the mistrust of patients with sickle cell disease, stigmatization, excessive control (including both overtreatment and undertreatment of pain) and neglect. Individuals responded to the challenge of negotiating care with various strategies. Patients with sickle cell disease who are frequently admitted to hospital may try to develop long-term relationships with their caregivers, become passive or aggressive in their interactions with health professionals, or regularly attend different hospitals. Those who usually manage their pain at home expressed a strong sense of responsibility for the management of their pain and advocated self-education, assertiveness, and resistance as strategies toward hospital services.The organization and delivery of management for the pain of a sickle cell crisis discourages self-reliance and encourages hospital dependence. Models of care should recognize the chronic nature of sickle cell disorders and give priority to patients' involvement in their care.
Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the Agricultural Heath Study
Authors: Leslie K. Dennis, Charles F. Lynch, Dale P. Sandler, Michael C.R. Alavanja
Journal: Environmental Health Perspectives (2010)

Melanoma rates continue to increase; however, few risk factors other than sun sensitivity and ultraviolet radiation (including sun exposure) have been identified. Although studies of farmers have shown an excess risk of melanoma and other skin cancers, it is unclear how much of this is related to sun exposure compared with other agricultural exposures.
Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity
Authors: Rebecca A. Stockton, Robert Shenkar, Issam A. Awad, Mark H. Ginsberg
Journal: The Journal of Experimental Medicine (2010)

Endothelial cell–cell junctions regulate vascular permeability, vasculogenesis, and angiogenesis. Familial cerebral cavernous malformations (CCMs) in humans result from mutations of CCM2 (malcavernin, OSM, MGC4607), PDCD10 (CCM3), or KRIT1 (CCM1), a Rap1 effector which stabilizes endothelial cell–cell junctions. Homozygous loss of KRIT1 or CCM2 produces lethal vascular phenotypes in mice and zebrafish. We report that the physical interaction of KRIT1 and CCM2 proteins is required for endothelial cell–cell junctional localization, and lack of either protein destabilizes barrier function by sustaining activity of RhoA and its effector Rho kinase (ROCK). Protein haploinsufficient Krit1+/− or Ccm2+/− mouse endothelial cells manifested increased monolayer permeability in vitro, and both Krit1+/− and Ccm2+/− mice exhibited increased vascular leak in vivo, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1–CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak.
Breast Cancer Adjuvant Therapy: Time to Consider Its Time-Dependent Effects
Authors: Ismail Jatoi, William F. Anderson, Jong-Hyeon Jeong, Carol K. Redmond
Journal: Journal of Clinical Oncology (2011)

Breast cancer is a chronic and heterogeneous disease that may recur many years after initial diagnosis and treatment.1 This has important implications for the practicing oncologist. For instance, an early effect of adjuvant treatment may diminish over time after cessation of therapy, or, alternatively, there may exist a lag time before some treatment effects become pronounced. Indeed, the risk of breast cancer recurrence and death (hazard rate) varies over time (ie, is nonproportional) according to prognostic and predictive factors (Figs 1 and ​and2;2; Table 1).6,13 The hazard curve for breast cancer death peaks between 2 and 3 years after initial diagnosis and then declines sharply, suggesting that the biologic mechanisms responsible for early and late cancer-specific events are fundamentally different. Thus the early and late effects of adjuvant therapy may vary accordingly.
Role of Apolipoprotein E-containing Lipoproteins in Abetalipoproteinemia
Authors: Conrad B. Blum, Richard J. Deckelbaum, Larry D. Witte, Alan R. Tall, Joseph Cornicelli
Journal: Journal of Clinical Investigation (1982)

Detailed studies of apolipoprotein E (apoE)-containing lipoproteins in abetalipoproteinemia have been performed in an attempt to resolve the apparent paradox of a suppressed low density lipoprotein (LDL) receptor pathway in the absence of apoB-containing lipoproteins. It was hypothesized that apoE-containing high density lipoproteins (HDL) in abetalipoproteinemia might functionally substitute for LDL in regulation of cholesterol metabolism in these patients.
Five Years of Tamoxifen--or More?
Authors: R. Peto
Journal: JNCI Journal of the National Cancer Institute (1996)

within the ovaries of women at increased risk of developing ovarian cancer and the ovaries of women without increased risk. It is quite likely that the biologic mechanisms of the development of ovarian cancer in sporadic cases is similar to the mechanisms of development in women with genetic predisposition to develop the disease. The elucidation of these biologic mechanisms will allow rational approaches to the diagnosis, treatment, and, most important, prevention of this deadly disease.
THE ETIOLOGY OF INFECTIOUS DIARRHEA (WINTER SCOURS) IN CATTLE
Authors: F. S. Jones, Ralph B. Little
Journal: The Journal of Experimental Medicine (1931)

A disease of cows manifested by severe diarrhea has been described. The condition is characterized by the frequent passage of dark brown or black feces, often containing mucus and blood. The principal lesions are catarrhal inflammation of the small intestine and liver degeneration. By feeding feces from spontaneous cases to calves a similar but milder disease characterized by the same type of enteritis was produced. Vibrios were cultivated from the inflamed intestinal tract of such experimentally induced cases. Pure cultures of the vibrios when fed to other calves, in certain instances, produced diarrhea and a well marked enteritis similar to that observed in both the spontaneous disease and in calves following the feeding of feces from naturally affected cows. Vibrios were recovered from the inflamed small intestine of three out of four animals fed such cultures.
The Value of Experimental Evidence in the Diagnosis of Diseases of the Cerebellum
Authors: J. S. R. Russell
Journal: BMJ (1895)

1MCAL JNAL 1079 two conditions well known and referred to in all standard works as signs of great significance-namely, certain disturb- ances of breathing, especially the peculiar form of breathing known as Chfyne-Stokes respiration, and a rapid rise of tem- perature.Disturbances of respiration in cases of apoplexy are, I have no doubt, of grave omen.So long as the respira- tion remains regular, however noisy and stertorous it may be, other things not being unfavourable, I believe the patient may recover, but when irregular breathing sets in, and above all when undoubted Cheyne-Stokes respiration is present, the patient is, 1 believe, in the greatest danger. 1 am speak' ing of course of Cheyne-Stokes respiration along with in- sensibility; without insensibility it has no serious meaning at the moment.A certain, always moderate, amount of pyrexia occurs in many cases of cerebral haemorrhage after the initial depres- sion due to shock has passed away, but a temperature rapidly rising to 1040, 1060, or even 1080 is of absolutely fatal sig- nificance.Hyperpyrexia is not, I believe, of any great value in showing the locality and extent of the lesion; it indicates probably an extension to, or involvement of, the basal ganglia and pons, and so probably means an invasion of the ventricles.There are then, as I have tried to show, in my opinion at least, three important prognostic indications to be looked for in any given case of apoplexy due to haemorrhage into the substance of the hemisphere-namely, 1. Renal disease.2. Cheyne-stokes respiration.3. Hyperpyrexia.By far the most important of these is renal disease.If, in conclusion, I may state my opinion in the form of a rule for prognosis, I would say this.In any case of apoplexy due to haeruorrhage into the hemisphere, if renal disease, Cheyne-Stokes respiration, or hyperpyrexia, any one, two, or all three be present, the patient will in all probability not recover.If no one of these is present, and does not make its appearance, he may, and probably will, recover, however long insensibility may last and however deep it may be.The presence of other serious conditions, such as diabetes, chronic alcoholism, typhoid fever, idiopathic anaemia, will, I have no doubt-for I have seen examples to this effeet-exert just as fatal an influence as renal disease upon the course of sanguineous apoplexy.
CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases
Authors: Jinxiang Xi, JongWon Kim, Xiuhua A. Si, Richard A. Corley, Senthil Kabilan, Shengyu Wang
Journal: Theranostics (2015)

Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.
Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study
Authors: Howard H Feldman, Steven Ferris, Bengt Winblad, Nikolaos Sfikas, Linda Mancione, Yunsheng He, Sibel Tekin, Alistair Burns, Jeffrey Cummings, Teodoro del Ser, Domenico Inzitari, Jean-Marc Orgogozo, Heinrich Sauer, Philip Scheltens, Elio Scarpini, Nathan Herrmann, Martin Farlow, Steven Potkin, H Cecil Charles, Nick C Fox, Roger Lane
Journal: The Lancet Neurology (2007)
Mutational escape from CD8+ T cell immunity
Authors: David G. Bowen, Christopher M. Walker
Journal: The Journal of Experimental Medicine (2005)

The mechanisms by which the hepatitis C virus (HCV) establishes persistence are not yet fully understood. Previous chimpanzee and now human studies suggest that mutations within MHC class I–restricted HCV epitopes might contribute to viral escape from cytotoxic T lymphocyte (CTL) responses. However, there are several outstanding questions regarding the role of escape mutations in viral persistence and their fate in the absence of immune selection pressure.