tbuckley/cabot-search huggingface dataset:
A further physiological role for naturally occurring trypsin inhibitors: the evidence for a trophic stimulant of the pancreatic acinar cell
Authors: R. N. Melmed, I. A. D. Bouchier
Journal: Gut (1969)

The oral ingestion of naturally occurring purified trypsin inhibitors from soybean, ovomucoid, and bovine pancreas has been demonstrated to be a potent stimulus to pancreatic digestive enzyme synthesis.This effect may be so marked as to lead to impairment of growth in the rat and chicken through the faecal loss of essential amino acids.This is thought to be due to the markedly potentiated secretion of pancreatic digestive enzyme protein overwhelming the normal digestive capacity of the gastrointestinal tract and resulting in a pancreatogenous protein-losing enteropathy.Experimental evidence is presented to suggest that this response to the trypsin inhibitors requires the mediation of the gastrointestinal tract and is independent of vagal innervation to the pancreas.The most satisfactory hypothesis would favour the release of a trophic stimulus from the intestinal mucosa (possibly pancreozymin-cholecystokinin) to the acinar cell of the pancreas in response to the presence of the trypsin inhibitor in the bowel lumen.It is suggested that a primary function of the endogenously secreted pancreatic trypsin inhibitor may be to potentiate enzyme synthesis by the acinar cell, providing an important stimulus for the repletion of the digestive enzymes.Some of the potential physiological and clinical implications of such a mechanism are discussed.In 1917 Osbourne and Mendel observed that the poor nutritive value of raw soybean meal could be improved by heating.The discovery of a heat-labile trypsin inhibitor in raw soybean (Ham and Sanstedt, 1944; Bowman, 1944) was incriminated as the cause of the poor growth in rats fed on raw soybean meal through interfering with normal intestinal tryptic activity (Riesen, Clandinin, Elvehjem, and Cravens, 1947; Melnick, Oser, and Weiss, 1946).This hypothesis was supported by the observation of an increased faecal nitrogen excretion after feeding raw soybeans.However, that inhibition of proteolysis per se could not adequately account for these obser- vations was shown by Klose, Hill, Greaves, and Fevold (1948) and Westfall, Bosshardt, and Barnes (1948) who demonstrated inhibition of growth in animals fed trypsin inhibitor with predigested protein.
The Coordinated Action of CC Chemokines in the Lung Orchestrates Allergic Inflammation and Airway Hyperresponsiveness
Authors: Jose-Angel Gonzalo, Clare M. Lloyd, Danyi Wen, Juan P. Albar, Timothy N.C. Wells, Amanda Proudfoot, C. Martinez-A, Martin Dorf, Torbjörn Bjerke, Anthony J. Coyle, Jose-Carlos Gutierrez-Ramos
Journal: The Journal of Experimental Medicine (1998)

The complex pathophysiology of lung allergic inflammation and bronchial hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated accumulation and activation of different leukocyte subsets in the lung. The development and maintenance of these processes correlate with the coordinated production of chemokines. Here, we have assessed the role that different chemokines play in lung allergic inflammation and BHR by blocking their activities in vivo. Our results show that blockage of each one of these chemokines reduces both lung leukocyte infiltration and BHR in a substantially different way. Thus, eotaxin neutralization reduces specifically BHR and lung eosinophilia transiently after each antigen exposure. Monocyte chemoattractant protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of inflammatory leukocytes in the airways, but rather by altering the trafficking of the eosinophils and other leukocytes through the lung interstitium. Neutralization of RANTES (regulated upon activation, normal T cell expressed and secreted) receptor(s) with a receptor antagonist decreases significantly lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and RANTES. In contrast, neutralization of one of the ligands for RANTES receptors, macrophage-inflammatory protein 1α, reduces only slightly lung eosinophilia and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and inflammation, and this correlates with a pronounced decrease in monocyte- and lymphocyte-derived inflammatory mediators. These results suggest that different chemokines activate different cellular and molecular pathways that in a coordinated fashion contribute to the complex pathophysiology of asthma, and that their individual blockage results in intervention at different levels of these processes.
The Activity of Zoledronic Acid on Neuroblastoma Bone Metastasis Involves Inhibition of Osteoclasts and Tumor Cell Survival and Proliferation
Authors: Hongjun Peng, Yasuyoshi Sohara, Rex A. Moats, Marvin D. Nelson, Susan G. Groshen, Wei Ye, C. Patrick Reynolds, Yves A. DeClerck
Journal: Cancer Research (2007)

Metastasis to the bone is seen in 56% of patients with neuroblastoma and contributes to morbidity and mortality. Using a murine model of bone invasion, we have reported previously that neuroblastoma cells invade the bone by activating osteoclasts. Here, we investigated the antitumoral and antiosteolytic activities of zoledronic acid, a bisphosphonate inhibitor of osteoclasts, in combination with cytotoxic chemotherapy in our model. We first show that zoledronic acid given at the same time (early prevention) or 2 weeks after tumor cell injection (late prevention) significantly prevented the formation of severe osteolytic lesions. It also prevented formation of these lesions when given 4 weeks after tumor cell injection (intervention) when combined with chemotherapy including cyclophosphamide and topotecan. The combination of zoledronic acid + cyclophosphamide/topotecan also significantly improved survival (P < 0.001). In mice treated with zoledronic acid, we observed a marked inhibition of osteoclasts inside the bone associated with a decrease in tumor cell proliferation and increase in tumor cell apoptosis. In vitro, zoledronic acid inhibited neuroblastoma cell proliferation and induced apoptosis, and these effects were significantly enhanced by the addition of 4-hydroxyperoxycyclophosphamide (4-HC). The proapoptotic effect of zoledronic acid and zoledronic acid in combination with 4-HC on tumor cells was associated with an increase in caspase-3 activity and a decrease in phosphorylated Bcl-2, Bcl-2, and Bcl-X(L) expression. Zoledronic acid inhibited the association of Ras with the plasma membrane and activation of c-Raf, Akt, and extracellular signal-regulated kinase 1/2. The data indicate that zoledronic acid, in addition to inhibiting osteoclasts, is active against tumor cells and suggest that zoledronic acid in combination with cytotoxic chemotherapy may be effective in children with neuroblastoma that has metastasized to the bone.
Is explosive performance influenced by androgen concentrations in young male soccer players?
Authors: C Baldari, L Di Luigi, G P Emerenziani, M C Gallotta, P Sgrò, L Guidetti
Journal: British Journal of Sports Medicine (2008)

Objective: There is growing interest in the implementation and assessment of strength and conditioning programmes among young children. The purpose of this study was to examine the association between given anthropometric characteristics, pubertal development, salivary androgen hormones and explosive leg power in young soccer players. Methods: 51 (age range 10–14 years) soccer players were investigated. The relations between age, pubertal developmental stages, testicular volume, weight, height, body fat, fat free mass, salivary DHEAS concentrations, salivary testosterone concentrations and lower limb explosive power were evaluated. Results: Standing long jump length was positively correlated (p&lt;0.05) with age (11.7 (SD 1.2) years, r = 0.66), pubertal developmental stages (mode and range: 1 (1–4), r = 0.64), testicular volume (8.8 (5.2) ml, r = 0.58), height (1.50 (0.10) m, r = 0.34), weight (43.7 (9.1) kg, r = 0.34), fat free mass (35.4 (7.2) kg, r = 0.67), salivary DHEAS concentrations (4.4 (1.2) ng/ml, r = 0.38) and negatively correlated with body fat (18.6 (7.0) kg; r = −0.49, p&lt;0.05). There was no significant correlation between salivary testosterone concentrations (0.3 (0.1) ng/ml, r = 0.12) and standing long jump. Conclusions: Results of the present investigation demonstrated that age, pubertal developmental stages, testicular volume, weight, height, fat free mass, and salivary DHEAS concentrations were associated with standing long jump performance. In addition, salivary testosterone concentrations were not related to explosive leg power. Results of the present investigation suggest that the teacher/coach should evaluate long jump performance relative to the subject’s given biological characteristics, and not simply established standards based on chronological age.
Bloodletting for pneumonia, prolonged bed rest for low back pain, is subacromial decompression another clinical illusion?
Authors: Jeremy Lewis
Journal: British Journal of Sports Medicine (2014)

In 1972 Charles Neer published a clinical commentary proposing that abrasion from the anteroinferior aspect of the acromion resulted in 95% of all rotator cuff (RC) pathology. The associated condition, termed subacromial impingement syndrome (SIS), has become the most commonly diagnosed musculoskeletal condition involving the shoulder. Others went on to suggest a causative relationship between acromial morphology and RC pathology, and clinical tests such as the Neer sign and the Hawkin's test were described to support a diagnosis. Acromioplasty, also known as subacromial decompression (SAD), is a surgical procedure widely used to eradicate the hypothesised source of the irritation. Between 1996 and 2006 the number of SADs increased in New York State (USA) by 254% and from 2001 to 2010 in England (UK) by 746%,1 with successful outcomes being reported in up to 80% of cases. There has been a concomitant 141% increase in the number of surgical repairs of the RC performed between 1996 and 2006. Embedded within this figure is a 600% increase in the number of repairs performed arthroscopically. Many physiotherapists and other health professional have embraced the SIS model describing how poor upper body posture, colloquially termed a forward head posture, is associated with an increase in the thoracic kyphosis with an imbalance of the shoulder girdle muscles. This results in an abnormal scapular posture (typically anterior tilt and downward rotation) resulting in impingement and RC pathology. The extent by which postural abnormalities follow a …
Massage--the scientific basis of an ancient art: Part 2. Physiological and therapeutic effects.
Authors: G C Goats
Journal: British Journal of Sports Medicine (1994)

The physiological and therapeutic effects of massage are frequently questioned. This article reviews previous research into the effects of massage on blood flow and composition, oedema, connective tissue, muscle and the nervous system. Although further investigations are clearly required in certain areas, the discussion demonstrates that the use of massage in sports medicine can be justified according to orthodox scientific criteria.
Drug interaction networks: an introduction to translational and clinical applications
Authors: Francisco Azuaje
Journal: Cardiovascular Research (2012)

This article introduces fundamental concepts to guide the analysis and interpretation of drug–target interaction networks. An overview of the generation and integration of interaction networks is followed by key strategies for extracting biologically meaningful information. The article highlights how this information can enable novel translational and clinically motivated applications. Important advances for the discovery of new treatments and for the detection of adverse drug effects are discussed. Examples of applications and findings originating from cardiovascular research are presented. The review ends with a discussion of crucial challenges and opportunities.
Cardiac events among patients with CV comorbidities: Pooled analysis of COPD trials comparing tiotropium with salmeterol
Authors: Kai-Michael Beeh, Klaus Rabe, Thomas Glaab, Diego Wyszynski, Inge Leimer, Norbert Metzdorf, Claus Vogelmeier, Leonardo Fabbri
Journal: European Respiratory Journal (2013)

Background:  Subgroup analyses of patients with concomitant cardiovascular (CV) diseases may help characterise safety profiles of COPD maintenance therapies.   Aims and objectives : To compare the serious cardiac adverse event (SCAE) profiles, including fatalities, of patients with baseline CV conditions in a pooled analysis of 4 double-blind, randomized, parallel-group clinical trials of tiotropium HandiHaler® (HH) vs salmeterol metered dose inhaler (MDI).   Methods:  Incidence rates (IR): number of patients with event divided by 100 patient-years at risk. Rate ratios (RR) and 95% confidence intervals (CI): derived from Cochran-Mantel-Haenszel test stratified by study.   Results:  In total, 8836 patients were included. The IRs of SCAEs, and fatalities from cardiac diseases, during treatment by CV conditions at baseline are in the table.   Conclusion:  Tiotropium once daily via HH showed a comparable cardiac safety profile to salmeterol MDI in subgroups with CV conditions at baseline.
On the relationship between gastric pH and pressure in the normal human lower oesophageal sphincter.
Authors: M D Kaye
Journal: Gut (1979)

The effect upon the lower oesophageal sphincter (LOS) of acid in the proximal stomach was investigated in 12 young healthy subjects. The cardia was perfused in turn with solutions at pH 7, 4, 3, 2, and 1, during successive withdrawals of three perfused pressure-recording catheters, openings of which were at the same axial level. Although there was considerable individual variation, there was a direct and significant relationship between LOW pressure and the acidity of the solution perfused. The results suggest that resting LOS pressure and the acidity of the solution perfused. The results suggest that resting LOS pressure may be determined in part by the pH of the gastric content.
Emerging infections: a perpetual challenge
Authors: David M Morens, Gregory K Folkers, Anthony S Fauci
Journal: The Lancet Infectious Diseases (2008)

SummaryEmerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival.
Adipocytokines Attenuate the Association Between Visceral Adiposity and Diabetes in Older Adults
Authors: Alka M. Kanaya, Tamara Harris, Bret H. Goodpaster, Fran Tylavsky, Steven R. Cummings
Journal: Diabetes Care (2004)

OBJECTIVE—To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes. RESEARCH DESIGN AND METHODS—A nested case-control study from the Health, Aging, and Body Composition (Health ABC) study. We measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis factor-α, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area was determined by computed tomography scan. The 519 case subjects had diabetes defined by fasting plasma glucose level ≥126 mg/dl or by use of diabetes medications. The 519 control subjects had normal glucose tolerance and were matched by sex, race, and study site. Sex-specific logistic models were adjusted for age, race, site, total adiposity, smoking, and physical activity. RESULTS—Higher adiponectin levels were associated with lower risk of diabetes (P &amp;lt; 0.001). Visceral fat was the only adiposity measure associated with diabetes after adjusting for BMI (odds ratio 3.0 [2.1–4.3] in women and 1.3 [1.0–1.6] in men, P &amp;lt; 0.001 between-sex comparison). Adipocytokines attenuated the association between visceral fat and diabetes for both sexes but more strongly in men (women 2.3 [1.5–3.3], men 1.1 [0.9–1.4]). In men, adiponectin, IL-6, and PAI-1 remained independently associated with diabetes after adjusting for fat depots; in women, adiponectin was the only independently associated adipocytokine. Controlling for insulin, HDL, triglycerides, and blood pressure did not change these results. CONCLUSIONS—Adiponectin is associated with lower odds of diabetes in older men and women. Whereas several adipocytokines explained the relationship between visceral adiposity and diabetes in men, only adiponectin partially mediated this association among women.
Toward a Comprehensive Developmental Model for Major Depression in Women
Authors: Kenneth S. Kendler, Charles O. Gardner, Carol A. Prescott
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Major depression is a multifactorial disorder with many etiologic variables that are interrelated through developmental pathways. The authors used structural equation modeling to generate a developmental model for the etiology of major depression in women. METHOD: Data from 1,942 adult female twins, interviewed up to four times over a 9-year period, were used to construct a developmental model to predict depressive episodes in the year before the most recent interview. Eighteen risk factors in five developmental tiers were considered: 1) childhood (genetic risk, disturbed family environment, childhood sexual abuse, and childhood parental loss), 2) early adolescence (neuroticism, self-esteem, and early-onset anxiety and conduct disorder), 3) late adolescence (educational attainment, lifetime traumas, social support, and substance misuse), 4) adulthood (history of divorce and past history of major depression), and 5) the last year (marital problems, difficulties, and stressful life events). RESULTS: The best fitting model included six correlations and 64 paths, provided an excellent fit to the data, and explained 52% of the variance in liability to episodes of major depression. The findings suggest that the development of risk for major depression in women results from three broad pathways reflecting internalizing symptoms, externalizing symptoms, and psychosocial adversity. CONCLUSIONS: Major depression is an etiologically complex disorder, the full understanding of which will require consideration of a broad array of risk factors from multiple domains. These results, while plausible, should be treated with caution because of problems with causal inference, retrospective recall bias, and the limitations of a purely additive statistical model.
Evaluation of moxifloxacin for the treatment of tuberculosis: 3 years of experience
Authors: A. D. Pranger, R. van Altena, R. E. Aarnoutse, D. van Soolingen, D. R. A. Uges, J. G. W. Kosterink, T. S. van der Werf, J. W. C. Alffenaar
Journal: European Respiratory Journal (2011)

Moxifloxacin (MFX) is a powerful second-line anti-tuberculosis (TB) agent, but the optimal dose has not yet been established and long-term safety data are scarce. We retrospectively reviewed the medical charts of TB patients treated at the Tuberculosis Centre Beatrixoord, University Medical Centre Groningen (Haren, the Netherlands) receiving MFX 400 mg once daily as part of their TB treatment between January 1 2006 and January 1 2009. Safety data and drug-drug interactions were evaluated. Efficacy was predicted based on the area under the concentration-time curve up to 24 h post-dosage (AUC(0-24h))/minimal inhibitory concentration (MIC) ratio. 89 patients were treated with a median dose of 6.9 mg · kg(-1) MFX once daily for a median period of 74 days. Discontinuation of therapy occurred in only three patients due to gastrointestinal side-effects and hypersensitivity. Pharmacokinetic analysis showed an AUC(0-24h)/MIC ratio <100 in eight out of 16 patients. A large variation in protein binding affected the unbound AUC(0-24h) considerably. These data show that MFX treatment was well tolerated in 89 patients receiving a dose of 400 mg once daily for a prolonged period. Considering the variability in (un)bound AUC(0-24h)/MIC ratio, therapeutic drug monitoring is recommended in selected patients (i.e. rifampicin co-medication; MIC ≥ 0.25 mg · L(-1)) to assess optimal therapy.
Breast cancer and acute leukemia: Report of 24 cases and review of the literature
Authors: Fred Rosner, Robert W. Carey, Mohammad H. Zarrabi
Journal: American Journal of Hematology (1978)

Abstract Twenty‐four cases of breast cancer and acute leukemia and three cases of breast cancer and chronic myelocytic leukemia are reported. An additional 54 cases of acute leukemia and 13 cases of chronic myelocytic leukemia associated with breast cancer from the literature are reviewed. The mean interval between the diagnosis of breast cancer and the occurrence of acute leukemia is 6.9 years. In eight patients, the two diseases occurred simultaneously or within one year of each other. Four patients had acute lymphoblastic leukemia; the remainder had acute myelocytic leukemia or one of its variants. Seven patients received no postmastectomy radiotherapy or chemotherapy and the occurrence of acute leukemia between 1 and 23 years later cannot, therefore, be attributed to the therapy given for the breast cancer. Forty‐one patients received postoperative radiotherapy to the mastectomy site. Combination chemotherapy was administered to eight patients, five of whom were also treated with radiotherapy. Acute leukemia is estimated to occur in patients treated for breast cancer with a sevenfold increased frequency over the expected number. This may be due to an increased risk of a second neoplasm in patients with a primary tumor; alternatively, the acute leukemia may be related to the radiotherapy and/or chemotherapy administered to treat the breast cancer. Late death from leukemia after chemotherapeutic or radiotherapeutic remission of metastatic breast cancer is preferable to morbidity and/or early death from inadequately treated breast cancer.