tbuckley/cabot-search huggingface dataset:
Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance
Authors: J McCarthy
Journal: Gut (2003)

Prophylactic efficacy against colitis following lactobacillus consumption in interleukin 10 (IL-10) knockout (KO) mice has been reported. Whether this applies equally to other probiotic strains is unknown, and the mechanism is unclear.(1) To compare the effect of feeding Lactobacillus salivarius subspecies salivarius 433118 and Bifidobacterium infantis 35624 against placebo on enterocolitis, the intestinal microflora, and (2) to compare the systemic immunological response to in vitro microbial challenge in probiotic fed and control IL-10 KO mice.Three groups of 10 IL-10 KO mice were fed fermented milk products containing Lb salivarius 433118 at 10(9) CFU/ml, B infantis 35624 at 10(8) CFU/ml, and unmodified milk, respectively, for 19 weeks. Faecal samples were taken at regular intervals to confirm gut transit, recovery of fed probiotics, and to assess the impact on the microflora. At sacrifice, the bowels were histologically scored. Cytokine production from Peyers' patches and splenocytes was measured in vitro by ELISA.Faecal recovery of probiotics was confirmed in all probiotic fed mice but not in controls. Colonic and caecal inflammatory scores were significantly decreased in both groups of probiotic fed mice (p<0.05). Proinflammatory cytokine production by Peyers' patches and splenocytes was significantly reduced in probiotic fed animals whereas transforming growth factor beta (TGF-beta) levels were maintained.Both Lactobacillus salivarius 433118 and Bifidobacterium infantis 35624 significantly attenuate colitis in this murine model. Attenuation of colitis is associated with a reduced ability to produce Th1-type cytokines systemically and mucosally, while levels of TGF-beta are maintained.
Acupuncture in epidemic HBV hepatitis: In china too?
Authors: Harold O. Conn
Journal: Hepatology (1988)

An epidemiologic investigation of an acupuncturist’s practice in Rhode Island identified 35 patients who were infected with hepatitis B virus during 1984. Of 366 patients seen by the acupuncturist during 1984,316 (86%) completed questionnaires and submitted serum for hepatitis B serology. Use of tests for immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) identified 17 case-patients who otherwise may have gone undetected. Thirty-four of the 35 case-patients were treated in only one of the two clinics run by the acupuncturist. Patients who received a greater number of acupuncture needles during their treatment course were more likely to have been infected; the attack rate for patients who received &lt;150 needles was 9%, compared with 33% for patients who received ≥450 needles (p &lt; 0.001). Attack rates were higher during a one-month period when the index case-patient was more likely to have been viremic than during any other period in 1984 (relative risk = 4.1, 95% confidence interval = 2.3-7.3). While observing the acupuncturist’s technique, the investigators noted several potential mechanisms for needle contamination. This study highlights the potential for transmission of hepatitis B in situations of repeated needle use.
The loss of NKX3.1 expression in testicular--and prostate--cancers is not caused by promoter hypermethylation.
Authors: Guro E Lind, Rolf I Skotheim, Mario F Fraga, Vera M Abeler, Rui Henrique, Fahri Saatcioglu, Manel Esteller, Manuel R Teixeira, Ragnhild A Lothe
Journal: Molecular Cancer (2005)

Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing. Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens.
Visceral fat decreased by long-term interdisciplinary lifestyle therapy correlated positively with interleukin-6 and tumor necrosis factor–α and negatively with adiponectin levels in obese adolescents
Authors: Fábio Santos Lira, Jose Cesar Rosa, Ronaldo Vagner dos Santos, Daniel Paulino Venancio, June Carnier, Priscila de Lima Sanches, Claudia Maria Oller do Nascimento, Aline de Piano, Lian Tock, Sergio Tufik, Marco Túlio de Mello, Ana R. Dâmaso, Lila Missae Oyama
Journal: Metabolism (2010)
Type I Interferons (IFNs) Regulate Tumor Necrosis Factor–related Apoptosis-inducing Ligand (TRAIL) Expression on Human T Cells: A Novel Mechanism for the Antitumor Effects of Type I IFNs
Authors: Nobuhiko Kayagaki, Noriko Yamaguchi, Masafumi Nakayama, Hiroshi Eto, Ko Okumura, Hideo Yagita
Journal: The Journal of Experimental Medicine (1999)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a proapoptotic member of the TNF family of type II membrane proteins, which constitutes one component of T cell cytotoxicity. In this study, we investigated the expression and function of TRAIL in human peripheral blood T (PBT) cells. Although freshly isolated PBT cells did not express a detectable level of TRAIL on their surface, a remarkable TRAIL expression was rapidly induced on the surface of both CD4+ and CD8+ PBT cells upon stimulation with anti-CD3 monoclonal antibody and type I interferons (IFNs). This enhancement of TRAIL expression was a unique feature of type I IFNs (IFN-α and IFN-β), and neither type II IFN (IFN-γ) nor various other cytokines enhanced TRAIL expression on anti-CD3–stimulated PBT cells. Type I IFNs have been used for clinical treatment of renal cell carcinomas (RCCs), and we found that most RCC cell lines were susceptible to TRAIL-induced apoptosis. Type I IFNs substantially augmented cytotoxic activity of anti-CD3–stimulated PBT cells against RCC cell lines in a TRAIL-dependent manner. These results indicate a unique feature of type I IFNs to regulate TRAIL-mediated T cell cytotoxicity, which may be involved in the antitumor effects of type I IFNs against various tumors.
Current and future status of ovulation induction in polycystic ovary syndrome
Authors: I. Messinis
Journal: Human Reproduction Update (1997)

Great progress has been achieved during the last 20 years in the field of ovulation induction in patients with polycystic ovary syndrome (PCOS). Clomiphene citrate remains the first line of treatment for all anovulatory women with PCOS, since in properly selected patients the cumulative pregnancy rate approaches that in normal women. Human urinary gonadotrophins have been used extensively for ovulation induction but the development of low-dose regimens has opened a new era in the management of anovulation related to PCOS. This article discusses the main advantages and disadvantages of the principal methods and regimens currently used for ovulation induction in patients with PCOS including clomiphene citrate, gonadotrophins, pulsatile gonadotrophin-releasing hormone (GnRH) and GnRH agonists. It also discusses new drugs discovered recently, particularly recombinant gonadotrophins and GnRH antagonists, and provides some thoughts regarding their use in future protocols. Finally, based on the discovery of new ovarian substances which specifically control luteinizing hormone (LH) secretion, this article develops assumptions on possible implications of these substances in the pathophysiology of PCOS and their potential use in the management of the syndrome.
CK2 Phosphorylates the Angiotensin-Converting Enzyme and Regulates Its Retention in the Endothelial Cell Plasma Membrane
Authors: Karin Kohlstedt, Firouzeh Shoghi, Werner Müller-Esterl, Rudi Busse, Ingrid Fleming
Journal: Circulation Research (2002)

Soluble angiotensin-converting enzyme (ACE) is derived from the membrane-bound form by proteolytic cleavage of its C-terminal domain. Because intracellular events might be involved in the regulation of the cleavage process, we determined whether the cytoplasmic tail of ACE is phosphorylated and whether this process regulates secretion. Immunoprecipitation of ACE (180 kDa) from (32)P-labeled endothelial cells revealed that ACE is phosphorylated. Phosphorylation was not observed in endothelial cells overexpressing a mutant form of ACE (ACEDeltaS, all five cytoplasmic serine residues replaced by alanine). CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation. In ACE-overexpressing endothelial cells, ACE was mostly localized to the plasma membrane. However, no ACE was detected in the plasma membrane of ACEDeltaS-overexpressing cells, although a precursor ACE (170 kDa) was prominent in the endoplasmic reticulum and the cell supernatant contained substantial amounts of the soluble protein (175 kDa). A correlation between ACE-phosphorylation and secretion was confirmed in endothelial cells treated with the CK2-inhibitor, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which time-dependently decreased the phosphorylation of ACE and increased its shedding. These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels.
A STUDY OF THE METABOLISM OF CALCIUM, MAGNESIUM, SULPHUR, PHOSPHORUS, AND NITROGEN IN ACROMEGALY
Authors: Olaf Bergeim, F. T. Stewart, P. B. Hawk
Journal: The Journal of Experimental Medicine (1914)

A distinct retention of calcium, magnesium, and phosphorus was noted, which was not accompanied by corresponding changes in general metabolism, as evidenced by a practical balance of nitrogen and sulphur. It is concluded that there is a primary disturbance in the metabolism of the mineral elements mentioned, with the probable formation of new bony tissue. The distribution of elements between urine and feces shows no abnormal variations. A suggestion is made as to the reasons for variable calcium output in the urine on a uniform diet.
Renaming cytokines: MCP-1, Major Chemokine in Pancreatitis
Authors: F Marra
Journal: Gut (2005)

Evidence of a mechanistic role for monocyte chemoattractant protein 1 (MCP-1) in the pathogenesis of inflammation and fibrosis associated with experimental pancreatitis

Fibrosclerotic organ diseases, a major cause of morbidity and mortality in the Western world, involve tissues as diverse as the liver, kidney, heart, lung, skin, and intestine. The causes of these diseases are manifold, and specific noxae are implicated in different settings. Nevertheless, most (if not all) of these conditions share common pathogenetic grounds, such as being characterised by derangement of the tissue “wound healing” response. The ability of tissues to respond to injury has evolved to neutralise infectious agents and to limit parenchymal cell damage. The wound healing response comprises recruitment of inflammatory cells, deposition and remodelling of extracellular matrix, and regeneration (or an attempt thereof) of parenchymal cells. The ultimate outcome of this process is dependent on the duration of damage, and on the ability of parenchymal cells of specific tissues to reconstitute the original architecture. Thus chronic damage is often characterised by simultaneous and uncoordinated activation of all components of the wound healing response, resulting in chronic inflammation, destruction of the parenchyma, and progressive scarring. Chronic pancreatitis is a typical example of the transferability of these concepts to the clinical field. In response to several causes, most frequently alcohol abuse, metabolic abnormalities, or autoimmunity, damage to acinar cells leads to chronic inflammation, eventually resulting in substitution of pancreatic parenchyma with bundles of scar tissue and loss of function.1

The contribution of inflammation to the development of fibrosis varies in different conditions, and understanding the interaction between these processes is relevant to devise therapeutic strategies for chronic diseases such as pancreatitis. Identification of the chemokine system has elucidated the molecular mechanisms regulating leucocyte trafficking in a given tissue. Chemokines are a family of small cytokines …
The new enlightenment hypothesis: All learners are rational
Authors: Rita Nolan
Journal: Behavioral and Brain Sciences (2009)

Abstract The proposal to recruit available formal structures to build an algorithmic model of all learning falters on close examination of its essential assumption: that the input and output of the model are propositional in structure. After giving three framework considerations, I describe three possibly fatal problems with this assumption, concluding each with a question that needs answering to avoid fatality.
Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group
Authors: Agop Y. Bedikian, Michael Millward, Hubert Pehamberger, Robert Conry, Martin Gore, Uwe Trefzer, Anna C. Pavlick, Ronald DeConti, Evan M. Hersh, Peter Hersey, John M. Kirkwood, Frank G. Haluska
Journal: Journal of Clinical Oncology (2006)

Purpose Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium) could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods We randomly assigned chemotherapy-naïve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m 2 ) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P &lt; .001), overall response (13.5% v 7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v 3.6%; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events. Conclusion The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.
Dynamic quadriceps angle: a comparison of female elite volleyball players with and without patellofemoral pain syndrome
Authors: M Massada, R Aido, C Magalhães, N Puga
Journal: British Journal of Sports Medicine (2011)

Background Patellofemoral pain syndrome (PFPS) is the most common complaint in female volleyball players. Larger quadriceps femoris angle (Q angle) has been implicated as a source of patellofemoral pain but values measured during functional tasks (dynamic Q angle) have not been adequately documented in the literature. Objective With this study, we attempt to determine whether excessive Q angle during a functional task is related with PFPS. Design A correlational study. Setting The study was conducted among high performance female athletes all participating in the Portuguese A1 Division. Participants 50 female volleyball players participated. They were included in one of two groups, according to the presence or absence of patellofemoral pain. Interventions Static Q angle was measured using a goniometer. Subjects were videotaped during the execution of simple functional tasks and dynamic Q angle was determined ‘a posteriori’ using a video analysis program. Main outcome measurements A correlation was examined between static and dynamic Q angle and the prevalence of patellofemoral pain. Results When averaged across all conditions, the average dynamic Q-angle was significantly higher in the PFP group compared to the control group (34.9° vs 22.3°). We found a relationship between larger dynamic Q angles and PFPS (r=-0.517) that remained significant (p&lt;0.01) when the static Q angle was normal. Conclusions The results substantiate the belief that lower extremity motion during dynamic tasks may increase Q-angle and the lateral force acting on the patella, even on individuals with a ‘normal’ static Q-angle. Static Q-angle measurements in this study showed little relationship to dynamic Q-angle measurements and with the presence of PFP.
Have the attitudes of Australian squash players towards protective eyewear changed over the past decade?
Authors: R M Eime, C F Finch
Journal: British Journal of Sports Medicine (2002)

To assess indicative trends in the use of protective eyewear by Australian squash players and their attitudes towards its use since 1989.Data were extracted from three Australian surveys of squash players conducted in 1989, 1995, and 2000. Responses to directly similar attitudinal questions relating to protective eyewear use from each survey were compared. The proportion of players giving each response was calculated for each survey, along with 95% confidence intervals for the differences between the 2000 survey and those from the earlier surveys.Self reported use of protective eyewear ranged from 10.0% in 1989, to 8.6% in 1995, and 18.8% in 2000. However, only 8.9% of the players surveyed in 2000 actually wore appropriate standards approved/polycarbonate lens eyewear. This can be compared with 8.0% and 2.0% of players who reported wearing appropriate polycarbonate lens eyewear in the 1989 and 1995 surveys respectively. Compared with the 1995 survey, significantly more players in 2000 believed that more players should wear protective eyewear (95% confidence interval (CI) for difference 1 to 18). A significantly higher proportion of players also supported the compulsory use of protective eyewear by juniors in 2000 than in both 1989 (95% CI for difference 6 to 24) and 1995 (95% CI for difference 5 to 22). No other attitudes had significantly changed over the decade.These data suggest that self reported use of protective eyewear has probably increased over the past decade. However, many players report wearing inappropriate eyewear. A transition from positive attitudes to appropriate eyewear behaviours is required before mandatory protective eyewear use can be effectively introduced.
Relation of bronchoalveolar lavage T lymphocyte subpopulations to rate of regression of active pulmonary tuberculosis.
Authors: C T Yu, C H Wang, T J Huang, H C Lin, H P Kuo
Journal: Thorax (1995)

Effective host defence against mycobacterial infection chiefly depends on the interactions between macrophages and T lymphocytes. This study investigated the relation of cellular components and their activity of cells obtained by bronchoalveolar lavage (BAL) from the lower respiratory tract to disease regression in patients with active pulmonary tuberculosis without HIV infection.Clinical indices including age, sex, the presence of diabetes, fever, the presence of resistant strains of mycobacteria, the bacterial load in sputum, and disease extent on chest radiography at presentation were assessed before commencing four-drug antituberculous therapy. Twenty two patients with active pulmonary tuberculosis were divided into rapid, intermediate, and slow regression groups. Subpopulations of alveolar macrophages separated using discontinuous Percoll density gradient centrifugation and T lymphocytes (with CD3, CD4, CD8, and CD25 monoclonal antibodies) were quantified.There were no differences among rapid, intermediate, and slow regression groups in terms of age, sex, the presence of diabetes, the presence of resistant strains of mycobacteria, or the bacterial load in sputum. No differences were found between the groups in terms of subpopulations of alveolar macrophages or numbers of CD3 and CD4 lymphocytes. By contrast, an increase in CD8 cells was shown in the slow regression group compared with the rapid and intermediate regression groups. CD25 cell numbers were increased in the rapid regression group compared with the slow regression group. The CD4/CD8 ratio was decreased in the slow regression group compared with the rapid and intermediate regression groups and the relation between the proportion of CD25 cells and the CD4/CD8 ratio in BAL fluid was significant.A decreased CD4/CD8 ratio with an increase in CD8 cells in the alveolar spaces was associated with slow disease regression in patients with active pulmonary tuberculosis without HIV infection, suggesting that the balance of T lymphocyte subsets may play a central part in the modulation of host defence against mycobacterial infection.
STUDIES ON THE NASAL HISTOLOGY OF EPIDEMIC INFLUENZA VIRUS INFECTION IN THE FERRET
Authors: Thomas Francis, C. H. Stuart-Harris
Journal: The Journal of Experimental Medicine (1938)

A study of the respiratory mucous membrane was made in the turbinates of ferrets which had received repeated inoculations of influenza virus. There was no evidence that persistent immunity is related to the presence of a structural modification of the respiratory epithelium. In fact, the respiratory epithelium in fully immune animals differs histologically only in minor respects from that of the normal, untreated ferret. On the other hand, a functional difference exists between the normal and the previously infected animals as evidenced by a marked acceleration of the repair process in the latter. Serological studies at the time of reinfection, 4 months or more after the previous attack, indicate that a relation exists between the height of antibody titer and resistance. The degree of immunity is probably a product of serological immunity and the rate of tissue repair. The implications of these studies to the problem of influenza in man are discussed.