tbuckley/cabot-search huggingface dataset:
Esculetin inhibits cartilage resorption induced by interleukin 1alpha in combination with oncostatin M
Authors: S Elliott
Journal: Annals of the Rheumatic Diseases (2001)

To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage.Interleukin 1alpha (IL1alpha, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant culture. Proteoglycan and collagen loss were assessed by dimethylmethylene blue and hydroxyproline assays, respectively. Collagenase levels were measured by assay of bioactivity and by enzyme linked immunosorbent assay (ELISA). The effects of EST on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the transformed human chondrocyte cell line T/C28a4 were assessed by northern blot analysis. TIMP-1 protein levels were assayed by ELISA. The effect of EST on the MMP-1 promoter was assessed using a promoter-luciferase construct in transient transfection studies.EST inhibited proteoglycan and collagen resorption in a dose dependent manner with significant decreases seen at 66 microM and 100 microM EST, respectively. Collagenolytic activity was significantly decreased in bovine nasal cartilage cultures. In human articular cartilage, EST also inhibited IL1alpha + OSM stimulated resorption and decreased MMP-1 levels. TIMP-1 levels were not altered compared with controls. In T/C28a4 chondrocytes the IL1alpha + OSM induced expression of MMP-1, MMP-3, and MMP-13 mRNA was reduced to control levels by 250 microM EST. TIMP-1 mRNA levels were unaffected by EST treatment. All cytokine stimulation of an MMP-1 luciferase-promoter construct was lost in the presence of the inhibitor.EST inhibits degradation of bovine nasal cartilage and human articular cartilage stimulated to resorb with IL1alpha + OSM.
The Relationship Between Avoidant Personality Disorder and Social Phobia: A Population-Based Twin Study
Authors: Ted Reichborn-Kjennerud, Nikolai Czajkowski, Svenn Torgersen, Michael C Neale, Ragnhild E Ørstavik, Kristian Tambs, Kenneth S Kendler
Journal: American Journal of Psychiatry (2007)

Objective: The purpose of this study was to determine the sources of comorbidity for social phobia and dimensional representations of avoidant personality disorder by estimating to what extent the two disorders are influenced by common genetic and shared or unique environmental factors versus the extent to which these factors are specific to each disorder. Method: Young adult female-female twin pairs (N=1,427) from the Norwegian Institute of Public Health Twin Panel were assessed at personal interview for avoidant personality disorder and social phobia using the Structured Interview for DSM-IV Personality and the Composite International Diagnostic Interview. Bivariate Cholesky models were fitted using the Mx statistical program. Results: The best-fitting model included additive genetic and unique environmental factors only. Avoidant personality disorder and social phobia were influenced by the same genetic factors, whereas the environmental factors influencing the two disorders were uncorrelated. Conclusions: Within the limits of statistical power, these results suggest that there is a common genetic vulnerability to avoidant personality disorder and social phobia in women. An individual with high genetic liability will develop avoidant personality disorder versus social phobia entirely as a result of the environmental risk factors unique to each disorder. The results are in accordance with the hypothesis that psychobiological dimensions span the axis I and axis II disorders.
Ex-professional association footballers have an increased prevalence of osteoarthritis of the hip compared with age matched controls despite not having sustained notable hip injuries
Authors: G J Shepard, A J Banks, W G Ryan
Journal: British Journal of Sports Medicine (2003)

To compare the prevalence of self reported, physician diagnosed osteoarthritis (OA) of the hip in ex-professional footballers with that in age matched controls in the general public.A questionnaire was sent to the 92 football league and premiership managers to assess the prevalence of OA of various joints. The prevalence of OA of the hip in those managers that were ex-professional footballers was assessed. Radiographic controls were obtained and used to assess the prevalence of OA of the hip in the general population. The results of the two groups were compared statistically using chi(2) tabulation.Seventy four (80%) of the managers responded to the questionnaire. Nine of the 68 ex-professional footballers who replied had OA of the hip, and six of these had undergone a total of eight total hip replacements. Of the 18 managers who did not respond, 12 were known to be ex-professionals. In the control group of 136, two had OA of the hip. The two groups differed significantly (p<0.001). The odds ratio for OA of the hip was 10.2 (95% confidence interval 2.1 to 48.8).The ex-professional footballers had a significantly higher prevalence of OA of the hip than an age matched group of radiographic controls.
Mechanisms of lymphatic metastasis
Authors: Sinem Karaman, Michael Detmar
Journal: Journal of Clinical Investigation (2014)

Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs, thereby promoting LN metastasis. Surprising recent evidence suggests that lymphatic vessels do not merely represent passive channels for tumor spread, but that they may actively promote tumor cell recruitment to LNs, cancer stem cell survival, and immune modulation. New imaging approaches allow the sensitive visualization of the earliest LN metastases and the quantitative, noninvasive measurement of the function of tumor-draining lymphatic vessels, with potential applications in the development of biomarkers for prognosis and measurement of therapeutic response.
Hypomagnesaemia in chronic, stable asthmatics: prevalence, correlation with severity and hospitalization
Authors: O.S.B. Alamoudi
Journal: European Respiratory Journal (2000)

Magnesium (Mg) deficiency is associated with airway hyperreactivity, wheeze and impairment of lung function. The prevalence of hypomagnesaemia, and its effect on asthma is unclear. Therefore, this prospective study was undertaken to evaluate the prevalence of low serum Mg level, to correlate whether hypomagnesaemia (serum Mg level <0.74 mmol x L(-1)) is associated with severity of asthma and increased frequency of hospitalizations in chronic, stable asthmatics. Ninety-three chronic stable asthmatics, who were on regular follow-up in an asthma clinic, were studied. On attendance to the asthma clinic, each subject was interviewed and clinically evaluated. The serum Mg level (normal 0.74-1.2 mmol x L(-1)), as well as the severity of asthma was measured. The medications used were recorded. The total number of hospitalizations due to asthma exacerbation was scored for the last three months that preceded the date of measuring the serum Mg level. Twenty-five patients (27%) had a low Mg level with a mean+/-SD of 0.69+/-0.04 mmol x L(-1), while 68/93 (73%) had a normal Mg level (0.82+/-0.08 mmol x L(-1)). The number of hospitalizations in asthmatics with low Mg levels was 10/25 (40%), compared to 8/68 (12%) (p<0.01) in asthmatics with normal Mg levels. Multiple logistic regression analysis showed that severe asthma was the only factor associated significantly with hypomagnesaemia (p=0.04). No effect was observed for inhaled beta-agonist, inhaled steroid or theophylline therapy on serum Mg level. To conclude, hypomagnesaemia is common in chronic asthmatics. Chronic asthmatics with low Mg tend to have more hospitalizations than chronic asthmatics with normal Mg. Hypomagnesaemia was also associated with more severe asthma.
Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo
Authors: Philipp Nuhn, Beat M Künzli, René Hennig, Tomas Mitkus, Tadas Ramanauskas, Rainer Nobiling, Stefan C Meuer, Helmut Friess, Pascal O Berberat
Journal: Molecular Cancer (2009)

Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy in vitro. Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells. PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested in vivo and in vitro.High HO-1 expression in PaCa cell lines was associated with increased chemoresistance in vitro. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects in vivo significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy in vivo. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.
Nut and Peanut Butter Consumption and Risk of Type 2 Diabetes in Women
Authors: Rui Jiang
Journal: JAMA (2002)

Context Nuts are high in unsaturated (polyunsaturated and monounsaturated) fat and other nutrients that may improve glucose and insulin homeostasis.Objective To examine prospectively the relationship between nut consumption and risk of type 2 diabetes.Design, Setting, and Participants Prospective cohort study of 83818 women from 11 states in the Nurses' Health Study.The women were aged 34 to 59 years, had no history of diabetes, cardiovascular disease, or cancer, completed a validated dietary questionnaire at baseline in 1980, and were followed up for 16 years.Main Outcome Measure Incident cases of type 2 diabetes. ResultsWe documented 3206 new cases of type 2 diabetes.Nut consumption was inversely associated with risk of type 2 diabetes after adjustment for age, body mass index (BMI), family history of diabetes, physical activity, smoking, alcohol use, and total energy intake.The multivariate relative risks (RRs) across categories of nut consumption (never/almost never, Ͻonce/week, 1-4 times/week, and Ն5 times/week) for a 28-g (1 oz) serving size were 1.0, 0.92 (95% confidence interval [CI], 0.85-1.00),0.84 (0.95% CI, 0.76-0.93),and 0.73 (95% CI, 0.60-0.89)(P for trend Ͻ.001).Further adjustment for intakes of dietary fats, cereal fiber, and other dietary factors did not appreciably change the results.The inverse association persisted within strata defined by levels of BMI, smoking, alcohol use, and other diabetes risk factors.Consumption of peanut butter was also inversely associated with type 2 diabetes.The multivariate RR was 0.79 (95% CI, 0.68-0.91;P for trend Ͻ.001) in women consuming peanut butter 5 times or more a week (equivalent to Ն140 g [5 oz] of peanuts/week) compared with those who never/almost never ate peanut butter.Conclusions Our findings suggest potential benefits of higher nut and peanut butter consumption in lowering risk of type 2 diabetes in women.To avoid increasing caloric intake, regular nut consumption can be recommended as a replacement for consumption of refined grain products or red or processed meats.
Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers
Authors: M. L. Gillison
Journal: JNCI Journal of the National Cancer Institute (2000)

High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC.Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis.HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88).These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
Requirement for Protein Kinase C Activation in Basic Fibroblast Growth Factor–Induced Human Endothelial Cell Proliferation
Authors: K. Craig Kent, Shinsuke Mii, Elizabeth O. Harrington, James D. Chang, Sheila Mallette, J. Anthony Ware
Journal: Circulation Research (1995)

Abstract The intracellular signaling mechanisms that mediate basic fibroblast growth factor (bFGF)–induced angiogenesis have not been fully identified. In particular, whether activation of the intracellular enzyme protein kinase C (PKC) is necessary or sufficient for bFGF-induced mitogenesis of human endothelial cells is not clear. Accordingly, the effect of bFGF stimulation on the Ca 2+ increase and PKC activity of normal human endothelial cells (HEC) was studied, as was the effect of inhibition of PKC and the distribution of PKC isoenzymes in these cells. The addition of bFGF to cultured HEC increased overall PKC activity in the absence of an increase in intracellular Ca 2+ and markedly stimulated their proliferation, as did the addition of PKC-activating phorbol esters. bFGF-induced proliferation was prevented by the PKC inhibitors chelerythrine and H-7 and by downregulation of PKC after prolonged incubation with phorbol esters. In contrast, these inhibitors did not prevent HEC proliferation induced by epidermal growth factor. Because of the failure of bFGF to increase Ca 2+ , we determined whether bFGF-induced proliferation could be mediated by novel or atypical PKC isoenzymes (which are not regulated by Ca 2+ ). Investigation of the isoenzyme distribution of confluent and subconfluent HEC by immunoblotting, Northern transfer analysis, and polymerase chain reaction of reverse-transcribed RNA revealed the presence of several novel and atypical isoenzymes (PKC-δ, -η, -θ, and -ζ) as well as small amounts of the conventional (Ca 2+ -regulated) isoenzymes PKC-α and -β. Activation of PKC by bFGF, in the absence of an increase in intracellular Ca 2+ , suggests that one or more of these Ca 2+ -independent PKC isoenzymes are both necessary and sufficient for HEC proliferation after bFGF.
Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications
Authors: Theodore Kelesidis, Iosif Kelesidis, Sharon Chou, Christos S Mantzoros
Journal: Annals of Internal Medicine (2010)

Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.
The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities
Authors: Ira D. Goldfine, Betty A. Maddux, Jack F. Youngren, Gerald Reaven, Domenico Accili, Vincenzo Trischitta, Riccardo Vigneri, Lucia Frittitta
Journal: Endocrine Reviews (2008)

Insulin resistance is a major feature of most patients with type 2 diabetes mellitus (T2D). A number of laboratories have observed that membrane glycoprotein plasma cell antigen 1 (PC-1) [ectonucleotide pyrophosphatase phosphodiesterase 1] is either overexpressed or overactive in muscle, adipose tissue, fibroblasts, and other tissues of insulin-resistant individuals, both nondiabetic and diabetic. Moreover, in cultured cells in vitro and in transgenic mice in vivo, PC-1 overexpression impairs insulin stimulation of insulin receptor (IR) activation and downstream signaling. PC-1 binds to the connecting domain of the IR α-subunit that is located in residues 485–599. The connecting domain transmits insulin binding in the α-subunit to activation of tyrosine kinase activation in the β-subunit. When PC-1 is overexpressed, it inhibits insulin-induced IR β-subunit tyrosine kinase activity. In addition, a polymorphism of PC-1 (K121Q) in various ethnic populations is closely associated with insulin resistance, T2D, and cardio- and nephrovascular diseases. The product of this polymorphism has a 2- to 3-fold increased binding affinity for the IR and is more potent than the wild-type PC-1 protein (K121K) in inhibiting the IR. These data suggest therefore that PC-1 is a candidate protein that may play a role in human insulin resistance and T2D by its overexpression, its overactivity, or both.
Vestibular Hair Cells and Afferents: Two Channels for Head Motion Signals
Authors: Ruth Anne Eatock, Jocelyn E. Songer
Journal: Annual Review of Neuroscience (2011)

Vestibular epithelia of the inner ear detect head motions over a wide range of amplitudes and frequencies. In mammals, afferent nerve fibers from central and peripheral zones of vestibular epithelia form distinct populations with different response dynamics and spike timing. Central-zone afferents are large, fast conduits for phasic signals encoded in irregular spike trains. The finer afferents from peripheral zones conduct more slowly and encode more tonic, linear signals in highly regular spike trains. The hair cells are also of two types, I and II, but the two types do not correspond directly to the two afferent populations. Zonal differences in afferent response dynamics may arise at multiple stages, including mechanoelectrical transduction, voltage-gated channels in hair cells and afferents, afferent transmission at calyceal and bouton synapses, and spike generation in regular and irregular afferents. In contrast, zonal differences in spike timing may depend more simply on the selective expression of low-voltage-activated ion channels by irregular afferents.
Validation and Characterization of Human Kallikrein 11 as a Serum Marker for Diagnosis of Ovarian Carcinoma
Authors: Martin W. McIntosh, Yan Liu, Charles Drescher, Nicole Urban, Eleftherios P. Diamandis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas, and currently, one of the most promising early detection strategies for ovarian cancer uses CA 125 level in conjunction with imaging. However, CA 125 is elevated in only 50% of early-stage ovarian cancer and is often elevated in women with benign ovarian tumors and other gynecologic diseases. Additional markers may improve on its individual performance if they increase sensitivity and specificity and are less sensitive to other gynecologic conditions. The human kallikrein 11 (hK11) marker has been reported to have favorable predictive value for ovarian cancer, although, by itself, it may be inferior to CA 125. Experimental Design: We here validate the performance of hK11 on an independent data set and further characterize its behavior in multiple types of controls. We also investigate its behavior when combined with CA 125 to form a composite marker. hK11 had not previously been evaluated on these serum samples. CA 125, hK11, and the composite marker were evaluated for their performance in identifying ovarian cancer and for temporal stability. Results: hK11 significantly distinguished ovarian cancer cases from healthy controls and is less sensitive to benign ovarian disease than is CA 125. Conclusion: We conclude that hK11 is a valuable new biomarker for ovarian cancer and its temporal stability implies that it may do even better when used in a longitudinal screening program for early detection.