tbuckley/cabot-search huggingface dataset:
Evidence for involvement of IgA1 hinge glycopeptide in the IgA1-IgA1 interaction in IgA nephropathy.
Authors: T Kokubo, Y Hiki, H Iwase, A Horii, A Tanaka, J Nishikido, K Hotta, Y Kobayashi
Journal: Journal of the American Society of Nephrology (1997)

The study was performed to investigate the role of the IgA1 hinge region in the IgA1-IgA1 interaction, which was observed previously in IgA nephropathy. The competitive inhibition assays of the IgA1-IgA1 binding were performed using the following candidates for inhibitors: native IgA1 hinge glycopeptide (nHGP), IgA1, IgA2, and IgG. The IgA1-IgA1 binding was definitely inhibited by the nHGP and the IgA1 (maximum of percent inhibition: 66.1 and 60.5%, respectively). There was no obvious inhibition in the IgA2 and the IgG. The inhibition curves of the nHGP and the IgA1 were significantly different from that of the IgG (P < 0.01, respectively). Furthermore, to reveal the detailed binding sites in the interaction, the same inhibition assays were performed using the following substances composing the IgA1 hinge glycopeptide: galactose (Gal), N-acetyl-galactosamine (GalNAc), Gal beta 1-3GalNAc, sialic acid, tetrapeptide PTPS, and synthesized hinge proline-rich peptide PVPSTPPTPSPSTPPTPSPS (sHP). sHP, Gal beta 1-3GalNAc, Gal, and GalNAc inhibited the binding (69.3, 34.1, 14.9, 14.6%, respectively). No obvious inhibition was observed in sialic acid and tetrapeptide PTPS. The inhibition curve of sHP was significantly different from that of the PTPS (P < 0.05). Those of Gal beta 1-3GalNAc, Gal, and GalNAc were also significantly different from that of sialic acid (P < 0.05, respectively). These results suggested that the IgA1-IgA1 interaction could be mediated by the core structure including the peptide and the sugars, except for sialic acid in the hinge region, resulting in the formation of the circulating macromolecular IgA1 in IgA nephropathy.
Importance of dose intensity in neurooncology clinical trials: Summary Report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium
Authors: Nancy D. Doolittle, Clarke P. Anderson, W. Archie Bleyer, J. Gregory Cairncross, Timothy Cloughesy, Stephen L. Eck, Paul Guastadisegni, Walter A. Hall, Leslie L. Muldoon, Sunil J. Patel, David Peereboom, Tali Siegal, Edward A. Neuwelt
Journal: Neuro-Oncology (2001)

Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed.
Lung growth and computed tomography
Authors: A.A. Hislop
Journal: European Respiratory Journal (2003)

Studies on normal lung development have shown that all airways are present by half-way through gestation, and approximately one-third to one-half of the adult number of alveoli develop during the last trimester of pregnancy 1, 2. Modern treatment of premature babies born with immature lungs has led to the survival of a large cohort of infants and children who may have an abnormal lung or one that will not have the potential to reach the normal adult state. In addition, pre- and postnatal treatment of babies with congenitally hypoplastic lungs is now widespread. It is vital to know how these lungs will grow to establish or predict any problems of middle and old age. Very few pathological studies have been performed on either normal lung during development or abnormal cases, and for the latter only the worst affected cases are available. Lung function testing although noninvasive is still relatively time-consuming for young children and does not produce accurate information on the separate structures within the lungs.

The paper by de Jong et al. 3 in this issue of the journal is therefore timely. In this paper for the first time, computed tomography (CT) has been used to assess lung …
A Role for the <i>WWOX</i> Gene in Prostate Cancer
Authors: Haiyan R. Qin, Dimitrios Iliopoulos, Shuho Semba, Muller Fabbri, Teresa Druck, Stefano Volinia, Carlo M. Croce, Carl D. Morrison, Russell D. Klein, Kay Huebner
Journal: Cancer Research (2006)

Abstract Expression of the WWOX gene, encompassing the common chromosome fragile site FRA16D, is altered in a large fraction of cancers of various types, including prostate cancer. We have examined expression and biological functions of WWOX in prostate cancer. WWOX mRNA and protein expression were significantly reduced in prostate cancer-derived cells (LNCaP, DU145, and PC-3) compared with noncancer prostate cells (PWR-1E), and WWOX expression was reduced in 84% of prostate cancers, as assessed by immunohistochemical staining. Down-modulation of WWOX expression in the prostate cancer-derived cells is due to DNA hypermethylation in the WWOX regulatory region. Treatment with 5-aza-2′-deoxycytidine (AZA), a DNA methyltransferase inhibitor, and trichostatin A, a histone deacetylase inhibitor, led to increased WWOX mRNA and protein expression in prostate cancer-derived cells, most strikingly in DU145 cells. Transfection-mediated WWOX overexpression in DU145 cells suppressed colony growth (P = 0.0012), and WWOX overexpression by infection with Ad-WWOX virus induced apoptosis through a caspase-dependent mechanism and suppressed cell growth. Lastly, ectopic expression of WWOX by Ad-WWOX infection suppressed tumorigenicity of xenografts in nude mice, and intratumoral AZA treatment halted tumor growth. The data are consistent with a role for WWOX as a prostate cancer tumor suppressor and suggest that WWOX signal pathways should be further investigated in normal and cancerous prostate cells and tissues. (Cancer Res 2006; 66(13): 6477-81)
Multivitamin Use and Risk of Prostate Cancer in the National Institutes of Health-AARP Diet and Health Study
Authors: K. A. Lawson, M. E. Wright, A. Subar, T. Mouw, A. Hollenbeck, A. Schatzkin, M. F. Leitzmann
Journal: JNCI Journal of the National Cancer Institute (2007)

Multivitamin supplements are used by millions of Americans because of their potential health benefits, but the relationship between multivitamin use and prostate cancer is unclear. We prospectively investigated the association between multivitamin use and risk of prostate cancer (localized, advanced, and fatal) in 295344 men enrolled in the National Institutes of Health (NIH)–AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996. During 5 years of follow-up, 10241 participants were diagnosed with incident prostate cancer, including 8765 localized and 1476 advanced cancers. In a separate mortality analysis with 6 years of follow-up, 179 cases of fatal prostate cancer were ascertained. Multivitamin use was assessed at baseline as part of a self-administered, mailed food-frequency questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by use of Cox proportional hazards regression, adjusted for established or suspected prostate cancer risk factors. No association was observed between multivitamin use and risk of localized prostate cancer. However, we found an increased risk of advanced and fatal prostate cancers (RR = 1.32, 95% CI = 1.04 to 1.67 and RR = 1.98, 95% CI = 1.07 to 3.66, respectively) among men reporting excessive use of multivitamins (more than seven times per week) when compared with never users. The incidence rates per 100000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9, respectively, compared with 113.4 and 11.4 in never users. The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements, including selenium, β-carotene, or zinc. These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer. The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation.
Parameters affecting pharyngeal response to genioglossus stimulation in sleep apnoea
Authors: Y. Dotan, T. Golibroda, R. Oliven, A. Netzer, L. Gaitini, A. Toubi, A. Oliven
Journal: European Respiratory Journal (2010)

Chronic stimulation of the hypoglossus nerve may provide a new treatment modality for obstructive sleep apnoea (OSA). In previous studies we observed large differences in response to stimulation of the genioglossus (GG). We hypothesised that both individual patient characteristics and the area of the GG stimulated are responsible for these differences. In the present study, we compared the response to GG electrical stimulation at the anterior area (GGa-ES), which activates the whole GG and the posterior area (GGp-ES), which activates preferentially the longitudinal fibres. Studies were performed in 14 propofol-sedated OSA patients. The parameters evaluated included cephalometry, pressure-flow relationship and pharyngeal shape and compliance assessed by pharyngoscopy. Compared with GGa-ES, GGp-ES resulted in significantly larger decreases in the critical value of end-expiratory pressure (P(crit)) (from 3.8 ± 2.2 to 2.9 ± 3.3 and -2.0 ± 3.9 cmH(2)O, respectively (p<0.001)). Both tongue size and velopharyngeal shape (anteroposterior to lateral ratio) correlated significantly with the decrease in P(crit) during GGp-ES (R = 0.53 and -0.66, respectively; p<0.05). In the patients with the larger tongue size (n = 7), the decrease in P(crit) reached 8.0 ± 2.2 cmH(2)O during GGp-ES. We conclude that directing stimulation to longitudinal fibres of the GG improves the flow-mechanical effect. In addition, patients with large tongues and narrow pharynx tend to respond better to GGp-ES.
Bifunctional Role of Protein Tyrosine Kinases in Late Preconditioning Against Myocardial Stunning in Conscious Rabbits
Authors: Buddhadeb Dawn, Yu-Ting Xuan, Yumin Qiu, Hitoshi Takano, Xian-Liang Tang, Peipei Ping, Supratim Banerjee, Michael Hill, Roberto Bolli
Journal: Circulation Research (1999)

Although protein tyrosine kinases (PTKs) have been implicated in late preconditioning (PC) against infarction, their role in late PC against stunning is unknown. Furthermore, it is unknown whether PTK signaling is necessary only to trigger late PC on day 1 or also to mediate it on day 2. Thus, conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days (days 1, 2, and 3). In the control group (group I, n=7), the recovery of systolic wall thickening after the 6 occlusion/reperfusion cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PTK inhibitor lavendustin-A (LD-A, 1 mg/kg IV) before the first occlusion on day 1 (group II, n=7) completely prevented the late PC effect against stunning on day 2. Late PC against stunning was also abrogated when LD-A was given before the first occlusion on day 2 (group III, n=7); however, in these rabbits, the late PC effect became apparent on day 3, indicating that LD-A itself did not have any delayed deleterious actions on myocardial stunning. In group V (n=5), the sequence of 6 occlusion/reperfusion cycles resulted in a robust increase in the activity of inducible NO synthase (iNOS [assessed as Ca(2+)-independent L-citrulline formation]) and nitrite+nitrate (NO(x)) tissue levels 24 hours later (on day 2), with no concomitant change in Ca(2+)-dependent NO synthase (endothelial NO synthase and/or neuronal NO synthase) activity. Similar results were obtained on day 3 (group VIII, n=6), indicating sustained upregulation of iNOS. Administration of LD-A either on day 1 (group VI, n=5) or on day 2 (group VII, n=6) abrogated the increase in iNOS activity and NO(x) levels on day 2. LD-A had no effect on iNOS activity or NO(x) levels in the absence of PC (group X, n=5). This study demonstrates that in conscious rabbits, PTK activity is necessary not only to trigger late PC against stunning on day 1 but also to mediate the protection on day 2. This investigation also provides the first direct evidence that cardiac iNOS activity is upregulated during the late phase of ischemic PC in rabbits. Furthermore, the data indicate that PTK signaling is essential for the augmentation of iNOS activity and that PTKs modulate this enzyme at two distinct levels: at an early stage on day 1 and at a late stage on day 2. This bifunctional role of PTKs in late PC has broad implications for the signaling mechanisms that underlie the response of the heart to ischemic stress and, possibly, other stresses.
Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis
Authors: Tsutomu Masaki, Yasushi Shiratori, William Rengifo, Kouichi Igarashi, Michiko Yamagata, Kazutaka Kurokohchi, Naohito Uchida, Yoshiaki Miyauchi, Hitoshi Yoshiji, Seishiro Watanabe, Masao Omata, Shigeki Kuriyama
Journal: Hepatology (2003)

Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCV-induced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC.
Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial
Authors: M P Schwartz, H Wellink, H G Gooszen, J M Conchillo, M Samsom, A J P M Smout
Journal: Gut (2006)

<b>Background:</b> Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. <b>Design and setting:</b> A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. <b>Patients and interventions:</b> 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. <b>Outcome measures:</b> The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. <b>Results:</b> At 3 months, the percentage of patients who had reduced drug use by ⩾50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p&lt;0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p&lt;0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. <b>Conclusions:</b> Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.
Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy.
Authors: B C Morson, J E Whiteway, E A Jones, F A Macrae, C B Williams
Journal: Gut (1984)

The histopathological features and results of treatment of malignant polyps removed by endoscopic polypectomy from 60 patients are presented. The patients were followed for a minimum of five years. Forty six patients were treated by polypectomy alone as local excision was judged complete and the invasive carcinoma was well or moderately well differentiated. Thirty seven of these patients are alive and well after five years and the remaining nine have died of other causes up to four years later: there was no evidence of recurrence in any of these cases. Fourteen patients underwent a subsequent major surgical resection and residual tumour was found at the site of polypectomy in two cases but regional lymph nodes were not involved. Only one patient from this group with a high grade tumour developed metastases although the operative specimen was free of tumour. Malignant polyps can be successfully treated by polypectomy alone provided both the laboratory techniques of examination and the histopathological criteria are strictly applied.
IL-6 drives T cell proliferation
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Hyperresponsiveness to the IL-6 family of cytokines triggers a spontaneous rheumatoid arthritis (RA)-like disease in mice. On page 1459, Sawa and colleagues show that excessive IL-6 signaling drives hyperproliferation of CD4+ T cells, which then attack the joints.

IL-6 has been implicated in RA and other T cell–driven autoimmune diseases. Indeed, a previous study by this group showed that an activating mutation in the gp130 subunit of the IL-6 receptor caused a lymphocyte-driven arthritis in mice. But the mechanism was unclear. The authors now show that disease development in these mice depends on CD4+ T cells, but not on cytolytic CD8+ T cells or antibody-producing B cells.

The CD4+ cells did not appear to cause disease because of an affinity for joint-specific antigens. Rather, the cells simply proliferated excessively in the mutant mice. This hyperproliferation was not the fault of the T cell, as wild-type CD4+ T cells also multiplied excessively and caused disease when transferred into irradiated mutant mice.

Rather, the gp130 mutation caused nonhematopoietic cells to produce excess IL-7—a growth factor that triggers T cell proliferation. This is the first evidence that IL-6 family cytokines can trigger IL-7 production.

These data suggest that IL-6, which is elevated in the serum and joints of patients with RA, might exacerbate disease by inducing IL-7 and thus driving T cell activation. What causes the overstimulated T cells to attack the joints in the first place remains a mystery.
Lipid content of human costal and articular cartilage.
Authors: R A Stockwell
Journal: Annals of the Rheumatic Diseases (1967)

Sacerdotti (1900) established that fat is a normal and constant constituent of the chondrocyte.Extra- cellular lipid in normal cartilage was described by Putschar (1931).Many histological investigations of the lipid content of cartilage have since been made, culminating in the ultrastructural observa- tions of Zbinden (1953), Collins, Ghadially, and Meachim (1965), and Ghadially, Meachim, and Collins (1965).Few quantitative studies exist.Sacerdotti (1900) carried out a small number of analyses on rabbit ear cartilage, and Hass (1943) studied an age-series of specimens of human costal cartilage.No conclusive results were obtained with respect to age changes.In the present quantitative study, a comparison is made of the age changes in the lipid content of post mortem human costal and articular cartilage. Material and MethodsCartilage was used from 45 human post mortem cases with no history of joint disease.Ages at death ranged from 2 days to 89 years.The fourth costal cartilage was removed, the perichondrium stripped off, and tissue free of macroscopic degenerative changes taken for lipid extraction.Normal articular cartilage was taken from the medial femoral condyle.The complete thickness of the cartilage (superficial to the calcified zone) was pared off the bone from the middle region of the condyle.
Stage I–II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis
Authors: N.E. Verstegen, J.W.A. Oosterhuis, D.A. Palma, G. Rodrigues, F.J. Lagerwaard, A. van der Elst, R. Mollema, W.F. van Tets, A. Warner, J.J.A. Joosten, M.I. Amir, C.J.A. Haasbeek, E.F. Smit, B.J. Slotman, S. Senan
Journal: Annals of Oncology (2013)