tbuckley/cabot-search huggingface dataset:
A role for ovarian hormones in sexual differentiation of the brain
Authors: Roslyn Holly Fitch, Victor H. Denenberg
Journal: Behavioral and Brain Sciences (1998)

Historically, studies of the role of endogenous hormones in developmental differentiation of the sexes have suggested that mammalian sexual differentiation is mediated primarily by testicular androgens, and that exposure to androgens in early life leads to a male brain as defined by neuroanatomy and behavior. The female brain has been assumed to develop via a hormonal default mechanism, in the absence of androgen or other hormones. Ovarian hormones have significant effects on the development of a sexually dimorphic cortical structure, the corpus callosum, which is larger in male than in female rats. In the females, removal of the ovaries as late as Day 16 increases the cross-sectional area of the adult corpus callosum. Treatment with low-dose estradiol starting on Day 25 inhibits this effect. Female callosa are also enlarged by a combination of daily postnatal handling and exogenous testosterone administered prior to Day 8. The effects of androgen treatment are expressed early in development, with males and testosterone-treated females having larger callosa than control females as early as Day 30. The effects of ovariectomy do not appear until after Day 55. These findings are more consistent with other evidence of a later sensitive period for ovarian feminization as compared to androgenic masculinization.
Screening for pain in knee osteoarthritis: which question?
Authors: S C O'Reilly, K R Muir, M Doherty
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To compare three questions on knee pain with respect to determined prevalence and associations with disability and structural change. METHODS: Postal survey to 4057 men and women aged 40-79 years. Knee pain was defined by three questions: (A) "Have you ever had pain in or around the knee on most days for at least a month? If so, have you experienced any pain during the last year?" (B) "Have you had pain within the last year in or around the knee that occurred on most days for at least a month?" (C) "Have you had knee pain on most days of the last month?" [American College of Rheumatology (ACR) criteria for knee osteoarthritis]. Disability was assessed with the SF-36 health status questionnaire. Radiographs (AP weight bearing and skyline) were obtained on a proportion (n = 459) and graded for maximum osteophyte in any compartment. RESULTS: Prevalence of knee pain for questions A, B, and C were 28.3%, 25.3%, and 19.3% respectively. Highest rates of disability were observed for question C (71.3% compared with 60.9% for question A). There was no major difference between questions in terms of percentage with &gt; or = grade 1 osteophyte or &gt; or = grade 2 osteophyte. Sensitivity and specificity of each question for &gt; or = grade 1 osteophyte did vary, with question A being most sensitive but least specific (58.7% and 59.1%) and question C most specific (72.7%) but least sensitive (45.4%). CONCLUSIONS: Estimates of knee pain and disability are influenced by even minor changes in question content. The ACR criteria question may be a better predictor of disability but is relatively insensitive for use in the community.
Variants within the<i>COL5A1</i>gene are associated with Achilles tendinopathy in two populations
Authors: A V September, J Cook, C J Handley, L van der Merwe, M P Schwellnus, M Collins
Journal: British Journal of Sports Medicine (2008)

A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathy in a South African population. The aim of this case-control genetic association study was to investigate the BstUI and DpnII restriction fragment length polymorphisms (RFLP) in a second population from Australia and to identify a predisposing haplotype for Achilles tendinopathy in both populations.85 Australian and 93 South African patients with tendinopathy, as well as 210 Australian and 132 white South African control subjects were genotyped for the BstUI (rs12722) and DpnII (rs13946) RFLP, as well as markers rs10858286, rs3196378, rs11103544, rs4504708 and rs3128575.The BstUI RFLP (p<0.001) and marker rs3196378 (p = 0.016) were associated with chronic Achilles tendinopathy in Australian subjects. Individuals within both populations with a CC genotype for the BstUI RFLP had a significantly decreased risk of developing tendinopathy versus any other genotypes (Australian odds ratio 0.42, 95% CI 0.20 to 0.86, p = 0.017). The TC inferred haplotype (rs12722, rs3196378) was found to be overrepresented (global p = 0.008) in the South African tendinopathy group compared with all other haplotypes.The BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and a region within the COL5A1 3' untranslated region may predispose individuals to an increased risk of developing chronic Achilles tendinopathy.
Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein.
Authors: F C de Beer, A K Soutar, M L Baltz, I M Trayner, A Feinstein, M B Pepys
Journal: The Journal of Experimental Medicine (1982)

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.
Dishevelled 2 Signaling Promotes Self-Renewal and Tumorigenicity in Human Gliomas
Authors: Teodoro Pulvirenti, Maartje Van Der Heijden, Leif A. Droms, Jason T. Huse, Viviane Tabar, Alan Hall
Journal: Cancer Research (2011)

Glioblastoma multiforme is the most common glioma variant in adults and is highly malignant. Tumors are thought to harbor a subpopulation of stem-like cancer cells, with the bulk resembling neural progenitor-like cells that are unable to fully differentiate. Although multiple pathways are known to be involved in glioma tumorigenesis, the role of Wnt signaling has been poorly described. Here, we show that Dishevelled 2 (Dvl2), a key component of the Wnt signaling pathway, is overexpressed in human gliomas. RNA interference-mediated depletion of Dvl2 blocked proliferation and promoted the differentiation of cultured human glioma cell lines and primary, patient-derived glioma cells. In addition, Dvl2 depletion inhibited tumor formation after intracranial injection of glioblastoma cells in immunodeficient mice. Inhibition of canonical Wnt/β-catenin signaling also blocked proliferation, but unlike Dvl2 depletion, did not induce differentiation. Finally, Wnt5a, a noncanonical Wnt ligand, was also required for glioma cell proliferation. The data therefore suggest that both canonical and noncanonical Wnt signaling pathways downstream of Dvl2 cooperate to maintain the proliferative capacity of human glioblastomas.
Randomized, Controlled, Double-Blind, Cross-Over Trial Assessing Treatment Preference for Pazopanib Versus Sunitinib in Patients With Metastatic Renal Cell Carcinoma: PISCES Study
Authors: Bernard Escudier, Camillo Porta, Petri Bono, Thomas Powles, Tim Eisen, Cora N. Sternberg, Jürgen E. Gschwend, Ugo De Giorgi, Omi Parikh, Robert Hawkins, Emmanuel Sevin, Sylvie Négrier, Sadya Khan, Jose Diaz, Suman Redhu, Faisal Mehmud, David Cella
Journal: Journal of Clinical Oncology (2014)

Patient-reported outcomes may help inform treatment choice in advanced/metastatic renal cell carcinoma (RCC), particularly between approved targeted therapies with similar efficacy. This double-blind cross-over study evaluated patient preference for pazopanib or sunitinib and the influence of health-related quality of life (HRQoL) and safety factors on their stated preference.Patients with metastatic RCC were randomly assigned to pazopanib 800 mg per day for 10 weeks, a 2-week washout, and then sunitinib 50 mg per day (4 weeks on, 2 weeks off, 4 weeks on) for 10 weeks, or the reverse sequence. The primary end point, patient preference for a specific treatment, was assessed by questionnaire at the end of the two treatment periods. Other end points and analyses included reasons for preference, physician preference, safety, and HRQoL.Of 169 randomly assigned patients, 114 met the following prespecified modified intent-to-treat criteria for the primary analysis: exposure to both treatments, no disease progression before cross over, and completion of the preference questionnaire. Significantly more patients preferred pazopanib (70%) over sunitinib (22%); 8% expressed no preference (P < .001). All preplanned sensitivity analyses, including the intent-to-treat population, statistically favored pazopanib. Less fatigue and better overall quality of life were the main reasons for preferring pazopanib, with less diarrhea being the most cited reason for preferring sunitinib. Physicians also preferred pazopanib (61%) over sunitinib (22%); 17% expressed no preference. Adverse events were consistent with each drug's known profile. Pazopanib was superior to sunitinib in HRQoL measures evaluating fatigue, hand/foot soreness, and mouth/throat soreness.This innovative cross-over trial demonstrated a significant patient preference for pazopanib over sunitinib, with HRQoL and safety as key influencing factors.
Regional blood flow, microvascular blood content and tissue haematocrit in canine myocardium
Authors: P. ELIASEN, O. AMTORP, E. TONDEVOLD, S. HAUNSO
Journal: Cardiovascular Research (1982)

Journal Article Regional blood flow, microvascular blood content and tissue haematocrit in canine myocardium Get access PER ELIASEN, PER ELIASEN * From the Department of Cardiology and Department of Clinical Physiology, Gentofte Hospital, Denmark *Correspondence and reprint requests: Per Eliasen, MD, Department of Cardiology, Gentofte Hospital, DK-2900 Hellerup, Denmark. Search for other works by this author on: Oxford Academic PubMed Google Scholar OLE AMTORP, OLE AMTORP From the Department of Cardiology and Department of Clinical Physiology, Gentofte Hospital, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar ERIK TØNDEVOLD, ERIK TØNDEVOLD From the Department of Cardiology and Department of Clinical Physiology, Gentofte Hospital, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar STIG HAUNSØ STIG HAUNSØ From the Department of Cardiology and Department of Clinical Physiology, Gentofte Hospital, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 10, October 1982, Pages 593–598, https://doi.org/10.1093/cvr/16.10.593 Published: 01 October 1982
The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.
Authors: R D Gordon, B J Mathieson, L E Samelson, E A Boyse, E Simpson
Journal: The Journal of Experimental Medicine (1976)

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.
A CLINICAL COMPARISON BETWEEN TRIACETOXYANTHRACENE AND DITHRANOL PASTES IN THE TREATMENT OF CHRONIC PSORIASIS
Authors: COURTNEY HODGSON, ELIZABETH HELL
Journal: British Journal of Dermatology (1970)

SUMMARY.—

A clinical comparison of the effects of triacetoxyanthracene and dithranol pastes in the treatment of 20 patients with chronic psoriasis has shown that in one-third of the cases the degree of suppression of the disease was approximately the same. In the remainder, dithranol proved to be more effective than triacetoxyanthracene. In those subjects who showed a satisfactory therapeutic response, dithranol had a more rapid suppressive effect in almost two-thirds. It was concluded that triacetoxyanthracene is less effective and slower to exert its therapeutic action than dithranol in the treatment of chronic psoriasis.



The relative absence of inflammatory reactions and staining of the skin during the use of triacetoxyanthracene was confirmed. Both dithranol and triacetoxyanthracene were shown to produce an injury response in animal skin. A possible relationship between the intensity of the inflammatory or injury response during clinical usage and the degree of therapeutic activity of dithranol and triacetoxyanthracene is discussed.
Intention-to-Treat Analysis of Pulmonary Artery Banding in Conditions With a Morphological Right Ventricle in the Systemic Circulation With a View to Anatomic Biventricular Repair
Authors: David S. Winlaw, Simon P. McGuirk, Christian Balmer, Stephen M. Langley, Massimo Griselli, Oliver Stümper, Joseph V. De Giovanni, John G. Wright, Sara Thorne, David J. Barron, William J. Brawn
Journal: Circulation (2005)

Background— Some patients with a morphological right ventricle (mRV) in the systemic circulation require early intervention because of progressive systemic ventricular dysfunction or atrioventricular valve regurgitation. They may be eligible for anatomic repair (correction of atrioventricular and ventriculoarterial discordance) but require prior training of the morphological left ventricle (mLV). Methods and Results— Forty-one patients with congenitally corrected transposition of the great arteries or a previous atrial switch procedure embarked on a protocol of pulmonary artery (PA) banding with a view to anatomic repair. All had an mRV in the systemic circulation and a subpulmonary mLV that was not conditioned by either volume or pressure load. Two patients were not banded, and 39 were followed up for a median of 4.3 years (range, 25 days to 12.6 years). Sixteen patients achieved anatomic repair, with 3 in the early stages of the training protocol. After 2 years, 12 patients were not suitable for anatomic repair and persisted with palliative banding; 8 were functionally improved; and 4 died, underwent transplantation, or required debanding. PA banding improved functional class but did not improve tricuspid regurgitation in the long term for patients not achieving anatomic repair. mLV function was a critical determinant of survival with a PA band as well as survival after anatomic repair. Patients &gt;16 years were unlikely to achieve anatomic repair. Conclusion— PA banding is a safe and effective method of training the mLV before anatomic repair. It is also an effective palliative procedure for those who do not attain this goal.
Proinflammatory and Prothrombotic Effects of Hypoglycemia
Authors: Paresh Dandona, Ajay Chaudhuri, Sandeep Dhindsa
Journal: Diabetes Care (2010)

Hypoglycemia is known to be intrinsic to the treatment of diabetes because insulin is a powerful glucose-lowering agent and sulfonylureas exert their effect through insulin release by the pancreatic β-cells. Hypoglycemia occurs in association with these two common modes of therapy and was previously accepted as a part of the treatment of this condition. With the arrival of other modes of diabetes treatment, such as metformin, thiazolidenediones, α2-glucosidase inhibitors, and incretins, which do not induce hypoglycemia except when administered in combination with insulin and sulfonylureas, the issue of hypoglycemia has to be assessed in the context of both the immediate risk related to neuroglycopenia and the possible long-term risk of diabetic vascular complications.

Vascular complications of hypoglycemia have to be tackled with greater urgency now because two recent trials of intensified diabetes treatment with insulin, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and Veteran's Affairs Diabetes Trial (VADT), did not demonstrate a reduction in cardiovascular events (1,2). In fact, the intensified insulin treatment arm of the ACCORD trial had to be halted because of an increase in overall mortality, despite a reduction in acute myocardial infarction. The rate of hypoglycemia in both trials was significantly increased with intensified insulin treatment. Although the analysis of the ACCORD data did not support the hypothesis that the increased mortality in the study was a result of hypoglycemia, the fact that hypoglycemia may often be asymptomatic leaves us with the possibility that it may be responsible.

The fact that hypoglycemia results in platelet hyperaggregability (3) and an increase in several factors involved …
Phase I/II study with a weekly 24-hour infusion of 5-fluorouracil plus high-dose folinic acid (HD-FU/FA) in intensively pretreated patients with metastatic breast cancer
Authors: H. Wilke, U. Klaassen, W. Achterrath, M. Losch, U. Vanhoefer, J. Hayungs, A. Harstrick, M. Stahl, W. Eberhardt, R. Becher, S. Seeber
Journal: Annals of Oncology (1996)

In metastatic breast cancer patients who have had prior exposure to anthracyclines, single agents induce less than 15% and combination chemotherapy less than 20%-30% of objective responses. Therefore more active and tolerable salvage regimens are needed.Forty-three patients with advanced breast cancer pretreated with 1-5 (median 2) different chemotherapy regimens were entered into this phase I/II trial. Treatment consisted of folinic acid (FA) (500 mg/m2, i.v., 2-hour infusion) followed by a 24-hour infusion of 5-fluorouracil (FU) which was escalated from 1.5 g/m2 (dose level (dl 1)), to 1.8 g/m2 (dl 2) to 2.1 g/m2 (dl 3). Therapy was given as outpatient treatment once weekly times 6 followed by a 2-week rest.HD-FU/FA was well tolerated. No dose-limiting toxicity occurred at dl 1 or 2. Only 3/32 (9%) patients had WHO grade 3/4 toxicities (gastrointestinal toxicities, hand-foot-syndrome) at dl 3. The response rate for all 32 of the patients treated at dl 3 was 41% (13/32). In the 24 patients with anthracycline-refractory disease, a response rate of 41% (10/24) was achieved. The median remission duration was 11 months and the median survival time 19 months.This schedule of FU/FA is a safe outpatient treatment with substantial activity in intensively pretreated breast cancer patients.
Subgroup Analysis of Asian Patients in the Phase III Trial (GRID) of Regorafenib in Pretreated Metastatic GIST
Authors: Y.-K. Kang, J. Xu, Y. Komatsu, S.-A. Im, J. Li, T. Nishida, R. Quek, C. Kappeler, I. Kuss, G.D. Demetri, R. Takimoto
Journal: Annals of Oncology (2013)
Rho Family Gtpase Cdc42 Is Essential for the Actin-Based Motility of <i>Shigella</i> in Mammalian Cells
Authors: Toshihiko Suzuki, Hitomi Mimuro, Hiroaki Miki, Tadaomi Takenawa, Takuya Sasaki, Hiroyuki Nakanishi, Yoshimi Takai, Chihiro Sasakawa
Journal: The Journal of Experimental Medicine (1999)

Shigella, the causative agent of bacillary dysentery, is capable of directing its movement within host cells by exploiting actin dynamics. The VirG protein expressed at one pole of the bacterium can recruit neural Wiskott-Aldrich syndrome protein (N-WASP), a downstream effector of Cdc42. Here, we show that Cdc42 is required for the actin-based motility of Shigella. Microinjection of a dominant active mutant Cdc42, but not Rac1 or RhoA, into Swiss 3T3 cells accelerated Shigella motility. In add-back experiments in Xenopus egg extracts, addition of a guanine nucleotide dissociation inhibitor for the Rho family, RhoGDI, greatly diminished the bacterial motility or actin assembly, which was restored by adding activated Cdc42. In N-WASP–depleted extracts, the bacterial movement almost arrested was restored by adding exogenous N-WASP but not H208D, an N-WASP mutant defective in binding to Cdc42. In pyrene actin assay, Cdc42 enhanced VirG-stimulating actin polymerization by N-WASP–actin-related protein (Arp)2/3 complex. Actually, Cdc42 stimulated actin cloud formation on the surface of bacteria expressing VirG in a solution containing N-WASP, Arp2/3 complex, and G-actin. Immunohistological study of Shigella-infected cells expressing green fluorescent protein–tagged Cdc42 revealed that Cdc42 accumulated by being colocalized with actin cloud at one pole of intracellular bacterium. Furthermore, overexpression of H208D mutant in cells interfered with the actin assembly of infected Shigella and diminished the intra- and intercellular spreading. These results suggest that Cdc42 activity is involved in initiating actin nucleation mediated by VirG–N-WASP–Arp2/3 complex formed on intracellular Shigella.
Conclusions: the relative safety of modern oral contraceptives
Authors: J Cohen
Journal: Human Reproduction Update (1999)

Published data on the relative safety of second and third generation oral contraceptives (OCs) is critically assessed. The original four studies published in 1995/1996 and their conclusions are examined in detail, including comments made by other investigators. Each study has advantages and flaws which are balanced in detail . Newer studies are then examined in the same manner. All recent papers indicate an equivalence of safety of second and third generation OCs, as the effects of various confounders and biases have been identified and analysed. We conclude that absolute risks are minor with both generations and that no reasons now exist to indicate any differences in their overall safety. We analyse finally how the pill crisis arose, ad make suggestions about future reporting on OC safety.