tbuckley/cabot-search huggingface dataset:
Tracing Past Human Male Movements in Northern/Eastern Africa and Western Eurasia: New Clues from Y-Chromosomal Haplogroups E-M78 and J-M12
Authors: F. Cruciani, R. La Fratta, B. Trombetta, P. Santolamazza, D. Sellitto, E. B. Colomb, J.-M. Dugoujon, F. Crivellaro, T. Benincasa, R. Pascone, P. Moral, E. Watson, B. Melegh, G. Barbujani, S. Fuselli, G. Vona, B. Zagradisnik, G. Assum, R. Brdicka, A. I. Kozlov, G. D. Efremov, A. Coppa, A. Novelletto, R. Scozzari
Journal: Molecular Biology and Evolution (2007)

Detailed population data were obtained on the distribution of novel biallelic markers that finely dissect the human Y-chromosome haplogroup E-M78. Among 6,501 Y chromosomes sampled in 81 human populations worldwide, we found 517 E-M78 chromosomes and assigned them to 10 subhaplogroups. Eleven microsatellite loci were used to further evaluate subhaplogroup internal diversification. The geographic and quantitative analyses of haplogroup and microsatellite diversity is strongly suggestive of a northeastern African origin of E-M78, with a corridor for bidirectional migrations between northeastern and eastern Africa (at least 2 episodes between 23.9–17.3 ky and 18.0–5.9 ky ago), trans-Mediterranean migrations directly from northern Africa to Europe (mainly in the last 13.0 ky), and flow from northeastern Africa to western Asia between 20.0 and 6.8 ky ago. A single clade within E-M78 (E-V13) highlights a range expansion in the Bronze Age of southeastern Europe, which is also detected by haplogroup J-M12. Phylogeography pattern of molecular radiation and coalescence estimates for both haplogroups are similar and reveal that the genetic landscape of this region is, to a large extent, the consequence of a recent population growth in situ rather than the result of a mere flow of western Asian migrants in the early Neolithic. Our results not only provide a refinement of previous evolutionary hypotheses but also well-defined time frames for past human movements both in northern/eastern Africa and western Eurasia.
Phase I study of terameprocol in patients with recurrent high-grade glioma
Authors: S. A. Grossman, X. Ye, D. Peereboom, M. R. Rosenfeld, T. Mikkelsen, J. G. Supko, S. Desideri
Journal: Neuro-Oncology (2012)

Terameprocol is a global transcription inhibitor that affects cell division apoptosis, drug resistance, hypoxia responsive genes, and radiation resistance in hypoxia. A multicenter, dose-escalation study was conducted in heavily pretreated patients with recurrent, measurable, high-grade gliomas. Terameprocol was administered intravenously for 5 consecutive days each month and discontinued for toxicity or progression. Patients taking enzyme-inducing antiseizure drugs (EIASDs) were escalated independently. Thirty-five patients with a median Karnofsky performance status of 80, median age of 46 years, and median of 2 prior treatment regimens were accrued. Doses of 750, 1100, 1700, and 2200 mg/day were administered. Terameprocol was reformulated to avoid acidosis related to the excipient and was well tolerated at 1700 mg/day. Hypoxia and interstitial nephritis were noted at 2200 mg/day. Concurrent administration of EIASD did not significantly affect the serum pharmacokinetics of the terameprocol. Although no responses were seen, stable disease was noted in 9 (28%) of 32 evaluable patients, with 5 (13%) continuing treatment for >6 months (≥6, 8, 10, 10, and ≥21 months). The overall median survival was 5.9 months. This phase I study defined the toxicity of terameprocol, determined that EIASDs do not affect its pharmacokinetics, and identified 1700 mg/day as the dose for future studies. Preclinical and human data suggest that this novel transcription inhibitor is worthy of further study. The long-term stability noted in some patients and the lack of associated myelosuppression suggest that terameprocol could be safely combined with radiation and temozolomide in newly diagnosed high-grade gliomas.
Randomized Study of the Duration of Treatment With Interferon Alfa-2B in Patients With Hairy Cell Leukemia
Authors: H. M. Golomb, M. J. Ratain, A. Fefer, J. Thompson, D. W. Golde, H. Ozer, C. Portlock, R. Silber, J. Rappeport, E. Bonnem, R. Spiegel, L. Tensen, J. S. Burke, J. W. Vardiman
Journal: JNCI Journal of the National Cancer Institute (1988)

Several previous studies have demonstrated that both partially purified and recombinant α-interferons (α-IFNs) have high response rates in advanced hairy cell leukemia. However, the optimal dose and duration of therapy have not yet been defined. In this study, 90 patients were randomized after 12 months of IFN alfa-2b therapy with a standard dose of 2 × 106 U/m2 sc three times weekly to either no further therapy or an additional 6 months of therapy (18 mo total). There was no significant difference in the peripheral blood cell counts between the two groups (when analyzed) dating from the end of IFN therapy rather than from the time of randomization. Eighteen evaluable patients relapsed and were re-treated with IFN: 11 in the no-further-therapy group and 7 in the treated group. No patient was resistant to re-treatment with IFN. There was a significantly greater incidence of fatigue in the treated group (44% vs. 21%; P = .02) during the first 6 postrandomization months. We conclude that the duration of IFN therapy does not influence the clinical course after therapy is discontinued, but responses are maintained while patients receive therapy. However, because of a high incidence of fatigue with prolonged therapy and the ability to reinduce a second response, we recommend that IFN therapy be discontinued after 12 months in asymptomatic patients.
RASTA-Bacteria: a web-based tool for identifying toxin-antitoxin loci in prokaryotes
Authors: Emeric W Sevin, Frédérique Barloy-Hubler
Journal: Genome biology (2007)

Toxin/antitoxin (TA) systems, viewed as essential regulators of growth arrest and programmed cell death, are widespread among prokaryotes, but remain sparsely annotated. We present RASTA-Bacteria, an automated method allowing quick and reliable identification of TA loci in sequenced prokaryotic genomes, whether they are annotated open reading frames or not. The tool successfully confirmed all reported TA systems, and spotted new putative loci upon screening of sequenced genomes. RASTA-Bacteria is publicly available at http://genoweb.univ-rennes1.fr/duals/RASTA-Bacteria .
Lamprey proglucagon and the origin of glucagon-like peptides
Authors: D. M. Irwin, O. Huner, J. H. Youson
Journal: Molecular Biology and Evolution (1999)

We characterized two proglucagon cDNAs from the intestine of the sea lamprey Petromyzon marinus. As in other vertebrates, sea lamprey proglucagon genes encode three glucagon-like sequences, glucagon, and glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). This observation indicates that all three glucagon-like sequences encoded by the proglucagon gene originated prior to the divergence of jawed and jawless vertebrates. Estimates of the rates of evolution for the glucagon-like sequences suggest that glucagon originated first, about 1 billion years ago, while GLP-1 and GLP-2 diverged from each other about 700 MYA. The two sea lamprey intestinal proglucagon cDNAs have differing coding potential. Proglucagon I cDNA encodes the previously characterized glucagon and the glucagon-like peptide GLP-1, while proglucagon II cDNA encodes a predicted GLP-2 and, possibly, a glucagon. The existence of two proglucagon cDNAs which differ with regard to their potential to encode glucagon-like peptides suggests that the lamprey may use differential gene expression as a third mechanism, in addition to alternative proteolytic processing and mRNA splicing, to regulate the production of proglucagon-derived peptides.
STABLE SUSPENSIONS OF AUTOAGGLUTINABLE BACTERIA
Authors: Paul H. De Kruif, John H. Northrop
Journal: The Journal of Experimental Medicine (1923)

Autoagglutinating cultures of Type G, bacillus of rabbit septicemia, can be rendered stable by suspension in glycocoll-acetate-phosphate buffer mixtures pH 7.5 and 7.1. Distilled water suspensions can also be employed if the normal and immune serum under test is diluted with buffers of this pH instead of with 0.85 per cent NaCl. Five intensely autoagglutinable strains of Streptococcus haemolyticus have been stabilized by washing and by suspending in 0.001 N NaOH. Specific agglutination of these stable suspensions by rabbit antistreptococcus serum could be demonstrated by diluting the serum with M/320 NaCl.
Surgery of the Primary Tumor in Metastatic Breast Cancer: Closing the Barn Door After the Horse Has Bolted?
Authors: Monica Morrow, Lori Goldstein
Journal: Journal of Clinical Oncology (2006)

Traditionally, metastatic breast cancer is considered to be incurable, and the goals of treatment are the prolongation of life and the palliation or prevention of symptoms. Within this context, it is not surprising that local therapy is not routinely recommended for patients presenting with stage IV disease and intact primary tumors. Surgery is reserved for patients who develop complications such as bleeding, ulceration, and infection at the primary tumor site, a type of surgery that historically has been described as “toilette” mastectomy. In this issue of the Journal of Clinical Oncology, Rapiti et al 1 present the results of a retrospective, population-based study of the impact of surgical therapy of the primary tumor on survival outcomes in 300 women with metastatic disease at the time of the initial diagnosis of breast cancer. The authors observed that women having surgery of the primary tumor had a 50% reduction in breast cancer mortality compared with women who did not undergo surgery, the survival benefit was limited to women with tumor-free margins of resection, and a significant survival benefit for axillary surgery was not observed. These results are strikingly similar to those reported by Khan et al 2 in a retrospective study of 16,023 patients presenting with stage IV disease at initial breast cancer diagnosis. In the work of Khan, surgery of the primary tumor was associated with a 39% reduction in the risk of death, with a 3-year survival of 35% for patients excised to negative margins, 26% for those with positive margins, and 17.3% for those not having surgery (P .0001). Again, axillary dissection was not found to contribute significantly to survival. Both Rapiti et al 1 and Khan et al 2 adjusted for factors such as number of metastatic sites, location of metastases (visceral v bone and soft tissue), and type of systemic therapy that might have differed between patients who had surgical treatment and those who did not. However, both studies concluded that unrecognized selection bias may have accounted for the observed benefit of surgery, and only a large, prospective randomized trial could determine reliably whether surgery of the primary tumor prolongs survival in the patient presenting with metastatic breast cancer. The merits of prospective, randomized trials are obvious, but
Neoadjuvant therapy of rectal carcinoma with UFT–leucovorin plus radiotherapy
Authors: J. Feliu, J. Calvillo, A. Escribano, J. de Castro, M.E. Sánchez, A. Mata, E. Espinosa, A. García Grande, A. Mateo, M. González Barón
Journal: Annals of Oncology (2002)

BackgroundThe object of this phase II study was to assess the impact of preoperative external radiation therapy combined with UFT and leucovorin on tumor response, sphincter preservation and tumor control in patients with rectal carcinoma.Patients and methodsForty-one patients with resectable extraperitoneal rectal adenocarcinoma received radiation therapy and two courses of chemotherapy. Chemotherapy consisted of a 2-h infusion of 6S-steroisomer of leucovorin (6SLV) 250 mg/m2 on day 1, oral 6SLV 7.5 mg every 12 h on days 2–14, and UFT either 350 or 300 mg/m2 on days 1 to 14 every 28 days. Six additional courses of chemotherapy were given after surgery.ResultsSeven of 16 patients (43%) who received 350 mg/m2/day of UFT had grade 3–4 diarrhea and two other patients (12%) had grade 3–4 dermatitis. The next 25 patients received 300 mg/m2/day of UFT and only 14% of them had grade 3–4 diarrhea. Surgery consisted of low-anterior resection in 26 patients (63%) and abdominal-perineal amputation in 15 (37%). There were six histological complete responses (15%). Downstaging occurred in 25 patients (63%). The overall survival at 3 years was 90% and the pelvic disease-free survival 92%.ConclusionsPreoperative therapy with radiotherapy and UFT–6SLV downstaged 63% of tumors and allowed a sphincter-preserving procedure in some patients. Toxicity was moderate. This scheme is convenient because of the oral administration of chemotherapy.
Role of vascular endothelial growth factor on erythropoietin-related endothelial cell proliferation.
Authors: M V Alvarez Arroyo, M A Castilla, F R González Pacheco, D Tan, A Riesco, S Casado, C Caramelo
Journal: Journal of the American Society of Nephrology (1998)

The vascular actions of recombinant human erythropoietin (rhEPO) are of particular relevance for fully understanding rhEPO effects. This study examines the mechanisms of action of rhEPO on endothelial cells from bovine aorta (BAEC). First, the studies demonstrated that rhEPO acts on BAEC proliferation as a comitogenic growth factor in the presence of fetal calf serum (FCS). The main experimental findings disclosed that an interaction between rhEPO and vascular endothelial growth factor (VEGF) is instrumental for the growth-promoting action of rhEPO, as shown by the blockade (92.8+/-2.2% inhibition, P < 0.01) of the rhEPO-induced BAEC proliferation by a specific anti-VEGF antibody and by the capability of VEGF for substituting FCS in the induction of rhEPO-related BAEC proliferation (increase in BAEC number in the absence of FCS: 20 U/ml rhEPO alone, 0.3+/-2.8%; 5 x 10(-11) M VEGF alone, 52.9+/-3.1%; 20 U/ml rhEPO + 5 X 10(-11) M VEGF, 117.8+/-6.9%, P < 0.01 between the two agents combined with respect to each agent alone). The existence of a positive interaction between rhEPO and VEGF was further demonstrated by observing an increased cytosolic Ca2+ ([Ca2+]i) mobilization response to VEGF (10(-11)M) in BAEC pretreated or not with 20 U/ml rhEPO (delta[Ca2+]i = 704+/-111 versus 246+/-36 nM, respectively, P < 0.01). To further examine the mechanism of the potentiation of VEGF effect by rhEPO, we analyzed the mRNA expression of the VEGF receptors KDR/flk-1 and flt-1. The results disclosed that BAEC pretreatment with rhEPO upregulated the expression of both KDR/flk-1 and flt-1, therefore providing a structural basis for the aforementioned positive interactions between VEGF and rhEPO. Furthermore, inhibition by genistein suggests that tyrosine phosphorylation was involved in the VEGF receptor upregulation. The mechanisms identified in the present study disclose an interaction at the level of mRNA expression and functional effects between a hormone with predominantly hemopoietic effects, namely, erythropoietin, and an angiogenic factor, namely, VEGF. This relationship between rhEPO and VEGF might be of particular importance in neovascularization processes and in patients receiving rhEPO as a treatment.
Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence
Authors: Matthieu Camus, Marie Tosolini, Bernhard Mlecnik, Franck Pagès, Amos Kirilovsky, Anne Berger, Anne Costes, Gabriela Bindea, Pornpimol Charoentong, Patrick Bruneval, Zlatko Trajanoski, Wolf-Herman Fridman, Jérôme Galon
Journal: Cancer Research (2009)

A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters that could describe in situ immune responses in human colorectal cancer according to clinical parameters of metastatic lymph node or distant organ invasion (META- or META+ patients). Primary tumor samples of colorectal carcinoma were analyzed by integrating large-scale phenotypic (flow cytometry, 39 patients) and gene expression (real time reverse transcription-PCR, 103 patients) data sets related to immune and protumoral processes. In META- colorectal cancer primary tumors with high densities of T cells, we observed significant positive correlations between markers of innate immune cells [tumor-associated macrophages, dendritic cells, natural killer (NK) cells, and NKT cells] and markers of early-activated T cells. Significant correlations were also observed between markers of cytotoxic and effector memory T-cell subpopulations. These correlation profiles were absent in tumors with low T-cell infiltrates and were altered in META+ tumors with high T-cell infiltrates. We show that the coexpression of genes mediating cytotoxicity (GNLY) and Th1 adaptive immune responses (IRF1) accurately predicted patient survival independently of the metastatic status. High intratumoral mRNA expression of the proangiogenic mediator vascular endothelial growth factor was associated with significantly reduced survival rates in patients expressing high mRNA levels of GNLY. Investigation of the colorectal cancer primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response.
Melanoma-Specific Memory T Cells Are Functionally Active in<i>Ret</i>Transgenic Mice without Macroscopic Tumors
Authors: Viktor Umansky, Oliver Abschuetz, Wolfram Osen, Marcel Ramacher, Fang Zhao, Masashi Kato, Dirk Schadendorf
Journal: Cancer Research (2008)

Abstract We previously reported that bone marrows of breast cancer patients contained tumor antigen–specific CD8+ T cells with central or effector memory phenotype. Using a recently developed ret transgenic mouse melanoma model, we now show that bone marrows and tumors of transgenic mice contain high frequencies of CD8+ T cells specific for the melanoma antigen tyrosinase-related protein 2 and showing mostly effector memory phenotype. Moreover, increased numbers of bone marrow tyrosinase-related protein-2–specific effector memory CD8+ T cells are also detected in transgenic animals older than 20 weeks with disseminated melanoma cells in the bone marrow and lymph nodes but showing no visible skin tumors and no further melanoma progression. After a short-term coincubation with dendritic cells generated from the bone marrow and pulsed with melanoma lysates, bone marrow memory T cells from mice without macroscopic melanomas produced IFN-γ in vitro and exerted antitumor activity in vivo after adoptive transfer into melanoma-bearing mice. Our data indicate that functionally active bone marrow–derived melanoma-specific memory T cells are detectable at the phase of microscopic tumor load, suggesting that thereby they could control disseminated melanoma cells. [Cancer Res 2008;68(22):9451–8]
Cytotoxic Effects of Topotecan Combined With Various Anticancer Agents in Human Cancer Cell Lines
Authors: S H Kaufmann, D Peereboom, C A Buckwalter, P A Svingen, L B Grochow, R C Donehower, E K Rowinsky
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited.
Toxoplasmosis
Authors: DONALD J. KROGSTAD
Journal: Annals of Internal Medicine (1972)

Toxoplasmosis is a common infection, but Toxoplasma gondii is not often diagnosed as the cause of illness. The manifestations of congenital toxoplasmosis include chorioretinitis, microcephaly, hydrocephaly, mental retardation, cerebral calcification, and seizure disorders; however, most congenital infections are asymptomatic. Acquired toxoplasmosis can mimic a viral syndrome with lymphadenopathy, infectious mononucleosis, viral pericarditis, or rickettsial spotted fevers. Documented modes of transmission are by eating raw meat and across the placenta of an infected pregnant woman to her child. Oocysts in the feces of cats infected with T. gondii have led to seroconversion in laboratory personnel working with this material. The significance of this change in regard to the epidemiology and natural transmission of toxoplasmosis, especially to pregnant women, remains unresolved. There have been no controlled clinical trials to establish the efficacy of drug therapy.
The Static Limit of Arterial Blood Pressure in the Dog's Hind Limb
Authors: MATTHEW N. LEVY, FRED A. PHILLIPS, SHIRLEY H. BRIND
Journal: Circulation Research (1954)

When the femoral artery is occluded in the anesthetized dog, the pressure in the distal segment usually declines progressively and approaches a static limit asymptotically. This static limit is independent of the original Degrees of vasomotor tone except under extreme conditions. It is concluded that the rapid supervention of reactive hyperemia in the dog vitiates the static limit as an index of vasomotor tone, unless an instantaneous method is developed for its estimation.
Clinical features of 31 patients with systemic contact dermatitis due to the ingestion of Rhus (lacquer)
Authors: S.D. Park, S-W. Lee, J-H. Chun, S-H. Cha
Journal: British Journal of Dermatology (2000)

Journal Article Clinical features of 31 patients with systemic contact dermatitis due to the ingestion of Rhus (lacquer) Get access S.D. Park, S.D. Park Department of Dermatology, Wonkwang University School of Medicine, 344‐2 Shinyong‐dong, Iksan, Chonbuk 570‐711, Korea Seok Don Park. E‐mail: sdpark@wonkwang.ac.kr Search for other works by this author on: Oxford Academic Google Scholar S‐W. Lee, S‐W. Lee Department of Dermatology, Wonkwang University School of Medicine, 344‐2 Shinyong‐dong, Iksan, Chonbuk 570‐711, Korea Search for other works by this author on: Oxford Academic Google Scholar J‐H. Chun, J‐H. Chun Department of Dermatology, Wonkwang University School of Medicine, 344‐2 Shinyong‐dong, Iksan, Chonbuk 570‐711, Korea Search for other works by this author on: Oxford Academic Google Scholar S‐H. Cha S‐H. Cha Department of Dermatology, Wonkwang University School of Medicine, 344‐2 Shinyong‐dong, Iksan, Chonbuk 570‐711, Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 937–942, https://doi.org/10.1046/j.1365-2133.2000.03474.x Published: 01 May 2000
Effect of propranolol on myocardial ischemia occurring during acute coronary occlusion.
Authors: R L Feldman, R G MacDonald, J A Hill, M C Limacher, C R Conti, C J Pepine
Journal: Circulation (1986)

In 16 patients undergoing angioplasty of the left anterior descending coronary artery, the clinical, electrocardiographic, and hemodynamic effects of short-term intravenous nonselective beta-adrenergic blockade with propranolol (0.1 mg/kg) were assessed during temporary occlusion of the artery. Myocardial ischemia during coronary occlusion was prevented, delayed in onset, or diminished in magnitude by propranolol in 10 of the 16 patients. Propranolol decreased values for indexes of myocardial oxygen demand, such as heart rate and blood pressure and their product, in all patients. Surprisingly, in patients who derived clinical benefit, propranolol did not change indexes of myocardial oxygen supply to the left ventricular region perfused by the occluded artery. For example, great cardiac vein flow (40 +/- 15 to 41 +/- 17 ml/min, p = NS) and coronary collateral resistance (2.1 +/- 1.0 to 2.1 +/- 1.1 mm Hg/ml/min, p = NS) were unchanged. In contrast, a worsening of supply occurred in patients who were not benefited: great cardiac vein flow (50 +/- 10 to 39 +/- 6 ml/min, p less than .05) decreased and coronary collateral resistance (1.6 +/- 0.5 to 2.0 +/- 0.6 mm Hg/ml/min, p less than .05) increased. Information obtained from this study demonstrates the value of this new experimental preparation in helping assess potential clinical effectiveness of drug interventions during the initial phase of acute coronary occlusion and providing insight into the mechanisms of drug effect.