tbuckley/cabot-search huggingface dataset:
SURFACE TENSION OF SERUM
Authors: P. Lecomte du Noüy
Journal: The Journal of Experimental Medicine (1923)

1. The initial surface tension of serum or serum solutions is not affected systematically by the presence of antibodies in the serum. On the contrary, the time-drop in 2 hours is always increased, from 25 to 100 per cent. 2. It is extremely important, in order to demonstrate these phenomena, that the greatest care be taken regarding the cleanness of the vessels and the purity of water and NaCl. 3. It is equally important to use a device, for example such as is pictured in this paper, capable of preventing the jarring and shaking of the liquid. 4. The value of the time-drop of a normal, healthy serum is never higher than 10 dynes. Should it be higher, the serum must not be used for immunity experiments.
Postoperative air leaks
Authors: M HENRY, J E HARVEY, A G ARNOLD;, D. A WALLER, J. G EDWARDS, P. B RAJESH
Journal: Thorax (1999)

An 11 year old boy with cystic fibrosis suffered a stroke, producing right sided weakness.Four years previously a totally implantable venous access device (Port-a-Cath) had been inserted.Magnetic resonance angiography revealed a filling defect in the left middle cerebral artery.Transoesophageal echocardiography demonstrated a thrombus attached to the tip of the Port-a-Cath and also the presence of a patent foramen ovale.After an initial period of anticoagulation the defect was closed using a septal occlusion device introduced via a cardiac catheter.The boy's neurological signs completely resolved and he remains free from further thromboembolic episodes.Whilst pulmonary embolism has been described before in relation to a totally implantable venous access device, this is believed to be the first description of a paradoxical embolism in relation to such a device.
Vascular Injury Involves the Overoxidation of Peroxiredoxin Type II and Is Recovered by the Peroxiredoxin Activity Mimetic That Induces Reendothelialization
Authors: Dong Hoon Kang, Doo Jae Lee, Jiran Kim, Joo Young Lee, Hyun-Woo Kim, Kihwan Kwon, W. Robert Taylor, Hanjoong Jo, Sang Won Kang
Journal: Circulation (2013)

Background— Typical 2-Cys peroxiredoxin (Prx) is inactivated by overoxidation of the peroxidatic cysteine residue under oxidative stress. However, the significance in the context of vascular disease is unknown. Methods and Results— Immunohistochemical analyses revealed that 2-Cys Prxs, particularly Prx type II, are heavily overoxidized in balloon-injured rodent carotid vessels and in human atherosclerotic lesions. Consistent with this observation, the selective depletion of Prx II exacerbated neointimal hyperplasia in injured carotid vessels. We also found that the epipolythiodioxopiperazine class of fungal metabolites exhibited an enzyme-like activity mimicking 2-Cys Prx peroxidase and manifestly eliminated the intracellular H 2 O 2 in the vascular cells. Functionally, the epipolythiodioxopiperazines reciprocally regulated the platelet-derived growth factor receptor-β– and vascular endothelial growth factor receptor–mediated signaling in these vascular cells by replacing Prx II. As a consequence, the epipolythiodioxopiperazines inhibited the proliferative and migratory activities of smooth muscle cells but promoted those of endothelial cells in vitro. Moreover, administration of the epipolythiodioxopiperazines to the injured carotid vessels resulted in a successful recovery by inhibiting neointimal hyperplasia without causing cytotoxicity and simultaneously inducing reendothelialization. Conclusions— This study reveals for the first time the involvement of the 2-Cys Prx overoxidation and thus the therapeutic use of their activity mimetic in vascular injuries like stenting.
Comparison of Two Cancer Vaccines Targeting Tyrosinase: Plasmid DNA and Recombinant Alphavirus Replicon Particles
Authors: Stacie M. Goldberg, Shirley M. Bartido, Jason P. Gardner, José A. Guevara-Patiño, Stephanie C. Montgomery, Miguel-Angel Perales, Maureen F. Maughan, JoAnn Dempsey, Gerald P. Donovan, William C. Olson, Alan N. Houghton, Jedd D. Wolchok
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Immunization of mice with xenogeneic DNA encoding human tyrosinase-related proteins 1 and 2 breaks tolerance to these self-antigens and leads to tumor rejection. Viral vectors used alone or in heterologous DNA prime/viral boost combinations have shown improved responses to certain infectious diseases. The purpose of this study was to compare viral and plasmid DNA in combination vaccination strategies in the context of a tumor antigen. Experimental Design: Using tyrosinase as a prototypical differentiation antigen, we determined the optimal regimen for immunization with plasmid DNA. Then, using propagation-incompetent alphavirus vectors (virus-like replicon particles, VRP) encoding tyrosinase, we tested different combinations of priming with DNA or VRP followed by boosting with VRP. We subsequently followed antibody production, T-cell response, and tumor rejection. Results: T-cell responses to newly identified mouse tyrosinase epitopes were generated in mice immunized with plasmid DNA encoding human (xenogeneic) tyrosinase. In contrast, when VRP encoding either mouse or human tyrosinase were used as single agents, antibody and T-cell responses and a significant delay in tumor growth in vivo were observed. Similarly, a heterologous vaccine regimen using DNA prime and VRP boost showed a markedly stronger response than DNA vaccination alone. Conclusions: Alphavirus replicon particle vectors encoding the melanoma antigen tyrosinase (self or xenogeneic) induce immune responses and tumor protection when administered either alone or in the heterologous DNA prime/VRP boost approaches that are superior to the use of plasmid DNA alone.
Study of the proliferation in human gastric mucosa after in vivo bromodeoxyuridine labelling.
Authors: S Patel, D A Rew, I Taylor, C S Potten, C Owen, S A Roberts
Journal: Gut (1993)

Studies to measure human gastric crypt or gland cell proliferation may have a number of practical clinical applications in relation to both benign and malignant gastric conditions. Bromodeoxyuridine (BrdUrd) labels human gastric mucosal cells in the S phase. Computer aided data analysis of labelled mucosa allows static proliferative indices to be estimated, including the crypt labelling index (LI), the peak labelling position, the distribution of labelled cells and indirectly the crypt growth fraction. Multiparameter flow cytometric analysis of labelled nuclei allows the S phase duration (Ts) of mucosal cells to be estimated. Specimens of histologically normal gastric body (GB, n = 16) and antral mucosa (GA, n = 10) were obtained from 25 patients with gastric carcinomas who received a bolus dose of 250 mg BrdUrd between 3.0 and 15.7 hours before surgery. Tissue sections were stained by an immunohistochemical method and subjected to detailed counting of up to 50 longitudinal crypts per specimen. The total crypt labelling index was calculated by a grid counting method. A significant difference existed between the proliferative compartments of gastric antral and body mucosa measured by a number of criteria. The median lengths of the crypts were 137 cells (GB) and 188 cells (GA). The median peak labelling positions were cell 26 (GB) and cell 61 (GA) from the crypt orifice. The mean crypt labelling indices were 2.8% (GB) and 4.8% (GA). The mean Ts of GA cells was 7.7 hours and of GB cells was 10.8 hours.
Combined Mycophenolate Mofetil and Losartan Therapy Arrests Established Injury in the Remnant Kidney
Authors: CLARICE KAZUE FUJIHARA, IRENE DE LOURDES NORONHA, DENISE MARIA AVANCINI COSTA MALHEIROS, GLÁUCIA RUTIGLIANO ANTUNES, IVONE BRAGA DE OLIVEIRA, ROBERTO ZATZ
Journal: Journal of the American Society of Nephrology (2000)

Previously it was shown that early treatment with mycophenolate mofetil (MMF) attenuated renal inflammation, glomerulosclerosis (GS), and interstitial expansion in the 5/6 ablation (NX) model. Angiotensin II antagonists also mitigate renal injury in NX, presumably by lowering glomerular pressure (PGC). This study investigated: (1) whether combined MMF/angiotensin II antagonists treatment affords superior protection compared with the respective monotherapies; and (2) whether this association is effective even when instituted late in the course of the disease. Adult male Munich-Wistar rats underwent NX, remaining untreated for 30 d. BP, albuminuria, and the extent of GS, interstitial expansion, and macrophage infiltration were then determined in 17 rats. The remaining 118 rats received either inert vehicle or one of the following: MMF, 10 mg/kg by gavage once daily; losartan potassium (L), 20 mg/dl in drinking water; or combined MMF/L treatment. Sixty days after ablation, untreated NX rats exhibited marked glomerular hypertension, which was attenuated by MMF and, more effectively, by either L or combined MMF/L treatment. At 120 d, hypertension and albuminuria were worsened in untreated NX rats, which exhibited intense macrophage infiltration and severe glomerular and interstitial disease. L and, to a lesser extent, MMF monotherapies attenuated these abnormalities, without preventing their progression. In rats given combined MMF/L therapy, macrophage infiltration, GS, and interstitial expansion remained at pretreatment levels. By acting on two distinct pathogenic mechanisms, combined MMF/L treatment arrested established renal injury in the NX model. Further investigation is needed to determine whether this association can prevent renal scarring in other models and in human disease.
Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial
Authors: Johan Hansson, Steinar Aamdal, Lars Bastholt, Yvonne Brandberg, Micaela Hernberg, Bo Nilsson, Ulrika Stierner, Hans von der Maase
Journal: The Lancet Oncology (2011)
Studies on the Control of Hypertension by Hyphex
Authors: HENRY A. SCHROEDER, JOHN D. MORROW, H. MITCHELL PERRY
Journal: Circulation (1954)

One hundred and six patients in malignant stages of hypertension were treated with continuous oral hexamethonium chloride and 1-hydrazinophthalazine. The courses of ten uremic individuals were unaffected. Twenty-eight discontinued therapy, three of whom survived two months. Sixty-eight nonuremic patients continued treatment and 54 are alive 15 to 36 months later; 17 who were azotemic have lived two to three years. Of the 14 who died, only three succumbed to hypertensive complications. Forty-six of the living patients have returned to full activity. Apparently the malignant stage of hypertension is reversible by drugs properly used to lower blood pressure and no longer need be the rapidly fatal disease that it has been in the past.
Taxane-Induced Blockade to Nuclear Accumulation of the Androgen Receptor Predicts Clinical Responses in Metastatic Prostate Cancer
Authors: Medha S. Darshan, Matthew S. Loftus, Maria Thadani-Mulero, Benjamin P. Levy, Daniel Escuin, Xi Kathy Zhou, Ada Gjyrezi, Chantal Chanel-Vos, Ruoqian Shen, Scott T. Tagawa, Neil H. Bander, David M. Nanus, Paraskevi Giannakakou
Journal: Cancer Research (2011)

Prostate cancer progression requires active androgen receptor (AR) signaling which occurs following translocation of AR from the cytoplasm to the nucleus. Chemotherapy with taxanes improves survival in patients with castrate resistant prostate cancer (CRPC). Taxanes induce microtubule stabilization, mitotic arrest, and apoptotic cell death, but recent data suggest that taxanes can also affect AR signaling. Here, we report that taxanes inhibit ligand-induced AR nuclear translocation and downstream transcriptional activation of AR target genes such as prostate-specific antigen. AR nuclear translocation was not inhibited in cells with acquired β-tubulin mutations that prevent taxane-induced microtubule stabilization, confirming a role for microtubules in AR trafficking. Upon ligand activation, AR associated with the minus-end-microtubule motor dynein, thereby trafficking on microtubules to translocate to the nucleus. Analysis of circulating tumor cells (CTC) isolated from the peripheral blood of CRPC patients receiving taxane chemotherapy revealed a significant correlation between AR cytoplasmic sequestration and clinical response to therapy. These results indicate that taxanes act in CRPC patients at least in part by inhibiting AR nuclear transport and signaling. Further, they suggest that monitoring AR subcellular localization in the CTCs of CRPC patients might predict clinical responses to taxane chemotherapy.
Efficacious proteasome/HDAC inhibitor combination therapy for primary effusion lymphoma
Authors: Shruti Bhatt, Brittany M. Ashlock, Ngoc L. Toomey, Luis A. Diaz, Enrique A. Mesri, Izidore S. Lossos, Juan Carlos Ramos
Journal: Journal of Clinical Investigation (2013)

Primary effusion lymphoma (PEL) is a rare form of aggressive B cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Current chemotherapy approaches result in dismal outcomes, and there is an urgent need for new PEL therapies. Previously, we established, in a direct xenograft model of PEL-bearing immune-compromised mice, that treatment with the proteasome inhibitor, bortezomib (Btz), increased survival relative to that after treatment with doxorubicin. Herein, we demonstrate that the combination of Btz with the histone deacetylase (HDAC) inhibitor suberoylanilidehydroxamic acid (SAHA, also known as vorinostat) potently reactivates KSHV lytic replication and induces PEL cell death, resulting in significantly prolonged survival of PEL-bearing mice. Importantly, Btz blocked KSHV late lytic gene expression, terminally inhibiting the full lytic cascade and production of infectious virus in vivo. Btz treatment led to caspase activation and induced DNA damage, as evidenced by the accumulation of phosphorylated γH2AX and p53. The addition of SAHA to Btz treatment was synergistic, as SAHA induced early acetylation of p53 and reduced interaction with its negative regulator MDM2, augmenting the effects of Btz. The eradication of KSHV-infected PEL cells without increased viremia in mice provides a strong rationale for using the proteasome/HDAC inhibitor combination therapy in PEL.
Epigenetic Silencing of the Sulfate Transporter Gene <i>DTDST</i> Induces Sialyl Lewisx Expression and Accelerates Proliferation of Colon Cancer Cells
Authors: Akiko Yusa, Keiko Miyazaki, Naoko Kimura, Mineko Izawa, Reiji Kannagi
Journal: Cancer Research (2010)

Abstract Colon cancer cells express the carbohydrate determinant sialyl Lewisx, while they exhibit markedly decreased the expression of its sulfated derivative, sialyl 6-sulfo Lewisx. In contrast, normal colonic epithelial cells strongly express sialyl 6-sulfo Lewisx, but they virtually do not express sialyl Lewisx. Impaired sulfation was therefore suggested to occur during the course of malignant transformation of colonic epithelial cells and was assumed to be responsible for the increased sialyl Lewisx expression in cancers. To elucidate the molecular biological background of the impaired sulfation in cancers, we studied the expression levels of mRNA for 6-O-sulfotransferase isoenzymes, PAPS synthases and transporters, and a cell membrane sulfate transporter, DTDST, in cancer tissues. The most striking decrease in cancer cells compared with nonmalignant epithelial cells was noted in the transcription of the DTDST gene (P = 0.0000014; n = 20). Most cultured colon cancer cells had a diminished DTDST transcription, which was restored when cultured with histone deacetylase inhibitors. Suppression of DTDST transcription under the control of a tet-off inducible promoter resulted in increased sialyl Lewisx expression and reduced sialyl 6-sulfo Lewisx expression. Unexpectedly, the growth rate of the cancer cells was markedly enhanced when transcription of DTDST was suppressed. These results show that the decrease in the transcription of the sulfate transporter gene is the major cause of decreased expression of sialyl 6-sulfo Lewisx and increased expression of sialyl Lewisx in colon cancers. The results also suggest that the diminished DTDST expression is closely related to enhanced proliferation of cancer cells. Cancer Res; 70(10); 4064–73. ©2010 AACR.
Functional Somatic Syndromes
Authors: Arthur J. Barsky
Journal: Annals of Internal Medicine (1999)

The term functional somatic syndrome has been applied to several related syndromes characterized more by symptoms, suffering, and disability than by consistently demonstrable tissue abnormality. These syndromes include multiple chemical sensitivity, the sick building syndrome, repetition stress injury, the side effects of silicone breast implants, the Gulf War syndrome, chronic whiplash, the chronic fatigue syndrome, the irritable bowel syndrome, and fibromyalgia. Patients with functional somatic syndromes have explicit and highly elaborated self-diagnoses, and their symptoms are often refractory to reassurance, explanation, and standard treatment of symptoms. They share similar phenomenologies, high rates of co-occurrence, similar epidemiologic characteristics, and higher-than-expected prevalences of psychiatric comorbidity. Although discrete pathophysiologic causes may ultimately be found in some patients with functional somatic syndromes, the suffering of these patients is exacerbated by a self-perpetuating, self-validating cycle in which common, endemic, somatic symptoms are incorrectly attributed to serious abnormality, reinforcing the patient's belief that he or she has a serious disease. Four psychosocial factors propel this cycle of symptom amplification: the belief that one has a serious disease; the expectation that one's condition is likely to worsen; the "sick role," including the effects of litigation and compensation; and the alarming portrayal of the condition as catastrophic and disabling. The climate surrounding functional somatic syndromes includes sensationalized media coverage, profound suspicion of medical expertise and physicians, the mobilization of parties with a vested self-interest in the status of functional somatic syndromes, litigation, and a clinical approach that overemphasizes the biomedical and ignores psychosocial factors. All of these influences exacerbate and perpetuate the somatic distress of patients with functional somatic syndromes, heighten their fears and pessimistic expectations, prolong their disability, and reinforce their sick role. A six-step strategy for helping patients with functional somatic syndromes is presented here.
Spontaneous Extradural Haematoma with Sinusitis
Authors: Marios C Papadopoulos, Aref Dyer, Carl Hardwidge
Journal: Journal of the Royal Society of Medicine (2001)

The most important causes of spontaneous intracranial extradural haematoma are coagulation disorders, dural vascular malformations and infection1. An association with frontal sinusitis has been reported on a few occasions.
Suppression of Ureteric Bud Apoptosis Rescues Nephron Endowment and Adult Renal Function in Pax2 Mutant Mice
Authors: Alison Dziarmaga, Michael Eccles, Paul Goodyer
Journal: Journal of the American Society of Nephrology (2006)

The molecular mechanisms that set congenital nephron number are unknown. However, humans with modest suboptimal nephron number may be at increased risk for essential hypertension, and those with more severe nephron deficits at birth may develop progressive renal insufficiency. A model of branching morphogenesis during fetal kidney development in which the extent of ureteric bud arborization is dependent on suppression of programmed cell death has been proposed. This study shows that the increased apoptosis and reduced ureteric bud branching of heterozygous <i>Pax2</i> mutant mice is associated with 40% decrease in nephron number at birth. This leads to postnatal glomerular hypertrophy and long-term renal insufficiency in the absence of glomerulosclerosis. To determine whether restoration of antiapoptotic factors alone is sufficient to rescue the nephron deficit in these mice, a <i>BCL2</i> transgene that is under the control of the <i>PAX2</i> promoter was targeted to the ureteric bud. The transgene suppressed programmed cell death in the ureteric bud lineage, increased nephron number to 90% of that of wild-type littermates at birth, and normalized renal function at 1 yr. These observations lend strong support to the hypothesis that factors that control ureteric bud apoptosis are powerful determinants of congenital nephron endowment.
Indications for total hip replacement: comparison of assessments of orthopaedic surgeons and referring physicians
Authors: K E Dreinhofer
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To analyse differences of opinions on indications for primary total hip replacements (THRs) within and between groups of orthopaedic surgeons and the physicians who refer patients to them. <b>Methods:</b> 22 orthopaedic centres in 12 European countries took part, resulting in a postal survey of 304 orthopaedic surgeons and 314 referring physicians. Each participant was asked to state what importance different domains (pain, functional impairment, physical examination and radiographs) have on their decision to recommend THR and to select the most appropriate level of severity of each symptom or sign for recommending THR. In addition, the participants were asked to prioritise other personal or environmental factors that affect their decision to undertake a THR. <b>Results:</b> Rest pain, pain with activity and functional limitations were the most important criteria for THR, although range of motion and radiographic changes were of least importance. Both similarities and differences were observed within and between groups of surgeons and referring physicians in the overall approach to indications and the most appropriate level of severity of disease for recommending THR. Most surgeons agreed on severity levels in only 4 of 11 items and most referring physicians in only one. Between the groups, major differences occurred with regard to the importance of activities of daily living and the appropriate level of symptoms for THR. In general, compared with surgeons, referring physicians reported that the disease needed to be more advanced to warrant surgery. <b>Conclusion:</b> Currently, no consensus exists on objective indication criteria for THR. The observed differences between the gatekeepers (referring physicians) and surgeons can lead to variations and perhaps inequities in the provision of care.