tbuckley/cabot-search huggingface dataset:
Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4.
Authors: N I Obiri, G G Hillman, G P Haas, S Sud, R K Puri
Journal: Journal of Clinical Investigation (1993)

Previously, Puri et al. (Puri, R. K., M. Ogata, P. Leland, G. M. Feldman, D. Fitzgerald, and I. Pastan. 1991. Cancer Res. 51:3011-3017) have demonstrated that murine sarcoma and colon adenocarcinoma cells express high affinity interleukin-4 receptors (IL-4R) which are internalized after binding to a chimeric ligand consisting of IL-4 and Pseudomonas exotoxin. In the present study, we have tested primary cultures of human renal cell carcinoma (RCC) cells, generated from tumor specimens obtained after nephrectomy, for the expression of IL-4R and their modulation by IL-4. By using iodinated IL-4 in a receptor binding assay, we observed that renal cell carcinoma cells expressed a single class of high affinity IL-4R ranging from 1,425 +/- 207 (mean +/- SEM) to 3,831 +/- 299 (mean +/- SEM) IL-4R molecules/cell with a Kd ranging from 112 +/- 11 pM to 283 +/- 71 pM. Northern blot analysis for IL-4R gene expression, performed with a cDNA probe to IL-4R, revealed that all RCC cells exhibited a single mRNA species of 4 kb. IL-4 downregulated the surface expression of IL-4R on one RCC tumor cell line. The function of IL-4R expression on RCC tumor cells was further determined by investigating the effect of IL-4 on tumor cell growth in vitro and comparing it with IL-4 effect on growth of normal fibroblast and endothelial cell lines. Tumor cell growth, as measured by [3H]thymidine incorporation, was inhibited by IL-4 from 20 to 68% in a dose-dependent manner. A neutralizing antibody to human IL-4 was able to reverse the growth inhibitory effect of IL-4. Normal human fibroblast and endothelial cell lines also expressed high affinity IL-4R, however, IL-4 did not inhibit their growth in vitro. In fact, IL-4 caused modest stimulation of their growth. Taken together, our findings can help develop strategies for the treatment of RCC in which IL-4R may be used as a target for IL-4 itself, for IL-4 toxin therapy or, alternatively, in gene therapy.
Abnormal sulfate metabolism in vitamin D-deficient rats.
Authors: I Fernandes, G Hampson, X Cahours, P Morin, C Coureau, S Couette, D Prie, J Biber, H Murer, G Friedlander, C Silve
Journal: Journal of Clinical Investigation (1997)

To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO4 cotransporter were evaluated in vitamin D-deficient (D-D-) rats and in D-D- rats rendered normocalcemic by either vitamin D or calcium/lactose supplementation. D-D- rats had significantly lower plasma sulfate levels than control animals (0.93+/-0.01 and 1.15+/-0.05 mM, respectively, P < 0.05), and fractional sulfate renal excretion was approximately threefold higher comparing D-D- and control rats. A decrease in renal cortical brush border membrane Na-SO4 cotransport activity, associated with a parallel decrease in both renal Na-SO4 cotransport protein and mRNA content (78+/-3 and 73+/-3% decreases, respectively, compared with control values), was also observed in D-D- rats. Vitamin D supplementation resulted in a return to normal of plasma sulfate, fractional sulfate excretion, and both renal Na-SO4 cotransport mRNA and protein. In contrast, renal sulfate excretion and renal Na-SO4 cotransport activity, protein abundance, and mRNA remained decreased in vitamin D-depleted rats fed a diet supplemented with lactose and calcium, despite that these rats were normocalcemic, and had significantly lower levels of parathyroid hormone and 25(OH)- and 1,25(OH)2-vitamin D levels than the vitamin D-supplemented groups. These results demonstrate that vitamin D modulates renal Na-SO4 sulfate cotransport and sulfate homeostasis. The ability of vitamin D status to regulate Na-SO4 cotransport appears to be a direct effect, and is not mediated by the effects of vitamin D on plasma calcium or parathyroid hormone levels. Because sulfate is required for synthesis of essential matrix components, abnormal sulfate metabolism in vitamin D-deficient animals may contribute to producing some of the abnormalities observed in rickets and osteomalacia.
Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts
Authors: Dylan Daniel, Becky Yang, David A. Lawrence, Klara Totpal, Inessa Balter, Wyne P. Lee, Alvin Gogineni, Mary J. Cole, Sharon Fong Yee, Sarajane Ross, Avi Ashkenazi
Journal: Blood (2007)

Abstract Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, and is currently in clinical trials. Preclinical studies have established antitumor activity of rhApo2L/TRAIL in models of epithelial cancers; however, efficacy in non-Hodgkin lymphoma (NHL) models is not well studied. Of 7 NHL cell lines tested in vitro, rhApo2L/TRAIL stimulated apoptosis in BJAB, Ramos RA1, and DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types of NHL, augmented rhApo2L/TRAIL-induced caspase activation in Ramos RA1 and DoHH2 but not BJAB or SC-1 cells, through modulation of intrinsic rather than extrinsic apoptosis signaling. In vivo, rhApo2L/TRAIL and rituximab cooperated to attenuate or reverse growth of tumor xenografts of all 4 of these cell lines. Depletion of natural killer (NK) cells or serum complement substantially reduced combined efficacy against Ramos RA1 tumors, suggesting involvement of antibodydependent cell- and complement-mediated cytotoxicity. Both agents exhibited greater activity against disseminated than subcutaneous BJAB xenografts, and worked together to inhibit or abolish disseminated tumors and increase survival. Moreover, rhApo2L/TRAIL helped circumvent acquired rituximab resistance of a Ramos variant. These findings provide a strong rationale for clinical investigation of rhApo2L/TRAIL in combination with rituximab as a novel strategy for NHL therapy.
Diagnostic Photoscanning of the Pancreas.
Authors: D. Bruce Sodee
Journal: Annals of Internal Medicine (1964)

s1 April 1964Diagnostic Photoscanning of the Pancreas.D. Bruce Sodee, Ph.D., F.A.C.P.D. Bruce Sodee, Ph.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-722_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe have completed 250 pancreatic photoscans using Selenomethionine-Se-75 in a series of 100 patients. Early in this study we found physiological difficulties in the stimulation of the pancreas. Delineation of the pancreas in the early studies was also impaired by the concentration of Se-75 in organs adjacent to the pancreas. We devised a protocol that stimulated the pancreas in its uptake of Selenomethionine-Se-75 and delayed pancreatic emptying, thereby providing a scanning period as long as 24 hr.Using a Au-198 liver scan, a ½-in. thick lead shield was placed over the liver, blocking out a major concentration of Se-75 that... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPancreatic Metabolism of Se76 Selenomethionine in Dogs 1 April 1964Volume 60, Issue 4Page: 722-722KeywordsAttentionLiverPancreas Issue Published: 1 April 1964 PDF DownloadLoading ...
Presence of esophageal varices in patients with a recent histoligic diagnosis of cirrhosis of the liver: evaluation of clinical predictors
Authors: Massimo Primignani, Valeria Savojardo, Alessandra Dell'Era, Linda Fazzini, Stefania Zatelli, Paola Pedotti, Emanuela Taioli, Roberto de Franchis
Journal: Journal of Hepatology (2002)
Agency warns about dosing error for amphotericin after patients with cancer die
Authors: Nigel Hawkes
Journal: BMJ (2007)

Two patients died in an oncology ward at Birmingham Heartlands Hospital in July after being treated with the wrong formulation of injectable amphotericin—a drug to treat fungal infections.

This National Patient Safety Agency (NPSA) has issued a warning over the use of the drug, but without disclosing where the two deaths referred to in its announcement had taken place. When questioned, the NPSA and the hospital confirmed that the deaths had taken place within hours of each other on 20 July ( BMJ 2007;335:274 doi: 10.1136/bmj.39300.394005.DB). …
Long-term Use of Diazepam
Authors: Leo E. Hollister
Journal: JAMA (1981)

Plasma concentrations of diazepam and its major active metabolite nordiazepam were measured in 108 neurosurgical patients taking diazepam in doses of 5 to 40 mg/day for periods from one month to 16 years. Diazepam was used for relief of pain or muscle spasm, or anxiety and sleeplessness associated with these two symptoms, and was considered to be beneficial by 83% of the patients, although use of other drugs confounded this evaluation. Concentrations of total diazepam-nordiazepam ranged from 0 to 2,584 ng/mL, with nordiazepam being the predominant metabolite. "Low" concentrations (&lt;250 ng/mL) were found in 35 of the 108 patients, with 19 having concentrations lower than 100 ng/mL. "High" concentrations (&gt;900 ng/mL) were found in 20 patients and did not occur more frequently than in other studies of long-term diazepam ingestion. Even with long-term use, diazepam seemed to retain its efficacy and did not lead to any clear-cut abuse. (<i>JAMA</i>1981;246:1568-1570)
Combination Therapy for NIDDM With Biosynthetic Human Insulin and Glyburide
Authors: Nicholas H E Mezitis, Stanley Heshka, Valerie Saitas, Timothy S Bailey, Rafaella Costa, F Xavier Pi-Sunyer
Journal: Diabetes Care (1992)

Objective To investigate the effects of the addition of glyburide to the regimen of insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients with regard to their overall insulin requirement and dosage schedule and to assess persistence of these effects. Research Design and Methods A double-blind randomized parallel-group, placebo-controlled, 20-wk outpatient trial at the Clinical Research Unit (CRU) at St. Luke's/Roosevelt Hospital (New York). Subjects were 20 insulindependent NIDDM patients previously managed on insulin alone. After a baseline period of satisfactory diabetes control on biosynthetic human insulin alone, insulin dosage was halved, and patients were placed on a combination with either glyburide or placebo. Diabetes control equivalent to baseline was reestablished by adjusting insulin as required on subsequent visits to the CRU. Results Insulin requirements in the glyburide group decreased by 29 U at 14 wk compared with 9 U in the placebo group (P &amp;lt; 0.05). At 20 wk, the decreases remained significant (25 vs. 11 U, respectively; P &amp;lt; 0.05). The mean ± SD reduction in insulin requirement in the glyburide group was relatively constant (25 ± 10 U) and was not related to premedication insulin requirement. Successful response to glyburide was inversely correlated with initial serum alkaline phosphatase level. Conclusions Glyburide reduces insulin requirements for 20 wk of combination therapy in NIDDM patients. Patients whose initial insulin requirement is ≤25 U have a 50% chance of achieving equivalent glycemic control on glyburide alone.
Nativism, neuroconstructivism, and developmental disorder
Authors: Philip Gerrans
Journal: Behavioral and Brain Sciences (2002)

Either genetically specified modular cognitive architecture for syntactic processing does not exist (neuroconstructivism), or there is a module but its development is so abnormal in Williams syndrome (WS) that no conclusion can be drawn about its normal architecture (moderate nativism). Radical nativism, which holds that WS is a case of intact syntax, is untenable. Specific Language Impairment and WS create a dilemma that radical nativism cannot accommodate.
Survey of the Law of Medical Practice
Authors: Sidney Shindell
Journal: JAMA (1965)

In the preceding communication we were concerned with an examination of the legal relationships of the physician to the public at large. It is our purpose here to examine the legal relationship that exists between the individual physician and the individual patient. In doing so, it might be helpful to begin by reviewing a philosophical analysis of the relationsip which was reported a few years ago by Szasz and Hollender. 1 These authors describe three distinct patterns (or models) which the relationship may take.  The traditional pattern is described as one of activity-passivity. Characteristic of this pattern is the emergency situation or the patient on the operating table. As stated by the authors, such a model places the physician in absolute control of the situation... It requires that the physician disidentify with the patient as a person. Psychologically this is not really an inter action between people because it is
NHS improved emergency waiting times during this winter
Authors: Susan Mayor
Journal: BMJ (2004)

The NHS in England avoided a winter crisis this year with reduced waiting times for emergency cases and hospital admissions, a report published this week says.

The report, Winter and the NHS 2003-4 , showed that during this winter—traditionally winter is the most pressured time of year for the health service—the NHS improved on previous performance in terms of waiting times and influenza vaccination. More than 90% of patients were treated within four hours (the government target) of arrival at hospital accident and emergency departments throughout the winter period—compared with 80% last winter.

Presenting the findings, Professor George Alberti, national clinical director for emergency access, suggested that increased capacity and investment had meant that …
Expanded Anticancer Therapeutic Window of Hexon-modified Oncolytic Adenovirus
Authors: Elena V Shashkova, Shannon M May, Konstantin Doronin, Michael A Barry
Journal: Molecular Therapy (2009)

One of the significant hurdles toward safe and efficacious systemic treatment of cancer with oncolytic adenoviruses (Ads) is dose-limiting hepatotoxicity that prevents the increase of a therapeutic dose. In this study, we expanded the therapeutic window of oncolytic serotype 5 Ad (Ad5) by a genetic modification of hypervariable loop 5 (HVR5) in the capsid protein hexon that prevented infection of hepatocytes due to ablation of binding to blood factors. This oncolytic virus, Ad-GL-HB, had significantly reduced levels of hepatocyte transduction in immunocompetent and immunodeficient mice as compared to parental virus Ad-GL. The hepatocyte detargeting decreased liver damage and increased the maximum tolerated dose of Ad-GL-HB tenfold relative to that of Ad-GL. Intravenous (i.v.) injection of Ad-GL or Ad-GL-HB into tumor-bearing mice produced equally increased survival rates demonstrating that while Ad-GL-HB detargeted hepatocytes, it sustained tumor cell infection after systemic administration. The significantly improved safety of the virus allowed it to be used at increased doses for improved systemic antitumor efficacy. Our results suggest that hexon modifications provide valuable strategies for systemic oncolytic Ad therapy. One of the significant hurdles toward safe and efficacious systemic treatment of cancer with oncolytic adenoviruses (Ads) is dose-limiting hepatotoxicity that prevents the increase of a therapeutic dose. In this study, we expanded the therapeutic window of oncolytic serotype 5 Ad (Ad5) by a genetic modification of hypervariable loop 5 (HVR5) in the capsid protein hexon that prevented infection of hepatocytes due to ablation of binding to blood factors. This oncolytic virus, Ad-GL-HB, had significantly reduced levels of hepatocyte transduction in immunocompetent and immunodeficient mice as compared to parental virus Ad-GL. The hepatocyte detargeting decreased liver damage and increased the maximum tolerated dose of Ad-GL-HB tenfold relative to that of Ad-GL. Intravenous (i.v.) injection of Ad-GL or Ad-GL-HB into tumor-bearing mice produced equally increased survival rates demonstrating that while Ad-GL-HB detargeted hepatocytes, it sustained tumor cell infection after systemic administration. The significantly improved safety of the virus allowed it to be used at increased doses for improved systemic antitumor efficacy. Our results suggest that hexon modifications provide valuable strategies for systemic oncolytic Ad therapy.
A study of benoxaprofen-induced photosensitivity
Authors: J. FERGUSON, H.A. ADDO, P.E. McGILL, K.R. WOODCOCK, B.E. JOHNSON, W. FRAIN-BELL
Journal: British Journal of Dermatology (1982)

A study of the abnormal sunlight response seen in nine patients taking benoxaprofen showed that the action spectrum was between 310 and 325 nm, which is similar to the drug's absorption spectrum. In vitro studies using three separate methods indicated that benoxaprofen has a powerful phototoxic action which may be directed mainly against cellular membranes.
Anti-Insulin Antibodies Are a Cause of Hypoglycemia Following Pancreas Transplantation
Authors: Minou P Tran, Jennifer L Larsen, William C Duckworth, Elizabeth I Ruby, Suzanne A Miller, Kecia Frisbie, Rodney J Taylor, Robert J Stratta
Journal: Diabetes Care (1994)

OBJECTIVE Hypoglycemie symptoms have been reported by more than half of pancreas transplantation (PTX) recipients. To better understand the mechanism for the hypoglycemia documented in some of these patients, we studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycemia following PTX. RESEARCH DESIGN AND METHODS Twelve patients with established, repeated episodes of hypoglycemia following PTX (hypo) were case-matched to PTX recipients without hypoglycemie symptoms (control; n = 7). On the day of the study, fasting glucose, free and total immunoreactive insulin (IR1), C-peptide, proinsulin, and glucagon were drawn (time 0); Sustacal was administered; and glucose, free and total IRI, and C-peptide were assayed at 15,30,45, 75,120,150,180, and 240 min. Based on the glucose response to Sustacal, the hypo group was further divided into those whose glucose rose after Sustacal (hypo-high; n = 7) and those with no increase in glucose from baseline concentration (hypo-flat; n = 5). RESULTS Before the administration of Sustacal, the hypo-high group had a lower fasting free/total IRI (0.26 ± 0.06, mean ± SE) than the hypo-flat (0.51 ± 0.02) or control (0.52 ± 0.04) groups (both P &amp;lt; 0.05 compared with hypo-high). The glucose response to Sustacal was greatest in the hypo-high group as defined. Area under the curve (AUC) for total IRI following Sustacal was also greatest in the hypo-high group (P &amp;lt; 0.05 compared with both control and hypo-flat groups), but there was no significant difference in free IRI AUC following Sustacal between the three groups. Two individuals developed hypoglycemia during the Sustacal challenge, both in the hypo-high group. CONCLUSIONS The lower fasting free/total IRI ratio and greater increase in glucose and total IRI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of significant quantities of anti-insulin antibodies in the hypo-high group. Because anti-insulin antibodies are, in turn, an established cause of episodic hypoglycemia, this study provides the first data to support the hypothesis that significant quantities of anti-insulin antibodies are a cause of symptomatic hypoglycemia following PTX in some recipients.
Internal Temperature of Steamed Clams
Authors: Raymond S. Koff, Hubert S. Sear
Journal: New England Journal of Medicine (1967)

INFECTIOUS hepatitis following ingestion of raw shellfish has been recognized as a significant public-health problem for only a decade. A recent epidemiologic study has suggested that steamed clams may also be an important vehicle for the agent of infectious hepatitis, at least in the New England region.1 These data made it necessary to assume that the steaming of clams, as routinely practiced, is inadequate to destroy or inactivate the virus of infectious hepatitis. No data, however, were available on the internal temperature of clam tissues during steaming. The present study was undertaken to determine how internal clam temperature and opening . . .
Double-blind comparison of cimetidine and placebo in the maintenance of healing of chronic duodenal ulceration.
Authors: K D Bardhan, D M Saul, J L Edwards, P M Smith, S J Haggie, J H Wyllie, H L Duthie, I V Fussey
Journal: Gut (1979)

<b>Aim:</b> To study alterations in choroidal blood flow (CBF) in the foveal region after panretinal photocoagulation (PRP) in patients with severe proliferative diabetic retinopathy. <b>Methods:</b> Seventeen eyes of 17 patients with severe non-proliferative diabetic retinopathy (PDR) or with non-high-risk PDR and no macular edema before PRP were included. All patients underwent four sessions of scatter PRP. We measured the choroidal blood velocity (CBVel), choroidal blood volume (CBVol), and CBF in the foveal region before and 1 month after PRP using a laser Doppler flowmetry. <b>Results:</b> Macular edema did not develop after PRP in any treated eyes. One month after PRP, there was no significant change in the mean CBVel (311.2 ± 61.2 Hz) compared with baseline (327.1 ±74.1 Hz) (P=0.17). In contrast, the mean CBVol and CBF values increased significantly by 51% (from 0.37 ± 0.12 arbitrary units [a.u.] at baseline to 0.52 ± 0.16 a.u., P=0.0025 ) and 46% (from 7.3 ± 2.4 a.u. at baseline to 10.4 ± 4.4 a.u., P=0.0014 ), respectively, 1 month after PRP. <b>Conclusion:</b> These results indicate that PRP may increase the CBF in the foveal region in eyes with severe diabetic retinopathy. The current results may be caused by vasodilation of the choriocapillaries in the foveal region.
Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages
Authors: Sanjay S Vasudevan, Neuza H M Lopes, Puvi N Seshiah, Tao Wang, Clay B Marsh, Dean J Kereiakes, Chunming Dong, Pascal J Goldschmidt-Clermont
Journal: Cardiovascular Research (2003)

Objective: We have previously shown that macrophage colony stimulating factor (M-CSF), a potent survival and mitogenic factor for monocytes/macrophages (MM), enables MM to induce vascular smooth muscle cell (VSMC) apoptosis. The killing requires the binding of MM to VSMC via Mac-1 (CD11b/CD18) on MM and intracellular adhesion molecule-1 (ICAM-1) on VSMC. We hypothesized that, in addition to Mac-1 binding, the killing process requires the activation of the Fas–death receptor pathway, which can be blocked at the level of Fas–Fas ligand interaction. Methods and Results: Human peripheral blood monocytes and VSMC were isolated and cultured as previously described. Soluble Fas (sFas) was overexpressed in VSMC by transduction using adenovirus specifying soluble Fas (Ad3hsFas). M-CSF markedly increased the expression of ICAM-1 in VSMC, resulting in enhanced clustering of MM on the surface of VSMC (≥3 MM per VSMC). MM, but not VSMC, expressed Fas-ligand (FasL), and VSMC apoptosis was inhibited by secretion of sFas by VSMC upon Ad3sFas transduction. Conclusions: MM and M-CSF-induced VSMC killing requires MM binding to VSMC mediated by Mac-1 and ICAM-1, and Fas–FasL interaction.