tbuckley/cabot-search huggingface dataset:
Effects of Preconceptional Irradiation on Mortality and Cancer Incidence in the Offspring of Patients Given Injections of Thorotrast
Authors: M. Andersson, K. Juel, Y. Ishikawa, H. H. Storm
Journal: JNCI Journal of the National Cancer Institute (1994)

Background: Findings from a British case–control study suggest that a pre-conceptional paternal external radiation dose of more than 100 mSv (10 rem) is significantly related to risk for leukemia and non-Hodgkin's lymphoma in offspring. The suggestion, however, has not been supported by experimental or other epidemiologic studies. Purpose: The purpose of this study was to investigate if preconceptional irradiation of males and females from internally deposited radionuclides affects mortality and risk of developing cancer in their offspring. Methods: The offspring of 260 females (n = 143) and 320 males (n = 226) who lived longer than 1 year after receiving Thorotrast (a compound no longer in use) for cerebral arteriography were studied for mortality rate and the risk for developing cancer. Thorotrast was used as a contrast medium containing a 20% colloidal solution of thorium dioxide-Th 232, an alpha particle-emitting radionuclide, which is retained lifelong in nearly all organs. The offspring of the exposed patients were identified by manual linkage with the municipal population registers and followed-up for vital status by computerized linkage with the Danish National Central Population Registry and for incidence of cancer by computerized linkage with the Danish National Cancer Registry. The standardized mortality/morbidity ratios (SMRs) for death and for site-specific incidence of cancer in the offspring were calculated as ratios of the observed rates in the study population to the expected rates in the general population. Results: After a median follow-up of 40 years, four cases of cancer (breast [one], uterine cervix [one], melanoma of skin [one], and retino-blastoma [one]) versus 2.9 cases expected, developed among 143 children born to mothers who received injections of Thorotrast (SMR = 1.4; 95% confidence interval [CI] = 0.4–3.5), while six cases of cancer (one case each of cancer of lung, testis, thyroid, and Hodgkin's lymphoma and two cases of melanoma of skin), versus 4.5 expected, occurred among 226 children of exposed fathers (SMR = 1.3; 95% CI = 0.5-2.9). No case of leukemia or non-Hodgkin's lymphoma occurred in any of the offspring studied. Mortality was lower than expected both for children of exposed mothers (SMR = 0.7; 95% CI = 0.3-1.5) and of exposed fathers (SMR = 0.5; 95% CI = 0.2-1.0). Conclusions: This study does not support the previously proposed association between parental exposure to radiation and the risk of childhood leukemia and lymphoma. Furthermore, since mortality from all causes was not increased in any offspring, our results do not support the belief that preconceptional parental low-dose exposure to alpha radiation increases the incidence of cancer or mortality in the offspring. [J Natl Cancer Inst 86:1866-1870, 1994]
Pulmonary complications of intravesicular BCG immunotherapy
Authors: Bethan Davies, Harpreet Ranu, Mark Jackson
Journal: Thorax (2012)

A 79-year-old man was admitted to hospital with fever, rigours and malaise 1 week after completing his seventh intravesicular BCG immunotherapy treatment for carcinoma in situ of the bladder. On admission, respiratory examination was normal with a peripheral oxygen saturation of 94% on air and a normal white cell count but raised C reactive protein of 111. His chest radiograph was normal (figure 1). He was treated for presumed urinary sepsis with intravenous antibiotics while awaiting results of microscopy and culture of urine and blood cultures.



Figure 1 
Chest radiograph on admission.



By day 5, the patient had become progressively breathless requiring high flow oxygen to maintain his oxygen saturations. Urine and blood cultures taken …
Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes
Authors: Shweta Rane, Minzhen He, Danish Sayed, Himanshu Vashistha, Ashwani Malhotra, Junichi Sadoshima, Dorothy E. Vatner, Stephen F. Vatner, Maha Abdellatif
Journal: Circulation Research (2009)

MicroRNAs are posttranscriptional gene regulators that are differentially expressed during various diseases and have been implicated in the underlying pathogenesis. We report here that miR-199a is acutely downregulated in cardiac myocytes on a decline in oxygen tension. This reduction is required for the rapid upregulation of its target, hypoxia-inducible factor (Hif)-1alpha. Replenishing miR-199a during hypoxia inhibits Hif-1alpha expression and its stabilization of p53 and, thus, reduces apoptosis. On the other hand, knockdown of miR-199a during normoxia results in the upregulation of Hif-1alpha and Sirtuin (Sirt)1 and reproduces hypoxia preconditioning. Sirt1 is also a direct target of miR-199a and is responsible for downregulating prolyl hydroxylase 2, required for stabilization of Hif-1alpha. Thus, we conclude that miR-199a is a master regulator of a hypoxia-triggered pathway and can be exploited for preconditioning cells against hypoxic damage. In addition, the data demonstrate a functional link between 2 key molecules that regulate hypoxia preconditioning and longevity.
Normal-Pressure Hydrocephalus
Authors: A. Everette James
Journal: JAMA (1970)

Normal-pressure hydrocephalus is characterized by neurological symptoms of dementia and awkwardness of movement, cerebrospinal fluid pressure in the normal range, and ventricular enlargement without cortical atrophy. Pneumoencephalograms reveal enlarged ventricles with failure of air to pass over the cerebral convexities. The cisternographic abnormalities are the presence of radioactivity in the enlarged ventricles, abnormality of movement of the injected radioactivity over the cerebral hemispheres, and failure of the radioactivity to concentrate in the sagittal area on delayed scans (24 or 48 hours). Since normal-pressure hydrocephalus is a treatable form of dementia, accurate diagnosis based on clinical manifestations, findings from lumbar puncture, pneumoencephalography, and cisternography is mandatory.
Platelet-activating factor stimulates gene expression and synthesis of matrix proteins in cultured rat and human mesangial cells
Authors: M Ruiz-Ortega, R Largo, C Bustos, D Gómez-Garre, J Egido
Journal: Journal of the American Society of Nephrology (1997)

Platelet-activating factor (PAF) is a potent inflammatory mediator that participates in the pathogenesis of proteinuria and glomerular damage. However, the role of this lipid in glomerular sclerosis remains unknown. This study examines the effect of PAF on the regulation of extracellular matrix proteins by rat and human mesangial cells. PAF increased in a dose-dependent manner the gene expression of fibronectin and type IV collagen, but not type I collagen. Moreover, an increase in cell-associated and soluble fibronectin synthesis was also seen. These effects were abolished by BN52021 and WEB2086, two different PAF receptor antagonists. Because transforming growth factor (TGF)-beta has been considered a profibrogenic cytokine, this study also evaluated whether PAF effects might be mediated by the production of endogenous TGF-beta. PAF caused an increase in TGF-beta1 mRNA expression (by a protein kinase C-dependent pathway) and TGF-beta activity. Moreover, PAF-induced fibronectin synthesis was totally abolished when an anti-TGF-beta-neutralizing antibody was added to the culture medium, suggesting that PAF stimulates fibronectin synthesis, at least in part, through the induction of TGF-beta. Addition of cycloheximide, a protein synthesis inhibitor, upregulated PAF-induced fibronectin mRNA expression but downregulated PAF-induced TGF-beta1 gene expression, suggesting the existence of different regulatory transcriptional factors of the two proteins. These results suggest that PAF may be implicated in matrix accumulation during renal injury and therefore contribute to the pathogenesis of glomerulosclerosis.
CD8 Epitope Escape and Reversion in Acute HCV Infection
Authors: Joerg Timm, Georg M. Lauer, Daniel G. Kavanagh, Isabelle Sheridan, Arthur Y. Kim, Michaela Lucas, Thillagavathie Pillay, Kei Ouchi, Laura L. Reyor, Julian Schulze zur Wiesch, Rajesh T. Gandhi, Raymond T. Chung, Nina Bhardwaj, Paul Klenerman, Bruce D. Walker, Todd M. Allen
Journal: The Journal of Experimental Medicine (2004)

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70–80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8–restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon γ enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8–associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.
Authors' reply to Chitnavis
Authors: L. S. Lohmander, E. M. Roos
Journal: BMJ (2015)

We thank Chitnavis for his response and wish to correct some misconceptions about published results.1 2

At least nine published randomised controlled trials have compared the benefit of arthroscopic meniscal surgery with non-surgical management or sham surgery. The most recent systematic review and meta-analysis concludes “there is no benefit to arthroscopic meniscal debridement for degenerative meniscal tears in comparison with nonoperative or sham treatments …
In vivo effect of indomethacin to potentiate the renal medullary cyclic AMP response to vasopressin.
Authors: G M Lum, G A Aisenbrey, M J Dunn, T Berl, R W Schrier, K M McDonald
Journal: Journal of Clinical Investigation (1977)

In a previous study we demonstrated that indomethacin potentiated the hydro-osmotic action of vasopressin in vivo. It was hypothesized that this action of indomethacin was due to its ability to suppress renal medullary prostaglandin synthesis, since in vitro studies have suggested that prostaglandins interfere with the ability of vasopressin to stimulate production of its intracellular mediator, cyclic AMP. In the present study this hypothesis was tested in vivo. Anesthetized rats undergoing a water diuresis were studied. In a control group, bolus injections of 200 muU of vasopressin caused a rise in urinary osmolality (Uosm) from 124 +/- 6 to 253 +/- 20 mosmol/kg H2O (P less than 0.005). In a group treated with 2 mg/kg of indomethacin the same dose of vasopressin caused a significantly greater (P less than 0.001) rise in Uosm from 124 +/- 7 to 428 +/- 19 mosmol/kg H2O. Medullary tissue cyclic AMP rose from 9.4 +/- 0.9 to 13.4 +/- 1.7 (P less than 0.05) pmol/mg tissue protein after vasopressin administration in animals receiving no indomethacin, while in indomethacin-treated animals there was a significantly greater rise (P less than 0.001) in medullary cyclic AMP from 10.4 +/- 0.9 to 21.6 +/- 2.1 pmol/mg tissue protein in response to the vasopressin injections. In neither control animals nor indomethacin-treated animals were there significant changes in renal hemodynamics, as measured by clearance techniques. Indomethacin, when given alone, had no effect on Uosm or medullary tissue cyclic AMP. Indomethacin did, however, reduce medullary prostaglandin E content from 84.7 +/- 15.0 to 15.6 +/- 4.3 pg/mg tissue. This study has shown that indomethacin, in a dose which suppresses medullary prostaglandin content, potentiates the ability of vasopressin to increase the tissue content of its intracellular mediator, cyclic AMP. Indomethacin caused no demonstrable inhibition of cyclic AMP phosphodiesterase. Therefore, it seems likely that indomethacin enhanced the ability of vasopressin to increase medullary cyclic AMP levels by causing an increased production rather than decreased destruction of the nucleotide. We conclude that this action of indomethacin contributes to its ability to potentiate the hydro-osmotic action of vasopressin in vivo. A corollary to this conclusion is that endogenous medullary prostaglandin E's may be significant physiological modulators of the renal response to vasopressin.
Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial
Authors: Laura A Guay, Philippa Musoke, Thomas Fleming, Danstan Bagenda, Melissa Allen, Clemensia Nakabiito, Joseph Sherman, Paul Bakaki, Constance Ducar, Martina Deseyve, Lynda Emel, Mark Mirochnick, Mary Glenn Fowler, Lynne Mofenson, Paolo Miotti, Kevin Dransfield, Dorothy Bray, Francis Mmiro, J Brooks Jackson
Journal: The Lancet (1999)

Background The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life. Methods From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6–8 weeks, and 14–16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis. Findings Nearly all babies (98·8%) were breastfed, and 95·6% were still breastfeeding at age 14–16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10·4% and 8·2% at birth (p=0·354); 21·3% and 11·9% by age 6–8 weeks (p=0·0027); and 25·1% and 13·1% by age 14–16 weeks (p=0·0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20–64) up to age 14–16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups. Interpretation Nevirapine lowered the risk of HIV-1 transmission during the first 14–16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
Reply to the Letter to the Editor from Jubb
Authors: Sherry X. Yang, Sandra M. Swain
Journal: Clinical Cancer Research (2008)

In Response: The letter to the Editor from Dr. Jubb has raised an important question as to whether the objective response rate is a useful indicator of treatment benefit from bevacizumab (BV) in combination with chemotherapy. Whether the response rate and progression-free survival are surrogates for
Infantile Urticaria Caused by Salicylamide Teething Powder
Authors: B. Bentley-Phillips
Journal: British Journal of Dermatology (1968)

British Journal of DermatologyVolume 80, Issue 5 p. 341-341 Infantile Urticaria Caused by Salicylamide Teething Powder B. Bentley-Phillips, B. Bentley-Phillips King Edward VIII Hospital, University of Natal, Durban, South Africa.Search for more papers by this author B. Bentley-Phillips, B. Bentley-Phillips King Edward VIII Hospital, University of Natal, Durban, South Africa.Search for more papers by this author First published: May 1968 https://doi.org/10.1111/j.1365-2133.1968.tb12310.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume80, Issue5May 1968Pages 341-341 RelatedInformation
A Preliminary Study of Left Frontal Region Error Negativity and Symptom Improvement in Geriatric Depression
Authors: Balu Kalayam, George S Alexopoulos
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study tested the hypothesis that frontal error negative wave amplitude on EEG during Stroop test activation predict change in depressive symptoms in depressed elders. METHOD: Twenty-two older patients with major depression received controlled treatment with citalopram at a target dose of 40 mg/day for 6 weeks. Paramedian error negative waves were recorded during Stroop activation before treatment. RESULTS: Nine subjects who remained symptomatic had larger left frontal error negative waves than the subjects who achieved remission. Left frontal error negative waves were correlated with percent change of depressive symptoms from baseline. Other paramedian error negative waves did not distinguish remitted from unremitted subjects. Left frontal error negative waves were negatively correlated with Mattis Dementia Rating Scale scores for initiation/perseveration; these scores were lower in unremitted than remitted patients. CONCLUSIONS: Increased left frontal error negative waves are associated with limited or slow change in depressive symptoms in elders receiving citalopram.
Protection from Lethal Gram-Positive Infection by Macrophage Scavenger Receptor–Dependent Phagocytosis
Authors: Christian A. Thomas, Yongmei Li, Tatsuhiko Kodama, Hiroshi Suzuki, Samuel C. Silverstein, Joseph El Khoury
Journal: The Journal of Experimental Medicine (2000)

Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II-deficient mice (MSR-A(-/-)) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A(+/+) control mice. MSR-A(-/-) mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A(-/-) macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II-dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.
Inhibition of ATR Leads to Increased Sensitivity to Hypoxia/Reoxygenation
Authors: Ester M. Hammond, Mary Jo Dorie, Amato J. Giaccia
Journal: Cancer Research (2004)

Abstract The transient opening and closing of tumor vasculature result in periods of severe oxygen deprivation (hypoxia) followed by reoxygenation. This exerts a positive selective pressure for cells that have lost their sensitivity to killing by reduced oxygen levels. These cells are effectively resistant to hypoxia-induced apoptosis and conventional therapeutic approaches. Here we show hypoxia-induced S-phase arrest results in regions of single-stranded DNA in stalled replication forks and signals the activation of ATR. S-phase cells represent the most sensitive phase of the cell cycle to the stress of hypoxia/reoxygenation. Loss of ATR or inhibition of ATR kinase activity results in a further loss of reproductive viability in S-phase cells when exposed to hypoxic conditions followed by reoxygenation but has little effect on the inhibition of DNA synthesis. This is, at least in part, mediated via Chk1 signaling because loss of Chk1 also results in increased sensitivity to hypoxia/reoxygenation. The observed decrease in reproductive survival is in part because of the accumulation of DNA damage in S-phase cells during hypoxia exposure in the absence of full ATR activity. Therefore, ATR acts to protect stalled replication forks during hypoxia exposure. In conclusion, ATR and Chk1 play critical roles in the cellular response to hypoxia/reoxygenation, and inhibitors of ATR and Chk1 represent new hypoxic cell cytotoxins.
Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons.
Authors: J W Ensinck, R E Vogel, E C Laschansky, D J Koerker, R L Prigeon, S E Kahn, D A D'Alessio
Journal: Journal of Clinical Investigation (1997)

Somatostatin-28 (S-28), secreted into the circulation from enterocytes after food, and S-14, released mainly from gastric and pancreatic D cells and enteric neurons, inhibit peripheral cellular functions. We hypothesized that S-28 is a humoral regulator of pancreatic B cell function during nutrient absorption. Consistent with this postulate, we observed in baboons a two to threefold increase in portal and peripheral levels of S-28 after meals, with minimal changes in S-14. We attempted to demonstrate a hormonal effect of these peptides by measuring their concentrations before and after infusing a somatostatin-specific monoclonal antibody (mAb) into baboons and comparing glucose, insulin, and glucagon-like peptide-1 levels before and for 4 h after intragastric nutrients during a control study and on 2 d after mAb administration (days 1 and 2). Basal growth hormone (GH) and glucagon levels and parameters of insulin and glucose kinetics were also measured. During immunoneutralization, we found that (a) postprandial insulin levels were elevated on days 1 and 2; (b) GH levels rose immediately and were sustained for 28 h, while glucagon fell; (c) basal insulin levels were unchanged on day 1 but were increased two to threefold on day 2, coincident with decreased insulin sensitivity; and (d) plasma glucose concentrations were similar to control values. We attribute the eventual rise in fasting levels of insulin to its enhanced secretion in compensation for the heightened insulin resistance from increased GH action. Based on the elevated postmeal insulin levels after mAb administration, we conclude that S-28 participates in the enteroinsular axis as a decretin to regulate postprandial insulin secretion.