tbuckley/cabot-search huggingface dataset:
Downregulation of myocardial beta-adrenergic receptors. Receptor subtype selectivity.
Authors: K H Muntz, M Zhao, J C Miller
Journal: Circulation Research (1994)

T he desensitization (loss of response) and down- regulation (loss of receptors) of p-adrenergic receptors (,BAR) have been observed in several cardiac conditions, including certain forms of heart failure and hypertension.The inability of the failing heart to respond to inotropic agents such as catecholamines represents a major clinical problem.The down- regulation of 131AR associated with certain forms of heart failure1 has been considered a consequence of the chronic high plasma catecholamine levels associated with this disorder.The purpose of this review is to examine agonist-induced downregulation of myocardial ,6AR in light of studies suggesting that f31AR are more resistant to downregulation than are /2AR.Potential mechanisms for differential downregulation of flAR subtypes will also be discussed, including the possibility that f82AR on cardiac myocytes are downregulated via coated pits but that f31AR are associated with plasma- lemmal vesicles known as caveolae.
Breast cancer in men: Group is exploring issues for men with breast cancer across the United Kingdom
Authors: R. Iredale
Journal: BMJ (2003)

EDITOR–The editorial by Perkins and Middleton on breast cancer in men in the United States was heartening.1 Breast cancer in men is rare,2 but every year 200-300 men in the United Kingdom are newly diagnosed with it. Whereas the common nature of female breast cancer has resulted in good general awareness, male breast …
The role of hepatic insulin receptors in the regulation of glucose production
Authors: Alan D. Cherrington
Journal: Journal of Clinical Investigation (2005)

The inability of insulin to suppress hepatic glucose production (HGP) is a key defect found in type 2 diabetes. Insulin inhibits HGP through both direct and indirect means, the latter of which include inhibition of glucagon secretion, reduction in plasma nonesterified fatty acid level, decrease in the load of gluconeogenic substrates reaching the liver, and change in neural signaling to the liver. Two studies in this issue of the JCI demonstrate that selective changes in the expression of insulin receptors in mouse liver do not have a detectable effect on the ability of insulin to inhibit HGP (see the related articles beginning on pages 1306 and 1314). These provocative data suggest that the indirect effects of insulin on the liver are the primary determinant of HGP in mice.
Moment of Truth for the Teaching Hospitals
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1982)

The nation's teaching hospitals — complex, expensive, and dependent on public support to sustain their many activities — are heading into more stressful times that will force many of these institutions to question and perhaps dramatically alter their basic operations. Like any set of American institutions that prospered in the bountiful times of yesterday, most teaching hospitals are resisting and will continue to resist major change; yet, given the policy directions of government and the expressed concerns of private insurers over cost shifting, maintaining the status quo no longer seems a viable option for many of them.Teaching hospitals are . . .
Catabolic Illness
Authors: Jeffrey S. Flier, Lisa H. Underhill, Douglas W. Wilmore
Journal: New England Journal of Medicine (1991)

RAPID weight loss, associated with the loss of body fat and skeletal-muscle mass, frequently accompanies short-term, self-limiting disease processes, such as infection and injury.1 , 2 Similar catabolic events are associated with other disorders, such as diabetic ketoacidosis,3 the failure of multiple organ systems,4 and extensive chemotherapy or radiation treatment for cancer.5 The loss of body tissue may be minimal and of little consequence in a patient with a normal nutritional status and a brief, self-limiting illness lasting only one week, but when the disease is prolonged and the patient is nutritionally depleted, a variety of clinical events occur in association with . . .
Ex Vivo Surgical Dissection
Authors: Martin G. McLoughlin
Journal: JAMA (1976)

Ex vivo dissection, reconstruction, and autotransplantation have been performed in a total of five patients. Two had intrarenal aneurysms, and in three, this treatment was deemed best suitable. One patient has sustained normal renal function with as little as one third of his remaining kidney. There are techniques now available to provide a means of ex vivo preservation of organs adequate to sustain renal viability during bench surgery.
No Major Differences in 30-Day Outcomes in High-Risk Patients Randomized to Off-Pump Versus On-Pump Coronary Bypass Surgery
Authors: Christian H. Møller, Mario J. Perko, Jens T. Lund, Lars W. Andersen, Henning Kelbæk, Jan K. Madsen, Per Winkel, Christian Gluud, Daniel A. Steinbrüchel
Journal: Circulation (2010)

Background— Off-pump coronary artery bypass grafting compared with coronary revascularization with cardiopulmonary bypass seems safe and results in about the same outcome in low-risk patients. Observational studies indicate that off-pump surgery may provide more benefit in high-risk patients. Our objective was to compare 30-day outcomes in high-risk patients randomized to coronary artery bypass grafting without or with cardiopulmonary bypass. Methods and Results— We randomly assigned 341 patients with a EuroSCORE ≥5 and 3-vessel coronary disease to undergo coronary artery bypass grafting without or with cardiopulmonary bypass. Patients were followed through the Danish National Patient Registry. The primary outcome was a composite of adverse cardiac and cerebrovascular events (ie, all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention). An independent adjudication committee blinded to treatment allocation assessed the outcomes. Baseline characteristics were well balanced between groups. The mean number of grafts per patient did not differ significantly between groups (3.22 in off-pump group and 3.34 in on-pump group; P =0.11). Fewer grafts were performed to the lateral part of the left ventricle territory during off-pump surgery (0.97 versus 1.14 after on-pump surgery; P =0.01). No significant differences in the composite primary outcome (15% versus 17%; P =0.48) or the individual components were found at 30-day follow-up. Conclusions— Both off- and on-pump coronary artery bypass grafting can be performed in high-risk patients with low short-term complications. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00120991.
Chronic caffeine administration exacerbates renovascular, but not genetic, hypertension in rats.
Authors: A Ohnishi, R A Branch, K Jackson, R Hamilton, I Biaggioni, G Deray, E K Jackson
Journal: Journal of Clinical Investigation (1986)

The purpose of this study was to determine whether or not caffeine would exacerbate renovascular hypertension. Therefore, we examined the effects of chronic caffeine administration on arterial blood pressure in rats subjected to either unilateral renal artery clipping (2K-1C rats) or sham-operation. Animals in each group were randomly assigned to receive either 0.1% caffeine in their drinking water or normal drinking water, and systolic blood pressure was monitored for 6 wk. Caffeine markedly exacerbated the severity of hypertension in 2K-1C rats and caused histological changes consistent with malignant hypertension. 6 wk after surgery, systolic blood pressure, plasma renin activity, and creatinine clearance in control 2K-1C rats were 169 +/- 5 mmHg (mean +/- SEM), 4.4 +/- 0.5 ng AI X ml-1 X h-1, and 2.9 +/- 0.2 ml/min, respectively; as compared with 219 +/- 4 mmHg, 31.8 +/- 7.8 ng AI X ml-1 X h-1, and 1.4 +/- 0.3 ml/min, respectively, in 2K-1C rats receiving caffeine (all values were significantly different compared with control 2K-1C). Chronic caffeine administration did not alter systolic blood pressure, plasma renin activity, or creatinine clearance in sham-operated rats or spontaneously hypertensive rats. Chronic treatment with enalapril (a converting enzyme inhibitor) prevented the development of hypertension in control 2K-1C rats and caffeine-treated 2K-1C rats; however, withdrawal of enalapril precipitated a rapid rise in systolic blood pressure in caffeine-treated 2K-1C rats, but not in control 2K-1C rats. These experiments indicate that caffeine specifically exacerbates experimental renovascular hypertension and might worsen the hypertensive process in patients with renovascular hypertension.
Oligodeoxynucleotides containing CpG motifs modulate the allergic TH2 response of BALB/c mice to Bet v 1, the major birch pollen allergen☆☆☆★
Authors: Beatrice Jahn-Schmid, Ursula Wiedermann, Barbara Bohle, Andreas Repa, Dietrich Kraft, Christof Ebner
Journal: Journal of Allergy and Clinical Immunology (1999)
Abstract 1325: PCI-5002 leads to enhanced radiosensitization via induction of necrotic cell death by promoting autophagy in non-small cell lung tumor xenograft model
Authors: Dae Kwang Jung, kwang woon kim, Bo Lu
Journal: Cancer Research (2010)

Abstract Purpose: We previously showed that Bax/Bak inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the specific mechanism by which radiation triggers necrotic cell death via autophagy in H460 cells treated with PCI-5002, water-soluble zinc ionophores, in vitro or in vivo. Methods: Clonogenic assay was used to determine radiosensitivity. H460 lung cancer xenografts was generated and immunohistochemistry (IHC) was performed on tumor sections for tumor cell proliferation (Ki67 staining), angiogenesis (von Willebrand Factor staining), and apoptosis (cleaved caspase-3 antibody staining). Autophagy was determined by p62 protein, which is named sequestosome 1(SQSTM1) and links polyubiquitinated proteins to the autophagic machinery in vivo and punctuate localization of GFP-LC3 fusion protein, which observed under a confocal fluorescence microscope in vitro. Necrosis was determined with HMGB1 release and Propidium lodide (PI) staining. Results: The PCI-5002 markedly enhanced sensitivity of MEF WT cells to radiation (DER=1.43, p=0.003) in clonogenic assay. This enhanced radiosensitization was associated with an increase in characteristic punctuate localization of GFP-LC3 when was blocked a cleaved caspase-3 in MEF WT cells treated with PCI-5002, suggesting that autophagy was induced simultaneously. We found that PCI-5002 with radiation showed a dramatically enhanced sensitivity of H460 cells to radiation (DER=1.92, p=0.001) in clonogenic assay, and tumor growth delay in a mouse hind limb xenograft model in vivo, and was well tolerated compared to control. In addition, the concurrent administration of PCI-5002 and radiation in vivo significantly decreased cell proliferation and vascular density compared to radiation alone. Consistent with the in vitro results, treatment both PCI-5002 and radiation showed a dramatically increase in HMGB1 as a marker for Necrosis and a significant decrease in p62 protein level for detecting autophagic flux in the lung tumor xenograft model. Conclusions: These results suggest that induction of necrosis via promotion of autophagy may be utilized as a novel strategy to enhance radiation therapy in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1325.
Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin
Authors: Marek Naruszewicz, Malgorzata Klinke, Krzysztof Dziewanowski, Anna Staniewicz, Hanna Bukowska
Journal: Metabolism (2001)
Chondrocalcinosis and Gitelman's syndrome. A new association?
Authors: J. C COBETA-GARCIA, A. GASCON, E. IGLESIAS, V. ESTOPINAN
Journal: Annals of the Rheumatic Diseases (1998)

Calcium pyrophosphate dihydrate (CPPD) deposition disease is in most cases idiopathic, but there are familial forms and others in connection with metabolic disease.1 One of the metabolic associations is with hypomagnesaemia, frequently because of Bartter’s syndrome (BS).2 Another cause of hypomagnesaemia is Gitelman’s syndrome (GS),3 a hypocalciuric variant of BS. Recent studies confirm that these are different processes, with diverse molecular bases that explain the clinical and analytical findings characteristic of each one of them.4 We present the case of a patient with chondrocalcinosis (CC) and pseudogout in whose study hypomagnesaemia secondary to GS is detected. In our search of the Medline database, we have not found reports of a similar association. However, reading of some of the CC and BS cases leads us to think that we are actually dealing with patients whose GS had not been diagnosed.5-7 

The patient is a 43 year old woman without pathological antecedents who consulted because of a four year history of bilateral mechanic knee pain with episodes of acute arthritis that remitted days after treatment with non-steroidal anti-inflammatory drugs. During …
Psychophysiologic Aspects of Malignancy
Authors: CHARLES GOLDFARB, JEROME DRIESEN, DONALD COLE
Journal: American Journal of Psychiatry (1967)

Three patients with advanced carcinomatosis and concomitant depression were treated with ECT and cancer chemotherapy. All three experienced positive cancerocidal effects, although in one case they were short-lived. Possible explanations for these results are discussed in the light of previous reports of certain psychodynamic and biochemical similarities between cancer patients and depressed patients.
Minimum Waist and Visceral Fat Values for Identifying Japanese Americans at Risk for the Metabolic Syndrome
Authors: Tomoshige Hayashi, Edward J. Boyko, Marguerite J. McNeely, Donna L. Leonetti, Steven E. Kahn, Wilfred Y. Fujimoto
Journal: Diabetes Care (2006)

Japanese American is an ethnic group with a high risk for type 2 diabetes, which is linked to the metabolic syndrome. Central adiposity is considered to play a key role in the metabolic syndrome. Not known are the optimal cut point values for central and visceral adiposity to identify Japanese Americans at risk for the metabolic syndrome.Study subjects included 639 Japanese Americans. The nonadipose variables of the metabolic syndrome were defined using modified International Diabetes Federation criteria, and the accuracy of identifying at least two of these by intra-abdominal fat area (IAFA) as measured by computed tomography and waist circumference was cross-sectionally assessed using area under receiver operating characteristic (ROC) curves. The values for IAFA and waist circumference that resulted in maximizing the Youden index were defined as "optimal."The area under the ROC curve for IAFA exceeded that for waist circumference (men 0.787 vs. 0.686; women 0.792 vs. 0.721). For women, the optimal cut points for IAFA and waist circumference were 51.5 cm(2) and 80.8 cm (age < or = 56 years) and 86.3 cm(2) and 89.0 cm (age > 56 years). For men, the optimal cut points for IAFA and waist circumference were 88.6 cm(2) and 90.0 cm (age < or = 57 years) and 96.1 cm(2) and 87.1 cm (age > 57 years).These results argue that current Japanese waist circumference cut points for the metabolic syndrome need to be revised. Moreover, the waist circumference and IAFA cut points should be age specific, especially in women. Appropriate waist circumference cut points are from 80 to 90 cm in women and from 87 to 90 cm in men.
Irradiation of the Primary Lesion of the Rectum and Rectosigmoid
Authors: Morton M. Kligerman
Journal: JAMA (1975)

SURGERY is currently the method of choice in the management of operable adenocarcinoma of the rectum. Unfortunately, as pointed out  Gilbertsen, 1 five-year survival is less than 50% in patients in whom resection is possible. Only 30% of all patients with rectal cancer are longterm survivors. Morson et al 2 state that surgery alone has little more to offer in the treatment of rectal cancer.... and in spite of all attempts at earlier diagnosis, there has been no significant change in the incidence of the different stages of rectal cancer over the past 25 years.  According to Gilbertsen, 1 by the time of diagnosis, most of these cancers have already spread beyond the intestine to adjacent lymph nodes, contiguous organs, or to more remote areas. He reports that among 125 patients who died of adenocarcinoma of the rectum after curative resections, approximately half died with local recurrence.  Rectal cancer,
Effect of in vitro metabolic acidosis on luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport in rabbit kidney proximal tubules.
Authors: M Soleimani, G L Bizal, T D McKinney, Y J Hattabaugh
Journal: Journal of Clinical Investigation (1992)

The aim of this study was to evaluate the role of the kidney in mediating the signals involved in adaptive changes in luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport systems in metabolic acidosis. Proximal tubular suspensions were prepared from rabbit kidney cortex and incubated in acidic (A) or control (C) media (pH 6.9 vs 7.4, 5% CO2) for 2 h. Brush border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from the tubular suspensions and studied for the activity of Na+/H+ exchange and Na+:HCO3- cotransport. Influx of 1 mM 22Na at 10 s (pH6 7.5, pH(i) 6.0) into BBM vesicles was 68% higher in group A compared to group C. The increment in Na+ influx in the group A was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.1 mM in C vs 9.2 in A and Vmax of 31 nmol/mg protein per min in group C vs 57 in A. Influx of 1 mM 22Na at 10 s (pH0 7.5, pH(i) 6.0, 20% CO2, 80% N2) into BLM vesicles was 83% higher in the group A compared to C. The HCO3-dependent increment in 22Na uptake in group A was 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid sensitive, suggesting that Na+:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 11.4 mM in C vs 13.6 in A and Vmax of 35 nmol/mg protein per min in C vs 64 in A. The presence of cyclohexamide during incubation in A medium had no effect on the increments in 22Na uptake in group A. We conclude that the adaptive increase in luminal Na+/H+ exchange and basolateral Na+:HCO3- cotransport systems in metabolic acidosis is acute and mediated via direct signal(s) at the level of renal tubule.
Vitiligo Associated With Subcutaneous Insulin Lispro Infusion in Type 1 Diabetes
Authors: Mark R. Burge, J. David Carey
Journal: Diabetes Care (2004)

Vitiligo vulgaris, the loss of skin pigmentation, is known to occur with increased frequency in patients with type 1 diabetes and, based on a preponderance of circumstantial evidence (1), presumed to be of autoimmune etiology. For example, 20% of 39 patients with vitiligo were found to have diabetes in a Romanian community study (2), and 9% of 457 consecutive Italian patients with diabetes had vitiligo in another study (including 54% of the type 1 patients) (3). However, the factors that can specifically precipitate vitiligo in type 1 diabetes …
Adult Fanconi Syndrome and Cirrhosis
Authors: C. E. Dent, J. M. Stowers
Journal: BMJ (1965)

SIR,-In 1947 we published a paper' entitled " Studies on the Mechanism of the Fanconi Syndrome."The subject of the study was a man aged 34, presenting in 1945 with gross osteomalacia.He was found to have the full renal-tubular abnormalities usually associated with the name " Fanconi syndrome "-namely, renal tubular reabsorp- tive defects of phosphate, glucose, and amino- acid, with renal-tubular acidosis.He was also found to have severe cirrhosis, from which he died in early 1946, his bone disease having been largely controlled by treatment.We thought then that cirrhosis was an occasional association of " Fanconi syndrome," indeed we then speculated that the cirrhosis might have resulted from amino-acid depletion in consequence of the amino-aciduria.'(We do not believe this any longer.)Our subsequent clinical studies at Univer- sity College Hospital have shown that cirrhosis is only consistently associated with a childhood form of the Fanconi syndrome, as in the case described by Baber.3One of us (C.E. D.) began to get worried about the original case in an adult man, since no further similar " idiopathic " cases have since been seen or heard of in this age group.The postmortem material was no longer available, but a measured aliquot of the patient's 24-hour urine of 7 January 1946 has been traced in our cold room.It has been sent to Professor J. N. Cumings, who reports that it contained 45 jeg./100 ml. of copper, or 594 pig. in the 24-hour specimen.He adds that this grossly excessive excretion is "undoubtedly diag- nostic of Wilson's disease if it cannot be explained by contamination."It would seem necessary to record now that the diagnosis of " idiopathic adult Fanconi syndrome with cirrhosis of the liver" prob- ably no longer exists on the basis of present evidence.Any apparent case should there- fore be carefully screened for causes of secondary renal tubular or of liver dysfunction such as myeloma, and heavy-metal poisoning-but especially for Wilson's dis- ease, for which we now have excellent treatment.4The existence of adult Fanconi syndrome without cirrhosis remains fully substantiated.-We are, etc.,
Blood Pressure and the Bladder
Authors: D. Whitteridge, D. E. M. Taylor
Journal: BMJ (1967)

<b><i>Background:</i></b> The antivirally active MxA protein is induced by interferon (IFN) α/β and inhibits the replication of single-stranded RNA viruses including measles virus (MV). The authors investigated whether the <i>MxA</i> gene contributed to the development of subacute sclerosing panencephalitis (SSPE) in Japanese individuals. <b><i>Methods:</i></b> Single-nucleotide polymorphisms (SNP) in the promoter region of the <i>MxA</i> gene were screened, association studies were performed between two SNP and SSPE, and then a functional difference in the promoter activities of the two SNP was investigated by a dual luciferase reporter assay. <b><i>Results:</i></b> Four SNP were found (−88 G/T, −123 C/A, −200 T/C, and −213 G/T), and SSPE patients exhibited a higher frequency of both the −88T allele and the −88TT genotype than controls (<i>p</i> = 0.040 and 0.003). The IFN-induced up-regulation of the <i>MxA</i> promoter activity of the sequence with −88T was found to be significantly higher than that with G. <b><i>Conclusions:</i></b><i>MxA</i> promoter −88 G/T SNP may confer host genetic susceptibility to SSPE in Japanese individuals. The finding that homozygotes of the <i>MxA</i> −88T allele with a high MxA-producing capability were more frequently seen in SSPE patients suggests that the MxA protein promotes the establishment of persistent MV infection of neural cells.