tbuckley/cabot-search huggingface dataset:
The unfolding story of megalin (gp330): now recognized as a drug receptor.
Authors: M G Farquhar
Journal: Journal of Clinical Investigation (1995)

In this issue of The Journal Moestrup et al. (1) report that polybasic drugs such as aprotinin, aminoglycosides, and poly- myxin B are taken up by the endocytic receptor, megalin/gp330.Antibiotics such as gentamycin and polymyxin B are well known to be both nephrotoxic and ototoxic, but the mechanisms by which these drugs become concentrated in lysosomes of the kidney and ear to produce tissue damage remain unknown.This carefully executed study demonstrates that they bind to mega- lin/gp330 both in vitro and in vivo and are taken up by receptor- mediated endocytosis in clathrin-coated pits.Thus, Moestrup et al.( 1 ) provide a clear explanation of the molecular mechanisms by which the kidney and probably also the ear take up and concentrate these toxic, polybasic drugs.At the same time the authors have added another dimension, a pathologic dimension, to the story of megalin ( gp330) by showing that it serves as a drug receptor.What is megalin/gp330?gp330 (megalin) is one of the most abundant membrane proteins in the renal proximal tubule.It was originally identified as the target antigen of Heymann nephritis, a rat model of membranous glomerulonephritis (2,3).Its location in clathrin-coated pits suggested from the begin- ning that gp330 is an endocytic receptor (3, 4).In addition to its expression in glomerular and proximal tubule epithelia, this receptor is expressed in a number of epithelia that are heavily engaged in receptor-mediated endocytosis, including type II cells of the lung and epithelial cells of the inner ear, epididymis, mammary gland, thyroid, parathyroid, yolk sac, and retina (5).Interest in this molecule was greatly enhanced when Raychowdhury et al. ( 6) obtained and sequenced a partial cDNA clone which clearly established that gp330 is a member of the LDL receptor gene family (7).The complete amino acid sequence was obtained only recently (8), and this receptor was found to possess all the structural motifs characteristic of the LDL recep- tor family, including ligand binding, growth factor and EGF repeats, YWTD spacer regions, and the consensus (FX)NPXY endocytic internalization signal.Structurally it is quite similar to the LDL receptor related protein/a2-macroglobulin receptor (LRP), another LDL receptor family member.Based on its large size (517,715 mol wt) which proved to be larger than originally anticipated the name "megalin" was introduced as an alternative to gp330 (8).Ligands that bind to megalin/gp330.In the meantime the search for its ligands has identified a surprisingly diverse group of molecules that are capable of binding to megalin/gp330 in vitro: RAP (receptor-associated protein), apoE-enriched
Microscopic Examination of Urine Sediment-Reply
Authors: Robert M. Donauer
Journal: JAMA (1979)

There are basically several differences between the study done by Dr Pai in a hospital laboratory and the one carried out in our insurance-oriented laboratory. The latter is geared to obtain maximum data for underwriting purposes from a single specimen. We do not have available to us a number of secondary definitive procedures to fill any gaps in our analysis. It would still not appear good policy to pay less attention to one part of a single test in the hope that some other procedure would cover the missing information. Obviously our sample of 13,479 specimens is larger than the reported hospital figure. Our population would not have the same amount of acute illness; I would naturally anticipate a higher percentage of positive test results in a hospital series. There are obvious differences between fresh specimens obtained at a medical center and urine specimens preserved and mailed. The
Acute Proximal Occlusion of a Nonaneurysmal Abdominal Aorta and Renal Arteries Detected by Renal Imaging
Authors: LAWRENCE A. GILBERT, NEIL KATZ, ANIL K. MANDAL, YUNG S. PARK, ZAHER KOUTOUBI
Journal: Clinical Nuclear Medicine (1997)

This report describes an unusual case of extensive vascular thrombosis involving the abdominal aorta and its branches. An 81-year-old man was admitted for anuric acute renal failure and congestive heart failure. An initial renal scan, performed to assess for the possibility of renal arterial embolus, showed scintigraphic evidence of obstruction of the proximal abdominal aorta, as well as markedly decreased perfusion to both kidneys and to the liver and spleen. The patient's condition progressively deteriorated and he expired. An autopsy showed total thrombotic occlusion of a mildly atherosclerotic nonaneurysmal abdominal aorta extending from the level of the superior mesenteric artery distally to the iliac arteries. There was involvement of the renal arteries and the splenic and superior mesenteric arteries by thrombosis. Thus, renal scintigraphy accurately detected the level of obstruction, which was further confirmed by autopsy.
Treatment Strategies for Prostate Cancer
Authors: William J. Catalona
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The study by Fleming et al<sup>1</sup>is of limited relevance to current prostate cancer management and fails to demonstrate that watchful waiting is as effective as active treatment in men over the age of 65 years. Moreover, it may impart misleading information for treating individual patients. Fleming et al based their estimates of cancer progression rates on a patient population that overrepresented patients most likely to die of other causes, such as elderly men with stage A disease, and underrepresented younger patients with more aggressive tumors. This introduced a bias in favor of watchful waiting. The historical data used for estimates of treatment outcomes do not accurately reflect the current ability to detect prostate cancer early and to treat it effectively. Recent studies have demonstrated a dramatic increase in the detection of early, curable prostate cancer through screening with serum prostate-specific antigen (PSA) measurements.<sup>2,3</sup>Fleming
Recovery from Prolonged Renal Failure in Patients with Accelerated Hypertension
Authors: Bashir H. Mamdani, Victoria Sy Lim, Sakharam D. Mahurkar, Adrian I. Katz, George Dunea
Journal: New England Journal of Medicine (1974)

WHEN oliguric renal failure persists for more than three months, recovery is unlikely, and lifelong hemodialysis is usually required. In the five patients with accelerated hypertension and uremia described below, delayed recovery of renal function occurred, so that maintenance hemodialysis could be discontinued six to 26 months after its initiation.PatientsAll patients were black, their ages ranged from 24 to 59 years, and four patients had diastolic blood pressures above 160 mm Hg. The duration of hypertension ranged from one to 13 years, and treatment with antihypertensive drugs had usually been irregular. All patients had cardiac enlargement, with electrocardiographic . . .
Software makes it easier for journals to spot image manipulation
Authors: Caroline White
Journal: BMJ (2007)

The digital age has made it easier to enhance the results of scientific studies, but it is also starting to provide means to counter the trend, delegates at an international seminar on research misconduct heard last week.

Mike Rosner, executive editor of the Journal of Cell Biology , said that “image manipulation” had become part of everyday culture, especially on the internet, and the widespread availability of computer software, such as Photoshop, had made it easy to do.

Dr Rosner was speaking at the annual seminar of the Committee on Publication Ethics (COPE) in London, attended by more than 85 scientific …
Atrial Natriuretic Factor
Authors: Z. A ABASSl
Journal: Cardiovascular Research (1993)

Journal Article Atrial Natriuretic Factor Get access ZAID A ABASSl ZAID A ABASSl Bethesda, MD, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 12, December 1993, Pages 2287–2288, https://doi.org/10.1093/cvr/27.12.2287 Published: 01 December 1993
An Evaluation of Poor Pregnancy Outcomes Among Burundian Refugees in Tanzania
Authors: Denise J. Jamieson
Journal: JAMA (2000)

Little is known about pregnancy outcomes among the approximately 11 million refugees worldwide, 25% of whom are women of reproductive age.To estimate incidence of and determine risk factors for poor pregnancy outcomes and to calculate the contribution of mortality from neonatal and maternal deaths to overall mortality in a refugee camp.Cross-sectional review of records and survey, conducted in February and March 1998.Mtendeli refugee camp, Tanzania.For the overall assessment, 664 Burundi women who had a pregnancy outcome during a recent 5-month period (September 1, 1997-January 31, 1998) and their 679 infants; 538 women (81%) completed the survey.Incidence of fetal death (fetus born > or =500 g or > or =22 weeks' gestation with no signs of life), low birth weight (<2500 g), neonatal death (death <28 days of life), and maternal death (deaths during or within 42 days of pregnancy from any cause related to or aggravated by the pregnancy or its management).The fetal death rate was 45.6 per 1000 births, the neonatal mortality rate was 29.3 per 1000 live births, and 22.4% of all live births were low birth weight. Compared with women without poor pregnancy outcome, those with poor pregnancy outcome were more likely to report prior high socioeconomic status (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.4), having a first or second pregnancy (OR, 2.2; 95% CI, 1.4-3.4), and having 3 or more episodes of malaria during pregnancy (OR, 2.0; 95% CI, 1.4-3.1). Neonatal and maternal deaths accounted for 16% of all deaths during the period studied.Poor pregnancy outcomes were common in this refugee setting, and neonatal and maternal deaths, 2 important components of reproductive health-related deaths, contributed substantially to overall mortality.
Effects of soybean flour on the pancreas of rats.
Authors: E E McGuinness, R G Morgan, K G Wormsley
Journal: Environmental Health Perspectives (1984)

We have reviewed the growth-promoting and carcinogenic effects of feeding raw soya flour to rats. If the raw soya flour-containing diets are fed for more than a year, about 10% of the animals develop pancreatic cancer. In addition, feeding raw soya flour markedly potentiates the action of even subthreshold amounts of pancreatic carcinogens. The raw soya flour therefore acts as a potent promoter, as well as a weak carcinogen. In view of this promotion, the rat fed raw soya flour is a sensitive model for screening pancreatic carcinogens. It is not known whether the human pancreas responds to dietary trypsin inhibitors in a manner similar to the rat. However, in view of the use of soya-based products in human nutrition--especially in infant foods--we urge that the effect of all soya-based products intended for human use be tested on the rat pancreas in long-term feeding studies, combined with subthreshold doses of azaserine to highlight any promoting activity of the product. It seems probable that if a product exerts no effect on the rat pancreas, the human pancreas will also be spared from noxious effects.
Gadolinium-based compounds induce NLRP3-dependent IL-1β production and peritoneal inflammation
Authors: Christian Schmidt-Lauber, Lukas Bossaller, Hani H Abujudeh, Gregory I Vladimer, Anette Christ, Katherine A Fitzgerald, Eicke Latz, Ellen M Gravallese, Ann Marshak-Rothstein, Jonathan Kay
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1β release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. <h3>Methods</h3> Bone marrow derived macrophages from C57BL/6, <i>Nlrp3<sup>−/−</sup></i> and <i>Asc<sup>−/−</sup></i> mice were incubated with three Gd-containing compounds and IL-1β activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)γ-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and <i>Nlrp3<sup>−/−</sup></i>mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). <h3>Results</h3> Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1β secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFNγ-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. <h3>Conclusions</h3> These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic presentation of NSF.
Psychosomatic Studies of Japanese Youth Under Social Changes
Authors: Tetsuya Nakagawa, Shigeyuki Nakano, Shū Mori, Mineyasu Sugita
Journal: Psychotherapy and Psychosomatics (1978)

Psychosomatic studies of adolescent patients were conducted at the Kyushu University Hospital. Among many adolescent psychosomatic disorders, the incidence of irritable colon syndrome ranked first. The dynamic mechanisms and therapeutic results of these patients were introduced. Next, an epidemiological study showed that the frequency of constipation and diarrhea rapidly increases over the period from junior high school to senior high school. Through matched pair studies conducted with high school students, significant interrelationships were proven to exist among the occurrence of diarrhea and constipation, awareness of illness and psychological factors.
Hypodipsic Hypernatremia with Normal Osmoregulation of Vasopressin
Authors: David N. Hammond, George W. Moll, Gary L. Robertson, Ewa Chelmicka-Schorr
Journal: New England Journal of Medicine (1986)

HYPODIPSIC hypernatremia is an uncommon syndrome that has been observed in children and adults with various congenital or acquired diseases of the brain.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 The syndrome is characterized by chronic or recurrent episodes of severe hypernatremia associated with dehydration and a lack of thirst. In all previous carefully evaluated cases, hypodipsia has been associated with some defect in secretion of the antidiuretic hormone arginine vasopressin.1 , 3 , 5 , 7 , 9 10 11 12 13 14 15 16 17 , 19 , 21 22 23 24 25 26 Often, the defect in secretion of vasopressin is clinically inapparent and can be demonstrated only by assay of the hormonal response to osmotic stimulation or suppression.1 , 7 , 15 16 17 , 19 , 23 24 25 26 This constellation of deficits suggests that the syndrome is due . . .
Value of Prolonged Bed Rest in Management of Cardiomegaly
Authors: George E. Burch, John J. Walsh, William C. Black
Journal: JAMA (1963)

Thirty-six patients with persistent cardiomegaly of indeterminable origin were studied to observe the effects of prolonged bed rest on heart size. All patients previously had exhibited little or no response to conventional treatment. Treatment consisted in the institution of prolonged bed rest and continuation of previous therapy, including digitalis and diuretics. The over-all response was good. Eleven of 21 patients who completed the prescribed course of bed rest showed return of heart size to normal, four showed definite decrease in heart size, and six experienced no change. Four deserters and an additional 11 patients currently on prolonged bed rest experienced the same level of response during incomplete observation periods. All patients showed marked clinical improvement.
Hemodynamic Effects of Angiotensin in Normal and Environmentally Stressed Monkeys
Authors: RALPH P. FORSYTH, BARRY I. HOFFBRAND, KENNETH L. MELMON
Journal: Circulation (1971)

Simultaneous regional blood flow and resistance measurements were made in 21 organs in 11 supine unanesthetized rhesus monkeys before and during two different doses of intravenously infused angiotensin II or saline. Systemic arterial pressure and total peripheral resistance significantly increased at both infusion rates in the six experimental monkeys, compared with changes in five control monkeys; cardiac output decreased at the high dose level. Among major organs, the kidneys, skin, liver (hepatic artery), and mesentery had reductions in the fraction of cardiac output they received and, thus, the greatst increase in resistance and decrease in blood flow. No organ had a significant increase in its blood flow; however, skeletal muscle and bone were normally perfused due to increases in the fraction of cardiac output they received. Four other monkeys received continuous intravenous angiotensin infusions at initially subpressor rates for periods of 26 to 30 days. There were steady increases of systemic arterial blood pressure due to a rise in total peripheral resistance which reached a plateau in about 5 days. Avoidance schedules or other environmental stresses in these angiotensin-infused monkeys produced much more marked pressor episodes than those which occur in noninfused monkeys. These observations support the hypothesis that small amounts of angiotensin can potentiate sympathetic mediated vasomotor activity.
MPs step in to save the UK's only mobile tuberculosis detection unit
Authors: A. Jack
Journal: BMJ (2010)

A group of MPs is to discuss ways to support Find & Treat, the UK’s only mobile x ray detection unit for tuberculosis, which is under threat of closure when existing government funding runs out later this year.

Baroness Masham, vice chair of the All Party Parliamentary Working Group on Global Tuberculosis, is convening a meeting with health service officials to discuss the problem in October, after a broader discussion next month on London’s position as the “TB capital of Europe.” Last year 3500 new cases were diagnosed in the city, falling into the World Health Organization’s definition of high incidence regions.

“Preventing drug resistant tuberculosis should be at the top …
THE PASSAGE OF DIFFEBENT FOODSTUFFS FROM THE STOMACH.
Authors: WALTER B. CANNON
Journal: JAMA (1905)

In the transfer of food from the stomach to the intestine two factors are concerned, the gastric waves of peristalsis and the pyloric sphincter. It is now known that under normal conditions the peristaltic waves course from the middle of the stomach to the pylorus without interruption during the whole of a digestive period. How the waves will affect the food is determined by the action of the pylorus. If the pylorus remains closed, the repeated waves over and over again churn the food with the gastric secretions; if the pylorus opens, these same waves act as the motive power to force the food onward. The determinative function of the pylorus was recognized by the fathers of medicine, for they gave the ancient terms<i>pylorus</i>(keeper of the gate),<i>rector</i>and<i>janitor</i>to the sphincter, and assumed that it possessed a "will" which fixed the fate of ingested food. Van
Understanding complex host-microbe interactions in<i>Hydra</i>
Authors: Thomas C.G. Bosch
Journal: Gut Microbes (2012)

Any multicellular organism may be considered a metaorganism or holobiont—comprised of the macroscopic host and synergistic interdependence with bacteria, archaea, fungi, viruses, and numerous other microbial and eukaryotic species including algal symbionts. Defining the individual microbe-host conversations in these consortia is a challenging but necessary step on the path to understanding the function of the associations as a whole. Dissecting the fundamental principles that underlie all host-microbe interactions requires simple animal models with only a few specific bacterial species. Here I present Hydra as such a model with one of the simplest epithelia in the animal kingdom, with the availability of a fully sequenced genome and numerous genomic tools, and with few associated bacterial species.
DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis.
Authors: K Inokuchi, K Miyake, H Takahashi, K Dan, T Nomura
Journal: Journal of Clinical Investigation (1996)

Using flow cytometry and immunoprecipitation (IP), we have investigated the deleted in colon cancer (DCC) protein expression on the bone marrow (BM) and peripheral blood (PB) cells of 16 normal subjects, 17 myelodysplastic syndrome (MDS) patients, and 10 acute myelogenous leukemia (AML) patients. With regard to the BM mononuclear cells (BM-MNCs) of normal subjects, the DCC protein expression ranged from 6.6 to 57.0%. Two-color flow cytometry revealed that among the IBM-MNCs the DCC protein was clearly expressed on the CD14+, CD13+, and factor 8+ cells, whereas it was low on the CD19+ and CD7+ cells and did not express on the CD34+, CD8+, and the glycophorin A+ cells. Further, the DCC protein expression was not seen on the PB CD11b+ and CD13+ cells. The IP results revealed that the 180-kD DCC protein was detected on the MNCs of both the BM and PB cells by the antibodies AF5, specific for the DCC extracellular domain, and G97-449, specific for the cytoplasmic domain. In contrast, flow cytometry did not detect the DCC protein on any BM-MNC MDS lineages (0.1-1.5%) or on AML leukemic cells (0.1-0.9%). The IP results indicated that the AF5 antibody did not detect the DCC protein on BM-MNCs of three of five MDS patients and four of five AML patients; however, the G97-449 antibody detected the 180-kD DCC protein in two MDS patients in whom AF5 had detected greatly reduced DCC band. These findings suggest that the DCC protein presence appears to be associated with normal hematopoiesis, and that its absence on the surfaces of the BM-MNCs and AML cells may contribute to the MDS and AML pathogenesis.
Uncommon Presentations of Thyroid Carcinoma
Authors: KENNETH P. BARTOLD, REZA ABGHARI, VINOD B. SANG
Journal: Clinical Nuclear Medicine (1986)

The most common presentation for carcinoma of the thyroid is as a cold nodule in the thyroid gland. Other appearances for thyroid carcinoma do exist, however; two such examples are presented. Incidence and presentation of thyroid carcinoma is discussed, as are guidelines for detecting patients that have a higher than average incidence of thyroid malignancy.