tbuckley/cabot-search huggingface dataset:
Calcium antagonists and converting enzyme inhibitors reduce renal injury by different mechanisms
Authors: Lance D. Dworkin, Judith A. Benstein, Miriam Parker, Evelyn Tolbert, Helen D. Feiner
Journal: Kidney International (1993)

Both glomerular hypertension and hypertrophy have been associated with the development of glomerular injury in models of hypertension and reduced renal mass. The purpose of this study was to examine the effects of antihypertensive therapy on these parameters in the remnant kidney model of progressive glomerular sclerosis. Rats underwent 5/6 nephrectomy and were randomly assigned to receive either no therapy, the calcium entry blocker (CEB), nifedipine, or the angiotensin converting enzyme inhibitor (CEI), enalapril. Administration of either drug was associated with a reduction in systemic blood pressure and in the severity of glomerular injury assessed eight weeks after renal ablation. Micropuncture studies four weeks after ablation revealed that systemic and glomerular capillary pressure were high in untreated remnant kidney rats and reduced by enalapril. Administration of nifedipine was associated with a decline in systemic pressure, however, plasma renin levels increased, causing efferent arteriolar vasoconstriction and persistence of glomerular hypertension. Morphometric analysis showed that kidney weight, glomerular volume and glomerular capillary radius were lower in nifedipine treated rats than in the other two groups, indicating that the CEB, but not enalapril, inhibited the hypertrophic response to ablation of renal mass. Therefore, both CEIs and CEBs reduce glomerular injury in rats with remnant kidneys but they may act by different mechanisms. CEI reduce glomerular capillary pressure while CEBs inhibit compensatory kidney growth.
Synergistic Activation of the Tumor Suppressor, HLJ1, by the Transcription Factors YY1 and Activator Protein 1
Authors: Chi-Chung Wang, Meng-Feng Tsai, Ting-Hao Dai, Tse-Ming Hong, Wing-Kai Chan, Jeremy J.W. Chen, Pan-Chyr Yang
Journal: Cancer Research (2007)

Abstract HLJ1 is a novel tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. However, the mechanism of HLJ1 activation is currently unclear. Here, we identify an enhancer segment in the HLJ1 gene at −2,125 to −1,039 bp upstream of the transcription start site. A 50-bp element between −1,492 and −1,443 bp is the minimal enhancer segment, which includes the activator protein 1 (AP-1) site (−1,457 to −1,451 bp), an essential regulatory domain that binds the transcriptional factors FosB, JunB, and JunD. Chromatin immunoprecipitation assays confirm that these AP-1 family members bind to a specific site in the HLJ1 enhancer segment in vivo. Overexpression of either YY1 at promoter or AP-1 at enhancer results in a 3-fold increase in the transcriptional activity of HLJ1. We propose a novel mechanism whereby expression of the tumor suppressor, HLJ1, is up-regulated via enhancer AP-1 binding to promoter YY1 and the coactivator, p300, through DNA bending and multiprotein complex formation. The combined expression of AP-1 and YY1 enhances HLJ1 expression by more than five times and inhibits in vitro cancer cell invasion. Elucidation of the regulatory mechanism of HLJ1 expression may facilitate the development of personalized therapy by inhibiting cancer cell proliferation, angiogenesis, and metastasis. [Cancer Res 2007;67(10):4816–26]
Infrequent Defecation in Children
Authors: Coulson A. Conn
Journal: JAMA (1987)

<h3>To the Editor.—</h3> I am writing in reference to the question concerning infrequent defecation or Hirschsprung's disease and the reply to it by Dr Kirschner in the Jan 23/30, 1987, issue of<i>JAMA</i>.<sup>1</sup>There are several points stated, implied, or omitted that should upset any physician caring for children. In the first place, two stools per week in a baby who is primarily breast-fed is, of itself, no cause for alarm. As there is little waste in breast milk, many children will go longer than a week between bowel movements; in this case, the supplemental bottle may be modifying the pattern. The main point of concern would be the foul odor of these soft stools (the green color may arise from iron in the formula). Good growth argues against a malabsorption problem, but nevertheless cystic fibrosis should be of at least equal concern to Hirschsprung's disease. Furthermore, the results
Effect of Saralasin in Hypertensive Patients on Chronic Hemodialysis
Authors: Meyer D. Lifschitz, Michael A. Kirschenbaum, Steven G. Rosenblatt, Richard Gibney
Journal: Annals of Internal Medicine (1978)

Hypertension in patients on chronic hemodialysis is thought to be largely of two types—volume dependent or renin dependent. If renin-dependent hypertension is mediated by angiotensin II, then angiotensin II antagonism should lower blood pressure. To test this hypothesis, the angiotensin II antagonist saralasin was given to 15 hypertensive patients on chronic hemodialysis. Patients were separated into two groups by their blood pressure response. In responders blood pressure was 191/112 mm Hg and fell to 147/85 during saralasin administration (P < 0.01). In contrast, nonresponders had blood pressures of 190/111 mm Hg before and 188/110 during saralasin administration. Five responders subsequently had nephrectomies with normalization of their blood pressures. Plasma renin activity averaged 70 ng/ml · 3 h of angiotensin I in responders and increased to 110 after saralasin (P < 0.05), while nonresponders had values of 21 before and after saralasin. These results offer strong support for the hypothesis that renin-dependent hypertension is an important mechanism in certain patients on chronic hemodialysis and that such patients will respond to angiotensin II antagonism.
The Wolf-Man
Authors: Marjorie C. Meehan
Journal: JAMA (1971)

"The Wolf-Man," subject of one of Freud's most famous case studies, was born in Russia on Christmas Eve, 1886. Brought up in luxury by wealthy but emotionally unstable parents, an uneducated peasant nurse, and a succession of governesses and tutors of various nationalities and personalities, he suffered many neurotic symptoms in childhood, including a wolf phobia. He gave up his university studies because of depressive and obsessive symptoms and traveled around Europe for several years seeking relief. After visiting several famous neurologists, including Kraepelin, and staying at several sanitoria, he came to Vienna and was treated by Freud from 1910 to 1914. After completing his analysis, he returned to Russia, married a German nurse, finished his law studies. Following the Russian revolution, he lost his fortune and came to Vienna with his wife. Then he got a job in an insurance company and held it for 30 years. Now, since
Lack of Effect of Pioglitazone on Postprandial Triglyceride Levels in Type 2 Diabetes
Authors: Dai Shimono, Naomitsu Kuwamura, Yoshio Nakamura, Hiroyuki Koshiyama
Journal: Diabetes Care (2001)

We read with interest an article by Aronoff et al. (1), which indicated that monotherapy of pioglitazone, a peroxisome proliferator–activated receptor (PPAR)-γ agonist, can improve lipid profile as well as glycemic control in type 2 diabetes. However, because they evaluated dyslipidemia in the fasted state, as most investigators do, it remains unknown whether pioglitazone may ameliorate postprandial dyslipidemia, which has recently been suggested to be an independent risk factor of atherosclerosis (456). We have previously indicated that troglitazone, another PPAR-γ agonist, can cause a decrease in postprandial triglyceride levels …
Profile of prostanoid release following antigen challenge in vivo in the skin of man
Authors: W.A. MASSEY, W.C. HUBBARD, M.C. LIU, ANNE KAGEY-SOBOTKA, P. COOPER, L.M. LICHTENSTEIN
Journal: British Journal of Dermatology (1991)

We have previously characterized the kinetics of prostaglandin D2 (PGD2) production at cutaneous sites of allergic inflammation employing a blister-chamber model. In this study, a more complete profile of prostaglandins released in vivo was obtained. PGD2 release, as measured by radioimmunoassay and by combined gas chromatography-mass spectrometry, was evident within 1 h after antigen challenge with maximal levels occurring 3-4 h post-challenge. The 11-ketoreductase metabolite of PGD2, 9 alpha, 11 beta-prostaglandin F2 was present in blister fluid from three of six patients at the time of maximal levels of PGD2. The stable non-enzymatic hydrolysis product of prostacyclin, 6-keto-prostaglandin F1 alpha, was significantly elevated in blister fluid from five of six patients following antigen challenge. In these subjects, the levels of 6 kappa-PGF1 alpha were highest in samples obtained 1 and 2 h after antigen challenge and remained significantly elevated until 5 h post-challenge. Levels of prostaglandin E2, prostaglandin F2 alpha and thromboxane B2 did not vary significantly. These studies suggest that following antigen challenge two fatty-acid cyclo-oxygenase products of arachidonic acid are released, PGD2 and prostacyclin. The 11-ketoreductase metabolism of PGD2 to 9 alpha, 11 beta-PGF2 could represent a mechanism by which the biological effects of PGD2 are prolonged in cutaneous tissue. The presence of 6 kappa-PGF1 alpha in the blister fluid suggests that significant prostacyclin release occurs as the result of antigen challenge and could represent a mechanism by which the prolonged microvascular response in cutaneous tissue may occur.
MEDICAL EDUCATION AND THE RURAL PHYSICIAN
Authors: J. E. Brosseau
Journal: JAMA (1925)

To the Editor:  —I have been reading the editorials in regard to medical education and the supply of rural physicians. The summary arrived at by the General Educational Board (The Journal, January 3, p. 41) is about as nearly correct as it is possible to make it. I have been practicing here more than sixteen years, and came here because I like country life, as many other physicians do. I am located in a town of about 450 population and a rural population of about 900. There are so many poor people who cannot pay that it leaves too few pay patients to make it remunerative. I have college degrees, and I cannot see where a shorter course would have benefited me. The country people are entitled to good physicians as well as those in larger places. A shorter or altered curriculum in our medical schools would not alter the
Incidence of Type 2 Diabetes in Individuals With Central Obesity in a Rural Japanese Population: The Tanno and Sobetsu Study 
Authors: H. Ohnishi
Journal: Diabetes Care (2006)

According to the new International Diabetes Federation (IDF) definition of metabolic syndrome, for a person to be defined as having metabolic syndrome they must have central obesity defined by waist circumference (1). In the definition, there are some ethnic or country-specific differences in the cutoff points of waist circumference, and Japanese cutoff points have been separately established in the IDF definition (≥85 cm for men and ≥90 cm for women). The Japanese Society of Internal Medicine and eight related scientific societies have also jointly announced new Japanese criteria of metabolic syndrome using the same cutoff points of waist circumference (2). However, the impact of central obesity using the cutoff points as a risk of type 2 diabetes is not known.

In this study, we investigated the incidence of type 2 diabetes in citizens of two rural communities in Japan to determine the relationship between type 2 diabetes and central obesity, and we also investigated the independent effects of central obesity compared with those of overall obesity.

The subjects were 348 men and 523 women selected from 938 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, both in 1994 and 2003 or 2004.

The following participants in medical examinations in 1994 were excluded: those with missing data on blood …
Screening for Diabetes Mellitus
Authors: Stephen Clement
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 April 1989Screening for Diabetes MellitusStephen Clement, MD, William Duncan, MD, Lauri Coffey, RD, Kathleen Dean, RN, Nancy Kinum, RNStephen Clement, MDSearch for more papers by this author, William Duncan, MDSearch for more papers by this author, Lauri Coffey, RDSearch for more papers by this author, Kathleen Dean, RNSearch for more papers by this author, Nancy Kinum, RNSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-7-572 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor:Singer and associates (1) comprehensively reviewed the data supporting the role of screening for gestational diabetes but not diabetes in the nonpregnant adult. Their argument against screening for diabetes in the nonpregnant adult was not based on a poor cost-benefit ratio but rather on the paucity of evidence showing that treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM) prevents microvascular complications. The study cited to support this recommendation was the University Group Diabetes Program (UGDP) study, which showed no difference in mortality or the progression of retinopathy or nephropathy in patients with NIDDM maintained on diet therapy...References1. SingerSametColeyNathan DJCD. Screening for diabetes mellitus. Ann Intern Med. 1988;109:639-49. LinkGoogle Scholar2. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes: VIII. Evaluation of insulin therapy: final report. Diabetes. 1982;31 (Suppl 5): 1-81. Google Scholar3. KleinKleinMossDavisDeMets RBSMD. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988;260:2864-71. CrossrefMedlineGoogle Scholar4. TeuscherSchnellWilson AHP. Incidence of diabetic retinopathy and relationship to baseline plasma glucose and blood pressure. Diabetes Care. 1988;11:246-51. CrossrefMedlineGoogle Scholar1. NathanSingerGodineHodgson HarringtonPerlmuter DDJCL. Retinopathy in older type II diabetics: association with glucose control. Diabetes. 1986;35:797-801. CrossrefMedlineGoogle Scholar2. KleinKleinMossDavisDeMets RBSMD. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988;260:2864-71. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Walter Reed Army Medical Center Washington, D.C. 20307-5001 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1989Volume 110, Issue 7Page: 572-573KeywordsDiabetes mellitusDietGestational diabetesMortalityPatientsRetinopathyType 2 diabetes Issue Published: 1 April 1989 PDF DownloadLoading ...
Abstract 5092: Geminin regulates pre-replicative complex formation through the stabilization of CDT1 in mitosis
Authors: Yasusei Kudo, Takaaki Tsunematsu, Naozumi Ishimaru
Journal: Cancer Research (2014)

Abstract Geminin, a factor essential to DNA replication, directly binds to the licensing factor CDT1 and inhibits pre-replicative complex (pre-RC) formation to avoid re-replication. Geminin protein expression is necessary during S, G2 and M phases of the cell cycle. In G1, geminin levels are kept in check by the anaphase-promoting complex/cyclosome ubiquitin ligase complex and its activator (APC/CCdh1), which targets geminin for proteasomal degradation to allow pre-RC formation. Conversely, from S to G2 is stabilized by the APC/C inhibitor Emi1 to ensure inhibition of Pre-RC formation. In this study, we found that Aurora-A phosphorylated geminin at Thr25 in M phase and the Aurora-A-mediated phosphorylation stabilized geminin by preventing its degradation via APC/C during mitosis. Aurora-A-mediated stabilization of geminin may further give rise to that of CDT1 protein to ensure pre-RC formation in the ensuing S phase. The Aurora-A-geminin-CDT1 axis, thus, represents a critical function for regulating proper DNA replication. Citation Format: Yasusei Kudo, Takaaki Tsunematsu, Naozumi Ishimaru. Geminin regulates pre-replicative complex formation through the stabilization of CDT1 in mitosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5092. doi:10.1158/1538-7445.AM2014-5092
Incidence of and Risk Factors for Atrial Fibrillation in Older Adults
Authors: Bruce M. Psaty, Teri A. Manolio, Lewis H. Kuller, Richard A. Kronmal, Mary Cushman, Linda P. Fried, Richard White, Curt D. Furberg, Pentti M. Rautaharju
Journal: Circulation (1997)

Background This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. Methods and Results In this cohort study, 5201 adults ≥65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of β-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF. Conclusions The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.
Biomonitoring brevetoxin exposure in mammals using blood collection cards.
Authors: E R Fairey, N G Shuart, M Busman, P D Moeller, J S Ramsdell
Journal: Environmental Health Perspectives (2001)

A method has been tested in laboratory mice to monitor for the presence of brevetoxins in blood after exposure. The use of blood collection cards is an adaptation of a method employed for routine diagnostic and genetic testing of newborns. Blood is collected and applied to a 0.5-inch diameter circle on a specially prepared blood collection card and allowed to dry. The blood spots are then extracted and the presence of toxin activity is first screened using a high throughput receptor binding assay. Positive samples are then examined for specific brevetoxin congeners by liquid chromatography-tandem mass spectrometry. Preliminary experiments tested the efficiency and linearity of toxin extraction from blood spiked with brevetoxin-3 (PbTx-3). Blood from treated mice was tested for the presence of brevetoxin at different times following exposure to a sublethal dose (180 microg/kg PbTx-3). Brevetoxin activity determined by receptor assay increased to 25 +/- 7.4 nM PbTx-3 equivalents within 4 hr after exposure and was still detectable in three of four animals 24 hr after exposure. Tandem mass spectrometry provided confirmation of PbTx-3, which also increased for the time points between 0.5 and 4.0 hr exposure. However, PbTx-3 was not detected at 24 hr, which suggested the formation of a biologically active metabolite. We anticipate that this approach will provide a method to biomonitor brevetoxins in living marine resources (e.g., finfish), protected species, and humans.
Abstract 2472: Small-molecule-induced reactivation of mutant p53 in cancer cells.
Authors: Xiangrui Liu, Rainer Wilcken, Andreas Joerger, Irina Chuckowree, John Spencer, Alan Fersht
Journal: Cancer Research (2013)

Abstract The tumour suppressor p53 inhibits tumour growth by induction of cell cycle arrest, apoptosis or senescence. However, p53 mutations occur frequently in human tumours. About one-third of the mutations lower the melting temperature of the protein and cause rapidly unfolds at body temperature. The p53 cancer mutant Y220C is an excellent paradigm for rescuing the function of conformationally unstable p53 mutants because it has a unique surface crevice that can be targeted by small-molecule stabilizers. Through biophysical and cell-based screening, we identified a compound, PK7088, which binds to the Y220C mutant with a dissociation constant of 140 μM. The binding mode of this compound class was determined by X-ray crystallography. In cancer cells carrying the Y220C mutant, PK7088 increased the amount of folded mutant protein with wild-type like conformation, as monitored by immunofluorescence, and restored its transcriptional functions. It induced p53-Y220C-dependent growth inhibition, cell-cycle arrest and apoptosis. This was confirmed by p53 silencing. Most notably, PK7088 increased the expression levels of p21 and the proapoptotic NOXA protein. PK7088 worked synergistically with Nutlin-3 on up-regulating p21 and NOXA expression, whereas Nutlin-3 on its own had no effect, consistent with its mechanism of action. PK7088 also restored non-transcriptional apoptotic functions of p53 by triggering nuclear export of BAX to the mitochondria. These findings provide novel insights into p53 mutant reactivation and may facilitate the development of more potent and selective small-molecule drugs for specific mutant p53 rescue. Citation Format: Xiangrui Liu, Rainer Wilcken, Andreas Joerger, Irina Chuckowree, John Spencer, Alan Fersht. Small-molecule-induced reactivation of mutant p53 in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2472. doi:10.1158/1538-7445.AM2013-2472
Reconciling genetic evolution and the associative learning account of mirror neurons through data-acquisition mechanisms
Authors: Arnon Lotem, Oren Kolodny
Journal: Behavioral and Brain Sciences (2014)

Abstract An associative learning account of mirror neurons should not preclude genetic evolution of its underlying mechanisms. On the contrary, an associative learning framework for cognitive development should seek heritable variation in the learning rules and in the data-acquisition mechanisms that construct associative networks, demonstrating how small genetic modifications of associative elements can give rise to the evolution of complex cognition.
STUDIES ON THE MECHANISM OF LYMPHOCYTE TRANSFORMATION INHIBITION IN SARCOIDOSIS
Authors: ANDRZEI LANGER, KRYSTYNA MOSKALEWSKA, MARIA PRONIEWSKA
Journal: British Journal of Dermatology (1969)

Journal Article STUDIES ON THE MECHANISM OF LYMPHOCYTE TRANSFORMATION INHIBITION IN SARCOIDOSIS Get access ANDRZEI LANGER, ANDRZEI LANGER Department of Dermatology, School of Medicine, Wacsar, Poland (Professor S. Jablonska) Search for other works by this author on: Oxford Academic Google Scholar KRYSTYNA MOSKALEWSKA, KRYSTYNA MOSKALEWSKA Department of Dermatology, School of Medicine, Wacsar, Poland (Professor S. Jablonska) Search for other works by this author on: Oxford Academic Google Scholar MARIA PRONIEWSKA MARIA PRONIEWSKA Department of Dermatology, School of Medicine, Wacsar, Poland (Professor S. Jablonska) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 11, 1 November 1969, Pages 829–834, https://doi.org/10.1111/j.1365-2133.1969.tb15952.x Published: 01 November 1969 Article history Accepted: 17 May 1969 Published: 01 November 1969