tbuckley/cabot-search huggingface dataset:
The Tumor Suppressor hSNF5/INI1 Modulates Cell Growth and Actin Cytoskeleton Organization
Authors: Souhila Medjkane, Eugene Novikov, Isabella Versteege, Olivier Delattre
Journal: Cancer Research (2004)

Abstract hSNF5/INI1, which encodes a component of the ATP-dependent chromatin remodeling hSWI-SNF complex, is a tumor suppressor gene mutated in malignant rhabdoid tumors. We have developed a tetracycline-based hSNF5/INI1-inducible system in a hSNF5/INI1-deficient malignant rhabdoid tumor cell line and studied time course variation of 22,000 genes/expressed sequence tags upon hSNF5/INI1 induction. A total of 482 responsive genes were identified and further clustered into 9 groups of coregulated genes. Among genes with early and strong inductions, the use of a fusion protein with the hormone-binding domain of the estrogen receptor enabled the identification of a subset of direct targets regulated independently of de novo protein synthesis. We show that the G1 arrest induced by hSNF5/INI1 is reversible and associated with the down-regulation of components of the DNA replication complex. We also identify an unsuspected role of hSNF5/INI1 in cytoskeleton organization. Indeed, induction of hSNF5/INI1 induces dramatic modifications of the cell shape including complete disruption of the actin stress fiber network and disappearance of focal adhesions associated with up-regulation of genes involved in the organization of the actin cytoskeleton. We document a strong decrease of Rho activity upon hSNF5/INI1 expression, suggesting that the regulation of this activity constitutes a crucial step of the hSNF5/INI1-induced reorganization of the actin network. This study identifies hSNF5/INI1 target genes and provides evidence that hSNF5/INI1 may modulate the cell cycle control and cytoskeleton organization through the regulation of the retinoblastoma protein-E2F and Rho pathways.
Abstract 1320: Effects of selective androgen-receptor and estrogen-receptor modulators on telomerase activity in melanoma and prostate cancer cells.
Authors: Yan Lu, Ramesh Narayanan, Jin Wang, Wei Li, Murali Yepuru, Lingling Liu, Vivian S. Loveless, Duane D. Miller
Journal: Cancer Research (2013)

Abstract Male hormones and the androgen receptor (AR) are well-known key targets for prostate cancer therapy. The potential cause of a gender-based disparity in melanoma has been suspected for many years. A recent analysis suggests that female patients have a 30% survival advantage in cutaneous melanoma. Telomerase has been shown to add protective telomere repeats to chromosome endings and cause cancer cells to become immortal. We have recently discovered that the AR is expressed in melanoma cell lines. In current report, we tested the telomerase activity in lysates of both melanoma and prostate cancer cell lines. Telomeric repeat amplification protocol (TRAP) was carried out to test the activity of telomerase in melanoma A375, androgen-sensitive prostatic cancer LNCap and androgen-insensitive prostatic cancer PC-3 cell lines under treatments of steroid hormones, SARM and SERM compounds. The effects of sex hormones, selective androgen-receptor modulators (SARMs), and estrogen-receptor modulators (SERMs) on telomerase activity in both melanoma and prostate cells were investigated. Citation Format: Yan Lu, Ramesh Narayanan, Jin Wang, Wei Li, Murali Yepuru, Lingling Liu, Vivian S. Loveless, Duane D. Miller. Effects of selective androgen-receptor and estrogen-receptor modulators on telomerase activity in melanoma and prostate 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 1320. doi:10.1158/1538-7445.AM2013-1320
Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes That Are More Potent and Immunogenic than Wild-Type Peptide
Authors: Shabnam Tangri, Glenn Y. Ishioka, Xiuqing Huang, John Sidney, Scott Southwood, John Fikes, Alessandro Sette
Journal: The Journal of Experimental Medicine (2001)

Certain peptide analogs that carry substitutions at residues other than the main major histocompatibility complex anchors and are surprisingly much more antigenic than wild-type peptide (heteroclitic analogs). To date, it was unknown how frequently wild-type epitopes could be modified to obtain heteroclitic activity. In this study, we analyzed a large panel of analogs of two different human histocompatibility leukocyte antigen (HLA)-A2.1-restricted epitopes and found that heteroclitic analogs were associated with higher magnitude responses and increased (up to 10(7)-fold) sensitivity to antigen, and corresponded to conservative or semiconservative substitutions at odd-numbered positions in the middle of the peptide (positions 3, 5, or 7). These findings were validated by performing additional immunogenicity studies in murine and human systems with four additional epitopes. The biological relevance of heteroclitic analogs was underlined when predicted analogs of the p53.261 epitope was shown to induce cytotoxic T lymphocytes (CTLs) that recognize low concentrations of peptide (high avidity) in vivo and demonstrate in vitro antitumor recognition. Finally, in vitro immunization of human peripheral blood mononuclear cells with two heteroclitic analogs resulted in recruitment of more numerous CTLs which were associated with increased antigen sensitivity. In conclusion, heteroclitic analogs were identified in each of the six cases studied and structural features were defined which allow identification of such analogs. The strong CTL immunity elicited by heteroclitic epitopes suggest that they could be of significant value in vaccination against tolerant or weakly immunogenic tumor-associated and viral antigens.
MYCOSIS FUNGOIDES.CASE REPORT WITH AUTOPSY AND HISTOLOGIC REPORT.
Authors: JOHN C. HANCOCK
Journal: JAMA (1904)

The report of this case is offered in view of the comparatively rare occurrence of the disease, and the question as to whether the process is that of infection or neoplasm, the unfavorableness of the prognosis, and the futility of treatment. <h3>History.</h3> —B. D. S., 39 years old, male, married, clergyman, was born in Missouri, but now resides in Iowa. He denies alcohol, tobacco and venereal history. I saw him June 29, 1899. <h3>Family History.</h3> —Father died at 71 years and had "gravel"; mother living at 73 years and well; five brothers living and well, one brother died of typhoid; two sisters living; one sister died of "croup"; otherwise negative. Wife and five children are living and well. <h3>Previous History.</h3> —Whooping cough at 4, chicken-pox at 5, scarlet fever at 6, measles at 10, pneumonia at 14, mumps and influenza at 30. During the 17 years preceding the present illness, patient had
Deletion of CD4 and CD8 Coreceptors Permits Generation of αβT Cells that Recognize Antigens Independently of the MHC
Authors: François Van Laethem, Sophia D. Sarafova, Jung-Hyun Park, Xuguang Tai, Leonid Pobezinsky, Terry I. Guinter, Stanley Adoro, Anthony Adams, Susan O. Sharrow, Lionel Feigenbaum, Alfred Singer
Journal: Immunity (2007)
THE VALUE OF EHRLICH'S TRIACID STAIN IN BLOOD WORK
Authors: ROGER S. MORRIS
Journal: JAMA (1910)

Within recent years the development of numerous modifications of the Romanowsky stain, by which blood smears may be fixed and stained in a few minutes, has limited the use of Ehrlich's triacid stain in many laboratories. The former, it is true, are far preferable in the study of pathologic changes in the erythrocytes, as cell nuclei, nuclear particles, polychromatophilia, basophilic granules, and Cabot's ring bodies, as well as certain parasites, are demonstrated to better advantage than with any other single stain. With Ehrlich's triacid, ring bodies and basophilic granules are not revealed, and polychromatophilia is shown very imperfectly. In studying the leukocytes, however, the Romanowsky stains are not to be compared with Ehrlich's triacid, and it seems unfortunate that they are so widely used at the present time in differential leukocyte counting. <h3>CLASSIFICATION OF LEUKOCYTES</h3> The generally accepted classification of the leukocytes is that suggested by Ehrlich, based on the
PWE-075 Lack of association between the PSCA rs2294008 polymorphism, or PSCA expression, and colorectal neoplasia
Authors: C Smith, P Lochhead, U Basavaraju, G Hold, N Fyfe, G Murray, E El-Omar
Journal: Gut (2012)

<h3>Introduction</h3> Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 (C&gt;T) polymorphism in the <i>PSCA</i> gene. From in vitro data, this polymorphism appears to be functional, and the risk allele (T) has been shown to be associated with gastric cancer risk in Asians and white individuals. Our study aimed to test for associations between the rs2294008 polymorphism, or PSCA protein expression, and risk of adenomatous polyps and colorectal cancer. <h3>Methods</h3> Between 2008 and 2010, we recruited individuals who had tested positively for faecal occult blood, and had undergone colonoscopic screening. Genomic DNA samples were available from 388 subjects with histologically-proven colorectal neoplasia and 493 subjects with no evidence of neoplasia. Genotyping for the rs2294008 polymorphism was performed using a pre-designed TaqMan® assay and the ABI 7900HT Fast Sequence Detection System. Immunohistochemical (IHC) staining for the PSCA protein was performed using normal and neoplastic tissues covering all stages of the adenoma-carcinoma sequence. The tissue set included adenomatous polyps displaying low-grade (n=10), and high-grade (n=10) epithelial dysplasia, and adenomatous polyps harbouring invasive carcinoma (n=10). Normal adjacent mucosa was assessed in the polyp sections in addition to separate normal mucosal sections (n=4). Positive staining of colonic crypt neuroendocrine cells served as an internal positive control. <h3>Results</h3> There was no association between the rs2294008 SNP and risk of colorectal neoplasia in either dominant (OR 0.97; 95% CI 0.73 to 1.28) or recessive (OR 0.88; 95% CI 0.61 to 1.27) genotype models. IHC analysis of colonic tissue samples indicated no alteration in the topographic distribution or intensity of PSCA staining between normal mucosa, adenomatous mucosa with low or high grade epithelial dysplasia, and invasive carcinoma. <h3>Conclusion</h3> Our results suggest that PSCA does not play an important role in the initiation or progression of colorectal carcinogenesis. Given that PSCA has been implicated in a variety of other solid tumours, continued efforts should be made to elucidate the normal and pathological cellular functions of PSCA. <h3>Competing interests</h3> None declared.
Diabetes complications and their potential prevention: Aldose reductase inhibition and other approaches
Authors: Luca Costantino, Giulio Rastelli, Paola Vianello, Giorgio Cignarella, Daniela Barlocco
Journal: Medicinal Research Reviews (1999)

Despite recent advances both in the chemistry and molecular pharmacology of antidiabetic drugs, diabetes still remains a life-threatening disease, which tends to spread all over the world. The clinical profile of diabetic subjects is often worsened by the presence of several long-term complications, namely neuropathy, nephropathy, retinopathy, and cataract. Several attempts have been made to prevent or at least to delay them. The most relevant are reported in this review, including the development of compounds acting as aldose reductase inhibitors, anti-advanced glycation end-product drugs, free radical scavengers, vasoactive agents, essential fatty acid supplementation, and neurotropic growth factors. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 1, 3–23, 1999.
Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.
Authors: S Banerjee, C Hawksby, S Miller, S Dahill, A D Beattie, K E McColl
Journal: Gut (1994)

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.
Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1
Authors: Nobuo Kuramoto, Toshihiro Takizawa, Takami Takizawa, Masato Matsuki, Hiroyuki Morioka, John M. Robinson, Kiyofumi Yamanishi
Journal: Journal of Clinical Investigation (2002)

Transglutaminase 1 (TGase 1) is one of the genes implicated in autosomal recessive congenital ichthyosis. Skin from TGase 1–/– mice, which die as neonates, lacks the normal insoluble cornified envelope and has impaired barrier function. Characterization of in situ dye permeability and transepidermal water loss revealed defects in the development of the skin permeability barrier in TGase 1–/– mice. In the stratum corneum of the skin, tongue, and forestomach, intercellular lipid lamellae were disorganized, and the corneocyte lipid envelope and cornified envelope were lacking. Neonatal TGase 1–/– mouse skin was taut and erythrodermic, but transplanted TGase 1–/– mouse skin resembled that seen in severe ichthyosis, with epidermal hyperplasia and marked hyperkeratosis. Abnormalities in those barrier structures remained, but transepidermal water loss was improved to control levels in the ichthyosiform skin. From these results, we conclude that TGase 1 is essential to the assembly and organization of the barrier structures in stratified squamous epithelia. We suggest that the ichthyosiform skin phenotype in TGase 1 deficiency develops the massive hyperkeratosis as a physical compensation for the defective cutaneous permeability barrier required for survival in a terrestrial environment.
Why treat chronic hepatitis B in childhood with interferon alpha ?
Authors: E A ROBERTS
Journal: Gut (2000)

<h3>Abstract</h3> There is growing awareness that our ability to tackle antibiotic resistance is limited by a lack of mechanistic understanding of the communities in which resistant microbes are embedded. The widespread coexistence of resistant and sensitive bacteria in microbial systems presents an especially frustrating paradox. Recent advances in ecological coexistence theory offer a powerful framework to probe the mechanisms regulating intra- and inter-specific coexistence, but the significance of this body of theory to the problem of antimicrobial resistance has been largely overlooked. In this Perspectives article, we draw on emerging ecological theory to illustrate how changes in both competitive ability and niche overlap are critical for understanding costs of resistance and the persistence of pathogens in microbial systems. We then show how trade-offs in resource acquisition strategies can have counter-intuitive consequences for the coexistence of resistant and susceptible genotypes in variable environments. These insights highlight numerous opportunities for innovative experimental and theoretical research into antibiotic resistance in the microbiome.
888-3 Racial differences in the prognostic value of the electrocardiographic strain pattern in hypertensive patients: The LIFE study
Authors: Peter M Okin, Richard B Devereux, Markku S Nieminen, Jackson T Wright, Sverker Jern, Anne L Taylor, Robert A Phillips, Vasilios Papademetriou, Luther T Clark, Elizabeth O Ofili, Otelio S Randall, Lasse Oikarinen, Matti Viitasalo, Lauri Toivonen, Björn Dahlöf
Journal: Journal of the American College of Cardiology (2004)
Epilepsy in a Longitudinal Survey of 5,000 Children
Authors: J. E. Cooper
Journal: BMJ (1965)

This paper records some of the findings concerning different types of epilepsy in a longitudinal study of approximately 5,000 children born in 1946. These children form the National Survey of Health and Development which has been described previously (Douglas and Rowntree, 1948 ; Douglas and Blomfield, 1956). The children are drawn from all parts of Great Britain and from all social classes, and have been kept under observation from their birth in March 1946 to the present. Apart from death and emigration, losses from the survey have been small, and at the age of 15 years were approximately 10% (for details of the survey method and losses see Douglas and Blomfield (1958), and Douglas (1964) ). During the 18 years of their lives a large amount of social, medical, and educational information has been gathered about each child, and the medical information referred to in this paper comes mainly from : (1) A home visit by a health visitor when the child was aged 2 years. The mother was asked if the child had ever had any sort of fit or convulsion, and if so, at what age and how many. She was also asked in detail about illnesses such as whooping-cough, measles, ear disease, chicken-pox, gastro-enteritis, and lower respiratory infections. (2) Medical examinations carried out specially for this survey by school medical officers at the ages of 6, 7, 11, and 15. The mothers, who accompanied the children, were asked if their child had had any sort of fits or convulsions in the previous year, and if so, how many and whether they had accompanied any other illness. In this report the definition of  a fit  is a definite reply of  yes  recorded by the doctor or the health visitor after asking these questions. The doctor was at liberty to ask other questions to clarify the mother's reply, and the extent of additional probing would obviously vary. In a widespread survey such as this, however, there was no way of avoiding this sort of variation.
BLOOD PRESSURE RESPONSES OF CHRONIC SCHIZOPHRENIC PATIENTS TO EPINEPHRINE AND MECHOLYL
Authors: K. H. GEOCARIS, J. E. KOOIKER
Journal: American Journal of Psychiatry (1956)

1. The recent work of Funkenstein, Greenblatt, and Solomon on the Epinephrine-Mecholyl Test, and on autonomic nervous system responses of mentally ill patients, has been applied to chronic schizophrenics. 2. Our hypothesis was that if chronic schizophrenics were tested by this technique, few would give responses of the type that are associated with a favorable prognosis. 3. Of 25 chronic schizophrenics with prolonged hospitalizations, none gave a "favorable" response. 4. The responses shown by chronic patients gave a distribution pattern practically identical with that seen in groups of normal subjects. The distribution into groups of the more acute cases described by Funkenstein et al. differs significantly from both normals and chronics. 5. Hypotheses have been formulated from the work of Funkenstein and from the results of this investigation which pertain to concepts of psychological equilibrium and homeostasis in mental illness. 6. Our results give support to the reliability of the Epinephrine-Mecholyl Test. Further work with this test should be done.
Encainide and its metabolites. Comparative effects in man on ventricular arrhythmia and electrocardiographic intervals.
Authors: E L Carey, H J Duff, D M Roden, R K Primm, G R Wilkinson, T Wang, J A Oates, R L Woosley
Journal: Journal of Clinical Investigation (1984)

To assess the relative contributions of encainide and its putatively active metabolites, O-demethyl encainide (ODE) and 3 methoxy-O-demethyl encainide (3MODE), to the drug's pharmacologic effects, we compared intravenous infusions and sustained oral therapy in two phenotypically distinct groups of patients, extensive and poor metabolizers of encainide. Unlike poor metabolizers, extensive metabolizers had appreciable quantities of both metabolites detectable in plasma and had fourfold shorter elimination half-lives for encainide. By quantitating electrocardiogram intervals, arrhythmia frequency, and plasma concentrations, we found that, in poor metabolizers, arrhythmia suppression and ventricular complex (QRS) prolongation were correlated positively with encainide concentrations (r greater than or equal to 0.570, P less than 0.014). In these two subjects, antiarrhythmic concentrations of encainide (greater than 265 ng/ml) were at least fivefold higher than those sustained in the six extensive metabolizers during steady state oral therapy. In extensive metabolizers, encainide concentrations were uncorrelated with effects. Arrhythmia suppression and QRS prolongation in extensive metabolizers correlated best with ODE (r greater than or equal to 0.816, P less than 0.001); QTc change correlated positively with both 3MODE and ODE. Arrhythmia suppression paralleled QRS prolongation; the relationship between them appeared similar in both phenotypic groups. In most patients, extensive metabolizers, encainide effects during oral therapy are mediated by metabolites, probably ODE.
Canine "Cadaver" Kidneys
Authors: William G. Manax
Journal: JAMA (1966)

To retrieve cadaver kidneys for human homotransplantation, organ viability must be maintained in vivo during the preterminal period when renal perfusion is low, and in vitro during the period while the recipient is being prepared. In the laboratory, experiments were designed to simulate the clinical situation in which canine cadaver kidneys are used. It was found that general profound hypothermia before death inhibits to a significant degree the untoward effects of renal ischemia by virtue of its suppressive action on metabolic activity. General body hypothermia to 28 C (82.4 F) applied three hours before death permits removal of viable, transplantable kidneys up to two hours postmortem. No treatment at all requires immediate removal of the kidney to retain its viability. This study suggests that for successful use of cadaver kidneys in human homotransplantation, both in vivo and in vitro renal protection from ischemia are of paramount importance for ultimate success.