tbuckley/cabot-search huggingface dataset:
Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis
Authors: Kazuhiko Matsuoka, Tomomi Tamura, Daisuke Tsuji, Yukie Dohzono, Keisuke Kitakaze, Kazuki Ohno, Seiji Saito, Hitoshi Sakuraba, Kohji Itoh
Journal: Molecular Therapy (2011)

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.
Role for monokines in the metabolic effects of endotoxin. Interferon-gamma restores responsiveness of C3H/HeJ mice in vivo.
Authors: S Adi, A S Pollock, J K Shigenaga, A H Moser, K R Feingold, C Grunfeld
Journal: Journal of Clinical Investigation (1992)

To examine the role of cytokines in mediating the lipogenic effects of endotoxin (LPS), we studied the effects of LPS and cytokines on hepatic fatty acid synthesis in LPS-sensitive C3H/OuJ mice and in LPS-resistant C3H/HeJ mice, whose macrophages are defective in the ability to produce tumor necrosis factor (TNF) and IL-1 in response to LPS. HeJ mice were 16-fold less sensitive than OuJ mice to the lipogenic effect of LPS. In OuJ mice, 10 micrograms of LPS caused a maximal increase in hepatic lipogenesis (3.86 +/- 0.41-fold), whereas in HeJ mice the maximal increase was only 1.79 +/- 0.32-fold after 100 micrograms of LPS. This lipogenic response paralleled the decreased ability of LPS to increase hepatic and splenic levels of mRNAs for TNF and IL-1 and serum levels of TNF in HeJ mice. In contrast, the maximal effect of TNF on lipogenesis was greater and the sensitivity to TNF was increased 2.4-fold in HeJ mice compared to OuJ mice. Administration of IFN-gamma before LPS in HeJ mice had no effect on IL-1 mRNA, but partially restored the LPS-induced increase in hepatic and splenic mRNA for TNF and serum TNF levels, which may account for the partial restoration of sensitivity to the lipogenic effect of LPS after IFN-gamma treatment. These results indicate that cytokines produced by mononuclear leukocytes mediate the lipogenic effects of LPS.
Short Telomere Length and Breast Cancer Risk: A Study in Sister Sets
Authors: Jing Shen, Mary Beth Terry, Irina Gurvich, Yuyan Liao, Ruby T. Senie, Regina M. Santella
Journal: Cancer Research (2007)

Abstract Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03–1.95) than in unaffected control sisters (mean, 0.74; range, 0.03–2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9–1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9–2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8–5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5–3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk. [Cancer Res 2007;67(11):5538–44]
Isocitrate dehydrogenase (IDH)2 R140Q mutation induces myeloid and lymphoid neoplasms in mice
Authors: E Mylonas, M Janin, O Bawa, P Opolon, M David, C Quivoron, O A Bernard, C Ottolenghi, S DeBotton, V Penard-Lacronique
Journal: Leukemia (2014)
Retrospective Study Assessing the Role of MRI in the Diagnostic Procedures for Early Breast Carcinoma: A Correlation of New Foci in the MRI with Tumor Pathological Features.
Authors: I. Calvo Plaza, L. Ugidos de la Verga, C. Miró, A. Suarez, P. Perez, P. Quevedo, M. Parras, M. Torres, M. Herrero, P. Buelga, L. García, P. Alonso, J. de la Cruz, F. López Ríos, M. Hidalgo, L. G Estévez
Journal: Cancer Research (2009)

Abstract Purpose: To analyze the role of MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, to correlate the detection of new foci with tumor pathological features.Methods: Early breast carcinoma patients that had undergone a MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen (ER)/progesterone (PR) receptors, HER2 and Ki67. HER2 status was established by FISH, while ER, PR and Ki67 status were established by inmunohistochemistry. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features.Results: To date, data from 98 patients have been analyzed: median age 49 years (range: 35-79); carcinoma type: a) infiltrative ductal carcinoma (n=73, 74%), b) infiltrative lobular cancer (n=13, 13%), c)ductal carcinoma in situ (n= 6, 6%); amplified HER2 (n=18, 18%); grade III (n=33, 33%);Ki67 ≥ 25%(n=33, 33%); positive ER and PR (n=78, 79%); triple negative tumors (n=8, 8%). MRI detected additional disease in 38 cases (39%) that led to an additional biopsy in 20 cases (20%). Thirty-nine patients (39%) underwent mastectomy. A statistically significant correlation was established between the finding of new foci in MRI and high proliferative tumors through the biomarker Ki67 (cutoff ≥ 25%) (p&amp;lt;0.005). No other statistically significant correlation was established with any of the other pathological features analyzed.Conclusion: In patients diagnosed with early breast cancer, MRI detected the presence of additional disease in 39% of the cases, requiring an additional biopsy in 20% of the cases. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI. An update of the results will be presented at the symposium. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4018.
Hair Theory Pelted
Authors: Nathan Sonkin
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Ashley Montagu's discussion, "Natural Selection and Man's Relative Hairlessness," in the Feb 1, 1964, issue ofThe Journal(<b>187</b>:356) proposed an exceedingly ingenious theory, but it was not conclusive. I should like to suggest an alternative theory which appears logical to me. It is known that many fur-bearing mammals grow a heavier fur pelt in the fall in preparation for a cold winter. Fur, or hair, which is phylogenetically derived from fur, serves two major functions—protection of the body from both cold and injury. In modern times our civilized culture has adopted fur for a third purpose —adornment for more privileged females. Over hundreds of thousands of years man gradually progressed to a tool-using stage and began to use weapons to augment his hunting skills. In time he became a great hunter. He killed the animals, ate their flesh, and began to use their pelts to
Transient Oculomotor Nerve Palsy
Authors: Neil R. Miller
Journal: JAMA (1978)

ISOLATED oculomotor nerve palsy frequently occurs in patients with diabetes mellitus. Most patients affected are aged 50 to 70 years and have mild adult-onset diabetes that is often under control at the time the palsy begins. The onset of diabetic oculomotor nerve palsy is usually sudden and may be associated with considerable homolateral ocular, retrobulbar, or cephalic pain. The palsy generally persists for several months before resolving spontaneously. In most instances, the pupil remains normal; however, when the pupil is paralyzed, the major differential diagnosis is between an intracranial aneurysm and diabetes.<sup>1</sup>The sudden onset of a painful, complete oculomotor nerve palsy developed in a patient while he was taking chlorothiazide. The patient's workup showed an elevated fasting blood glucose level and abnormal findings of a glucose tolerance test. After he discontinued therapy with the diuretic, the blood glucose abnormalities disappeared, and the oculomotor nerve palsy resolved. <h3>Report of</h3>
Hemopoietic inhibition in hairy cell leukemia
Authors: Anthony J. Janckila, Patrick S. Gentile, Lung T. Yam
Journal: American Journal of Hematology (1991)

Abstract Leukopenia, thrombocytopenia, and anemia are important features of hairy cell leukemia (HCL). They are generally considered to be due to hypersplenism and to inadequate production by bone marrow which is heavily infiltrated by the neoplastic hairy cells (HC). However, the cytopenias may also be caused by hemopoietic inhibition by cytokines derived from the mononuclear cells (MNC) of HCL. We studied the MNC of HCL with an in vitro assay for granulocyte‐macrophage progenitors (CFU‐GM) to search for this hemopoietic inhibitor(s) and to determine the cell source and mechanism of its production/release. We found that MNC conditioned media from 7 of 9 HCL cases exerted substantial inhibitory effect (23% to 66%) on normal marrow cells. Peak inhibitory activity was obtained in media conditioned with 10 6 MNC/ml for 90 minutes to 24 hours. Both HC and lymphocytes could release inhibitor(s) through mutually synergistic cell interactions. HC alone were inactive and lymphocytes alone were only weakly active. Mixtures of conditioned media of HC and of lymphocytes were not synergistic. The lymphocytes responsible for the inhibition were present in preparations depleted of cells bearing the cluster designation 4 antigen (CD4 + ) and B cells and were most likely the CD8 − T‐cells. In one patient so examined, a partial reversal of inhibition was achieved by treating MNC‐CM with antibodies to tumor necrosis factor (TNF)‐alpha suggesting that TNF‐alpha was at least partly involved in the inhibition of CFU‐GM. This mechanism of cytokine release may be operative in vivo to account for the cytopenias in HCL and, if so, could alter the concept of hypersplenism in this disease.
Routine examination in the neonatal period.
Authors: G D Moss, P H Cartlidge, B D Speidel, T L Chambers
Journal: BMJ (1991)

To assess the value of the second neonatal examination as a medical surveillance procedure.Prospective survey of routine neonatal examinations and the abnormalities identified during 8 March-30 June 1988.Maternity unit with an annual birth rate of 5700.For first neonatal examination: 1795 babies born in the unit during the 115 day observation period. For second routine examination: 1747 babies (97.3%) discharged from postnatal ward.Missed abnormalities (present but not previously noted); minor abnormalities (superficial infection or trivial or transient abnormalities not requiring intervention); and important abnormalities (unlikely to have been present at first examination but requiring intervention).An abnormality was detected in 158 (8.8%) infants on first neonatal examination. 1428 (79.6%) babies had a routine second examination, which disclosed 63 previously undetected abnormalities. Of these, seven (11%) would have been present on first examination, 49 (78%) were considered minor, and seven (11%) important--the most consequential being dislocatable hips (four infants). Thus an important finding was detected by only 0.5% of second examinations.A second thorough examination in the early neonatal period cannot be justified as a screening procedure. A repeat examination of the hips alone in the first week of life is necessary.
Acute gastric dilatation after trauma.
Authors: S U Rahman
Journal: BMJ (1976)

Pyloric stenosis and sustained-release iron tablets SIR,-The case reported below gives an interesting and salutary warning about the possible effects of giving long-acting iron tablets to patients with a history of peptic ulceration or long-standing dyspepsia.The patient, an arthritic spinster of 74 who was known to live on a diet of cake and Maltesers, was started on treatment with Ferrogradumet C for a
Principles for Making Difficult Decisions in Difficult Times
Authors: D M Eddy
Journal: JAMA (1994)

IN THE last article I described several issues or "battles" that will be particularly contentious in the coming decade.<sup>1</sup>They relate to the evidence needed to justify use of a treatment, to the need to balance a treatment's benefits against its costs, and to the autonomy of physicians to answer these questions for themselves. (I will use the word "treatment" very broadly to encompass any type of health intervention.) One way or another, these issues will be resolved in the next few years. Setting aside for a moment the actual solutions that are developed, the process by which these issues are addressed will provide one of the most visible displays of how the medical profession manages itself and responds to an urgent social need. The main battlefield on which these issues will be resolved will be debates over coverage and guidelines for individual treatments. These debates will occur in
Incidence, Time Course, and Determinants of Menstrual Bleeding After Breast Cancer Treatment: A Prospective Study
Authors: Jeanne A. Petrek, Michelle J. Naughton, L. Douglas Case, Electra D. Paskett, Elizabeth Z. Naftalis, S. Eva Singletary, Paniti Sukumvanich
Journal: Journal of Clinical Oncology (2006)

To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women.Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding.Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding.Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.
Suicide With, and Because of, Cocaine
Authors: Kris Sperry
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The proliferation of cocaine abuse has engendered an increase in deaths, emergency department visits, hospitalizations, and treatment programs. However, suicide with cocaine as the toxic agent has not yet, to my knowledge, been reported in the United States. In the past two years, two deaths from intentional intravenous cocaine use have been studied by autopsy by the New Mexico Office of the Medical Investigator. In each case, notes at the scene indicated that the primary reason for suicide was addiction to cocaine. <h3>Report of Cases.—Case 1.</h3> —A 25-year-old college student was found dead in his room, accompanied by insulin syringes, a spoon, and a piece of formed white granular material. The autopsy disclosed multiple fresh and healing intravenous injection sites involving both antecubital fossae, forearms, dorsal feet, and the medial ankles. A suicide note began, "I'm real sorry I had to do this but I
Phase I/II Study of Docetaxel/Cisplatin/Fluorouracil Combination Chemotherapy Against Metastatic Esophageal Squamous Cell Carcinoma
Authors: Hiroaki Takahashi, Yoshiaki Arimura, Kentaro Yamashita, Satoshi Okahara, Tokuma Tanuma, Junichi Kodaira, Kaku Hokari, Hiroyuki Tsukagoshi, Yasuhisa Shinomura, Masao Hosokawa
Journal: Journal of Thoracic Oncology (2010)
Radiocolloid Liver Imaging in Hepatic Steatosis
Authors: R LISBONA, C L RUSH, V DERBEKYAN, J A NOVALES-DIAZ
Journal: Clinical Nuclear Medicine (1986)

In a review of 60 patients with fatty infiltration of the liver documented by Xe-133 imaging, 43% had normal radiocolloid liver images, and 57% had abnormal images with various combinations of hepatomegaly, mottling, splenomegaly, and splenic shift of radioactivity. None, however, showed focal defects. Fatty infiltrates do not simulate mass lesions on the radiocolloid study of the liver, and an area of photon deficiency in the presence of hepatic steatosis points to an additional pathologic process. The interpretation of the radiocolloid liver image is unhindered by fatty infiltration when searching for discrete space-occupying lesions.
Management of the Patient With Cancer
Authors: Kirby I. Bland
Journal: JAMA (1986)

This tome, edited by a leading, nationally known oncologist and including contributions by 73 internationally respected authors, is organized as a comprehensive textbook for the clinical oncologist. The third edition continues to place emphasis within individual chapters on specific sites and pertinent information concerning multimodal approaches to management. The new developments in the diagnosis and management of many different tumors have made it possible to present the new material included in this edition. There have been several revisions and new contributions since the first and second editions. Many of the original authors have chosen totally to reorganize their chapters. Additionally, several of the authors have called on collaborators in other oncological disciplines to augment their presentation with the use of newer illustrations, tables, and supplemental data.  The text is organized by organ system. Essentially, every chapter provides an all-inclusive discussion of the incidence, etiology, and appropriate pathology of site-specific cancers.
Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence.
Authors: F Fernandez-Banares, M Esteve, E Navarro, E Cabre, J Boix, A Abad-Lacruz, J Klaassen, R Planas, P Humbert, C Pastor, M A Gassull
Journal: Gut (1996)

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.
Studies on the Control of Hypertension by Hyphex
Authors: JOHN D. MORROW, HENRY A. SCHROEDER, H. MITCHELL PERRY
Journal: Circulation (1953)

Although effective in maintaining relatively normal levels of blood pressure in hypertensive patients and retarding some of the serious and fatal secondary consequences of the disease, hexamethonium ion and 1-hydrazinophthalazine can cause severe immediate and late reactions. The latter drug has produced collagen diseases of varying degrees of severity, all of which have regressed on cessation of medication, in 14 of 253 patients. The combination has given rise to fatal interstitial pneumonia in 5 of 89 in malignant stages of hypertension. Less serious side effects of each agent are also discussed.