tbuckley/cabot-search huggingface dataset:
Application considered for immunotoxin in treatment of graft-vs-host disease
Authors: A. Skolnick
Journal: JAMA (1991)

THE Food and Drug Administration (FDA) is considering the product license application for a monoclonal antibody—toxin conjugate for use in preventing and treating graft-vs-host disease (GvHD) in bone marrow transplant patients. This and other new agents for treating T cell mediated diseases recently were discussed at the Hoag Cancer Center's Biotherapy of Cancer Symposium in Newport Beach, Calif, and at an American Cancer Society seminar in Phoenix, Ariz. If the FDA approves the antibody— toxin conjugate (called Orthozyme CD5plus by its developer, XOMA Corp, Berkeley, Calif), it would be the first immunotoxin to be licensed for the treatment of any disease. Although the license application proposes its use for treating bone marrow transplant patients with steroid-resistant GvHD, the antibody—toxin conjugate also shows promise for treating autoimmune diseases such as rheumatoid arthritis and type I diabetes, as well as certain hematologic malignancies, says Vera S. Byers, MD, PhD, who is director
Intersex
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstracts of the Annual Meeting of The Endocrine Society
Journal: Endocrine Reviews (1981)

Journal Article Abstracts of the Annual Meeting of The Endocrine Society Get access Endocrine Reviews, Volume 2, Issue 2, 1 April 1981, Page 249, https://doi.org/10.1210/edrv-2-2-249 Published: 01 April 1981
Abstract 189: Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice.
Authors: Masahito Shimizu, Daishi Terakura, Takahiro Kochi, Tomohiko Ohno, Masaya Kubota, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki
Journal: Cancer Research (2013)

Abstract Obesity and its associated disorders, such as non-alcoholic steatohepatitis, increase the risk of hepatocellular carcinoma (HCC). Branched-chain amino acids (BCAA), which improves protein malnutrition in patients with liver cirrhosis, reduces the risk of HCC in these patients with obesity. In the present study, the effects of BCAA supplementation on the spontaneous development of hepatic premalignant lesions, foci of cellular alteration (FCA), in db/db obese mice were examined. Male db/db mice were given a basal diet containing 3.0% of either BCAA or casein, a nitrogen content-matched control of BCAA, for 36 weeks. At sacrifice, supplementation with BCAA significantly inhibited the development of FCA when compared to casein supplementation by inhibiting cell proliferation, but inducing apoptosis. BCAA supplementation increased the expression levels of PPAR-γ, p21CIP1, and p27KIP1 mRNA and decreased the levels of c-fos and cyclin D1 mRNA in the liver. BCAA supplementation also reduced both the amount of hepatic triglyceride accumulation and the expression of IL-6, IL-1β, IL-18, and TNF-α mRNA in the liver. Increased macrophage infiltration was inhibited and the expression of IL-6, TNF-α, and MCP-1 mRNA in the white adipose tissue (WAT) were each decreased by BCAA supplementation. BCAA supplementation also reduced adipocyte size, while increasing the expression of PPAR-α, PPAR-γ, and adiponectin mRNA in the WAT compared to casein supplementation. These findings indicate that BCAA supplementation inhibits the early phase of obesity-related liver tumorigenesis by attenuating chronic inflammation in both the liver and WAT. BCAA supplementation may be useful in the chemoprevention of liver tumorigenesis in obese individuals. Citation Format: Masahito Shimizu, Daishi Terakura, Takahiro Kochi, Tomohiko Ohno, Masaya Kubota, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki. Preventive effects of branched-chain amino acids supplementation on the spontaneous development of hepatic preneoplastic lesions in C57BL/KsJ-db/db obese mice. [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 189. doi:10.1158/1538-7445.AM2013-189
British Journal of Radiology, London
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A phase I study evaluating a novel schedule of oral eniluracil (EU) combined with escalating doses of oral 5-fluorouracil (5- FU)
Authors: P. B. Murphy, E. Raefsky, H. A. Burris, J. R. Infante, S. F. Jones, D. R. Spigel, N. Dickson, M. Lawton, J. S. Dicksey, W. P. Peters
Journal: Journal of Clinical Oncology (2008)

13519 Background: 5-FU, a commonly utilized cytotoxic, is rapidly catabolized by dihydropyrimidine dehydrogenase (DPD), and requires anabolic conversion for anti-tumor activity. 5-FU has poor oral bioavailability due to DPD in the GI tract and liver, and toxicities such as hand-foot skin reaction. In addition, high levels of DPD are associated with 5-FU resistance. EU is a mechanism-based irreversible inactivator of DPD. Early studies in combination with oral 5-FU demonstrated activity; however, 3 Phase 3 studies were negative, due to an unrecognized inhibition of 5-FU anabolic activation by EU (Fourie et al; 2006 ASCO Proceedings; a 2058). Lower doses of EU given 12–20 hrs prior to 5-FU preserves the desired DPD inhibition, without inhibiting these anabolic enzymes. Methods: The objectives are to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), and DPD activity in peripheral blood mononuclear cells following administration of a fixed dose of EU in combination with escalating doses of 5-FU. The combination of oral 5.0 mg EU 12 to 20 hours prior to oral 5-FU, is given qW for 3 weeks in 28 day cycles. Results: Thirty-five subjects with generally extensive prior therapy have been enrolled at eight 5-FU doses levels between 30 mg and 160 mg. A total of 90 cycles have been administered. The oral combination of EU and 5-FU has been well tolerated. Nearly all toxicities have been grade 1 or 2; two grade 3 dose limiting toxicities were reported at the 50mg dose (neutropenia) and the 160mg dose (diarrhea). 95–100% of DPD inhibition achieved at the time of 5-FU dosing and 5- FU PK demonstrate a dose proportional increase in 5-FU Cmax (mean at 160 mg = 4860 ng/mL) and AUC (mean at 160 mg = 22100 ng*hr/mL), and a plasma half life of ∼3.5 hours. Four patients (2 previously treated with 5-FU) have shown ≥4 cycles of SD. Conclusions: The oral combination of 5mg of EU given 12–20 hrs prior to 5-FU has been well tolerated and is enrolling at the 210 mg dose. EU in combination with 5-FU achieves full functional inhibition of DPD in all patients, predictable 5-FU PK and may provide a promising oral therapeutic option to overcome DPD mediated 5-FU resistance and hand-foot syndrome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Adherex Technologies Adherex Adherex
Increased blood manganese in cirrhotic patients: Relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms
Authors: L Spahr
Journal: Hepatology (1996)

Increasing evidence suggests that manganese deposition is responsible for the T1-weighted magnetic resonance imaging (MRI) signal hyperintensity consistently observed in pallidum of cirrhotic patients. However, the relationship between blood manganese and the etiology or severity of liver disease, as well as the neurological symptomatology in these patients, has not been well established. In the present study, blood manganese concentrations were measured by atomic absorption spectrometry together with MRI and neurological evaluation in 57 cirrhotic patients with various etiologies and severity of liver disease. Blood manganese concentrations were elevated in 67% of cirrhotic patients and were significantly higher in patients with previous portacaval anastomoses or transjugular intrahepatic portosystemic shunt (TIPS). Pallidal signal hyperintensity was observed in 88% of patients, and significant correlations were demonstrated between blood manganese and pallidal index (PI) (a measure of pallidal signal hyperintensity), as well as Child-Pugh score. Assessment of extrapyramidal symptoms using the Columbia rating scale revealed a significant incidence of tremor, rigidity, or akinesia in up to 89% of cirrhotic patients. However, there was no significant correlation between blood manganese and extrapyramidal symptoms, although severity of akinesia was significantly greater in Child-Pugh C patients. Extrapyramidal symptoms could result from a toxic effect of manganese on basal ganglia dopaminergic function. These findings further support a role for manganese in the etiology of pallidal MRI signal hyperintensity in patients with chronic liver disease.
Illustrations of Exceptional Symptoms and Examples of Rare Forms of Disease
Authors: J. Hutchinson
Journal: BMJ (1886)

we 26, T88M.]THR ±*JITk*FI MRPIOA1 J0 gJA4Alcoholic cirrhosis is, the common "hob-nail," or gin-drinker's liver, generally small, hard, and granular; met with, clinically, very frequently in association with ascites.I thinkithis association is perhaps, too much insisted uponi.Frerichs found aseites absent in one third of his cases.Aniadvanced stage of this disease is quite compat- ible with apparent health, and the performance of-the ordinary duties of life.Some years ago, I examined the body of a foreman engineer at one of our collieries, who had died suddenly of hnematemosis from this cause.I was told that he had not lost a day's work for two years; and, in spite of being a hard drinker, was a, m;uch valued ser- vant and a good workman.Au eminent London physician of the last generation died suddenly in the same way at Bath railway station, Whither he had gone on professional business.Ascites is usually held to be simply a dropsical effusion dependent upon obstruction to the portal, circulation in the liver.But it is sometimes distinctly associated with inflammatory action.and it is possible that this may play a; more important part than is at present
Prostaglandin E1 stimulates mucin secretion and increases MUC3 mRNA levels in cultured human gallbladder epithelial cells , Boston University Medical Center, Boston, MA and *Medical College of Virginia, Richmond, VA
Journal: Hepatology (1995)

Acute cutaneous photosensitivity is a major manifestation of certain forms of human porphyria and also occurs in patients treated with hematoporphyrin derivative (HpD) photoradiation for the diagnosis and treatment of malignant tumors. In this study a quantitative animal model useful for in vivo studies of acute porphyrin photosensitization in cutaneous tissue was developed. C3H mice injected with HpD and irradiated 6 h later with 405 nm energy developed a 40–90% increase in ear thickness which was present immediately after irradiation and persisted for at least 24 h. No ear swelling occurred in animals receiving 405 nm radiation alone or HpD alone. Histologically, this photosensitivity reaction was manifest as edema, vascular dilatation, and mast cell degranulation immediately after irradiation followed by an influx of polymorphonuclear leukocytes and epidermal necrosis 24 h later. Tissue injury evoked by HpD and light was accompanied by extravasation of intravenously administered 125I-labeled albumin in the irradiated ears, indicating that photosensitization was accompanied by transudation of serum into the site of tissue injury. An in vivo correlation of this approach was verified by detection of measurable increase in ear thickness in irradiated mice rendered porphyric by the ingestion of griscofulvin-containing diet. The mouse ear swelling model offers a useful system with which to study acute porphyrin photosensitization in the skin, and may lead to important new insights into the pathogenesis and prevention of this form of phototoxicity.
Comparative validation of prognostic rules for community-acquired pneumonia in an elderly population
Authors: S Ewig, T Kleinfeld, T Bauer, K Seifert, H Schafer, N Goke
Journal: European Respiratory Journal (1999)

The aim of the study was to validate the prediction rule of M.J. Fine and coworkers for clinical outcome variables and three prognostic rules for the individual outcome of community-acquired pneumonia in an elderly population (rule 1: respiratory frequency &gt; or =30 breaths x min(-1), diastolic blood pressure &lt; or =60 mmHg, blood urea nitrogen &gt;7 mM; rule 2: respiratory frequency &gt; or =30 breaths x min(-1), diastolic blood pressure &lt; or =60 mmHg, mental confusion; and rule 3: systolic blood pressure &lt; or =80 mmHg, cardiac frequency &gt; or =90 beats x min(-1), lactate dehydrogenase activity &gt; or =260 IU x L(-1); death was predicted in the presence of at least two of three parameters). Overall 168 consecutive episodes of community-acquired pneumonia in patients aged &gt; or =65 yrs and hospitalized in a primary care hospital were studied prospectively. Fine's rule was tested for its ability to predict length of hospital stay, requirement for intensive care unit (ICU) admission and death. For the three prognostic rules of individual outcome, performance regarding predicting death was determined. Mortality was 17/168 (10%). Fine's rule accurately predicted length of stay, the requirement for ICU admission and the risk of death from pneumonia as compared to the original derivation and validation cohorts. All three rules achieved moderate-to-high specificity (73%, 88% and 80%, respectively) and high negative predictive values (95%, 94% and 93%, respectively) but had a low sensitivity (65%, 47% and 47%, respectively). Rule 2 most closely reflected the risk of death from pneumonia when Fine's classification was used as reference. Fine's rule proved to give valid estimations regarding clinical outcome variables of community-acquired pneumonia in the elderly. The prognostic rules may be useful in determining individual patients at lower risk of death caused by pneumonia.
Clinical Pharmacol &amp;amp; Therapeutics, St. Louis
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue Access Provided by Chonnam National University JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account
Tobacco-Specific Nitrosamine Adducts: Studies in Laboratory Animals and Humans
Authors: Stephen S. Hecht, Steven G. Carmella, Peter G. Foiles, Sharon E. Murphy, Lisa A. Peterson
Journal: Environmental Health Perspectives (1993)

This paper describes quantitation of human hemoglobin and DNA adducts of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are believed to be involved in cancers of the lung, esophagus, oral cavity, and pancreas in people who use tobacco products. The adduct dosimetry method employs GC-MS for quantitation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) released by mild base hydrolysis of hemoglobin or acid hydrolysis of DNA as a biochemical marker of the pyridyloxobutylation metabolic activation pathway. Approximately 22% of smokers (n = 101) had elevated levels of HPB released from hemoglobin (range, 200-1600 fmole/g Hb). Adduct levels in snuff dippers ranged from 200-1800 fmole/g Hb. HPB levels in nonsmokers were generally below the detection limit. Acid hydrolysis of lung and tracheal DNA obtained at autopsy and analysis for released HPB revealed levels ranging up to 50 fmole/mg DNA in smokers; the adduct was not detected in nonsmokers. These findings are consistent with data generated in studies of adduct formation by NNK in rats. The biological significance of the HPB-releasing DNA pyridyloxobutylation pathway was compared to that of the DNA methylation pathway in the A/J mouse. These studies demonstrated that the persistence of O6-methylguanine in lung DNA is critical for tumorigenesis by NNK and that pyridyloxobutylation enhances both persistence of O6-methylguanine and tumorigenesis by acetoxymethylmethylnitrosamine. In the rat, the relative roles of methylation and pyridyloxobutylation in lung tumorigenesis by NNK are not as clearly defined.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of bronchoconstriction by an orally active local anesthetic.
Authors: R H Brown, W Robbins, P Staats, C Hirshman
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Stimulation of airway irritant receptors produces reflex bronchoconstriction that can be prevented by pretreatment with anticholinergic drugs or local anesthetics delivered by aerosol or intravenously. We compared therapeutic doses of an orally administered local anesthetic, mexiletine hydrochloride, and intravenously administered lidocaine at blocking histamine-induced bronchoconstriction in five basenji-greyhound dogs, using high-resolution computed tomography (HRCT) to directly measure changes in airway size. In the dogs given placebo, a histamine infusion decreased airway area to 61 +/- 2% (mean +/- SEM) of control (p < 0.01). Mexiletine pretreatment completely prevented histamine-induced airway constriction, with an airway area that was 94 +/- 4% of the control value during the histamine infusion (p = 0.07 compared with baseline). Mexiletine serum levels were therapeutic (1.7 +/- 0.3 mg/L). Similarly, pretreatment with lidocaine significantly blunted the airway constriction provoked by intravenous histamine. In lidocaine-pretreated dogs, histamine decreased airway area to 79 +/- 4% of baseline (p < 0.01). As in the case of mexiletine, lidocaine serum levels were also therapeutic (2.4 +/- 0.3 mg/L). Mexiletine was more effective than lidocaine at preventing histamine-induced bronchoconstriction (p = 0.02). These data suggest that orally administered local anesthetics may be useful in preventing irritant-induced bronchoconstriction in humans.
Regional Distribution of Deaths From Residential Fires—United States, 1978-1984
Journal: JAMA (1987)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Leads from the MMWR. Recommendations for prevention of HIV transmission in health-care settings
Journal: JAMA (1987)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Index of Subjects&lt;subtitle&gt;Volume 22 January 1959 • June 1959&lt;/subtitle&gt;
Journal: JNCI Journal of the National Cancer Institute (1959)

Journal Article Index of Subjects: Volume 22 January 1959 • June 1959 Get access JNCI: Journal of the National Cancer Institute, Volume 22, Issue 6, June 1959, Pages 1189–1195, https://doi.org/10.1093/jnci/22.6.1189 Published: 01 June 1959