tbuckley/cabot-search huggingface dataset:
ATYPICAL HAY FEVER SEASONS; THEIR SIGNIFICANCE IN TREATMENT
Authors: Samuel M. Feinberg, O. C. Durham
Journal: Annals of Internal Medicine (1935)

Article1 April 1935ATYPICAL HAY FEVER SEASONS; THEIR SIGNIFICANCE IN TREATMENTSAMUEL M. FEINBERG, M.D., F.A.C.P., O. C. DURHAMSAMUEL M. FEINBERG, M.D., F.A.C.P.Search for more papers by this author, O. C. DURHAMSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-10-1282 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is now an accepted fact that specific and successful treatment of the hay fever patient presupposes a careful botanical investigation of the district in which the sufferer resides. Because of the marked variations in the flora of various parts of the country it has been necessary to make extended studies in many localities. While it cannot be said that the data which are at present available are entirely complete, nevertheless, we have information as to hay fever plants and pollen distribution in many representative sections of the country. The means used in surveying any locality consist of field observation...References1. KOESSLERDURHAM KKOC: A system for an intensive pollen survey, Jr. Am. Med. Assoc., 1926, lxxxvi, 1204-1209. HUBER, H. L.: Hay fever in the Chicago territory, Ill. Med. Jr., 1926, xlix, 133-138. CrossrefGoogle Scholar2. FEINBERG SM: Hay fever in the north central states, its causes and treatment, Ill. Med. Jr., 1932, lxi, 429-433. Google Scholar3. FEINBERGDURHAM SMOC: Hay fever in Chicago and suburbs; clinical, field and air observations, Ill. Med. Jr., 1933, lxiii, 464-471. Google Scholar4. FEINBERG SM: Allergy in general practice, 1934, Lea and Febiger, Philadelphia. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication November 1, 1934.From the Allergy Clinic, Department of Medicine, Northwestern University Medical School and the Botanical Laboratories of Abbott Laboratories. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe optimal doses in pollen therapy 1 April 1935Volume 8, Issue 10Page: 1282-1286KeywordsAllergy and immunologyFeversPollen ePublished: 1 December 2008 Issue Published: 1 April 1935 PDF downloadLoading ...
Abstract 8511: A Novel Type of Homozygous Familial Hypercholesterolemia:Double Heterozygous Mutations in LDL Receptor and LDL Receptor Adaptor Protein 1 Gene
Authors: Hayato Tada, Masa-aki Kawashiri, Chiaki Nakanishi, Toshinari Tsubokawa, Tetsuo Konno, Kenshi Hayashi, Katsuharu Uchiyama, Atsushi Nohara, Noboru Fujino, Hidekazu Ino, Akihiro Inazu, Junji Kobayashi, Hiroshi Mabuchi, Masakazu Yamagishi
Journal: Circulation (2011)

Introduction: Autosomal recessive hypercholesterolemia (ARH), which is due to mutations in LDL receptor adaptor protein 1 (LDLRAP1) gene is extremely rare disorder. Although it is described that this defect exhibits recessive form of inheritance, several heterozygous mutation carriers in this gene are reported to show elevated LDL-C levels. There is no data exists regarding clinical impact of double heterozygous mutations in LDLR and LDLRAP1 gene, both of which are involved in the metabolism of LDL particle. Hypothesis: We assessed the hypothesis that additional mutation in LDLRAP1 gene worsen clinical phenotype of heterozygous familial hypercholesterolemia (FH) that has a single mutation in LDLR gene. Methods: We performed genetic analyses of all coding regions in the LDLRAP1 gene for our mutation determined heterozygous FH patients with mutation in LDLR gene (n=146, mean age=56.5±16.0, mean LDL-C=265.6±57.7mg/dl). Results: We identified a case with double heterozygous mutations in LDLR gene (c.2431A&gt;T) and in LDLRAP1 gene (c.606dup). Seventy-nine-year-old Japanese female exhibits severe Achilles' tendon xanthomas, the thickness of which is as much as 24mm. She underwent coronary artery bypass graft surgery due to her three vessel disease at the age of 70. Although her coronary atherosclerosis including bypass grafts did not progress substantially for a period of 9 years on more intensive medical therapy, severe aortic valve stenosis developed to cause ventricular fibrillation. And we identified 2 other relatives with the same mutations in LDLR and LDLRAP1 gene in her family. Serum LDL-C level of these 3 subjects with double mutations was significantly higher than that of the subjects with a single LDLR mutation alone (284.0±43.5 versus 265.1±57.4, p &lt; 0.0001). Conclusions: These results indicate that additional mutation in LDLRAP1 gene worsens clinical phenotype of heterozygous FH that has a single mutation in LDLR gene. We suggest that ARH is not a fully “recessive” disorder, and that such cases should be diagnosed as novel type of “homozygous FH”.
Flower Still Life
Authors: M. Therese Southgate
Journal: JAMA (2003)

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
Abstract 1807: Pre-clinical evaluation of Mcl-1 inhibition through maritoclax in acute myeloid leukemia
Authors: Qiang Liu, Kenichiro Doi, Krishne Gowda, Brian M. Barth, David Claxton, Shantu Amin, Thomas P. Loughran, Hong-Gang Wang
Journal: Cancer Research (2014)

Abstract There is an urgent and unmet medical need for development of new therapeutics for acute myeloid leukemia (AML). The anti-apoptotic Bcl-2 family protein Mcl-1 plays a critical role in AML cell survival and chemoresistance. Mcl-1 is upregulated in relapsed AML and leukemic stem cells. Inhibition of Mcl-1 expression in AML cells by kinase inhibitors or gene targeting induces apoptosis and suppresses leukemogenesis. However, the impact of targeting Mcl-1 in AML therapy with selective pharmacological inhibitors remains to be assessed. Recently, we discovered a novel Mcl-1 inhibitor, maritoclax (marinopyrrole A), which antagonizes Mcl-1 by targeting Mcl-1 for proteasomal degradation. This unique mechanism of action is in contrast to BH3 mimetics that exert their inhibitory function through disruption of the interactions between pro- and anti-apoptotic Bcl-2 family proteins. In a panel of AML cell lines, the potency of maritoclax positively correlated with Mcl-1 expression and inversely correlated with Bcl-2 and Bcl-xL expression. Maritoclax was efficacious as a single agent and markedly synergized with ABT-737 to induce apoptosis in Mcl-1 overexpressing ABT-737 and multidrug resistant AML cell lines. Moreover, maritoclax was able to overcome stroma-mediated resistance to apoptosis in AML cells. Importantly, maritoclax induced Mcl-1 degradation and apoptotic cell death selectively in clinical AML specimens with high levels of Mcl-1. To evaluate the anti-tumor activity of maritoclax in vivo, we established U937 tumor xenografts in nude mice. As a single agent, maritoclax significantly inhibited the growth of established xenografts at a dose of 20 mg/kg/d intraperitoneally. At this dosing level, no significant difference in body weight change and complete blood count was observed between maritoclax and vehicle treatment groups. Collectively, our studies demonstrated that maritoclax represents a novel class of Mcl-1 inhibitors and that the selective pharmacological inhibition of Mcl-1 may be a viable approach for the treatment of AML. Citation Format: Qiang Liu, Kenichiro Doi, Krishne Gowda, Brian M. Barth, David Claxton, Shantu Amin, Thomas P. Loughran, Hong-Gang Wang. Pre-clinical evaluation of Mcl-1 inhibition through maritoclax in acute myeloid leukemia. [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 1807. doi:10.1158/1538-7445.AM2014-1807
Abstract 2901: Cell surface-associated anti-MUC1-derived signal peptide antibodies: implications for cancer diagnostics and therapy
Authors: Riva Kovjazin, Galit Horn, Nechama I. Smorodinsky, Michael Y. Shapira, Lior Carmon
Journal: Cancer Research (2014)

Abstract The MUC1 tumor associated antigen is highly expressed on a range of tumors. Its broad distribution on primary tumors and metastases renders it an attractive target for immunotherapy. After synthesis MUC1 is cleaved, yielding a large soluble extracellular alpha subunit containing the tandem repeats array (TRA) domain specifically bound, via non-covalent interaction, to a smaller beta subunit containing the transmembrane and cytoplasmic domains. Thus far, inconclusive efficacy has been reported for anti-MUC1 antibodies directed against the soluble alpha subunit. Targeting the cell bound beta subunit, may bypass limitations posed by circulating TRA domains. MUC1's signal peptide (SP) domain promiscuously binds multiple MHC class II and Class I alleles, which upon vaccination, generated robust T-cell immunity against MUC1-positive tumors. This is a first demonstration of non-MHC associated, MUC1 specific, cell surfaces presence for MUC1 SP domain. Polyclonal and monoclonal antibodies generated against MUC1 SP domain specifically bind a large variety of MUC1-positive human solid and hematological tumor cell lines; MUC1-positive bone marrow derived plasma cells obtained from multiple myeloma (MM)-patients, but not MUC1 negative tumors cells, and normal naive primary blood and epithelial cells. Membranal MUC1 SP appears mainly as an independent entity but also co localized with the full MUC1 molecule. MUC1-SP specific binding in BM-derived plasma cells can assist in selecting patients to be treated with anti-MUC1 SP therapeutic vaccine, ImMucin. A therapeutic potential of the anti-MUC1 SP antibodies was suggested by their ability to support of complement-mediated lysis of MUC1-positive tumor cells but not MUC1 negative tumor cells and normal naive primary epithelial cells. Moreover in preliminary studies, anti-MUC1 SP antibodies delayed tumor growth of murine DA-3 cells transfected with human MUC1. These findings suggest a novel cell surface presence of MUC1 SP domain, a potential therapeutic benefit for anti-MUC1 SP antibodies in MUC1-positive tumors and a selection tool for MM patients to be treated with the anti-MUC1 SP vaccine, ImMucin. Note: This abstract was not presented at the meeting. Citation Format: Riva Kovjazin, Galit Horn, Nechama I. Smorodinsky, Michael Y. Shapira, Lior Carmon. Cell surface-associated anti-MUC1-derived signal peptide antibodies: implications for cancer diagnostics and therapy. [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 2901. doi:10.1158/1538-7445.AM2014-2901
Minimisation: the platinum standard for trials?
Authors: T. Treasure, K. D MacRae
Journal: BMJ (1998)

When we have to decide which of two drugs, interventions, or management strategies is the better, the most secure evidence is generally obtained from a randomised controlled trial. The primary objective of randomisation is to ensure that all other factors that might influence the outcome will be equally represented in the two groups, leaving the treatment under test as the only dissimilarity. Any difference in outcome can then be attributed to the treatment effect. But how realistic is this assumption in practice?

When published a randomised trial typically includes a table listing all the prior factors known actually or possibly to influence outcome. The average age and its distribution in each group and the proportion of men and women usually head the list, followed by other likely determinants of outcome. In the case of heart disease these will probably include details of left ventricular function; the proportions in each group with diabetes, hypertension, hyperlipidaemia, or a smoking history; the relative incidence of arrhythmia, obesity, symptoms of heart failure; and any others factors that may have been collected. If these are similar in the two groups (which is …
Hypertrophic cardiomyopathy mutation is expressed in messenger RNA of skeletal as well as cardiac muscle.
Authors: Q T Yu, J Ifegwu, A J Marian, A Mares, R Hill, M B Perryman, L L Bachinski, R Roberts, A J Marlan
Journal: Circulation (1993)

The beta-myosin heavy chain (beta-MHC) gene has been identified as a major locus for familial hypertrophic cardiomyopathy (FHCM). We recently showed that one of the common mutations associated with FHCM is expressed in the cardiac muscle messenger RNA (mRNA) of an affected individual. Since beta-MHC is a major sarcomeric protein of cardiac and skeletal muscle, studies were performed to determine whether the mutation is also expressed in skeletal muscle.Biopsies were obtained of skeletal muscle (biceps brachii) from a proband with FHCM known to have the missense mutation in exon 13 of the beta-MHC gene. RNA was extracted from skeletal muscle and lymphocytes by the RNAzol method. First-strand complementary DNA was synthesized by reverse transcription using an antisense primer to exon 16. Polymerase chain reaction (PCR) was performed using primers to exons 12 and 14 to amplify the segment encompassing exon 13. The PCR products were digested with Ddel restriction endonuclease. Undigested PCR product in the control and the proband was 321 base-pairs (bp). Ddel digestion of the PCR product from normal skeletal and lymphocytes showed two DNA fragments of 181 and 140 bp as expected, whereas digestion of the PCR product from the proband's skeletal muscle and lymphocytes showed four DNA fragments of 181, 149, 140, and 32 bp due to the mutation in exon 13. This indicates that the mutation in affected individuals is also expressed in the mRNA of skeletal muscle and lymphocytes.To our knowledge, this is the first documentation of a beta-MHC gene mutation expressed in skeletal muscle. This finding is provocative. Does it impair skeletal muscle function? If so, how? If not, why not? Is the impairment, or lack of it, a clue to the molecular defect of cardiac muscle? Furthermore, skeletal muscle provides a readily accessible source of mRNA for expression studies and for purification of the beta-MHC protein, which is probably essential to future investigation designed to unravel the molecular basis of this disorder.
Follow-up results of transvenous occlusion of patent ductus arteriosus with the buttoned device11One of the authors of this article (EBS) is the inventor of the device used in this study.
Authors: P.Syamasundar Rao, Seong Ho Kim, Jae-Young Choi, Christian Rey, Jorge Haddad, Francois Marcon, Kevin Walsh, Eleftherios B Sideris
Journal: Journal of the American College of Cardiology (1999)
Regular review: Developing strategies for long term follow up of survivors of childhood cancer
Authors: W H. B Wallace, A. Blacklay, C. Eiser, H. Davies, M. Hawkins, G. A Levitt, M. E M Jenney
Journal: BMJ (2001)

The treatment of childhood cancer has been increasingly successful over the past 30 years. Most paediatric cancers are now curable with multiagent chemotherapy in combination with surgery and radiotherapy. The overall survival five years after diagnosis is now 70% for all paediatric malignancies. The incidence is low (1200-1300 children affected each year in Britain), but with the sustained improvement in survival the number of long term survivors is increasing—about 850 additional survivors of childhood cancer each year. With this improved survival, it is important to increase our knowledge of any long term costs in the form of physical and psychosocial adverse health outcomes.

This review looks at the evidence relating to long term clinical follow up after childhood cancer and considers ways to develop such follow up for the future. An awareness of the possible long term complications is important not only for optimising health care for the current survivors but also for modifying future treatment protocols to avoid therapies that are associated with unacceptable morbidity or mortality.

We have summarised the evidence on selected long term complications; this evidence is inevitably based on retrospective studies. In the final section we discuss the development of a strategy for the clinical follow up of long term survivors.

#### Summary points

Long term follow up strategies are needed because of increasing numbers of survivors of childhood cancers

Models for follow up need to be developed and formally evaluated

Increasing numbers of survivors may have medical problems that will require ongoing specialist follow up

The role, training programmes, and career structure of the late effects nurse practitioner needs to be developed

The primary care physician may have an important role in long term follow up

There is a need for prospective evaluation of new treatments and randomised studies of clinical interventions to resolve substantial uncertainties for …
Overexpression of NKG2D ligands MIC evokes NK cell-mediated inhibition in tumor intake and growth in prostate cancer xenografts
Authors: Jennifer D. Wu, Stephen R. Plymate, Lily M. Higgins, Catherine L. Atteridge
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

624 

The MHC I chain-related molecule (MIC) is an epithelial transformation induced surface molecule and can be recognized by NK cell stimulatory receptor NKG2D. In vitro studies have demonstrated that MIC-expressing prostate cancer cells are highly susceptible to NK cell immunity. We thus hypothesize that MIC-induced NK cell immunity may play a significant role in prostate tumor immune surveillance. To test this hypothesis, we overexpressed MICB molecule in human prostate cancer cell line M12 (M12 MICBHi cells). We also overexpressed MICB in M12 cells at a lower level (M12 MICBLo cells). Forty 4-6 week-old balb/c nu/nu male mice were randomized into four groups. Group 1 were injected with M12. Group 2 were injected with M12MICBHi. Group 3 were injected with M12MICBLo. Group 4 were injected with M12 cells mixed with M12MICBHi cells at 2:1 ratio. 2X10^6 cells/mouse were s.c. injected. Mice were monitored for tumor growth weekly. At six weeks after injection, all the mice implanted with M12 and M12 mixed with M12MICBHi developed tumors. Tumor growth was monitored continuously for eight additional weeks before sacrificing. Tumor volume (= L2xW/2) was calculated. Tumors in animals injected with M12 grew much faster (at the average rate of 105 mm3/week) than that in animals injected with M12 mixed with M12MICBHi (at the average rate of 51 mm3/week). None of mice injected with the M12MICBHi or M12MICBLo developed tumors throughout the experimental period. In subsequent experiments, we injected 20 more mice i.p. with anti-asialoGM1 (Wako Chemicals) antibody to deplete NK cells 24h prior to injection of M12MICBHi or M12MICBLo and continued the antibody injection twice a week for eight weeks. All the 20 animals developed tumors by seven weeks after tumor cell injection. Our findings demonstrated that MIC-induced NK cell immunity plays a significant role in controlling prostate tumor development and growth. Our data also demonstrated that NK cell anti-tumor activity was less influenced by the levels of tumor cell surface MIC expression (as far as over a positive threshold) than by the numbers (percentage) of tumor cells expressing MIC. These findings may have implications in potential NK cell-based immune therapy for prostate cancer.
Review: In patients with dementia who live in care homes, some nondrug interventions reduce agitation
Authors: Lionel S. Lim
Journal: Annals of Internal Medicine (2015)

Source Citation Livingston G, Kelly L, Lewis-Holmes E, et al. Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials. Br J Psychiatry. 2014;205:436-42. 25452601
One year follow-up of intrabronchial lung volume reduction in alpha-1-antitrypsin deficiency and severe emphysema
Authors: Gunnar Hillerdal, Stephanie Mindus
Journal: European Respiratory Journal (2011)

Introduction: In patients with alpha-1-antitrypsin (AAT) deficiency, severe emphysema mainly localized to the lower lobes can develop. Volume reduction surgery (LVRS) is not recommended in these patients.

Objectives: One-way valves in selected bronchi can reduce the size of hyper-inflated lung areas, and we decided to make a pilot study of intra-bronchial volume reduction (IBVR) in patients with AAT deficiency and severe lower lobe disease.

Methods: In patients aged 40-80 years, with RV >150% and FEV1sec 15-45% of predicted, and predominantly lower lobe disease, IBRV with installation of 3-4 valves in one selected lower lobe was performed.

Results: Five patients were included. There were no complications. An immediate improvement, both subjectively and objectively, occurred and remained during the six months the patients have been followed. FEV1sec increased from a mean of 0.76 to 1.2 L (57%) and RV decreased from 5.7 L to 4 L (42%).

Conclusion: IBRV seems to be a safe, reversible, and simple method to improve lung function in selected patients with AAT deficiency. Further studies are warranted.
Abstract 18830: Sodium Nitrate Recapitulates Sarcolemmal nNOS and Alleviates Functional Muscle Ischemia in Patients With Becker Muscular Dystrophy
Authors: Michael D Nelson, Florian Rader, Xiu Tang, Thomas Stabler, Sarah Shidban, Ryan Rosenberry, Shomari Hogan, Robert Elashoff, Jason D Allen, Ronald G Victor
Journal: Circulation (2014)

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is currently no treatment. Most BMD mutations disrupt sarcolemmal targeting of neuronal nitric oxide synthase (nNOS), causing functional muscle ischemia. In the mouse model of dystrophinopathy, chronic treatment with a nitric oxide (NO)-donating non-steroidal anti-inflammatory drug (NSAID) alleviates this ischemia and improves many features of the dystrophic phenotype. As a first step toward clinical translation, we tested whether acute treatment with sodium nitrat--a simple inorganic NO donor without a NSIAD moiety-- will alleviate functional muscle ischemia in patients with BMD. In 11 men with BMD we first performed an open-label and then a placebo-controlled acute treatment trial. Reflex sympathetic vasoconstriction was measured as a decrease in muscle oxygenation by near infrared spectroscopy, evoked by lower-body negative pressure at rest and during rhythmic handgrip exercise. Without treatment, reflex va...