tbuckley/cabot-search huggingface dataset:
Immunological Applications of Stem Cells in Type 1 Diabetes
Authors: Paolo Fiorina, Julio Voltarelli, Nicholas Zavazava
Journal: Endocrine Reviews (2011)

Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs.
Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis
Authors: Y. Zhao, A. Balato, R. Fishelevich, A. Chapoval, D.L. Mann, A.A. Gaspari
Journal: British Journal of Dermatology (2009)

Allergic contact dermatitis (ACD) is a typical delayed-type hypersensitivity to sensitizing haptens mediated by T cells. Th1/Tc1 cells are currently considered to be the primary effectors in ACD. There is little information concerning the role played in ACD in humans by Th17/Tc17 cells, a recently defined subpopulation of effector T cells.In the present report we attempted to characterize Th17/Tc17 cells in the infiltrates of the skin in the elicitation phase of ACD.Th17 as well as Th1/Th2 cytokine gene expression was examined by semiquantitative real-time polymerase chain reaction in paired samples of positive patch test biopsies and normal skin from 11 patients allergic to nine different allergens. The in situ characterization of interleukin (IL)-17-producing cells was carried out using anti-RORC and anti-T-cell subset antibodies by double immunofluorescence.Compared with normal paired skin samples, gene expression of transcription factor for human Th17 cells, RORC, and Th17-related cytokines IL-17A, IL-17F and IL-23 was significantly increased in positive patch test biopsies. The mRNA for interferon-gamma and IL-4 was also increased. In the dermal infiltrates, about 20% of the infiltrating cells were IL-17-producing cells as they expressed RORC, and such RORC-expressing cells were detected in both CD4+ (approximately 30%) and CD8+ (approximately 20%) subsets.This is the first demonstration of Th17/Tc17 cells in the elicitation phase of human ACD, showing that they are a regular participant in the immunopathology of this common allergic reaction regardless of the nature of the triggering allergen.
Clinical Outcomes in t(4;14) Multiple Myeloma: A Chemotherapy-Sensitive Disease Characterized by Rapid Relapse and Alkylating Agent Resistance
Authors: Wilfrid Jaksic, Suzanne Trudel, Hong Chang, Young Trieu, Xi Qi, Joseph Mikhael, Donna Reece, Christine Chen, A. Keith Stewart
Journal: Journal of Clinical Oncology (2005)

To determine whether primary drug resistance or rapid relapse explains the poor prognosis seen in t(4;14)-positive multiple myeloma (MM).A total of 131 patients treated with high-dose therapy (HDT) were assessed, of whom 19 were t(4;14) positive. We examined the presentation features, chemotherapy responsiveness at presentation and to salvage therapies at relapse, and overall survival outcomes.t(4;14)-positive patients had a predominance of the immunoglobulin A isotype (52.6%) but otherwise baseline characteristics were indistinguishable. After treatment with vincristine, doxorubicin, and dexamethasone or dexamethasone alone, 17 (89.7%) of the 19 patients achieved a partial response and 11 patients (57.9%) demonstrated an additional 50% reduction in paraprotein after HDT. Thus, t(4;14)-positive patients are chemotherapy sensitive; however, early progression was common, with 26% of patients progressing before HDT and a median progression-free survival after HDT of only 14.1 months. At relapse, a resistance to alkylating agents was evident, with no responses (zero of 11 patients) seen with conventional-dose alkylating agents. Salvage regimens using thalidomide and/or dexamethasone achieved at least minimal response in 59% of patients. The duration of response was short, however, with a median of only 4.7 months. The median overall survival after HDT was 24.2 months.We conclude that t(4;14)-positive MM is chemotherapy sensitive but rapid relapse occurs. Resistance to alkylating agents is evident at relapse. The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies.
The Operative Treatment of Hernia in Infants and Young Children
Authors: A. Fullerton
Journal: BMJ (1926)

OPERATIE TREATMENT OF HERMAA IN OHILDRHN.similar operations, and -Emmnet's work in 1880 was of tlhe same character.But n-o otie gave defilnite teaching as to how to cure prolapse.The multitudes of variation-is antd !flodfications that were.introdued show that in general results were niot good.Indeed, the opinion that up to 1899 there was no satisfactory surgical treatment for pioiapse is upheld by Dr. R. H. Paramore.'2There is iio more thorough student of the literatuei of prolapse thani this author, whom I thank for mnuch information anid many references.Ainother indication of the partial failure of vagoial ol)erations is the great popularity wbhicli was gainied, in spite of their ineffiviency, by vaiious abdominal suspension operations.But, though the results of plastic vaginaal surgery wvere not uniformily good, still most surgeons could say tihat many of their cases were successfu l, and certain operators secured permilantenit cure in nearly every case.Donald, ' for example, began operating in Manchester in 1888, and has always been so successful with a wide anterior colporrhaphy, amputation of the cervix, and a very efficienit posterior colporrihaphy, that he hias never thought it desir- able to use any abdominal suspension or other method.Mty owni personal experience dates from 1895, and the results were good from the first.But when amoputationi of the cervix was omitted recurrence was eccasionally noted, anad some cases failed to stanid the test of pregnancy and labour.I have never used suspension or other methiods, nor have I seen then employed in the Manchester Roval Infirmary or St. Mary's Hospital.RATIONALE OF VAGINAL OPERATIONS.Wliy did plastic vaginal operations sumceed in some hands anid in some cases while they still failed to satisfy the majority of surgeons?The objects of narrowing tile vagina, shortening the uterus, and restoring the-integrity of the perineum were genierally attained.Wlhy did the prolapse so frequently recur?Such questions disturbed our minds for long, and they were only answered in the light of new information gained by surgical experience and anatomical research as to the normal sulpports of thle pelvic viscera.Thie rationale of prolapse anid its treatment was only ex- plained when it was realized that the uterus, vagina, and Wl)adder are niot so much susp)ended from above or propped up from below as they are attached by their sides, whiere
Terodiline for treating detrusor instability in elderly people.
Authors: G Boyd
Journal: BMJ (1991)

specimen showed greatly increased cellularity with a blast cell infiltrate typical of acute myeloblastic leukaemia.Immunophenotyping (HLA-DR 85%, CD34 84%, CD13 81%, CD33 74%, CD7 55%, Tdt 40% positive) was consistent with a primitive acute myeloblastic leukaemia.Cytogenetic analysis showed a 45XY, -5, -7 karyotype with multiple clonal abnormalities typical of secondary acute myeloblastic leukaemia.The patient died two months later.Postmortem examination was not performed.Like many heavily treated patients with lymphoma (or other cancer) our patient was at risk of developing secondary acute myeloblastic leukaemia.2In this disease the cells are known to express receptors for granulocyte colony stimulating factor.The temporal relation between the start of treatment with recombinant granulocyte colony stimulating factor and the development of leukaemia is disturbing.The case indicates that the statement by Drs Khwaja and Goldstone above may, unfortunately, already require modification.As the use of haemopoietic growth factors rises clinicians should be aware of their adverse, as well as beneficial, effects.
Canary Cage and China
Authors: Joseph R. Thurn
Journal: Annals of Internal Medicine (1990)

Ad Libitum15 October 1990Canary Cage and ChinaJoseph R. Thurn, MDJoseph R. Thurn, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-8-641_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCovered with husks and wasted seedsthe drought field unfolds in the corner,beneath the canary cagealready the newspapers yellow.The headlines say we're going to mars,while stealth and guns and cracktake the young in arms,their bellies rife with parasites.Yet one stands before tanksand reaches toward knowledgeand water in the sand.For the starving childrenbeyond the squarewhere the sun sets round,stars turn to ash and fallin waves like flags,and the red blood runsbright on broken bone china.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: St. Paul, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1990Volume 113, Issue 8Page: 641-641KeywordsBloodBone fractureChildrenFalls ePublished: 1 December 2008 Issue Published: 15 October 1990 Copyright & Permissions© 1990 American College of PhysiciansPDF downloadLoading ...
Gangrene of Rectum as Complication of an Enema
Authors: M. Bendit
Journal: BMJ (1945)

arteries can be affected by pathological spasm sufficient to pro- duce migraine.Further investigation into the efficacy of the method described can best be carried out by the general practitioner, who has the opportunity of closely observing his cases.It should thus soon be possible accurately to assess the value of this treatment.
The Psychology of Postponement in the Medical Marriage
Authors: Glen O. Gabbard
Journal: JAMA (1989)

Many physicians' marriages are characterized by a strategy of postponement. The demands of medical training, the rigors of establishing a practice, and the expectations of colleagues are often used as excuses to avoid emotional intimacy in the marital relationship. Attention to the needs of the marriage is regularly postponed until some indefinite point in the future, resulting in considerable covert marital discord. The psychology of postponement ultimately proves to be a psychology of avoidance, growing directly out of the compulsive personality traits of most physicians and their preference for work over family life. Preventive measures are suggested to address the physician's tendency to avoid issues of marital intimacy. (<i>JAMA</i>. 1989;261:2378-2381)
NHS compensation fund gets 185m bailout as claims rise by 30% in a year
Authors: C. Dyer
Journal: BMJ (2012)

England’s health secretary, Andrew Lansley, has been forced to provide a £185m (€220m; $285m) bailout to the NHS compensation fund until April after a huge rise in negligence compensation payments and legal costs.

Mr Lansley has pumped the extra money into the NHS Litigation Authority, which is mainly financed by NHS trusts, after it threatened to run short of funds.

The rise in payouts, which have trebled over the past decade to more than £860m last year, has been blamed on a boom in “no win, no fee” cases—which entitle claimants’ lawyers to extra “success fees” if they win—and a …
Infestation by Dermatobia hominis
Authors: John M. Keshishian
Journal: JAMA (1976)

<h3>To the Editor.—</h3> I was interested in reading the article by Iannini et al (233:1375-1376, 1975). Over the past ten years, we have seen a number of cases of infestation by<i>Dermatobia hominis</i>. I have had two larvae removed from my hide, and a museum director from Charlotte was operated on for removal of a larva, which was in his scalp. He had been sent to a psychiatrist since his complaints of something moving about in his head were taken rather lightly by his physician. You may be interested to know that the natives of the Usumacinta River Valley in The Peten of Guatemala (and elsewhere in Guatemala as well) have a unique way of extracting the larva. They are quite familiar with the appearance of the skin lesion and can diagnose it in a moment or two. When the lesion is becoming mature, a tiny hole will become evident.
Abstract 2385: A highly sensitive detection system of genetic alterations in circulating tumor cells using a telomerase-specific replication-competent adenovirus
Authors: Kunitoshi Shigeyasu, Yuuri Hashimoto, Tatsuya Morikawa, Yoshiko Mori, Dong-Sheng Sun, Shunsuke Kagawa, Futoshi Uno, Hiroshi Tazawa, Takeshi Nagasaka, Satoru Kyo, Hiroyuki Mizuguchi, Yasuo Urata, Toshiyoshi Fujiwara
Journal: Cancer Research (2012)

Abstract Background: Malignant tumor cells often develop metastatic nodules at distant organs through circulation in blood flow and result in poor prognosis. Detection of circulating tumor cells (CTCs) is clinically an important issue to evaluate the metastatic potential of primary tumors in cancer patients. Furthermore, confirmation of genetic alterations in CTCs provides us the critical information to clarify the molecular mechanism in the acquisition of metastatic capability of tumor cells and to treat tumor metastasis by molecular targeted therapy. We recently developed a telomerase-specific replication-selective adenovirus (OBP-401; TelomeScan) expressing the green fluorescence protein (GFP). OBP-401-mediated GFP induction method was a simple and highly sensitive imaging system to detect a small population of viable CTCs in the peripheral blood. In this study, we assessed the potential of OBP-401-mediated CTC detection system to analyze the genetic alterations in CTCs. Methods: We used two types of human colon cancer cell lines SW480 and HCT116 that have the mutations in codon 12 and 13, respectively, of the K-ras gene. The detection method involved a 4-step procedure, including the lysis of red blood cells, the subsequent addition of OBP-401 to the cell pellets, the isolation of GFP-positive tumor cells using a fluorescence-activated cell sorting (FACS), and a confirmation of genetic mutations by direct sequencing. DNA was extracted from the captured cells using FACS and we investigated the mutation status in the K-ras gene by direct sequencing. Results: When only 10 cells of SW480 or HCT116 cells were added in a 5 ml of blood obtained from healthy volunteer, a total of 2-12 GFP-positive cells were captured from OBP-401-infected blood samples using FACS Aria. We confirmed the mutations in codon 12 and 13 of the K-ras gene in the FACS-captured cells from blood samples containing SW480 and HCT116 cells, respectively, by direct sequencing. Conclusion: These results suggest that OBP-401-mediated GFP induction and FACS-based capture system are useful methods to isolate small population of CTCs from peripheral blood samples and to evaluate the genetic alterations in CTCs. The combination method using OBP-401 and FACS would be a reliable strategy for the surveillance of genetic alterations in CTCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2385. doi:1538-7445.AM2012-2385
Intraocular Hemorrhage and Blindness Associated with Systemic Anticoagulation
Authors: Stephen S. Feman
Journal: JAMA (1972)

Systemic anticoagulation caused severe intraocular hemorrhage and blindness that necessitated enucleation. The patient's eye was predisposed to hemorrhage because of disciform degeneration of the macula. This ocular disease is related to a regional vasculopathy that causes macular exudation and hemorrhage with slowly progressive organization and loss of central vision.
Lower serum dehydroepiandrosterone sulphate concentration in chronic idiopathic urticaria: a secondary transient phenomenon?
Authors: A. Kasperska-Zajac, Z. Brzoza, B. Rogala
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, In some cases urticaria is associated with hormonal changes, including thyroid dysfunction1 and menstrual hormonal alterations.2 In addition, we have demonstrated for the first time that chronic urticaria may be accompanied by lower serum dehydroepiandrosterone sulphate (DHEA‐S) concentration, yet its significance and underlying mechanisms are unclear.3 4–5 However, it seems that the decline in DHEA‐S observed in patients with chronic urticaria may be a secondary phenomenon resulting from psychological distress.5 DHEA‐S is the major adrenal androgen converted into active DHEA hormone which may exert multiple immunomodulating effects.6 Decreased serum concentration of DHEA‐S can be observed in chronic inflammatory and immune‐mediated diseases as well as in stress.6, 7 Natural clinical remission is frequently observed in chronic urticaria.8 As chronic urticaria may be associated with lower serum DHEA‐S concentration in the active period of the disease, we wanted to determine whether such a phenomenon is present when the disease reaches the clinical spontaneous remission phase. Therefore, serum DHEA‐S concentrations were analysed in patients with symptomatic chronic idiopathic urticaria (CIU) and compared with levels in the same patients with CIU upon remission as well as in healthy controls.
Gene Transfer into Humans
Authors: Denis Cournoyer, C. Thomas Caskey
Journal: New England Journal of Medicine (1990)

The application of gene-transfer technology to human gene therapy has been intensively investigated during the past six years. The first experiment in humans, representing an intermediate step toward this objective, was approved by the National Institutes of Health in January 1989. At that time, permission was given for the infusion into patients with advanced melanoma of autologous tumor-infiltrating lymphocytes (TIL) that had been subjected to retrovirus-mediated gene transfer. Immunotherapy with interleukin-2 and TIL had previously been shown to induce regression of metastatic melanoma in approximately half the patients. In the gene-transfer experiments, an antibiotic-resistance gene was introduced into the TIL . . .
Sickle Cell Anemia
Authors: SAMUEL CHARACHE
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 July 1978Sickle Cell AnemiaSAMUEL CHARACHE, M.D.SAMUEL CHARACHE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-1-145_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The "natural history" of sickle cell anemia in Saudi Arabs (Ann Intern Med88:1-6, 1978) is certainly different from the disease as we see it in the United States but not as different as Table 2 in Perrine's paper would suggest. There is a paucity of good data, but 44% of all patients in Baltimore do not have ankle ulcers, 17% of all patients older than 5 years of age do not have hemiplegia, and 13% of all patients have not had osteomyelitis. The series quoted in Reference 12 probably includes patients with "tropical ankle ulcers," which...References1. SERJEANT G: The Clinical Features of Sickle Cell Disease. Amsterdam, North-Holland Publishing Co., 1974, pp. 121-129 Google Scholar2. REYNOLDS J: The Roentgenological Features of Sickle-Cell Disease and Related Hemoglobinopathies. Springfield, Illinois, Charles C Thomas, Publisher, 1965, p. 52 Google Scholar3. PORTNOYHERION BJ: Neurological manifestations in sickle-cell disease. With a review of the literature and emphasis on the prevalence of hemiplegia. Ann Intern Med 76:643-652, 1972 LinkGoogle Scholar4. BARRETT-CONNOR E: Bacterial infection and sickle cell anemia. An analysis of 250 infections in 166 patients and a review of the literature. Medicine (Baltimore) 50:97-U2, 1971 CrossrefGoogle Scholar5. PEMBREYWOODWEATHERALLPERRINE MWDR: Fetal haemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia. Br J Haematol, 1978, in press CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SAMUEL CHARACHE, M.D.Affiliations: The Johns Hopkins Medical Institutions Baltimore MD 21205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1978Volume 89, Issue 1Page: 145-145KeywordsAnemiaAnklesArabic peopleNatural history of diseaseOsteomyelitisSickle cell diseaseUlcers ePublished: 1 December 2008 Issue Published: 1 July 1978 PDF downloadLoading ...
The magic and mystery of miR-21
Authors: Edward E. Morrisey
Journal: Journal of Clinical Investigation (2010)

MicroRNAs (miRNAs) are potent regulators of mRNA stability and thereby protein expression. As such, miRNAs have become of interest as possible therapeutics and/or therapeutic targets. In this context, small complementary miRNA sequences known as antagomirs could be used to inhibit miRNA activity, while miRNA mimics could confer gain-of-function activity. However, a note of caution is sounded by Patrick et al. in this issue of the JCI, as they show that although recent reports have suggested that an miR-21 antagomir might be therapeutically useful in preventing heart failure in mice, genetic deletion of miR-21 does not confer a similar phenotype, suggesting possible confounding factors that are only now beginning to be revealed in the techniques used to study miRNA biology.