tbuckley/cabot-search huggingface dataset:
Antisense oligodeoxynucleotides selectively suppress expression of the mutant alpha 2(I) collagen allele in type IV osteogenesis imperfecta fibroblasts. A molecular approach to therapeutics of dominant negative disorders.
Authors: Q Wang, J C Marini
Journal: Journal of Clinical Investigation (1996)

We are investigating the use of antisense oligodeoxynucleotides to selectively suppress expression of the mutant type I collagen allele in osteogenesis imperfecta (OI). In this report, we target a human collagen mutation in its natural cellular context. We used cultured fibroblasts from a case of type IV OI, in which the mutant alpha 2(I) allele produces mRNA with exon 16 deleted due to a point mutation in the splice donor site. Lipid-mediated transfection was used to deliver antisense, sense and missense phosphorothioates targeted to both the abnormal mRNA exon 15/17 junction and the nuclear level point mutation. Significant suppression of the mutant protein chain and mRNA was achieved with antisense oligonucleotide to both mRNA and nuclear levels. Mutant protein was suppressed to 44-47% and mutant alpha 2(I) mRNA to 37-43% of their levels in control cells, indicating decreased mRNA as the basis for suppression. Selectivity of mutant allele suppression was better with an mRNA target: suppression was sequence specific and normal mRNA was expressed at 79% of its level in untreated cells. With a nuclear target, significant suppression of mutant mRNA occurred not only with antisense and sense, but also with missense oligonucleotide, which suppressed mutant mRNA to 60% of its level in untreated cells. We also investigated the time course of suppression of protein and mRNA in response to a 4 h transfection of antisense oligonucleotide. From 24-72 h after transfection, mutant protein was suppressed to approximately 50% of its untreated level and suppression of mutant message was significantly greater than that of normal message. The suppression achieved in these studies is insufficient for clinical intervention, but our results provide support for further development of antisense therapy as an approach to the treatment of dominant negative disorders.
A single nucleotide mutation in the mouse renin promoter disrupts blood pressure regulation
Authors: Keiji Tanimoto, Akiko Sugiura, Sumiyo Kanafusa, Tomoko Saito, Naoto Masui, Kazuyuki Yanai, Akiyoshi Fukamizu
Journal: Journal of Clinical Investigation (2008)

Renin, a major regulatory component of the renin-angiotensin system, plays a pivotal role in regulating blood pressure and electrolyte homeostasis and is predominantly expressed in the kidney. Several cAMP-responsive elements have been identified within renin gene promoters. Here, we study how 2 such elements, renin proximal promoter element-2 (RP-2) and overlapping cAMP and negative regulatory elements (CNRE), affect the transcriptional regulation of renin. We generated Tg mice (TgM) bearing BACs containing either WT or mutant RP-2 or CNRE, integrated at single chromosomal loci. Analysis of the TgM revealed that RP-2 was essential to basal promoter activity in the kidney, while renin mRNA levels did not significantly change in any tissues tested in the CNRE mutant TgM. To evaluate the physiological significance of these mutations, we used the BAC Tg to rescue hypotensive Renin-null mutant mice. As predicted, no renin expression was observed in the kidneys of RP-2 mutant/Renin-null compound mice, whereas renin expression in CNRE mutant compound mice was indistinguishable from that in control mice. Consistent with this, RP-2 mutant animals were hypotensive, while CNRE mutants had normal blood pressure. Thus, transcriptional regulation of renin expression via RP-2 but not CNRE is critical for blood pressure regulation by this gene.
CD56 expression in myeloperoxidase‐negative FAB M5 acute myeloid leukemia
Authors: Julio Delgado, Marta Morado, Mª Carmen Jimenez, Arancha Garcia‐Grande, Fernando Hernandez‐Navarro
Journal: American Journal of Hematology (2001)

CD56 is a natural killer (NK) cell marker that has been identified in approximately 15-20% of acute myeloid leukemia (AML) cases, where it has been associated with monocytic morphology and chromosomal abnormalities such as trisomy 8, t(8;21), t(15;17), and 11q23 rearrangements. The clinical presentation, chromosomal abnormalities as detected by fluorescent in-situ hybridization (FISH), and clinical outcomes of 7 patients with AML are presented. These cases were characterized by French-American-British (FAB) M5 morphology, myeloperoxidase (MPO) negativity, and co-expression of myelomonocytic and NK cell-associated antigens (CD11c(+), CD13(+), CD15(+), CD33(+), HLA-DR(+), and CD56(+)). All patients presented lymph node, hepatic, or splenic involvement at diagnosis. Despite the homogeneous morphologic and immunophenotypic characteristics the outcomes varied considerably. Two patients died during induction therapy, but the other five patients attained complete remission (CR). Of these five patients, 4 have received a bone marrow transplantation (autologous or allogeneic) and 3 of them are in CR (median follow-up: 45 months). The three patients with 11q23 rearrangements had a poor outcome and died of their disease within 1 year of diagnosis. Further studies with a larger group of patients would help establish the actual prognostic value of these morphologic, immunophenotypic and cytogenetic features.
Double-strength beclomethasone dipropionate (84 μg/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis
Authors: Bruce M. Prenner, Paul Chervinsky, Frank C. Hampel, William C. Howland, Michael Lawrence, Eli O. Meltzer, Zev M. Munk, Paul H. Ratner, James M. Seltzer, Guy A. Settipane, Richard R. Lorber, Judy E. Harrison
Journal: Journal of Allergy and Clinical Immunology (1996)
Eruptive melanocytic naevi following severe bullous disease
Authors: J. D. KIRBY, C. R. DARLEY
Journal: British Journal of Dermatology (1978)

Two patients developed eruptive naevi following severe bullous disease. The naevi developed after an interval of months and remain unchanged 4 years later. Eruptive naevi have been described after convulsions and both patients developed bullous disease after treatment for convulsions.
Combined Factor V and Factor VIII Deficiency among Non-Ashkenazi Jews
Authors: Uri Seligsohn, Ariela Zivelin, Ety Zwang
Journal: New England Journal of Medicine (1982)

Combined factor V and factor VIII deficiency is a well-documented hereditary bleeding disorder that has so far been reported in 21 families.1 , 2 The study of this disorder is of great interest, since the normal function of factor V and factor VIII is controlled by separate genes — a fact that can be inferred from the existence of hemophilia A and von Willebrand's disease (factor VIII deficiencies), on the one hand, and of parahemophilia (a factor V deficiency), on the other. Recently, a mechanism for the combined factor V and factor VIII deficiency has been proposed by Marlar and Griffin,3 who . . .
Employment Medical Advisory Service
Authors: M. E. M. Herford
Journal: BMJ (1970)

MEDICALTJISORNALembolus.However, the rash and pyrexia suggested a sensitivity reaction to nitro- furantoin.Withdrawal of the drug resulted in prompt relief of all her symptoms.Such mild reactions are probably com- moner than only 24 reported cases would suggest.Since the publication of your lead- ing article your correspondents have added four more cases (24 January, pp.
The robotic surgery monopoly is a poor deal
Authors: A. Trehan, T. J. Dunn
Journal: BMJ (2013)

The lack of competition in the surgical robots market may mean that this technology represents a poorer deal than it need do for healthcare buyers—ultimately patients, insurance companies, and taxpayers, write <b>Abhishek Trehan</b> and <b>Tristan J Dunn</b>
Points: Public not private property
Authors: S. Lightman, B. Everitt
Journal: BMJ (1987)

Dr Norman D Noah (16 May, p 1270) rightly draws attention to the comparatively limited information available on compulsory childhood immunisation and its impact in eastern European countries.He specifically mentions Czechoslovakia, a country which I recently visited as a medical geographer with a specific interest in vaccination uptake and the epidemiology of infectious disease.In Czechoslovakia virtual eradication ofmeasles seems to have been attained by a combination of compulsory childhood immunisation and the measures which Dr Noah commends: administrative methods, health education, and service delivery.Though immunisa-
The acute phase response and exercise: court and field sports
Authors: K E Fallon, S K Fallon, T Boston
Journal: British Journal of Sports Medicine (2001)

Objective —To determine the presence or absence of an acute phase response after training for court and field sports. Participants —All members of the Australian women's soccer team (n = 18) and all members of the Australian Institute of Sport netball team (n = 14). Methods —Twelve acute phase reactants (white blood cell count, neutrophil count, platelet count, serum iron, ferritin, and transferrin, percentage transferrin saturation, α 1 antitrypsin, caeruloplasmin, α 2 acid glycoprotein, C reactive protein, and erythrocyte sedimentation rate) were measured during a rest period and after moderate and heavy training weeks in members of elite netball and women's soccer teams. Results —Responses consistent with an acute phase response were found in five of 24 tests in the soccer players, and in three of 24 tests in the netball players. Responses in the opposite direction were found in seven of 24 tests in the soccer players and two of 24 tests in the netballers. The most sensitive reactant measured, C reactive protein, did not respond in a manner typical of an acute phase response. Conclusion —An acute phase response does not seem to occur as a consequence of the levels of training typical of elite female netball and soccer teams. This has implications for the interpretation of biochemical variables in these groups.
Health Care Reform and the Opportunity to Implement a Family-Centered Medical Home for Children
Authors: Danielle Laraque
Journal: JAMA (2010)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Grants for Childhood Trauma
Authors: Brian Vastag
Journal: JAMA (2002)

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
Expression of Tac antigen on activated normal human B cells.
Authors: M Tsudo, T Uchiyama, H Uchino
Journal: The Journal of Experimental Medicine (1984)

Two-color fluorescence analysis revealed that Tac antigen, which was previously reported to be restricted to T cells, was expressed on a proportion of normal B cells activated by Staphylococcus aureus Cowan I (SAC). Immunoaffinity-purified interleukin 2 (IL-2) induced the proliferation of SAC-activated B cells, and the proliferation was completely inhibited by anti-Tac antibody, which blocked the membrane binding and action of IL-2. These results suggest that an IL-2 receptor system is directly involved in the B cell immune response.
Preeclampsia selectively impairs endothelium-dependent relaxation and leads to oscillatory activity in small omental arteries.
Authors: I F Pascoal, M D Lindheimer, C Nalbantian-Brandt, J G Umans
Journal: Journal of Clinical Investigation (1998)

The vascular pathophysiology of preeclampsia, a hypertensive disorder unique to human pregnancy, has been postulated to be due to endothelial dysfunction, primarily manifest as deficient nitric oxide (NO) synthesis. We evaluated contraction (KCl and arginine vasopressin [AVP]) and dilation (acetylcholine and bradykinin) in small resistance-size omental arteries obtained during surgery from women with preeclampsia, postulating that these vessels would exhibit augmented contraction and diminished endothelium-dependent relaxation, most likely due to decreased NO synthesis. For comparison, vessels were also obtained from normotensive gravidas, pregnant women with chronic hypertension, or with chronic hypertension and superimposed preeclampsia, as well as from premenopausal nonpregnant controls. Vessels of approximately 200 micron in internal diameter were studied in vitro using a Mulvany-Halpern myograph. Maximal contraction due to either KCl or AVP was significantly augmented in vessels from women with preeclampsia; these vessels all exhibited endothelium- and cyclooxygenase-dependent phasic oscillations while vessels from all other groups exhibited only tonic contractions. Acetylcholine and bradykinin both led to dose- and endothelium-dependent relaxation which was unaffected by inhibitors of NO synthesis. Responses to bradykinin were similar in vessels from normal pregnant and preeclamptic women while those to acetylcholine were absent in vessels from women with preeclampsia. These data suggest specific defects in resistance-artery endothelium from women with preeclampsia.
BCG priming enhances endotoxin-induced acute lung injury independent of neutrophils.
Authors: S Tasaka, A Ishizaka, T Urano, K Sayama, F Sakamaki, H Nakamura, T Terashima, Y Waki, K Soejima, Y Oyamada
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Bacillus Calmette Guérin (BCG) is known to increase susceptibility to endotoxin in some animal species. We investigated the effect of BCG-priming and the role of neutrophils in the priming process on the pathogenesis of acute lung injury caused by intravenously administered Escherichia coli endotoxin (LPS). Guinea pigs were divided into seven groups: (1) control (n = 8), (2) BCG-alone (n = 6), (3) cyclophosphamide (CPA)-alone (n = 6), (4) CPA+LPS (n = 6), (5) LPS-alone (n = 6), (6) BCG+LPS (n = 6), and (7) BCG+CPA+LPS (n = 6). A BCG dose of 8 mg/kg was injected subcutaneously 10 d before the study. CPA was administered intraperitoneally to induce peripheral neutropenia. Animals were observed for 4 h after intravenous administration of 0.2 mg/kg of LPS. The plasma TNF level was measured 2 h after LPS challenge. Lung wet-to-dry weight ratio, [125I] albumin leakage in lung tissue, differential cell count in bronchoalveolar lavage (BAL) fluid, and histopathologic features were examined immediately after death. Although the LPS-alone group showed PMN accumulation in lung tissue, neither excess lung water nor increased albumin leakage was induced by this dose of LPS. The BCG+LPS group showed increased lung water, histopathologic edema, and increases in BAL fluid cell counts and plasma TNF in comparison with the LPS-alone group. The BCG+CPA+LPS group also showed enhanced lung injury comparable to that seen in the BCG+LPS group. In both the CPA-alone and the CPA+LPS groups, no parameter was increased as compared with those in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Anatomic Studies of the Cardiac Conduction System in Congenital Malformations of the Heart
Authors: KEITH REEMTSMA, W. M. COPENHAVER
Journal: Circulation (1958)

A frequent and serious complication of certain intracardiac procedures is heart block, produced by operative injury to the conduction pathways. The anatomic relationship of the conduction system to cardiac defects has previously been studied only in isolated cases of heart block. This report deals with a study, by means of serial sections and reconstructions, of the relationships of the atrioventricular node and bundle to a variety of congenital defects in the area of the membranous ventricular septum.
THE PROBLEMS OF THE TECHNIC OF URETERAL CATHETERIZATION.
Authors: GUSTAV KOLISCHER
Journal: JAMA (1904)

While the rapid development of kidney and ureteral surgery in recent years has put ever-increasing demands on refined diagnosis, it is remarkable that one of the most necessary and expedient means for this aim, ureteral catheterization, did not become popular among the surgeons. Surely, to a great extent, this was due to the lack of a complete and authoritative treatise concerning the appropriate instruments and to the absence of a practical discussion and minute explanation of the technic. There is a large number of surgeons who, though anxious to catheterize ureters, still have neither the time nor the material nor the intention to work through all the failures, mistakes and disagreeable experiences connected with the adoption of a rather new and peculiar instrumentation. Others, after studying the pertinent literature, are disappointed because in actual application they find out that a great many of the instructions laid down are either not explicit enough, or faulty, or are simply advertisements for certain obsolete or inadequate instruments.
Why doesn't audit work?
Authors: A. Berger
Journal: BMJ (1998)

When representatives from 10 British hospital trusts met last September to tackle the issue of why clinical audit has failed to bring about change, the NHS white paper and the term “clinical governance” had not been born. It is now clear, however, that the Action on Clinical Audit project, which brought these trusts together, was conceived in the same camp—and with the same aim, to improve clinical services.

Action on Clinical Audit is a two year project, funded by the NHS Executive, that is devised to unravel the complex relationships that seem to render audit unworkable.* On paper, clinical audit takes the form of a neat cycle of events, leading to harmonious improvement in the activity under scrutiny.1 In the gritty world of doctors, patients, and managers, the cycle can all too easily lose its shape, stop short, or simply vanish. The promised improvement never materialises.

The founders of …
Retinal haemorrhages in infancy.
Authors: A N Stanton
Journal: BMJ (1979)

acceptable" must be rejected.Any method of delivery that increases perinatal morbidity is open to challenge, particularly when that method is directly responsible for a perinatal mortality rate of 35 per 1000.In their second paper Drs Chiswick and James ignore the role of the active management of labour in avoiding the type of complications leading up to Kielland's delivery.Several papers have been published which conclusively demonstrate that these problems are avoid- able.-'-5None of the correspondents appear to recognise the essential difference between intracranial haemorrhage due to trauma and that due to asphyxia.Tentorial tears, which cause subdural haemorrhage, have been shown to be 11 times more common when forceps have been applied, with or without intrapartum hypoxia,6 and virtually all cases of gross intracranial haemorrhage occurring during labour are due to trauma.In contrast, asphyxial intracranial haemorrhage in the mature infant is characteristically subarachnoid and petechial.Finally, in the broader context of the role of Kielland's forceps in modern obstetrics my experience convinces me that they have no place.This personal experience is based on exposure to about 12 000 deliveries where labour was actively managed and Kielland's forceps unavailable (at the National Maternity Hospital, Dublin).
Methoxyflurane, Tetracycline, and Renal Failure
Authors: Ethem Y. Kuzucu
Journal: JAMA (1970)

Among 115 patients who had abdominal or thoracic surgery after the administration of methoxyflurane anesthesia, seven received tetracycline hydrochloride immediately before or after the operation. Five of them had increasing levels of blood urea nitrogen (BUN) and serum creatinine. Three patients died, and autopsy of the kidneys showed numerous calcium oxalate crystals. The remaining 108 patients either did not receive any antibiotic or received penicillin, streptomycin sulfate, or chloramphenicol. None of them had postoperative renal failure or significant increase in BUN and creatinine levels. Forty patients received tetracycline after spinal anesthesia without evidence of renal failure postoperatively. It is likely that methoxyflurane and tetracycline, when administered concurrently, may seriously impair renal function leading to death.
Spinal Fluid in Coccidioidal Meningitis
Authors: HANS E. EINSTEIN
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 April 1973Spinal Fluid in Coccidioidal MeningitisHANS E. EINSTEIN, M.D., F.A.C.P.HANS E. EINSTEIN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-4-621 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Our group have also been interested in simultaneous ventricular and lumbar cerebrospinal fluid findings in coccidioidal meningitis, as reported by Goldstein, Winship, and Pappagianis, in the August issue (77:243-246, 1972); our findings have been similar. The comment by Drs. Holt, Gray, and Lerner, in the November issue (77:814, 1972), makes the point that in their case of cryptococcal meningitis the cisternal fluid had a consistently higher cell count than the lumbar fluid.A review of the published studies on the pathology of central nervous cryptococcosis (1, 2) shows clearly that this is frequently a ventriculitis, whereas coccidioidomycosis...References1. LEWISRABINOVICH JS: The wide spectrum of cryptococcal infection. Am J Med 53:315-322, 1972 CrossrefMedlineGoogle Scholar2. FETTERKLINTWORTHHENDRY BGW: Mycoses of the Central Nervous System. Baltimore, The Williams & Wilkins Co., 1967, pp. 96-99 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMedical and Surgical Considerations of Coccidioidomycosis Infection 1 April 1973Volume 78, Issue 4Page: 621-621KeywordsCerebrospinal fluidCoccidioidomycosisCryptococcal meningitisCryptococcosisMeningitis Issue Published: 1 April 1973 PDF DownloadLoading ...