tbuckley/cabot-search huggingface dataset:
156. Update on Genomic HSV Vector-Related Cytotoxicity: A Vector Preserving the Differentiation Potential of Embryonic and Adult Adipose Stem Cells
Authors: Julie Fradette, Steven K. Wendell, Jim Wechuck, David M. Krisky, Darren Wolfe, William F. Goins, Joseph C. Glorioso
Journal: Molecular Therapy (2005)

Replication-deficient genomic HSV vectors have been used for transfer of genes to a variety of cell types including neuronal cells, embryonic stem cells as well as adult precursors from human adipose tissue. Human adipocytes and their precursors (Zen-Bio Inc.) are both excellent targets for HSV-mediated transduction and transgene expression (Fradette et al. 2005). Similarly, murine embryonic stem cells express HSV entry receptors, leading to more than 90% of transduced cells at low multiplicity. However, highly defective HSV vectors (e.g. QOZHG) deleted for the majority of immediate early genes including ICP4, ICP27 and ICP22 remain cytotoxic in non-neuronal cells, resulting in the majority of precursor cells dying within 4-5 days post-infection. Therefore, when induced towards differentiation, QOZHG-infected embryonic stem cells do not efficiently generate embryoid bodies (<35%), while preadipocytes are unable to differentiate into lipid-filled adipocytes. Vector cytotoxicity has been linked to expression of the remaining IE gene product encoded by ICP0. ICP0 is a ubiquitin ligase that prevents vector genome silencing and overcomes the cells anti-viral state in response to virus invasion. Here, we report that a derivative of the vector TOZHG.2 has been altered in its toxic effects on both embryonic and adult adipose stem cells while maintaining high levels of eGFP transgene expression following low multiplicity of infection. For example, at least 70% of human preadipocytes are transduced by TOZHG.2, displaying transgene expression for up to 30 days in culture. Upon infection with this vector, these cells preserved their ability to respond to differentiation signals and gave rise to mature adipocytes as effectively as uninfected cells (100 +/|[minus]|0 10%), as quantified by Oil Red O staining, a measure of lipid accumulation into cells. Many GFP positive adipocytes (40% of transduced cells) were observed for as long as 31 days after infection whereas none were seen among QOZHG-infected cultures. In a similar fashion, TOZHG.2-transduced embryonic stem cells were efficiently transduced (99%) and formed embryoid bodies at greater than 70% of the levels seen for mock-infected cells. The precise reason for the lack of apparent cytoxicity of this peculiar recombinant virus is to be determined but may be related to ICPO expression, since 10.0 +//0 1.5 lower ICPO protein levels are expressed by TOZHG.2-transduced cells compared to QOZHG-infected ones. In addition to this reduction in ICPO expression levels, we are currently investigating whether an alteration of ICPO's structure or biological function may explain the lack of cytotoxic effects of this vector derivative.
CASE 3. Benign Pleural Nodules in a Patient With Esophageal Cancer
Authors: Wan Teck Lim, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2006)

CASE 3. Benign Pleural Nodules in a Patient With Esophageal Cancer A 29-year-old was diagnosed with esophageal cancer when he presented with dysphagia.A computed tomography (CT) scan revealed multiple pleural-based soft tissue lesions in the left hemithorax, suspicious for metastases (Fig 1).His history was significant for a previous gunshot injury.A technetium-99 -labeled heat-damaged autologous RBC scan demonstrated multiple foci of uptake corresponding to the CT findings, suggesting splenosis (Fig 2).A repeat CT scan 2 years later showed no interval change in the pleural masses.Thoracic splenosis is the rare autotransplantation of splenic tissue intrathoracically following traumatic splenic injury.Functional imaging with radiolabeled RBCs is a noninvasive method of diagnosis that may be utilized instead of biopsy.The appearance on the CT images, as in this case, can be confused with metastatic tumor nodules.As the presence of pleural metastasis may affect treatment decisions in the setting of localized disease, thoracic splenosis should be considered in the differential diagnosis in patients with cancer, pleural nodules, and a history of splenic injury.
PROTECTION AGAINST ACUTE RENAL FAILURE IN RATS BY PASSIVE IMMUNISATION AGAINST ANGIOTENSIN II
Authors: J.D. Powell-Jackson, A.F. Lever, R.F. Macadam, J.I.S. Robertson, J.J. Brown, J. Macgregor, D.M. Titterington, M.A. Waite
Journal: The Lancet (1972)
Multiple Myeloma: An Old Disease with New Hope for the Future
Authors: A. A. Zaidi, D. H. Vesole
Journal: CA A Cancer Journal for Clinicians (2001)

Multiple myeloma is a currently incurable malignancy of terminally differentiated plasma cells. It typically occurs in older patients (median age 71 years). Clinical manifestations result from monoclonal protein (immunoglobulin) production and its accumulation in the serum and/or urine, anemia, lytic bone disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells have low proliferative activity—most myeloma experts opine that the initial oncogenic event occurs 10-15 years before clinical disease manifestation. In addition, myeloma cells develop multiple chromosomal abnormalities, which may explain the native resistance of myeloma patients to conventional therapy and our inability to completely eradicate the disease. Indeed, with conventional therapy, only 5% of patients achieve complete response. Minimal improvement has been observed with conventional therapies over the past 20-30 years; the median duration of initial response remains approximately 18 months with median survival in the 36-month range. However, recent clinical trials have established high-dose therapy with autologous hematopoietic stem cell transplant as superior to conventional therapy: complete remission rates of 25-30% can be affected with median survival exceeding 5 years. Newer approaches to improve treatment outcomes are in active clinical trials including: more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone; tandem transplants to improve complete remission rates; newer approaches to maintenance therapy using thalidomide with corticosteroids; non-myeloablative therapy with allogeneic transplant; and post-transplant vaccinations.
Homosexuality and mental health services
Authors: P McColl
Journal: BMJ (1994)

It is often junior doctors who decide, possibly without consciously recognising that they have thereby pre-empted organ donation.Moreover, even when a patient suitable for organ donation dies in an intensive care unit, in nearly one third of cases family representatives are unfortunately not able to agree that the person who has died had expressed no objection to organ retrieval after his or her death.3Thus kidneys that could have given new life to others are lost with these patients.Public opinion is strongly in favour of organ donation.A majority would approve of a change in legislation to allow organs to be removed after death unless the patient had registered an objection beforehand.In one recent survey 28% of a random sample carried a kidney donor card saying, "I would like to help someone to live after my death."(E Ward for the British Kidney Patient Association, 1993).How many of them realise that death must occur in an intensive care unit for their wishes to be fulfilled?Unless, that is, the removal of organs from non-heart beating donors can be shown to be both practical and worth while.
Views from the gallery
Authors: F. Haslam
Journal: BMJ (1995)

the settlement reached.'Where facilities are not provided or are not sufficiently fimded, it is not always possible to provide the optimum care.The fate of the landless idiot or lunatic in medieval England may have been little different from that of mentally ill people who roam the streets today, but most madmen probably had more support in the community than do their modem counterparts.
Renal function in patients over 40 with homozygous sickle-cell disease.
Authors: A G Morgan, G R Serjeant
Journal: BMJ (1981)

Renal function was examined in 25 patients aged 40-64 with homozygous sickle-cell (SS) disease. Investigations included intravenous urography and measurement of blood urea and creatinine concentrations and creatinine and protein excretion in 24-hour collections of urine. Serum creatinine concentrations did not differ significantly from those of 25 other patients with SS disease aged 18-39 years, but serum urea concentrations were significantly higher (p less than 0.001). Intravenous urography showed loss of caliceal cupping (nine patients), irregular renal outline (five), and cystic extension from the calix (one). Six patients had creatinine clearances below the fifth percentile for age and sex. Proteinuria was more common in these patients, and haemoglobin concentrations were much lower than in the 19 patients without renal insufficiency (mean 5.6 v 8.2 g/dl; p less than 0.001). Haemoglobin concentration was strongly correlated with creatinine clearance (r=0.70), particularly with clearances below 100 ml/min/1.73 m2 (r=0.96; p less than 0.001). A possible mechanism of renal insufficiency in SS disease is cortical scarring, which is asymptomatic, not associated with hypertension, and accompanied by only minor proteinuria. A falling haemoglobin concentration is a sensitive and early indicator of renal impairment in SS disease.
CD137 Is Expressed in Human Atherosclerosis and Promotes Development of Plaque Inflammation in Hypercholesterolemic Mice
Authors: Peder S. Olofsson, Leif Å. Söderström, Dick Wågsäter, Yuri Sheikine, Pauline Ocaya, François Lang, Catherine Rabu, Lieping Chen, Mats Rudling, Pål Aukrust, Ulf Hedin, Gabrielle Paulsson-Berne, Allan Sirsjö, Göran K. Hansson
Journal: Circulation (2008)

Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L have been implicated in atherosclerosis.This study shows that the tumor necrosis factor superfamily members CD137 and CD137 ligand (CD137L), which play a major role in several autoimmune diseases, may constitute a pathogenic pair in atherogenesis. We detected CD137 protein in human atherosclerotic lesions not only on T cells but also on endothelial cells and showed that CD137 in cultured endothelial cells and smooth muscle cells was induced by proinflammatory cytokines implicated in atherosclerosis. Activation of CD137 by CD137L induced adhesion molecule expression on endothelial cells and reduced smooth muscle cell proliferation. In addition, treatment of atherosclerosis-prone apolipoprotein E-deficient mice with a CD137 agonist caused increased inflammation. T-cell infiltration, mainly of CD8(+) cells, and expression of the murine major histocompatibility complex class II molecule I-A(b) increased significantly in atherosclerotic lesions, as did the aortic expression of proinflammatory cytokines.Taken together, these observations suggest that CD137-CD137L interactions in the vasculature may contribute to the progression of atherosclerosis via augmented leukocyte recruitment, increased inflammation, and development of a more disease-prone phenotype.
Contributions of the Social Sciences to the Solution of Health Problems
Authors: Hugh R. Leavell
Journal: New England Journal of Medicine (1952)

RELATIONS between medicine and the social sciences, long a field for interesting discussion, have been explored intensively from both sides of the fence in recent years. It is convenient arbitrarily to separate the natural sciences, such as chemistry, physics and biology, from the social sciences, including sociology, social anthropology and social and personality psychology. Psychology, usually grouped under the social sciences, is sometimes considered a natural science. Strictly speaking, mathematics falls into neither group but is used by both. Probably many physicians practicing today have had relatively little contact with the social sciences in their premedical education. It is comparatively . . .
Rapid Activation of Neutral Sphingomyelinase by Hypoxia-Reoxygenation of Cardiac Myocytes
Authors: Olga M. Hernandez, Daryl J. Discher, Nanette H. Bishopric, Keith A. Webster
Journal: Circulation Research (2000)

Abstract —Elevated levels of oxygen free radicals have been implicated in the pathways of reperfusion injury to myocardial tissue. The targets for free radicals may include specific as well as random intracellular components, and part of the cellular response is the induction of extracellularly activated and stress-activated kinases. The intermediate signals that initiate these stress responses are not known. Here we show that one of the earliest responses of cardiac myocytes to hypoxia and reoxygenation is the activation of neutral sphingomyelinase and accumulation of ceramide. Ceramide increased abruptly after reoxygenation, peaking at 10 minutes with 225±40% of the control level. Neutral sphingomyelinase activity was induced with similar kinetics, and both activities remained elevated for several hours. c-Jun N-terminal kinase (JNK) was also activated within the same time frame. Treatment of cardiac myocytes with extracellular ceramides also activated JNK. Pretreating cells with antioxidants quenched sphingomyelinase activation, ceramide accumulation, and JNK activation. Ceramide did not accumulate in reoxygenated nonmuscle fibroblasts, and JNK was not activated by reoxygenation in these cells. The results identify neutral sphingomyelinase activation as one of the earliest responses of cardiac myocytes to the redox stress imposed by hypoxia-reoxygenation. The results are consistent with a pathway of ceramide-mediated activation of JNK.
Expression of human islet amyloid polypeptide/amylin impairs insulin secretion in mouse pancreatic β cells
Authors: Tatsuhiko Tokuyama, Kazuo Yagui, Takahide Yamaguchi, Choung I. Huang, Nobuhiko Kuramoto, Fumio Shimada, Jun-ichi Miyazaki, Hiroshi Horie, Yasushi Saito, Hideichi Makino, Azuma Kanatsuka
Journal: Metabolism (1997)
Characteristics of Highly Ranked Applicants to General Surgery Residency Programs: Are We Assessing the Right Criteria?
Authors: James C. Hebert
Journal: JAMA Surgery (2013)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Erratum: Corrigendum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases
Authors: Kevin J Whitehead, Aubrey C Chan, Sutip Navankasattusas, Wonshill Koh, Nyall R London, Jing Ling, Anne H Mayo, Stavros G Drakos, Christopher A Jones, Weiquan Zhu, Douglas A Marchuk, George E Davis, Dean Y Li
Journal: Nature Medicine (2009)
The Use of Brilliant Green in the Treatment of Chronic Ulcers of the Skin
Authors: Arthur W. Feinberg
Journal: New England Journal of Medicine (1948)

THE multiplicity of treatments reported in the literature on the subject of chronic ulcers of the skin is evidence that no one treatment has adequately met the required standards of being bactericidal, nontoxic, stimulating to the growth of epithelium and granulation tissue, giving prompt, effective and uniform results and being cheap and easy to use. During a tour of duty with the Army in the Pacific Theater of Operations, I had occasion to see a number of cases of chronic skin ulcerations, of varied etiologies. Each of these cases was treated with the rosaniline dye, brilliant green, and the results . . .
Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII).
Authors: S G Stuart, M L Trounstine, D J Vaux, T Koch, C L Martens, I Mellman, K W Moore
Journal: The Journal of Experimental Medicine (1987)

We have cloned and expressed a cDNA encoding a human receptor for IgG (Fc gamma R) from the monocyte cell line U937. The deduced structure is a 35-kD transmembrane protein with homology to the mouse Fc[gamma 2b/gamma 1] receptor amino acid sequence of approximately 60% in the extracellular domain. The signal sequence is homologous to the mouse Fc gamma R alpha cDNA clone, while the transmembrane domain shares homology with mouse Fc gamma R beta cDNAs. The cytoplasmic domain is apparently unique. The extracellular domain shows significant homology to proteins of the Ig gene superfamily, including the human c-fms protooncogene/CSF-1 receptor. Mouse Ltk- cells transfected with the human Fc gamma R cDNA express a cell-surface receptor that selectively binds human IgG and is recognized by the anti-Fc gamma RII mAb IV.3. Antibodies against peptides derived from the human Fc gamma R sequence specifically stain U937 cells, but not an Fc gamma RII-bearing B-lymphoblastoid cell line (Daudi). These results identify the human Fc gamma RII as the homologue of mouse Fc[gamma 2b/gamma 1] R, and provide evidence for heterogeneity of Fc gamma RII expressed on monocytes and B cells.
AGRANULOCYTOSIS IN A PATIENT TREATED WITH MERCURIAL DIURETICS
Authors: Jacob J. Silverman
Journal: JAMA (1952)

Mercurial diuretics are of prime importance in the management of congestive circulatory failure. Since the introduction of organic mercurial diuretics in 1920,<sup>1</sup>an extraordinarily large number of patients have been treated successfully by mercurial diuretics, with relatively few serious reactions. Nevertheless, undesirable and toxic effects, including fatalities, are occasionally reported. The purpose of this report is to record the development of a profound neutropenic state in a patient under treatment with mercurial diuretics for congestive circulatory failure. <h3>REPORT OF CASE</h3> A 59-year-old white businessman was admitted to the Staten Island Hospital Sept. 13, 1950, because of progressive weakness of two months' duration. The patient had been admitted to this hospital on two previous occasions in the preceding year for congestive circulatory failure for treatment of arteriosclerotic heart disease and the Kimmelstiel-Wilson syndrome. He had had diabetes for 10 years, which was controlled by both diet and insulin. His diet
Effect of α-thalassemia and β-globin gene cluster haplotypes on the hematological and clinical features of sickle-cell anemia in Brazil
Authors: M.S. Figueiredo, J. Kerbauy, M.S. Gonçalves, V.R. Arruda, S.T.O. Saad, M.F. Sonati, T. Stoming, F.F. Costa
Journal: American Journal of Hematology (1996)

To compare the features of sickle-cell anemia in Brazil with those in other locales, we studied the effects of the β-globin-like gene cluster haplotype and α-thalassemia upon the clinical and hematological features in 85 patients. The distribution of haplotypes differed from that in the United States and Jamaica. The Central African Republic (CAR) haplotype predominated; 34% of patients were CAR haplotype homozygotes, 45% CAR/Benin homozygotes, and 11% Benin homozygotes. No Senegal haplotype chromosomes were observed. α-thalassemia was present in 17.5% of patients. HbF levels were higher in Benin homozygotes, compared with the other two groups (P < 0.05). Nearly half the patients with a CAR haplotype had leg ulcers, compared to 12.5% of the Benin homozygote group; stroke did not occur in α-thalassemia carriers, but neither result was statistically significant. As in other studies, our results indicate that the CAR haplotype may be associated with more severe disease. © 1996 Wiley-Liss, Inc.
Oritin and properties of the blister formation factor in blister fluids from recessive dystrophic epidermolysis bullosa
Authors: S. IKEDA, K. NAITO, R. IMAI, M. MANABE, K. TAKAMORI, H. OGAWA
Journal: British Journal of Dermatology (1985)

The origin and properties of the blister formation factor in recessive dystrophic epidermolysis bullosa (RDEB) blister fluids were investigated. Organ cultures of normal human skin incubated with RDEB dermis extract or with RDEB fibroblast culture medium (FCM) produced a clear subepidermal blister with histology similar to that of a RDEB blister in vivo. The injection of RDEB dermis extract into guinea-pig skin also induced dermal-epidermal separation with similar histology to the skin lesions of RDEB patients. The blister forming activity of RDEB FCM which induces the subepidermal blister was inactivated by heat (60 degrees C for 30 min), trypsin digestion and by treating with EDTA, EGTA, alpha 2-macroglobulin, diisopropyl fluorophosphate and N-ethylmaleimide, but was not affected by dialysis. These results suggest that the RDEB fibroblast produces a blister formation factor(s), and that blister formation may be caused by a combination of a metallo-protease, serine protease and SH protease.
Autoregulation of the Total Systemic Circulation Following Destruction of the Central Nervous System in the Dog
Authors: Harris J. Granger, Arthur C. Guyton
Journal: Circulation Research (1969)

The quantitative importance of total systemic autoregulation in the whole body was studied in dogs in which the cardiovascular control loops of the central nervous system were eliminated by decapitation and alcohol destruction of the spinal cord. Transient changes in cardiac output, right atrial pressure, oxygen consumption, arteriovenous oxygen difference, and hematocrit that occurred immediately after single-step changes of 25 to 50 mm Hg in arterial pressure were followed by gradual return of the variables toward control values. The time required to reach a new steady state ranged from 13 to 75 minutes with an average of 35 minutes. The calculated open-loop gain of the autoregulation control system ranged from 0.93 to 9.5 with an average gain of 3.32±0.7 (SE) indicating more than 75% compensation. In a second group of animals the arterial pressure was increased from 50 mm Hg to as high as 150 mm Hg in small steps of 10 to 15 mm Hg allowing 5 to 20 minutes on each step for the autoregulation response to occur. The pressure-flow curves showed significant total systemic autoregulation. The return of arteriovenous oxygen difference and oxygen consumption toward control values is consistent with a metabolic mechanism of autoregulation. The absence of significant transcapillary fluid flux in autoregulating preparations indicates (a) that the locus of autoregulatory resistance changes is completely or almost completely in the precapillary vessels of the circulatory system and (b) that autoregulation is important in maintaining capillary pressure at a normal level as well as in maintaining blood flow at the level required by the tissues.