tbuckley/cabot-search huggingface dataset:
Antigen-specific T cell clones restricted to unique F(1) major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-Ia antibody
Authors: B Sredni, LA Matis, EA Lerner, WE Paul, RH Schwartz
Journal: The Journal of Experimental Medicine (1981)

The existence of T cells specific for soluble antigens in association with unique F(1) or recombinant major histocompatibility complex (MHC) gene products was first postulated from studies on the proliferative response of whole T cell populations to the antigen poly(Glu(55)Lys(36)Phe(9))(n) (GLφ). In this paper we use the newly developed technology of T lymphocyte cloning to establish unequivocally the existence of such cells specific for GLφ and to generalize their existence by showing that F(1)- specific cells can be isolated from T cell populations primed to poly(Glu(60)Ala(30)Tyr(10))(n) (GAT) where such clones represent only a minor subpopulation of cells. Gl.4b-primed B10.A(5R) and GAT-primed (B10.A × B10)F(1) lymph node T cells were cloned in soft agar, and the colonies that developed were picked and expanded in liquid culture. The GLφ-specific T cells were then recloned under conditions of high-plating efficiency to ensure that the final colonies originated from single cells. T cells from such rigorously cloned populations responded to stimulation with GILφ but only in the presence of nonimmune, irradiated spleen cells bearing (B10.A × B10)F(1) or the syngeneic B 10.A(5R) recombinant MHC haplotype. Spleen cells from either the B10 or B 10.A parental strains failed to support a proliferative response, even when added together. (B10 × B10.D2)F(1) and (B10 × B10.RIII)F(1) spleen cells also supported a proliferative response but (B10 × B10.Q)F(1) and (B10 X B10.S)F(1) spleen cells did not. These results suggested that the T cell clones were specific for GL[phi} in association with the β(AE)(b)-α(E) (k,d,r,) Ia molecule and that recognition required both gene products to be expressed in the same antigen-presenting cells. Support for this interpretation was obtained from inhibition experiments using the monoclonal antibody Y-17 specific for a determinant on the β(AE)(b)-αE Ia molecule. Y-17 completely inhibited the proliferative response of a GLφ-specific clone but had no effect on the response of either a PPD-specific or GAT-specific clone, both of which required the β(A)-α(A) Ia molecule as their restriction element. No evidence could be found for the involvement of suppressor T cells in this inhibition. We therefore conclude that the phenomenon of F(1)-restricted recognition by proliferating T cells results from the presence of antigen- specific clones that must recognize unique F(1) or recombinant Ia molecules on the surface of antigen-presenting cells in addition to antigen in order to be stimulated.
Changes in Left Ventricular Wall Movement after Acute Myocardial Infarction Measured by Reflected Ultrasound
Authors: C. F. P. Wharton, C. S. Smithen, E. Sowton
Journal: BMJ (1971)

Serial measurements of left ventricular posterior wall movement were made in eight patients with acute myocardial infarction by an ultrasound technique. Maximum posterior wall velocity and excursion were decreased during the first 36-hour period after infarction. In two patients a reduction in posterior wall velocity was associated with an increased pulmonary artery pressure and as the pressure returned towards normal the posterior wall motion also improved. It is suggested that this method provides a convenient, non-invasive bedside assessment of left ventricular function after acute myocardial infarction.
314. The Epithelial Glycoprotein-2 Promoter for Highly Specific and Efficient Cancer Gene Therapy for a Broad Range of Tumors
Authors: Willemijn M. Gommans, Gerben Duns, Pamela M.J. McLaughlin, Simone J. van Eert, Masato Yamamoto, David T. Curiel, Hidde J. Haisma, Marianne G. Rots
Journal: Molecular Therapy (2005)

Top of pageAbstract
Adenoviral cancer gene therapy is hampered by the lack of specific and efficient transgene expression in tumor cells. Employing tissue specific promoters to restrict transgene expression will increase specificity towards the tumor tissue. In addition, specific promoters can be used to increase the efficiency of adenoviral gene therapy by controlling adenoviral replication. However, many specific promoters are restricted to specific tumor types. The tumor specific promoter epithelial glycoprotein-2 (EGP-2) is known to be active in various epithelial-derived cancers including ovarian, colon, and breast cancer and might therefore be a good candidate to target a broad range of tumor types. In this study, the EGP-2 promoter was employed to improve the therapeutic potential of adenoviral cancer gene therapy.

The EGP-2 promoter demonstrated an outstanding specificity and activity profile in vivo. In mouse liver tissue, 3 log lower activity compared to the strong constitutively active CMV promoter was shown compared with only 1 log lower activity in EGP-2 positive tumor tissue. Subsequently, the EGP-2 promoter was employed to control the expression of the suicide gene thymidine kinase (AdEGP-2 SR39TK). In vitro selective cell killing after infection with AdEGP-2 SR39TK and GCV administration was seen in EGP-2 positive cell lines, but not in EGP-2 negative cells. After iv injection of AdEGP-2 SR39TK in mice an absence of liver toxicity was demonstrated after administration of GCV, in contrast to AdCMV SR39TK which showed clear liver damage. These promising findings are currently being explored in tumor bearing mice.

To successfully treat cancer, all tumor cells have to be eradicated. However, even after local administration adenoviral vectors will infect only a limited amount of tumor cells. Therefore, to increase the efficiency of the adenovirus the EGP-2 promoter was utilized to control the E1A gene, which is essential for adenoviral replication. This conditionally replicating adenovirus (CRAd) should replicate selectively in EGP-2 positive tumor cells, causing cell lysis and spread into the tumor mass. This cycle of selective replication and cell lysis is continued until no further tumor cells can be infected. The EGP-2 based CRAd was as efficient in cell killing as wild-type adenovirus in EGP-2 positive cell lines. In contrast, in EGP-2 negative cell lines replication of the EGP-2 based CRAd was attenuated up to 2 log when compared with the wild-type adenovirus. Currently, the EGP-2 based CRAd is further investigated in tumor bearing mice. Overall, it can be concluded that the EGP-2 promoter demonstrates high specificity and efficiency in adenoviral context and can therefore be a powerful tool in cancer gene therapy for the treatment of a broad range of tumor types.
Non-Invasive Evaluation of Regional Ventricular Dysfunction
Authors: Edmund H. Sonnenblick
Journal: New England Journal of Medicine (1971)

Localized abnormalities of motion of the left ventricular wall commonly follow inadequate or absent coronary blood flow to a region of the heart, and may greatly impair the overall function of the heart as a pump.1 These localized areas of wall dysfunction may be transient, as in the setting of angina pectoris or an evolving myocardial infarction, or may be persistent as the presence of true aneurysm formation. When coronary-artery disease is present, various stresses that raise oxygen demands of the heart, such as increased heart rate or augmented contractility, may induce transient localized ischemia with abnormal wall motion, although . . .
OCCUPATIONAL SKIN DISEASE FROM EXPOSURE TO ROCK SALT AND WATER
Authors: Floyd Thurber
Journal: JAMA (1928)

The marked incidence of pyogenic infection among workers exposed to rock salt and water in the handling of wholesale ice cream has made salt infection a common term among the workers and the industrial surgeons. Since these so-called salt infections commonly manifest themselves as furuncles, the question of liability under workmen's compensation laws prompted my investigation of a series of cases during 1926 and 1927. Three types of cases referable to combined rock salt and water exposure presented themselves. In order of frequency they were: (1) infected lacerations and abrasions; (2) local furuncles, and (3) chronic fissured palms. Many patients did not give any history of direct injury. Lesions occurred only in exposed areas. The infection was superficial and essentially limited to the skin. Where furuncles occurred they showed no tendency to become systemic. Causative organisms were found to be staphylococci or mixed staphylococci and streptococci. No predominant
Association between Acquired Uniparental Disomy and Homozygous Gene Mutation in Acute Myeloid Leukemias
Authors: Jude Fitzgibbon, Lan-Lan Smith, Manoj Raghavan, Matthew L. Smith, Silvana Debernardi, Spyros Skoulakis, Debra Lillington, T. Andrew Lister, Bryan D. Young
Journal: Cancer Research (2005)

Abstract Genome-wide single nucleotide polymorphism analysis has revealed large-scale cryptic regions of acquired homozygosity in the form of segmental uniparental disomy in ∼20% of acute myeloid leukemias. We have investigated whether such regions, which are the consequence of mitotic recombination, contain homozygous mutations in genes known to be mutational targets in leukemia. In 7 of 13 cases with uniparental disomy, we identified concurrent homozygous mutations at four distinct loci (WT1, FLT3, CEBPA, and RUNX1). This implies that mutation precedes mitotic recombination which acts as a “second hit” responsible for removal of the remaining wild-type allele, as has recently been shown for the JAK2 gene in myeloproliferative disorders.
The Appropriateness of Tympanostomy Tubes for Children
Authors: Terence M. Davidson
Journal: JAMA (1995)

To the Editor.  —The uncontrolled study by Dr Kleinman and colleagues 1 concludes that less than 50% of the tympanostomy tubes placed for recurrent or persistent otitis media were appropriate. The data obtained were all retrospective and taken from the office charts of presumably busy practitioners. I suggest an alternate conclusion. This sort of physician documentation does not produce valid clinical research studies.  A good otolaryngologist or pediatrician is generally busy, and it is far better to devote one's time to examining the child and talking with the parents than it is to write in the chart. An astute otolaryngologist listens to the referring pediatrician, listens to the parents, and examines the child. From all of this, a clinical decision is made. The diagnosis and the treatment alternatives are then presented to the parents, who then make a decision to have tympanostomy tubes placed. The entirety and complexity of this
Intravariceal versus paravariceal sclerotherapy: a prospective, controlled, randomised trial.
Authors: S K Sarin, R Nanda, G Sachdev, S Chari, B S Anand, S L Broor
Journal: Gut (1987)

Fifty four consecutive patients with oesophageal variceal bleeding were randomised to undergo intravariceal (28 patients) or paravariceal (26 patients) sclerotherapy, every three weeks. Intravariceal technique was found significantly (p less than 0.01) more effective in controlling active variceal bleeding than the paravariceal technique (91% v 18.7% respectively). The mean (+/- SD) time taken for variceal eradication by intravariceal sclerotherapy (15.4 +/- 5.3 weeks) was significantly (p less than 0.001) less than paravariceal (26.8 +/- 6.6 weeks) technique. The number of sclerotherapy sessions needed with intravariceal technique were also significantly less. Rebleeding was seen in 38.5% patients after para and 14.3% after intravariceal injections (NS). Except for retrosternal pain, which occurred more often (p less than 0.01) with paravariceal technique, there was no difference in the incidence of other complications or mortality between the two groups. Variceal recurrence was seen in seven patients (25%) in the intra and one (3.9%) patient in the paravariceal group (p less than 0.01) after a mean follow up of 29.4 +/- 9.1 weeks. Intravariceal sclerotherapy was superior to paravariceal in the control of active variceal bleeding and for total variceal obliteration, but was associated with a higher variceal recurrence.
Congenital Goiter with Defective Iodide Transport
Authors: J. WOLFF
Journal: Endocrine Reviews (1983)

Journal Article Congenital Goiter with Defective Iodide Transport Get access J. Wolff J. Wolff 1National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland *Address requests for reprints to: Dr. Wolff, NIH, Bldg. 10, Room 8N315, Bethesda, MD 20205. Search for other works by this author on: Oxford Academic Google Scholar Endocrine Reviews, Volume 4, Issue 3, 1 July 1983, Pages 240–254, https://doi.org/10.1210/edrv-4-3-240 Published: 01 July 1983
Effect of Pulse Pressure and Mean Arterial Pressure Modification on Renal Hemodynamics and Electrolyte and Water Excretion
Authors: EWALD E. SELKURT
Journal: Circulation (1951)

Studies were conducted to evaluate the influence of pulsatile versus nonpulsatile arterial perfusion pressure on plasma flow, filtration rate, sodium excretion, and urine volume. Through a wide range of mean renal arterial pressures, reduction of pulse pressure was without effect on renal function. The level of the mean arterial pressure, however, had a very dominant role in the electrolyte and water handling, decreases and increases in excretion paralleling the direction of change of the mean pressure. These alterations were observed even though filtration rate and plasma flow exhibited a marked degree of autonomy in the face of these pressure variations. Mechanisms by which these modifications in salt and water excretion could result from alteration in the mean arterial pressure are discussed.
Jaundice and liver-function tests.
Authors: L. G. Whitby, J. Richmond, D. W. Moss
Journal: BMJ (1968)

BRITISH 379 contacts as necessary the district nurses, welfare officers, almoners, health visitors, and hospital ward sisters-all at the behest of the doctor, whose real job is thereby both enlarged and made easier.As general practice develops the doctor can fulfil his role only by having efficient and tolerant secretarial help, a practice nurse, good district nurses and midwives, and an up-to-date health visitor.There seems no reason why the last three should not be run by the local authorities across practice boun- daries as at present, but the first two are personal as regards duties and hours and can only be employed by the general practitioner himself.In spite of political interference this mode of practice developing in Britain is probably many years ahead of any arrangements offered in Europe or the North American continent.It will be a great pity if excessive demands reduce a practice nurse to the role of a " feldsher," when, losing the confidence of the public, general practice as we know it today will disintegrate.-Iam, etc.,
Long-Term Mortality after Transsphenoidal Surgery for Cushing Disease
Authors: Brooke Swearingen
Journal: Annals of Internal Medicine (1999)

Background: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. Objective: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. Design: Retrospective case series. Setting: Tertiary care center. Patients: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. Intervention: Transsphenoidal adenomectomy and as-needed adjunctive therapy. Measurement: Record review with follow-up interview. Results: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). Conclusion: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.
Cannabinoid-1 Receptor Antagonist, Rimonabant, for Management of Obesity and Related Risks
Authors: Kishore M. Gadde, David B. Allison
Journal: Circulation (2006)

T he prevalence of obesity has risen substantially during the past 25 years in the United States and most developed countries, with a related increase in type 2 diabetes mellitus. 1,2Almost one third of the adult US population is considered to be obese (body mass index [BMI] Ն30), and 1 in 20 is extremely obese (BMI Ն40). 3 Nearly 17% of children and adolescents are overweight in the United States. 3Obesity is associated with increased risk for type 2 diabetes mellitus, coronary heart disease (CHD), hypertension, obstructive sleep apnea, and cancer, higher overall mortality rate, 4 -6 and decreased longevity. 7,8Extreme obesity can truncate life expectancy in young adults by 5 to 20 years. 8Accordingly, the expected benefits of weight reduction for obese individuals are profound.
Natural History of Alkaptonuria
Authors: Chanika Phornphutkul, Wendy J. Introne, Monique B. Perry, Isa Bernardini, Mark D. Murphey, Diana L. Fitzpatrick, Paul D. Anderson, Marjan Huizing, Yair Anikster, Lynn H. Gerber, William A. Gahl
Journal: New England Journal of Medicine (2002)

Alkaptonuria, caused by mutations in the HGO gene and a deficiency of homogentisate 1,2-dioxygenase, results in an accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue. There is no effective therapy for this disorder, although nitisinone inhibits the enzyme that produces HGA. We performed a study to delineate the natural history of alkaptonuria.
AN ANALYSIS OF THE TRENDS IN CANCER RESEARCH
Authors: JAMES B. MURPHY
Journal: JAMA (1942)

It is not surprising that there should exist a degree of skepticism as to the value of experimental cancer research, for it is true that so far no answer has been found to the broad problem of the concrete cause and cure of the disease. Yet during the last four decades an impressive number of definite fundamental facts regarding the nature of malignancy has been established. It has perhaps been difficult for any one outside the field to get a comprehensive picture of the meaning of the progress. Until recently the experimental studies have been developed along three main lines more or less independently of one another. It is now evident that the cancer problem is so complex that no one approach is likely to give the complete answer. With the rapid accumulation of new knowledge it has become progressively more important to attempt the correlation of each advance so
Megestrol Acetate in Patients with AIDS-related Cachexia
Authors: Michelle H. Oster, Sheila R. Enders, Steven J. Samuels, Lawrence A. Cone, Thomas M. Hooton, Henry P. Browder, Neil M. Flynn
Journal: Annals of Internal Medicine (1994)

Objectives: To compare the effects of oral suspensions of megestrol acetate, 800 mg/d, and placebo on body weight in patients with acquired immunodeficiency syndrome (AIDS)-related weight loss. Design: Randomized, double-blind, placebo-controlled trial. Setting: Outpatient community and university patient care setting. Patients: Consecutive patients with AIDS who had substantial weight loss and anorexia were enrolled. Of 271 patients, 270 and 195 were evaluable for safety and efficacy, respectively. Interventions: Patients were randomly assigned to receive placebo or megestrol acetate (100 mg, 400 mg, or 800 mg) daily for 12 weeks. Main Outcome Measures: The primary efficacy criterion was weight gain. Patients were evaluated at 4-week intervals for changes in weight and body composition, caloric intake, sense of well-being, toxic effects, and appetite. Results: For evaluable patients receiving 800 mg of megestrol acetate per day, 64.2% gained 2.27 kg (5 pounds) or more compared with 21.4% of patients receiving placebo (P < 0.001). An intent-to-treat analysis showed significant differences (P = 0.002) between those receiving placebo and those receiving 800 mg of megestrol acetate for the number of patients who gained 2.27 kg (5 pounds) or more (8 of 32 [25%] compared with 38 of 61 [62.3%], respectively). Compared with patients receiving placebo at the time of maximum weight change, evaluable patients receiving megestrol acetate, 800 mg/d, reported improvement in overall well-being and had an increase in mean weight gain (−0.725 compared with 3.54 kg [ −1.6 compared with +7.8 pounds]; P < 0.001), lean body mass (−0.772 compared with +1.14 kg [ −1.7 compared with +2.5 pounds]; P < 0.001), appetite grade (P < 0.001), and caloric intake (−107 compared with +645.6 calories/d; P = 0.001). Conclusions: In patients with AIDS-related weight loss, megestrol acetate can stimulate appetite, food intake, and statistically significant weight gain that is associated with a patient-reported improvement in an overall sense of well-being.
The Marlboro Grand Prix
Authors: A Blum
Journal: New England Journal of Medicine (1991)

COVERAGE of motor racing in the mass media has grown dramatically in recent years. Hardly a day now goes by in the United States without a nationally televised automobile, motorcycle, "monster truck," or powerboat race on either a major network or a cable network devoted to sports.1 Major daily newspapers now cosponsor auto races, most notably the Atlanta Journal 500, and blend advertising for the events with stepped-up news coverage. Organized motorcycle, dirt-bike, and kart racing for teenagers and children attracts an increasing number of participants each year.2Yet, in contrast to the widespread attention given to head injuries in . . .
51. Adenoviral BDNF/Noggin-Induced Neurogenesis from Endogenous Neural Stem Cells Delays Motor Impairment and Extends Survival in a Transgenic Model of Huntington's Disease
Authors: Sung-Rae Cho, Eva Chmielnicki, Aris Economides, Steven A. Goldman
Journal: Molecular Therapy (2005)

Ependymal overexpression of BDNF stimulates neuronal addition to the adult striatum, from subependymal progenitors. Noggin, by suppressing subependymal gliogenesis, potentiates this process. We asked if BDNF/Noggin overexpression might be used to recruit new striatal neurons in R6/2 transgenic Huntington's mice. In series 1, 18 R6/2 mice and matched wild-type (WT) controls were given bilateral intraventricular injections of either adenoviral (Ad) BDNF/Noggin, AdBDNF, AdNull or saline at 6 weeks of age. The mice were given daily injections of BrdU for 4 weeks to tag new mitotic cells, sacrificed at 10 weeks, and their brains cut at 15 |[mu]|m. Sections were stained for BrdU and either bIII-tubulin, DARPP-32, GAD67, enkephalin, or substance P. AdBDNF/Noggin-treatment resulted in the addition of approximately 300 BrdU+/bIII-tubulin+ neurons/mm3 in both R6/2 and WT striata. These developed largely as DARPP32+ medium spiny neurons, with enkephalin+ and substance P+ GABAergic subpopulations generated in roughly equal proportions; each type extended fibers to the globus pallidus, as revealed by Fluorogold backfills.
Assessment of area of involvement in skin disease: a study using schematic figure outlines
Authors: S. TILING-GROSSE, J. REES
Journal: British Journal of Dermatology (1993)

The ability to assess the severity of dermatoses by measurement of area of involvement is important in both clinical practice and research. Using schematic figure outlines we have shown that physicians, nurses and other groups are unable to assess area accurately, and that the degree of error is partially dependent on absolute area, but also on other factors. The pattern and magnitude of the errors varied between the groups examined, but overall was such that it calls in question the use of area indices such as the PASI (psoriasis area and severity index) score in the assessment of inflammatory dermatoses.