tbuckley/cabot-search huggingface dataset:
Abstract 3519: Appropriate crosslinking is required for co-stimulatory activity of human CD27 antibody in a transgenic mouse model
Authors: Li-Zhen He, Naseem Prostak, Andrea Crocker, Jeffery Weidlick, Jenifer Widger, Crystal Sisson, Laura Vitale, Martin J. Glennie, Tibor Keler
Journal: Cancer Research (2012)

Abstract CD27 is a member of TNFR superfamily. It constitutively expresses on the majority of T cell and a subset of NK cells, playing key roles in T cell activation and survival and in NK cell proliferation and cytotoxicity upon interaction with ligand CD70. Some antibodies to mouse CD27 have been reported that display agonistic and anti-tumor activities while other mAbs had less anti-tumor activity and were depleting. We hypothesized that differences in these antibodies may be due to Fc receptor engagement, as has recently been shown for the adjuvant and anti-tumor activities of agonistic mouse CD40 mAbs, which is also member of TNFR superfamily. We have developed and previously described a human anti-human CD27 antibody (1F5) and a human CD27 transgenic mouse model (hCD27-Tg) to explore the therapeutic potential of targeting CD27. In this study, we examined the effect of modifying the constant regions of the 1F5 mAb on its ability to enhance antigen specific T cell responses. With the original 1F5 hIgG1 as template, a panel of 1F5 variants was made including 1F5 mIgG1, 1F5 mIgG2a, 1F5 mIgG1D265A and 1F5 hIgG1N297S using molecular cloning techniques. All of the variants retained equal binding to hCD27 as shown by ELISA and flow cytometry studies. In addition, Biacore analysis confirmed the expected pattern of binding to human and mouse FcαRs. Co-injection of 1F5 or its variants with ovalbumin enhanced antigen-specific CD8 T cell response to different extents, as detected by SIINFEKL-specific IFNα-ELISPOT and ICS. The 1F5 mIgG1 induced the highest number of IFNα-producing CD8+ cells, whereas 1F5 mIgG2a was very weak at enhancing the CD8 T cell response. The hIgG1 version of 1F5 was intermediate in activity. Introduction of the D265A mutation that disrupts FcαRs binding into the mIgG1 eliminated the co-stimulatory function of 1F5. Similarly, the 1F5 hIgG1N297S also showed reduced activity compared to the original 1F5 hIgG1. The isotype-specific effects on our anti-hCD27 mAb are surprisingly consistent with the findings described for the agonistic anti-mCD40 mAbs, and imply that engagement of the inhibitory Fcα receptors (FcαRIIb) is driving the co-stimulatory activity in this model. Interestingly, the 1F5 hIgG1 triggered a significant T cell response, despite the lack of FcαRIIb binding by Biacore analysis. The effect of these variants on anti-tumor activity in hCD27 transgenic mice is currently being investigated. The 1F5 hIgG1 mAb (CDX-1127) is currently undergoing clinical evaluation in a phase 1 trial of patients with advanced cancers. 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 3519. doi:1538-7445.AM2012-3519
Criminalisation of HIV transmission: implications for public health in Scotland
Authors: S. M Bird, A. J L. Brown
Journal: BMJ (2001)

Molecular investigation of an outbreak of HIV at Glenochil Prison contributed to the conviction of a former Glenochil drug injector, Mr Stephen Kelly, for culpably and recklessly transmitting HIV to a female sexual partner. We explain why the case of R v Kelly has brought the medical and legal professions into conflict and explore its implications for public health and molecular science in Scotland. Firstly, even a modest decline in the uptake of HIV testing by those who are actually infected could herald a one third increase in new sexually transmitted HIV infections. Secondly, there is now need for a national proforma to assure the quality and legality of HIV counselling in Scotland as a safeguard for both counsellors and clients. Thirdly, we discuss curtailment of molecular research investigations with the potential to discover incriminating evidence about HIV transmissions unless laboratory protocols, or legal safeguards, can be designed which obviate deductive disclosure about individuals. Urgent review by the Scottish Executive is required to minimise negative impacts of the Glenochil judgement on public health and molecular science.

#### Summary points

Knowingly transmitting HIV is a criminal offence in Scotland as a result of the Glenochil judgment

Even a modest fall in the uptake of HIV testing as a result of the judgment could produce a one third increase in new sexually transmitted HIV infections

A national proforma is needed to assure the quality and legality of HIV counselling in Scotland as a safeguard for both counsellors and clients

Molecular research investigations may be hampered because of the ability of the police to use them to discover incriminating evidence about HIV transmissions

The Scottish Executive needs to take urgent steps to minimise the negative effects of the Glenochil judgment on public health and molecular science

Stephen Kelly was one of at least 14 drug injectors …
Studies of Alpha-methyl-para-tyrosine, L-dopa, and L-tryptophan in Depression and Mania
Authors: WILLIAM E. BUNNEY, H. KEITH H. BRODIE, DENNIS L. MURPHY, FREDERICK K. GOODWIN
Journal: American Journal of Psychiatry (1971)

L-dopa and L-tryptophan, metabolic precursors of norepinephrine and serotonin respectively, and αMPT, a blocker of catecholamine synthesis, were administered to depressed and manic patients in an attempt to decrease their psychopathology and to test the monoamine theory of affective disorders. L-dopa and αMPT clearly altered mood and thought patterns in some patients, while L-tryptophan was less active. Analysis of urinary and cerebrospinal fluid amine metabolites documented the metabolic effects of the compounds during periods of behavioral change.
Portopulmonary hypertension: Results from a 10-year screening algorithm
Authors: Michael J. Krowka, Karen L. Swanson, Robert P. Frantz, Michael D. McGoon, Russell H. Wiesner
Journal: Hepatology (2006)

Portopulmonary hypertension (POPH) is the elevation of pulmonary artery pressure due to increased resistance to pulmonary blood flow in the setting of portal hypertension. Increased mortality has occurred with attempted liver transplantation in such patients and thus, screening for POPH is advised. We examined the relationship between screening echocardiography and right heart catheterization determinations of pressure, flow, volume, and resistance. A prospective, echocardiography-catheterization algorithm was followed from 1996 to 2005. Consecutive transplantation candidates underwent Doppler echocardiography to determine right ventricular systolic pressure (RVSP). Of 1,235 patients, 101 with RVSP >50 mm Hg underwent catheterization to measure mean pulmonary artery pressure (MPAP), flow via cardiac output (CO), central volume via pulmonary artery occlusion pressure (PAOP), and resistance via calculated pulmonary vascular resistance (PVR). Bland-Altman analysis suggested marked discordance between echocardiography-derived RVSP and catheterization results. All-cause pulmonary hypertension (MPAP >25 mm Hg) was documented in 90/101 (90%) patients. Using current pressure and resistance diagnostic guidelines (MPAP >25 mm Hg, PVR > or =240 dynes/s/cm(-5)), POPH was documented in 66/101 (65%) patients. Elevated MPAP was due to increased CO and/or PAOP in 35/101 (35%) patients with normal resistance (PVR <240 dynes/s/cm(-5)). The transpulmonary gradient (MPAP-PAOP) further characterized POPH in the presence of increased volume. Model for end stage liver disease (MELD) scores correlated poorly with MPAP and PVR. In conclusion, right heart catheterization is necessary to confirm POPH and frequently identifies other reasons for pulmonary hypertension (e.g., high flow and increased central volume) in liver transplantation candidates. Severity of POPH correlates poorly with MELD scores.
Cardiogenic shock induced by cocaine in swine with normal coronary arteries
Authors: B. D Nunez, L. Miao, R. E Kuntz, J. N Ross, S. Gladstone, D. S Bairn, P. C Gordon, J. P Morgan, J. P Carrozza
Journal: Cardiovascular Research (1994)

The aim was to test the hypothesis that acute intravenous cocaine administration can cause coronary microvascular constriction culminating in myocardial ischaemia and cardiogenic shock.Systemic haemodynamic variables and coronary blood flow were measured in 14 Yorkshire swine at baseline and following intravenous administration of 1, 3, and 10 mg.kg-1 of cocaine. Epicardial coronary artery diameter was measured from coronary arteriograms and coronary flow velocity was recorded with a Doppler flow wire.Cocaine produced a decrease in mean arterial pressure (65%), cardiac output (80%), and stroke volume (80%), and an increase in pulmonary artery diastolic pressure (60%). Although coronary blood flow decreased by 70%, epicardial coronary cross sectional area decreased by only 37-45%. Pretreatment with prazosin did not abolish the decrease in coronary blood flow. After administration of 10 mg.kg-1 of cocaine, five of 14 animals developed myocardial ischaemia and cardiogenic shock, culminating in ventricular fibrillation and death.In anaesthetised Yorkshire swine, cumulative intravenous doses of cocaine caused a significant reduction in coronary blood flow resulting in myocardial ischaemia, which cannot be attributed to epicardial vasoconstriction alone. This suggest that cocaine-induced coronary ischaemia may result from microvascular constriction, which is only partially prevented by alpha 1 blockade. In addition, direct toxic effects of cocaine on the myocardium may also contribute to the development of cardiogenic shock.
Establishment of a Serum Tumor Marker for Preclinical Trials of Mouse Prostate Cancer Models
Authors: Isaac Van Huizen, Guojun Wu, Madeleine Moussa, Joseph L. Chin, Aaron Fenster, James C. Lacefield, Hideki Sakai, Norman M. Greenberg, Jim W. Xuan
Journal: Clinical Cancer Research (2005)

Abstract Current prostate cancer research in both basic and preclinical trial studies employ genetically engineered mouse models. However, unlike in human prostate cancer patients, rodents have no counterpart of prostatic-specific antigen (PSA) for monitoring prostate cancer initiation and progression. In this study, we established a mouse serum tumor marker from a mouse homologue of human prostate secretory protein of 94 amino acids (PSP94). Immunohistochemistry studies on different histologic grades from both transgenic and knock-in mouse prostate cancer models showed the down-regulation of tissue PSP94 expression (P &amp;lt; 0.001), the same as for PSA and PSP94 in humans. The presence of mouse serum PSP94 was shown by affinity column and immunoprecipitation purification using a polyclonal mouse PSP94 antibody. A competitive ELISA protocol was established to quantify serum PSP94 levels with a sensitivity of 1 ng/mL. Quantified serum levels of mouse PSP94 ranged from 49.84 ng/mL in wild-type mice to 113.86, 400.45, and 930.90 ng/mL in mouse prostatic intraepithelial neoplasia with microinvasion, well differentiated, moderately differentiated, and poorly differentiated prostate cancer genetically engineered prostate cancer mice, respectively (P &amp;lt; 0.01, n = 68). This increase in serum PSP94 is also well correlated with age and tumor weight. Through longitudinal monitoring of serum PSP94 levels of castrated mice (androgen ablation therapy), we found a correlation between responsiveness/refractory prostate tissues and serum PSP94 levels. The utility of mouse serum PSP94 as a marker in hormone therapy was further confirmed by three-dimensional ultrasound imaging. The establishment of the first rodent prostate cancer serum biomarker will greatly facilitate both basic and preclinical research on human prostate cancer.
Abstract 1323: Reciprocal regulation of Stat3 and caveolin-1 in normal fibroblasts and breast carcinoma lines
Authors: Mulu Geletu, Reva Mohan, Rozanne Arulanandam, Bharat Joshi, Ivan Robert Nabi, Leda Helen Raptis
Journal: Cancer Research (2011)

Abstract Membrane tyrosine kinases known to activate the signal transducer and activator of transcription-3 (Stat3) concentrate in caveolae, where they are sequestered in an inactive state through binding to the main caveolae protein, caveolin-1 (cav1). We previously demonstrated that cell-to-cell adhesion can cause a dramatic increase in Stat3 activity in cultured cells. Therefore, to examine the effect of cav1 upon Stat3, experiments were conducted at several confluences. Our results indicate that cav-1 downregulation through expression of anti-sense or shRNA constructs or treatment of cells with the pharmacological inhibitor, methyl-cyclo-dextran which destroys caveolae, activates Stat3 as well as Erk1/2, at all densities. Conversely, cav1 overexpression downregulates Stat3 and induces growth retardation or apoptosis in NIH3T3 fibroblasts and in breast cancer lines. In all cases, apoptosis was inhibited by co-expression of the constitutively active form of Stat3, Stat3C. Taken together, these findings point to cav1 as an inhibitor of Stat3 activity. In addition, it was previously demonstrated that cav1 upregulates p53, although the exact mechanism is unclear. Since Stat3 is known to inhibit p53 transcription through promotor binding, these data also point to the possibility that cav1 upregulation may, in fact, activate p53 through Stat3 inhibition. Our results further demonstrate for the first time that, in a feedback loop, Stat3 inhibition results in a dramatic increase in cav1 levels, indicating that Stat3 also downregulates cav1 expression. The above findings reveal the presence of a potent, negative regulatory loop between cav1, p53 and Stat3 that plays a crucial role in cellular survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1323. doi:10.1158/1538-7445.AM2011-1323
Relief of acute pain in herpes zoster ophthalmicus by stellate ganglion block.
Authors: S P Harding, J R Lipton, J C Wells, J A Campbell
Journal: BMJ (1986)

Relief of acute pain in herpes zoster ophthalmicus by steliate ganglion blockStellate ganglion block has been suggested as a useful treatment for trigeminal herpes zoster,'4 being most effective if started within two weeks of the onset of the disease.'We evaluated the efficacy of this treatment in a randomised prospective controlled study for the first time and assessed its complications. Patients, methods, and resultsThirty patients aged 60 and over who presented with herpes zoster ophthalmicus were recruited and randomly allocated to one oftwo groups: treated (group A; mean age 71-5 (range 60-87) years) or untreated (group B; mean age 72 *2 (62- 92) years).Pain was assessed by visual-analogue scale set horizontally for 100 mm.Patients in group A underwent stellate ganglion block within 14 days of the onset of the rash as previously described.5After verbal consent a 0-5 ml test dose, followed 30 seconds later by a 9-5 ml bolus ofequal parts 1% lignocaine and 0-5% marcaine, was injected on to the C5/C6 prevertebral fascia.Effect was assessed from miosis, hyperthermia, and pain relief at 60 minutes.Patients were followed up for at least three months.In group A mean pain score before block was 41-9 mm; at one hour it was 5-2 mm, a highly significant reduction (p<0001, paired t test).Pain scores in subsequent time bands were compared with those at presentation in patients from each group by paired t tests (table).In group A there was a highly significant Mean visual analogue scale pain scores for patients treated by stellate ganglion block and untreated patients at presentation and at subsequent time bands 2 Weeks-6 Weeks-Presentation I month 2 months 3 Months Treated 42 53 12 43* 31-45t 10-46* Untreated 26-67 16 45t 14 85f 11 71t
Delayed small-intestinal transit in tropical malabsorption.
Authors: G C Cook
Journal: BMJ (1978)

The time of breath hydrogen appearance (T) after oral lactulose was determined in 98 patients in London who had been to the tropics. Fifty-six controls from three different ethnic groups had no evidence of gastrointestinal disease; 23 had tropical malabsorption, which was severe in 10; and 19 had chronic diarrhoea without malabsorption. Mean T was significantly delayed in patients with tropical malabsorption compared with controls, indicating that their mouth-caecum transit rate was abnormally slow. In six patients with tropical malabsorption who were reinvestigated after treatment a fall in the value for T seemed to parallel clinical improvement. Three patients with diarrhoea due to chronic colonic disease had delayed T. Patients with tropical malabsorption have bacterial colonisation of the small intestine, which is important in the pathogenesis of the disease. Bacterial overgrowth, which sometimes occurs after infective diarrhoea in the tropics and gives rise to tropical sprue, is a result of stasis.
Adoption and Inheritance
Authors: Arthur Harris Rosenberg
Journal: New England Journal of Medicine (1968)

THE emotional welfare of adopted children must be safeguarded against a double set of emotional and legal relations if the adoptive process is to be successful. The transition, therefore, from prior family to present family is undertaken in a number of specific ways, familiar to physicians, and designed to ensure that an adopted child will be truly treated as the natural issue of the adoptive parents. These methods encourage the relinquishment of former parental relations, both emotional and legal, in favor of new such relations and a new identity within the adoptive family.From a legal point of view, the . . .
Excimer laser angioplasty in the treatment of instent restenosis: An intravascular ultrasound study
Authors: Roxana Mehran, Gary S. Mintz, Jeffrey J. Popma, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, S.Chiu Wong, Martin B. Leon
Journal: Journal of the American College of Cardiology (1996)
Casting of Recurrent Diabetic Foot Ulcers
Authors: Marrigje H. Nabuurs-Franssen, Maya S.P. Huijberts, Ron Sleegers, Nicolaas C. Schaper
Journal: Diabetes Care (2005)

With appropriate wound care and biomechanical off-loading, 80–90% of neuropathic foot ulcers can heal (1). Unfortunately, many ulcers recur (2), and recurrence rates up to 70% have been reported (3–5). Little information is available on the management and outcome of these ulcers. In addition, it is unclear how to approach a patient for whom customized shoes fail to prevent ulceration and whose repetitive ulceration could result in progressive scar formation and impaired wound healing. The total contact cast (TCC) is currently seen as the gold-standard treatment of neuropathic ulcers (1,6,7), but the efficacy and safety of repeated treatment is unknown. For this reason, the present study was undertaken to determine whether repeated casting in patients with recurrent foot ulceration remains effective and is not associated with unwanted complications.

A prospective data collection study (from 1999 to 2003) was performed in which diabetic patients with polyneuropathy and a first or recurrent foot ulcer in whom off-loading was indicated but not possible with simple measures (e.g., felt) were included. All patients were evaluated and graded according to the PEDIS system and were treated with a TCC, as previously described by Nabuurs-Franssen and Schaper (8). Exclusion criteria were critical limb ischemia and infection …
The History of American Internal Medicine: A New Series of Articles
Authors: RUSSELL C. MAULITZ
Journal: Annals of Internal Medicine (1986)

Editorials1 September 1986The History of American Internal Medicine: A New Series of ArticlesRUSSELL C. MAULITZ, M.D., Ph.D.RUSSELL C. MAULITZ, M.D., Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-3-452_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe article by Paul Beeson (1) in the History of Medicine section of this issue inaugurates a new series. These papers will consider the evolution in the United States of this protean specialty from two points of view. Some authors are historians, others internists who were "participant-observers" in the development of 20th century internal medicine. Each has prepared an essay surveying key aspects of the subject. Topics include internal medicine's continued search for direction, redefinition, and purpose; its literature; and some of its subspecialties. The essays have grown out of a conference, "Grand Rounds: One Hundred Years of Internal Medicine,"...References1. BEESON P. One hundred years of American internal medicine: a view from the inside. Ann Intern Med. 1986;105:436-44. LinkGoogle Scholar2. WINTROBE M. Hematology: the Blossoming of a Science. Philadelphia: Lea & Febiger; 1985:6. Google Scholar3. STEVENS R. Issues in the history of internal medicine. Ann Intern Med. 1986;105. (In press). Google Scholar4. HARVEY A. Science at the Bedside: Clinical Research in American Medicine, 1905-1945. Baltimore: Johns Hopkins University Press; 1981. Google Scholar5. LUDMERER K. Learning to Heal. The Development of American Medical Education. New York: Basic Books; 1985. Google Scholar6. ROGERS D. The early years: the medical world in which Walsh McDermott trained. Daedalus. 1986;115:1-18. MedlineGoogle Scholar7. EBERT R. Medical education at the peak of the era of experimental medicine. Daedalus. 1986;115:55-81. MedlineGoogle Scholar8. BEESON P. The changing role model and the shift in power. Daedalus. 1986;115:83-97. MedlineGoogle Scholar9. PETERSDORF R. Medical schools and research: is the tail wagging the dog? Daedalus. 1986;115:99-118. MedlineGoogle Scholar10. ROGERS D. Where have we been? where are we going? Daedalus. 1986;115:209-29. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: RUSSELL C. MAULITZ, M.D., Ph.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1986Volume 105, Issue 3Page: 452-452KeywordsHistory of medicineSub-specialty care ePublished: 1 December 2008 Issue Published: 1 September 1986 PDF downloadLoading ...
Current Status of Steroid Therapy in Rheumatic Disorders
Authors: J. Sydney Stillman
Journal: New England Journal of Medicine (1958)

CORTISONE, the first of a growing family of corticosteroids, was introduced to the medical profession by Dr. Philip S. Hench nine years ago. All the investigators who were fortunate enough to obtain some of the scarce hormone were immediately impressed by its power to bring about striking, widespread changes in the human physiology. They confirmed its capacity for suppressing the signs and symptoms of rheumatoid arthritis and other rheumatic diseases when it was given in daily amounts greater than those normally produced by the patient's own adrenal glands.In the past nine years a great deal of basic and clinical . . .
Running with the pantomime horses
Authors: Des Spence
Journal: BMJ (2007)

After four children a man can lose his figure. I would smile with resignation at the predictable comments: “You're looking well!” (translation: “Aren't you fat!”) But most days I was lucky to have time to brush my teeth, let alone fret about my body mass index or go to the gym. Anyway, the exercising class exercised me. It was demanding, unrealistic, and never satisfied with my explanation that simply resting might be sensible. The accessories were ridiculous: orthotic insoles, straps, isotonic fluids, food supplements. Jogging from one specialist physiotherapist …