tbuckley/cabot-search huggingface dataset:
Myeloma cells exhibit an increase in proteasome activity and an enhanced response to proteasome inhibition in the bone marrow microenvironment in vivo
Authors: Claire M. Edwards, Seint T. Lwin, Jessica A. Fowler, Babatunde O. Oyajobi, Junling Zhuang, Andreia L. Bates, Gregory R. Mundy
Journal: American Journal of Hematology (2009)

The proteasome inhibitor bortezomib has a striking clinical benefit in patients with multiple myeloma. It is unknown whether the bone marrow microenvironment directly contributes to the dramatic response of myeloma cells to proteasome inhibition in vivo. We have used the well-characterized 5TGM1 murine model of myeloma to investigate myeloma growth within bone and response to the proteasome inhibitor bortezomib in vivo. Myeloma cells freshly isolated from the bone marrow of myeloma-bearing mice were found to have an increase in proteasome activity and an enhanced response to in vitro proteasome inhibition, as compared with pre-inoculation myeloma cells. Treatment of myeloma-bearing mice with bortezomib resulted in a greater reduction in tumor burden when the myeloma cells were located within the bone marrow when compared with extra-osseous sites. Our results demonstrate that myeloma cells exhibit an increase in proteasome activity and an enhanced response to bortezomib treatment when located within the bone marrow microenvironment in vivo.
Intravenous Methocarbamol in Reduction of Shoulder Dislocations
Authors: Gerald W. Shaftan, Horace Herbsman
Journal: JAMA (1964)

THE CLINICAL USE of muscle relaxant drugs has been substantiated by studies based primarily on the subjective evaluation of the relief of muscle spasm.<sup>1-7</sup>Even the objective determinations of drug efficacy were related to the diminution of pain with subsequent decreased requirement for analgesics. To evaluate the effectiveness of an intravenous muscle relaxant, its ability to facilitate reduction of recent shoulder dislocations was investigated. <h3>Method and Materials</h3> One hundred and sixteen consecutive patients with recent shoulder dislocations seen at the Kings County Hospital Center were admitted to the study group. One patient had simultaneous dislocation of both shoulders. Dislocations were verified by x-ray. Each patient was then given a one-half hour trial of shoulder dislocation reduction without medication or with moderate analgesia not exceeding 30 mg of codeine. The classical, Hippocratic, Kocher, or Milch prone<sup>8</sup>method of reduction was used. If reduction was not effected within 30 minutes,
Micelles of methoxy poly(ethylene oxide)-b-poly(ɛ-caprolactone) as vehicles for the solubilization and controlled delivery of cyclosporine A
Authors: Hamidreza Montazeri Aliabadi, Abdullah Mahmud, Annahita Dehmoobed Sharifabadi, Afsaneh Lavasanifar
Journal: Journal of Controlled Release (2005)
The effect of venous occlusion on capillary size in man
Authors: N. K. Burki, A. Guz
Journal: Cardiovascular Research (1970)

Human nail bed capillaries have been photographed while venous pressure has been raised to 40 mm Hg. Diameters of the loop and venular ends of the capillary were measured with a discrimination of 1·5 μ. No increase in these diameters was found with venous occlusion and there was no increase in the number of capillaries open in any given area.
Regulatory T cells interfere with the development of bronchus-associated lymphoid tissue
Authors: Jessica R. Kocks, Ana Clara Marques Davalos-Misslitz, Gabriele Hintzen, Lars Ohl, Reinhold Förster
Journal: The Journal of Experimental Medicine (2007)

Presence and extent of bronchus-associated lymphoid tissue (BALT) is subject to considerable variations between species and is only occasionally observed in lungs of mice. Here we demonstrate that mice deficient for the chemokine receptor CCR7 regularly develop highly organized BALT. These structures were not present at birth but were detectable from day 5 onwards. Analyzing CCR7(-/-)/wild-type bone marrow chimeras, we demonstrate that the development of BALT is caused by alterations of the hematopoietic system in CCR7-deficient mice. These observations together with the finding that CCR7-deficient mice possess dramatically reduced numbers of regulatory T cells (T reg cells) in the lung-draining bronchial lymph node suggest that BALT formation might be caused by disabled in situ function of T reg cells. Indeed, although adoptive transfer of wild-type T reg cells to CCR7-deficient recipients resulted in a profound reduction of BALT formation, neither naive wild-type T cells nor T reg cells from CCR7(-/-) donors impair BALT generation. Furthermore, we provide evidence that CCR7-deficient T reg cells, although strongly impaired in homing to peripheral lymph nodes, are fully effective in vitro. Thus our data reveal a CCR7-dependent homing of T reg cells to peripheral lymph nodes in conjunction with a role for these cells in controlling BALT formation.
Metabolic Assessment of Internal Mammary Artery Implantation in the Dog
Authors: GEORGE C. KAISER, HENDRICK B. BARNER, MAX JELLINEK, J. GERARD MUDD, C. ROLLINS HANLON
Journal: Circulation (1970)

The metabolic and physiologic contributions of an implanted internal mammary artery have been assessed in five dogs 24 to 34 months following internal mammary artery implantation and concomitant ameroid constrictor application to coronary arteries. All implants were patent angiographically prior to evaluation by right heart bypass and continual autoanalyzer assessment of myocardial oxygen, pyruvate, and lactate extraction. Control internal mammary artery flow averaged 17.5 ml/100 g LV/min. Occlusion of the internal mammary artery failed significantly to alter myocardial extraction of oxygen, pyruvate and lactate or ventricular function, nor did these patent implants prevent significant changes in oxygen, pyruvate, and lactate extraction and ventricular function during and following occlusion of a remaining patent left coronary artery. In only one animal did internal mammary artery flow increase with left coronary artery occlusion, and this only transiently. These results indicate that demonstration of angiographic patency of an internal mammary artery implant does not necessarily indicate significant metabolic or functional contribution of this extracardiac blood supply to the heart.
Early Opening of the New Baths of Bormio
Authors: C. J. B. Williams
Journal: BMJ (1870)

of its members not less important than their practical and scientific at- tainments." This was the principle introduced by the founders of King's College; and no one believed its truth more steadfastly, or endeavoured to carry it into practice more earnestly, than Dr. Todd.Long ago he endeavoured to remove many of the difficulties which beset the medi- cal student on his first coming to London; and in a letter to the Prin- cipal in I842, strongly advocated the extension of the collegiate system to students of this department.From a very early period of his life, Dr. Todd endeavoured to increase the intimacy of the relationship between student
The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice
Authors: Natalia Lowry, Susan K. Goderie, Patricia Lederman, Carol Charniga, Michael R. Gooch, Kristina D. Gracey, Akhilesh Banerjee, Supriya Punyani, Jerry Silver, Ravi S. Kane, Jeffrey H. Stern, Sally Temple
Journal: Biomaterials (2012)
ORIGINAL FEATURES OF ARTHROPLASTY OF THE HIP AND KNEE
Authors: FRED H. ALBEE
Journal: JAMA (1933)

With regard to the wisdom of mobilizing ankylosed hips, one finds considerable difference of opinion among the best of surgeons. Henderson, reviewing the end-results of arthroplasties of the jaw, elbow, knee and hip, found those for the hip the poorest. Murphy, on the other hand, found that the hip gave him the best results. The problem is obviously more complicated in weight-bearing joints. The occupation and social status of the patient, as well as his temperament, are often determining factors in deciding whether or not to operate. When the hip and knee on the same side are both ankylosed, the advantages of arthroplasty are much increased. It must always be remembered that stability is very important in the hip, and, although the rotary nature of the joint lends itself to arthroplasty, unfortunate results have followed arthroplasty when stability was not obtained. Arthroplasty in cases of tuberculosis should be approached with
Primary CNS Lymphoma
Authors: Tracy Batchelor, Jay S. Loeffler
Journal: Journal of Clinical Oncology (2006)

Primary CNS lymphoma (PCNSL), an uncommon form of extranodal non-Hodgkin's lymphoma (NHL), has increased in incidence during the last three decades and occurs in both immunocompromised and immunocompetent hosts. PCNSL in immunocompetent patients is associated with unique diagnostic, prognostic, and therapeutic issues, and the management of this malignancy is different from that of other forms of extranodal NHL. Characteristic imaging features should be suggestive of the diagnosis, avoidance of corticosteroids, if possible, and early neurosurgical consultation for stereotactic biopsy. Because PCNSL may involve the brain, CSF, and eyes, diagnostic evaluation should include assessment of all of these regions as well as screening for possible occult systemic disease. Resection provides no therapeutic benefit and should be reserved for the rare patient with neurologic deterioration due to brain herniation. Whole-brain radiation therapy (WBRT) alone is insufficient for durable tumor control and is associated with a high risk of neurotoxicity in patients older than age 60. Neurotoxicity typically is associated with significant cognitive, motor, and autonomic dysfunction, and has a negative impact on quality of life. Chemotherapy and WBRT together improve tumor response rates and survival compared with WBRT alone. Methotrexate-based multiagent chemotherapy without WBRT is associated with similar tumor response rates and survival compared with regimens that include WBRT, although controlled trials have not been performed. The risk of neurotoxicity is lower in patients treated with chemotherapy alone.
Chronic Leg Ulcers in Non-thrombocytopenic Purpura
Authors: A. R. Horler, S. C. Truelove
Journal: BMJ (1955)

Apart from a probable case reported by Osler in 1914, we have been unable to find in the literature any account of leg ulcers occurring in non-thrombocytopenic purpura.As we have seen three such cases in the last two years we think it worth while to report them.Case 1 A married butcher aged 57 first came to the out-patient department in December, 1953, with a complaint of swollen joints for 10 days.He had a history of developing painful swollen joints 30 years previously while serving in the Army in Egypt.They became normal in six months with no residual disability (he was later a racing cyclist).In 1943 he was treated for a prolapsed intervertebral disk by laminectomy, and post-operatively developed a thrombosis of the left small saphenous vein.Following this episode he was sub- ject to mild ankle oedema after standing for prolonged periods, but no other disability.His present illness began suddenly with swelling of the right knee and a blotchy rash on the skin surrounding that joint.In the course of the next few days, the left knee, right ankle, both elbows, and right wrist also became swollen and painful.At the same time the rash spread over both legs, and, to a less extent, on the trunk.It came as a series of crops, and the patient noticed that the spots were raised above the skin and did not itch.There was no past history of any allergic disorder and he had never taken any drugs.On examination he was well nourished, with a purpuric rash in which there was an urticarial component, richly distributed over the legs, buttocks, and extensor surfaces of the arms, and more sparsely over the trunk.Several joints were swollen and painful on movement-namely, both knees, both ankles, both elbows, both wrists, and the left shoulder.The spleen was not palpable.Small, discrete, painless lymph nodes were felt in the occipital, the cervical, and both axillary regions.The left
Denys ("Peter") Horton
Authors: R. Horton
Journal: BMJ (2003)

Former general practitioner Billinghay, Lincolnshire (b 1918; q Birmingham 1940), died on 26 March 2003 following a stroke.

Following house jobs he entered the Royal Naval Volunteer Reserve as surgeon lieutenant, serving on destroyers and with the Royal Marines. Entering practice in Billinghay in 1946, he stayed until his retirement in 1978. He combined work with a large garden, family caravan holidays, and field sports. Political life was not ignored, with service on the local medical committee and chairmanship of Lincoln Medical Society. Retirement to Lincoln enabled him to develop another garden. He and his wife celebrated their diamond wedding in 2000. Predeceased by his wife, he leaves three sons and five grandchildren.
A New Therapy for the Adult Respiratory Distress Syndrome
Authors: Roger C. Bone
Journal: New England Journal of Medicine (1993)

In the 26 years since Ashbaugh et al.1 first described the adult respiratory distress syndrome (ARDS), we have progressed considerably in our understanding of the pathogenesis of this disorder. Unfortunately, we have made much less progress in our ability to improve its outcome. In this issue of the Journal, Rossaint et al. describe a new treatment for ARDS -- inhaled nitric oxide2. Their results may represent an important advance in therapy for ARDS.ARDS may sometimes result from direct injury to the lungs (for example, from aspiration of gastric contents, pneumonia, or inhalation of a toxic substance); it may . . .
A Change in the Air: Smoking Bans Gain Momentum Worldwide
Authors: Charles W. Schmidt
Journal: Environmental Health Perspectives (2007)

O n 29 March 2004, Ireland became the first country in the world to ban smoking in all indoor workplaces, including in restaurants and bars.That landmark event followed a ten-year period during which it was shown that voluntary bans and partial bans allowing workplace smoking in certain designated areas didn't protect Irish workers from secondhand smoke, a known cause of cancer and other lethal diseases.So in a move to protect its workers, Ireland took the extraordinary step of banning indoor workplace smoking completely.In so doing, it launched a wave of similar national-level policies now spreading across the globe. The Ripple EffectSince 2004, countries including Norway, New Zealand, Uruguay, Malta, Italy, Sweden, Scotland, Bhutan, Lithuania, and the British Virgin Islands have gone smoke-free, protecting the health of millions by banning smoking in public places.The European Union is now considering smoke-free legislation for all of its 27 member countries.France-the latest country to move in this direction-issued a workplace ban in January 2007, which will apply to restaurants and bars next year.Other countries and territories now preparing to adopt national bans include England, Wales, Northern Ireland, Kazakhstan, Finland, and Hong Kong.Most of Canada and Australia is covered by smoke-free policies.Ireland didn't spawn the trend in isolation.Beginning in the early 1980s, U.S. cities and towns began enacting ordinances that restricted, but did not eliminate, smoking in public places, workplaces, and restaurants.However, as understanding of the health effects of secondhand smoke grew, especially as a matter of worker protection, ordinances more commonly completely prohibited smoking,
Roles of Nonphysician Clinicians as Autonomous Providers of Patient Care
Authors: Richard A. Cooper
Journal: JAMA (1998)

Studies were undertaken to assess the practice prerogatives of nonphysician clinicians (NPCs) in 10 disciplines that, collectively, are the major nonphysician contributors to the delivery of medical and surgical services. These disciplines include nurse practitioners, physician assistants, nurse-midwives, chiropractors, acupuncturists, naturopaths, optometrists, podiatrists, nurse anesthetists, and clinical nurse specialists. Marked differences were found in the practice prerogatives that states granted NPCs in the various disciplines. For most disciplines, the magnitude of their prerogatives correlated with the numbers of NPCs practicing in each state. At their maximal levels, state practice prerogatives authorized a high degree of autonomy and a broad range of authority to provide discrete levels of uncomplicated primary and specialty care. The recent growth in these prerogatives is fostering new opportunities for NPCs; however, it also is creating a pluralism that has the potential to further fragment the US health care system. It is time for regulatory integration and professional collaboration so that a health care workforce that includes a diversity of disciplines can be assured of providing a coherent set of patient care services in the future.
The Pathogenesis of Mucosal Inflammation in Murine Models of Inflammatory Bowel Disease and Crohn Disease
Authors: Warren Strober
Journal: Annals of Internal Medicine (1998)

In recent years, it has become apparent that overproduction of the Th1 cytokines interleukin-12 and interferon-γ is the probable driving force behind murine models of intestinal inflammation resembling Crohn disease and intestinal inflammation in humans with Crohn disease. In addition, studies of murine models strongly suggest that this overproduction is associated with inadequate secretion of the counter-regulatory and anti-inflammatory cytokine transforming growth factor-β. Thus, mucosal inflammation in models (and possibly in humans) may result from an imbalance between normally occurring positive (immunogenic or inflammatory) responses and negative (tolerogenic or anti-inflammatory) mucosal immune responses. These new findings and the hypotheses that arise from them are being used to construct new approaches to the treatment of Crohn disease that are based on the administration of anti-inflammatory cytokines and anti-cytokine antibodies.
N-6-Adenine-Specific DNA Methyltransferase 1 ( <i>N6AMT1</i> ) Polymorphisms and Arsenic Methylation in Andean Women
Authors: Florencia Harari, Karin Engström, Gabriela Concha, Graciela Colque, Marie Vahter, Karin Broberg
Journal: Environmental Health Perspectives (2013)

In humans, inorganic arsenic is metabolized to methylated metabolites mainly by arsenic (+3 oxidation state) methyltransferase (AS3MT). AS3MT polymorphisms are associated with arsenic metabolism efficiency. Recently, a putative N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) was found to methylate arsenic in vitro.
Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis
Authors: M Cuchacovich
Journal: Annals of the Rheumatic Diseases (2002)

The antidiuretic effect of vasopressin is mediated by V2 receptors (V2R) that are located in kidney connecting tubules and collecting ducts. This study provides evidence that V2R signaling is negatively regulated by regulator of G protein signaling 2 (RGS2), a member of the family of RGS proteins. This study demonstrates that (<i>1</i>) RGS2 expression in the kidney is restricted to the vasopressin-sensitive part of the nephron (thick ascending limb, connecting tubule, and collecting duct); (<i>2</i>) expression of RGS2 is rapidly upregulated by vasopressin; (<i>3</i>) the vasopressin-dependent accumulation of cAMP, the principal messenger of V2R signaling, is significantly higher in collecting ducts that are microdissected from the <i>RGS2</i><sup>−/−</sup> mice compared with their wild-type littermates; and (<i>4</i>) analysis of urine output of mice that were exposed to water restriction followed by acute water loading revealed that <i>RGS2</i><sup>−/−</sup> mice exhibit an increased renal responsiveness to vasopressin. It is proposed that RGS2 is involved in negative feedback regulation of V2R signaling.
A CLINICAL STUDY OF PNEUMONIA: WITH NOTES OF ONE HUNDRED CONSECUTIVE CASES OCCURRING IN HOSPITAL PRACTICE
Authors: J. A. Lindsay
Journal: BMJ (1913)

PNEUMONIA constitutes one of the most formidable problems which-confront thei physician.Tile disease is upon the increase; nothing. is known as regards its prevention; it involves a very heavy mortality; the treat- meilt is a matter of much difficulty and anxiety.On all tIlese grounds it calls for the best t-hought and study wllich we can devote to it.The series of 100 consecutive cases here recorded were treated in my wards of the Royal Victoria Hospital, Belfast, in the years 1899-1913.They are recorded as they arose, without any selection.The deaths include 2 cases which were moribund on admission.Hospital mortality is everywhere somewhat high, inasmuch as, speaking generally, only cases of considerable severity seek admission; patients are in some cases only admitted when the disease has run its course for several days; and the number of children admitted to general hospitals is relatively small.All these factors have a bearing upon tile mortality.I. Age.
Who dominates who in the dark basements of the brain?
Authors: Tony J. Prescott, Mark D. Humphries
Journal: Behavioral and Brain Sciences (2007)

Subcortical substrates for behavioural integration include the fore/midbrain nuclei of the basal ganglia and the hindbrain medial reticular formation. The midbrain superior colliculus requires basal ganglia disinhibition in order to generate orienting movements. The colliculus should therefore be seen as one of many competitors vying for control of the body's effector systems with the basal ganglia acting as the key arbiter.
Intestinal monocytes and macrophages are required for T cell polarization in response to <i>Citrobacter rodentium</i>
Authors: Heidi A. Schreiber, Jakob Loschko, Roos A. Karssemeijer, Amelia Escolano, Matthew M. Meredith, Daniel Mucida, Pierre Guermonprez, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2013)

Dendritic cells (DCs), monocytes, and macrophages are closely related phagocytes that share many phenotypic features and, in some cases, a common developmental origin. Although the requirement for DCs in initiating adaptive immune responses is well appreciated, the role of monocytes and macrophages remains largely undefined, in part because of the lack of genetic tools enabling their specific depletion. Here, we describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. Although neither cell type was required to initiate immunity, monocytes and macrophages contributed to the adaptive immune response by secreting IL-12, which induced Th1 polarization and IFN-γ secretion. Thus, whereas DCs are indispensable for priming naive CD4+ T cells, monocytes and macrophages participate in intestinal immunity by producing mediators that direct T cell polarization.