tbuckley/cabot-search huggingface dataset:
Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease.
Authors: M I Bukrinsky, H S Nottet, H Schmidtmayerova, L Dubrovsky, C R Flanagan, M E Mullins, S A Lipton, H E Gendelman
Journal: The Journal of Experimental Medicine (1995)

Mononuclear phagocytes (monocytes, macrophages, and dendritic cells) play major roles in human immunodeficiency virus (HIV) persistence and disease pathogenesis. Macrophage antigen presentation and effector cell functions are impaired by HIV-1 infection. Abnormalities of macrophage effector cell function in bone marrow, lung, and brain likely result as a direct consequence of cellular activation and HIV replication. To further elucidate the extent of macrophage dysfunction in HIV-1 disease, a critical activation-specific regulatory molecule, nitric oxide (NO.), which may contribute to diverse pathology, was studied. Little, if any, NO. is produced by uninfected human monocytes. In contrast, infection with HIV-1 increases NO. production to modest, but significant levels (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor necrosis factor alpha, or through interactions with astroglial cells) further enhances NO. production in HIV-infected cells, whereas its levels are diminished by interleukin 4. These results suggest a possible role for NO. in HIV-associated pathology where virus-infected macrophages are found. In support of this hypothesis, RNA encoding the inducible NO synthase (iNOS) was detected in postmortem brain tissue from one pediatric AIDS patient with advanced HIV encephalitis. Corresponding iNOS mRNA was not detected in brain tissue from five AIDS patients who died with less significant brain disease. These results demonstrate that HIV-1 can influence the expression of NOS in both cultured human monocytes and brain tissue. This newly described feature of HIV-macrophage interactions suggests previously unappreciated mechanisms of tissue pathology that result from productive viral replication.
Primum Non Nocere: Of Course! But How?
Authors: Jan Oldenburg, Ronald de Wit
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: “Primum non nocere” stands for nonmaleficence in the Hippocratic Corpus, meaning “first, do no harm.” Colleagues who favor active surveillance for all patients with stage I testicular cancer consider adjuvant chemotherapy a potentially harmful and unnecessary intervention. However, the “surveillance for all” recommendation may infringe on patient autonomy and prove harmful. Adjuvant chemotherapy is, with few exceptions, well tolerated and without relevant long-term toxicities. Salvage treatment for relapsing patients, on the other hand, causes acute and long-term toxicities in a dose-dependent manner. Therefore, the fear of potential long-term effects of adjuvant chemotherapy seems disproportionate to the real and established toxicities after three to four cycles of bleomycin, etoposide, and cisplatin, including additional postchemotherapy RPLND in 26% of nonseminoma patients. Recently, Vidal et al published their article “Long-Term Outcome of Patients With Clinical Stage I High-Risk Nonseminomatous Germ Cell Tumors 15 Years After One Adjuvant Cycle of Bleomycin, Etoposide and Cisplatin Chemotherapy” in Annals of Oncology, in which essentially no relevant toxicity was reported. The editorial “Primum Non Nocere. Do We Harm Stage I Testicular Cancer Patients Less by Applying Adjuvant Chemotherapy Than by Failing to Present This Option?” hailed this report. Primum non nocere is thereby embraced both by the proponents of a risk-based management as well as by those advocating active surveillance for all patients with stage I testicular cancer. Both sides consider unnecessary treatment as the potential harm, identifying either adjuvant or salvage chemotherapy as the culprit. According the Spanish Germ Cell Group, a patient with a 6-cm testicular seminoma invading the rete testis and vasculature, like the one discussed by Vaughn, has a 40% risk of micrometastases. Typically, such men vote for adjuvant treatment, when counseled by proponents of a risk-based strategy like us. The majority of patients whose outcomes were published by Kollmannsberger et al were managed by the Swedish and Norwegian Testicular Cancer Group with a risk-based approach in which low-risk patients were selected for surveillance. Unfortunately, the Oncology Grand Rounds article appears biased in favor of active surveillance: Stating that “only 13% of 1,344 patients with CS I seminoma relapsed” while failing to mention the selection bias by including predominantly low-risk patients renders these numbers not representative for high-risk patients. Merely pointing to a lack of publications on long-term toxicities 20 to 30 years after carboplatin (while confirming their absence within 9 years) might cause patients to refrain from this “potentially harmful” treatment. This evasive approach appears, in light of the considerable toxicities after salvage treatment, questionable and potentially more harmful.
Characterization of physiochemical and biological properties of spherical protein crystals for sustained release
Authors: Kai Shi, Hongshu Bi, Yanbo Jiang
Journal: Asian Journal of Pharmaceutical Sciences (2013)

This study presents an exploration on extending the action of therapeutic proteins by crystallization strategy without new molecular entities generation. Recombinant human interferon α-2b (rhIFN), a model protein drug in this case, was crystallized using a hanging drop vapor diffusion method. A novel chelating technique with metal ions was employed to promote crystals formation. The physico-chemical characterization of the protein crystals, including morphology, particle size, X-ray diffraction, circular dichroism and biological potency evaluations were performed. In addition, the in vitro release behavior of rhIFN from crystal lattice suggested an exciting possibility of protein crystals as a long-acting formulation. The work described here demonstrates the possibility of spherical crystals of biomacromolecules for controllable delivery application of therapeutic proteins.
The gluteal triangle: a clinical patho-anatomical approach to the diagnosis of gluteal pain in athletes
Authors: A Franklyn-Miller, E Falvey, P McCrory
Journal: British Journal of Sports Medicine (2008)

Gluteal pain is a common presentation in sports medicine. The aetiology of gluteal pain is varied, it may be referred from the lower back, mimic other pathology and refer to the hip or the groin. The complex anatomy of the buttock and pelvis, variability of presentation and non specific nature of signs and symptoms make the diagnostic process difficult. To date the approaches to this problem have focused on individual pathologies. The paper proposes a novel educational system based on patho-anatomic concepts. Anatomical reference points were selected to form a diagnostic triangle, which provides the discriminative power to restrict the differential diagnosis, and form the basis of ensuing investigation. This paper forms part of a series addressing the three dimensional nature of proximal lower limb pathology. The 3G approach (groin, gluteal and greater trochanter triangles) acknowledges this, permitting the clinician to move throughout the region, considering pathologies appropriately. These papers should be read in conjunction with one another in order to fully understand the conceptual approach.
Successful treatment with recombinant factor VIIa of therapy‐resistant severe bleeding in a patient with acquired von Willebrand disease
Authors: Philip W. Friederich, Peter C. Wever, Ernest Briët, Cornelis J. Doorenbos, Marcel Levi
Journal: American Journal of Hematology (2001)

Abstract We describe an elderly man who presented with life‐threatening hematuria and gastrointestinal bleeding caused by acquired von Willebrand disease associated with monoclonal gammopathy of undetermined significance (MGUS). Standard therapy with desmopressin, von Willebrand factor‐containing factor VIII concentrate, tranexamic acid, and immunoglobulin failed to achieve adequate hemostasis. However, treatment with recombinant activated factor VII (rFVIIa) arrested the bleeding completely. Since acquired von Willebrand disease can lead to life‐threatening hemorrhage, clinicians should consider rFVIIa as an effective treatment option if standard therapy fails. Am. J. Hematol. 66:292–294, 2001. © 2001 Wiley‐Liss, Inc.
C<scp>AROTENOID</scp> B<scp>IOAVAILABILITY AND</scp> B<scp>IOCONVERSION</scp>
Authors: Kyung-Jin Yeum, Robert M. Russell
Journal: Annual Review of Nutrition (2002)

The possible role of carotenoids and their metabolites in disease prevention is far from fully understood, because the bioavailabilities of carotenoids are complicated by multiple factors that affect their absorption, breakdown, transport, and storage. Rapid progress in developing sophisticated methodologies, including use of stable-isotope dilution methods, now allows for an accurate determination of the true vitamin A activity of provitamin A carotenoids. The recent identification of specific enzymes, which catalyze the breakdown of beta-carotene as well as nonprovitamin A carotenoids, is providing a better understanding of the functions of carotenoids at the molecular level. The pathways and possible mechanisms of carotenoid breakdown and factors affecting the bioavailability of carotenoids, such as carotenoid type, food matrix, interaction with other carotenoids and other food components, nutritional status, aging, and infection, are discussed in this review.
Recurrent Amebic Abscess of the Liver
Authors: Stephen G. Jenkinson
Journal: JAMA (1975)

WITH modern chemotherapy, the mortality rate for amebic abscess of the liver is low. Complete recovery without permanent functional or anatomical abnormality is the rule.<sup>1</sup> We have had experience with a patient who had an amebic abscess of the liver in 1967, 1968, and 1972. Such recurrence or reinfection of the liver after proper chemotherapy is unusual.<sup>2</sup> <h3>Report of a Case</h3> A 34-year-old man was admitted in March 1967 because of intermittent fever (to 38 C [100 F]) for one month and a 5-kg (10-lb) weight loss. For several days there had been cough, dyspnea, and right pleuritic chest pain. Pedal edema developed one week before admission. There were physical signs of a right pleural effusion and the liver was enlarged to the level of the umbilicus. A right thoracentesis on the day of admission yielded 250 ml of bloody fluid and a pleural biopsy specimen showed necrotic
Successful Implementation of the Randomized Discontinuation Trial Design: An Application to the Study of the Putative Antiangiogenic Agent Carboxyaminoimidazole in Renal Cell Carcinoma—CALGB 69901
Authors: Walter M. Stadler, Gary Rosner, Eric Small, Donna Hollis, Brian Rini, S. Donald Zaentz, John Mahoney, Mark J. Ratain
Journal: Journal of Clinical Oncology (2005)

To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.
Expression of cyclooxygenase 1 and 2 by human gastric endothelial cells
Authors: M A Hull, J L Thomson, C J Hawkey
Journal: Gut (1999)

<h3>BACKGROUND</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. NSAIDs also impair granulation tissue angiogenesis and healing of established gastric ulcers in humans. The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inhibition of either or both COX isoforms (COX-1 and COX-2). <h3>AIMS</h3> To investigate COX expression by human gastric endothelial (HuGE) cells during angiogenesis in vitro. <h3>METHODS</h3> COX-1 and COX-2 expression by HuGE cells was investigated by western blot analysis, indirect immunofluorescence, reverse transcriptase polymerase chain reaction, and measurement of prostaglandin E<sub>2</sub> synthesis. Plating onto basement membrane matrix and stimulation by phorbol ester were used as in vitro models of angiogenesis. <h3>RESULTS</h3> Under normal culture conditions (30% serum), HuGE cells expressed COX-1 and low levels of COX-2. COX-2 expression was induced in HuGE cells in both angiogenesis models. Prostaglandin E<sub>2</sub> production and tubular structure formation by HuGE cells on basement membrane matrix was significantly inhibited by a selective COX-2 inhibitor (NS-398). <h3>CONCLUSION</h3> Angiogenesis by HuGE cells in vitro was associated with induction of functional COX-2 expression. A selective COX-2 inhibitor significantly decreased HuGE cell angiogenesis on basement membrane matrix. Extrapolation of these data to human gastric ulcer angiogenesis in vivo suggests that selective COX-2 inhibitors could delay gastric ulcer healing to the same extent as traditional NSAIDs which are non-selective COX inhibitors.
CLPTM1L Promotes Growth and Enhances Aneuploidy in Pancreatic Cancer Cells
Authors: Jinping Jia, Allen D. Bosley, Abbey Thompson, Jason W. Hoskins, Adam Cheuk, Irene Collins, Hemang Parikh, Zhen Xiao, Kris Ylaya, Marta Dzyadyk, Wendy Cozen, Brenda Y. Hernandez, Charles F. Lynch, Jadranka Loncarek, Sean F. Altekruse, Lizhi Zhang, Christopher J. Westlake, Valentina M. Factor, Snorri Thorgeirsson, William R. Bamlet, Stephen M. Hewitt, Gloria M. Petersen, Thorkell Andresson, Laufey T. Amundadottir
Journal: Cancer Research (2014)

Genome-wide association studies (GWAS) of 10 different cancers have identified pleiotropic cancer predisposition loci across a region of chromosome 5p15.33 that includes the TERT and CLPTM1L genes. Of these, susceptibility alleles for pancreatic cancer have mapped to the CLPTM1L gene, thus prompting an investigation of the function of CLPTM1L in the pancreas. Immunofluorescence analysis indicated that CLPTM1L localized to the endoplasmic reticulum where it is likely embedded in the membrane, in accord with multiple predicted transmembrane domains. Overexpression of CLPTM1L enhanced growth of pancreatic cancer cells in vitro (1.3-1.5-fold; PDAY7 < 0.003) and in vivo (3.46-fold; PDAY68 = 0.039), suggesting a role in tumor growth; this effect was abrogated by deletion of two hydrophilic domains. Affinity purification followed by mass spectrometry identified an interaction between CLPTM1L and non-muscle myosin II (NMM-II), a protein involved in maintaining cell shape, migration, and cytokinesis. The two proteins colocalized in the cytoplasm and, after treatment with a DNA-damaging agent, at the centrosomes. Overexpression of CLPTM1L and depletion of NMM-II induced aneuploidy, indicating that CLPTM1L may interfere with normal NMM-II function in regulating cytokinesis. Immunohistochemical analysis revealed enhanced staining of CLPTM1L in human pancreatic ductal adenocarcinoma (n = 378) as compared with normal pancreatic tissue samples (n = 17; P = 1.7 × 10(-4)). Our results suggest that CLPTM1L functions as a growth-promoting gene in the pancreas and that overexpression may lead to an abrogation of normal cytokinesis, indicating that it should be considered as a plausible candidate gene that could explain the effect of pancreatic cancer susceptibility alleles on chr5p15.33.
CLINICAL AND ELECTROENCEPHALOGRAM INVESTIGATION ON LARGACTIL IN PSYCHOSIS (PRELIMINARY STUDY)
Authors: A. SZATMARI
Journal: American Journal of Psychiatry (1956)

1. Experimental investigations have been carried out with Largactil on chronic and acute mental patients. 2. The over-all improvement in chronic cases was 69% and in acute cases 60%. 3. However, the transitory effects in acute cases indicate that while Largactil is extremely valuable in chronic psychosis, in acute psychotic breakdowns, it has value only as a sedative. 4. Electroencephalogram investigations showed that Largactil markedly decreases the muscle artefacts, decreases the frequency, and increases the voltage, causing a mild progressive synchronization and, in epileptics, it lessens the convulsive threshold. 5. In spastics it decreases spasticity through intravenous route, as tested by electromyogram.
Regulation of Food Intake Through Hypothalamic Signaling Networks Involving mTOR
Authors: Stephen C Woods, Randy J Seeley, Daniela Cota
Journal: Annual Review of Nutrition (2008)

To maintain normal activity, single cells must assure that their energy needs and utilization are continuously matched. Likewise, multicellular organisms must constantly coordinate energy intake and expenditure to maintain energy homeostasis. The brain, and the hypothalamus in particular, plays a critical role in integrating and coordinating several types of signals, including hormones and nutrients, to guarantee such homeostasis. Like single cells, the hypothalamus also profits from intracellular pathways known to work as fuel sensors to maintain energy balance. One such pathway is the mammalian target of rapamycin (mTOR). mTOR integrates different sensory inputs to regulate protein synthesis rates in individual cells, and it has recently been implicated in the central nervous system to regulate food intake and body weight as well. This review provides an overview of the role of hypothalamic intracellular fuel sensors in the overall control of energy balance and discusses the potential contribution of these fuel-sensing mechanisms to the metabolic dysregulation associated with obesity.
THE ALLOGENEIC EFFECT IN INBRED MICE
Authors: David P. Osborne, David H. Katz
Journal: The Journal of Experimental Medicine (1973)

The allogeneic effect has been shown to replace the requirement for carrier-specific helper thymus-derived (T) lymphocytes in secondary antihapten antibody responses in guinea pigs or mice. Attempts to enhance primary antibody responses to either 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH) or DNP-ovalbumin (OVA) by the allogeneic effect have failed, and frequently result in suppression. However, the present studies have demonstrated a clear allogeneic effect on primary anti-DNP responses to a DNP-conjugate of the copolymer of D-glutamic acid and D-lysine, DNP-D-GL. This compound, for which no carrier-specific helper T cells exist, normally induces a state of DNP-specific tolerance in the doses employed. However, normal (BALB/c x A/J)F(1) recipients developed primary anti-DNP antibody responses, and of the IgG class, when DNP-D-GL was administered shortly after the transfer of allogeneic parental A strain lymphoid cells. To test the possibility that the presence of KLH-specific T lymphocytes might inhibit the expression of the allogeneic effect on the primary response to DNP-KLH, studies were undertaken using T cell-depleted spleen cells. In this model, the allogeneic effect again enhanced the primary response to DNP-D-GL, but still failed to enhance the primary response to DNP-KLH. These studies indicate that the structure of the molecule employed and its specific interaction with the bone marrow-derived (B) cell membrane may be critical in the capacity of primed and unprimed B cells to be influenced by the allogeneic effect.
Recent Declines in Chronic Disability in the Elderly U.S. Population: Risk Factors and Future Dynamics
Authors: Kenneth G. Manton
Journal: Annual Review of Public Health (2007)

As U.S. life expectancy has increased, questions arise as to how the quality of health and functioning in the elderly population has changed. Data from the 1982–2004 National Long-Term Care Survey (NLTCS) suggested that chronic disability prevalence above age 65 declined at an increasing rate with a 2.2% per annum rate of decline from 1999 to 2004 ( 71 ). Inflation-adjusted per capita Medicare expenditure rates in nondisabled persons also declined, 0.9% per annum from 1982 to 2004, which suggests that declines in disability were driven by improving health—not by increases in per capita health expenditures. Declines in disability prevalence were found in other U.S. national health surveys. Analyses of U.S. Civil War veterans suggest recent disability declines were continuations of declines in both chronic disease and disability occurring over the past century due to improved nutrition, sanitation, and education. Concerns exist about whether disability declines will continue because of recent increases in obesity prevalence.
Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial
Authors: Adriana H Tremoulet, Sonia Jain, Preeti Jaggi, Susan Jimenez-Fernandez, Joan M Pancheri, Xiaoying Sun, John T Kanegaye, John P Kovalchin, Beth F Printz, Octavio Ramilo, Jane C Burns
Journal: The Lancet (2014)
Resistance of Fc receptor- deficient mice to fatal glomerulonephritis.
Authors: S Y Park, S Ueda, H Ohno, Y Hamano, M Tanaka, T Shiratori, T Yamazaki, H Arase, N Arase, A Karasawa, S Sato, B Ledermann, Y Kondo, K Okumura, C Ra, T Saito
Journal: Journal of Clinical Investigation (1998)

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.
Incompetency To Stand Trial: Is Psychiatry Necessary?
Authors: RICHARD H. BENDT, EUGENE J. BALCANOFF, GREGORY S. TRAGELLIS
Journal: American Journal of Psychiatry (1973)

Although psychiatrists disagree about whether they should have a role in the courtroom, the legal system continues to ask their help in evaluating defendants' competency to stand trial. The authors present four case reports that illustrate how psychiatrists can and should participate in the legal process. They also suggest that psychiatrists may be able to help protect a defendant's right to a speedy trial by preventing unnecessary hospitalization.