tbuckley/cabot-search huggingface dataset:
Book: Practical Neurology
Authors: R. Kale
Journal: BMJ (2002)

Ed Charles Warlow ![Graphic][1]</img>Bimonthly, Blackwell Science Ltd Annual subscription £68 to £170 Rating: ![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img>![Graphic][5]</img> Here is a challenge. Clinical neurology is difficult, neurologists clever bores, and neurological journals unreadable. How many want to debate this? An editorial in this issue linked to a paper in the Journal of Neurology, Neurosurgery & Psychiatry (JNNP) and common knowledge among students and doctors are evidence that neurology is perceived as difficult by most who grapple with it—especially part time. According to their peers, neurologists are diagnosticians who astonish others with the superiority of their diagnostic skills and a virtually empty medicine bag—an opinion perhaps self inflicted … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif
Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo
Authors: De-Kuan Chang, Raymond J. Moniz, Zhongyao Xu, Jiusong Sun, Sabina Signoretti, Quan Zhu, Wayne A. Marasco
Journal: Molecular Cancer (2015)

Carbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). Therapeutic approaches targeting CAIX have focused on the development of CAIX inhibitors and specific immunotherapies including monoclonal antibodies (mAbs). However, current in vivo mouse models used to characterize the anti-tumor properties of fully human anti-CAIX mAbs have significant limitations since the role of human effector cells in tumor cell killing in vivo is not directly evaluated.The role of human anti-CAIX mAbs on CAIX(+) RCC tumor cell killing by immunocytes or complement was tested in vitro by antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) as well as on CAIX(+) RCC cellular motility, wound healing, migration and proliferation. The in vivo therapeutic activity mediated by anti-CAIX mAbs was determined by using a novel orthotopic RCC xenograft humanized animal model and analyzed by histology and FACS staining.Our studies demonstrate the capacity of human anti-CAIX mAbs that inhibit CA enzymatic activity to result in immune-mediated killing of RCC, including nature killer (NK) cell-mediated ADCC, CDC, and macrophage-mediated ADCP. The killing activity correlated positively with the level of CAIX expression on RCC tumor cell lines. In addition, Fc engineering of anti-CAIX mAbs was shown to enhance the ADCC activity against RCC. We also demonstrate that these anti-CAIX mAbs inhibit migration of RCC cells in vitro. Finally, through the implementation of a novel orthotopic RCC model utilizing allogeneic human peripheral blood mononuclear cells in NOD/SCID/IL2Rγ(-/-) mice, we show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in inhibition of CAIX(+) tumor growth.Our findings demonstrate that these novel human anti-CAIX mAbs have therapeutic potential in the unmet medical need of targeted killing of HIF-driven CAIX(+)RCC. The orthotopic tumor xenografted humanized mouse provides an improved model to evaluate the in vivo anti-tumor capabilities of fully human mAbs for RCC therapy.
HEMATOPORPHYRIN THERAPY IN THE AFFECTIVE PSYCHOSES
Authors: Edward A. Strecker, Harold D. Palmer, Francis J. Braceland
Journal: American Journal of Psychiatry (1936)

1. Synthetic hematoporphyrin hydrochloride when injected into experimental animals (white rat and frog) produces photosensitization and motor activation with evidences of skin irritation. 2. When injected in test doses intradermally in human beings it produces marked local photosensitization and residual pigmentation after exposure to sunlight. 3. The changes in body metabolism and blood chemistry of 12 patients do not seem to be significant. 4. When administered either orally or intramuscularly or by both techniques to psychotic patients it seems to produce activation, in some cases mental stimulation and in others general somatic improvement. In 55 cases of affective reactions treated 36.4 per cent showed marked sustained improvement, 18.2 per cent moderate clinical improvement, 18.2 per cent general physical improvement but no change in the course of the psychosis, while 27.2 per cent were not benefited. 5. The activation in some instances cannot be regarded as a good therapeutic result. 6. The specific effects of its photosensitizing power seem to be made evident in the sensitization of the skin to sunlight and in at least one case in photophobia. 7. It is suggested that the beneficial physiologic and psychologic actions of the drug are not necessarily due to some poorly understood changes in the vegetative nervous system resulting from skin sensitization. They may be due to the improved oxygen uptake of the brain cells. This is greatly enhanced in the presence of light and by the increased sensitization of the patient to light.
A non-tight junction function of claudin-7—Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment
Authors: Zhe Lu, Do Hyung Kim, Junming Fan, Qun Lu, Kathryn Verbanac, Lei Ding, Randall Renegar, Yan-Hua Chen
Journal: Molecular Cancer (2015)

Claudins are a family of tight junction (TJ) membrane proteins involved in a broad spectrum of human diseases including cancer. Claudin-7 is a unique TJ membrane protein in that it has a strong basolateral membrane distribution in epithelial cells and in tissues. Therefore, this study aims to investigate the functional significance of this non-TJ localization of claudin-7 in human lung cancer cells.Claudin-7 expression was suppressed or deleted by lentivirus shRNA or by targeted-gene deletion. Cell cycle analysis and antibody blocking methods were employed to assay cell proliferation and cell attachment, respectively. Electron microscopy and transepthelial electrical resistance measurement were performed to examine the TJ ultrastructure and barrier function. Co-immunolocalization and co-immunoprecipitation was used to study claudin-7 interaction with integrin β1. Tumor growth in vivo were analyzed using athymic nude mice.Claudin-7 co-localizes and forms a stable complex with integrin β1. Both suppressing claudin-7 expression by lentivirus shRNA in human lung cancer cells (KD cells) and deletion of claudin-7 in mouse lungs lead to the reduction in integrin β1 and phospho-FAK levels. Suppressing claudin-7 expression increases cell growth and cell cycle progression. More significantly, claudin-7 KD cells have severe defects in cell-matrix interactions and adhere poorly to culture plates with a remarkably reduced integrin β1 expression. When cultured on uncoated glass coverslips, claudin-7 KD cells grow on top of each other and form spheroids while the control cells adhere well and grow as a monolayer. Reintroducing claudin-7 reduces cell proliferation, upregulates integrin β1 expression and increases cell-matrix adhesion. Integrin β1 transfection partially rescues the cell attachment defect. When inoculated into nude mice, claudin-7 KD cells produced significantly larger tumors than control cells.In this study, we identified a previously unrecognized function of claudin-7 in regulating cell proliferation and maintaining epithelial cell attachment through engaging integrin β1.
Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases
Authors: Maartje C P Cleophas, Tania O Crişan, Heidi Lemmers, Helga Toenhake-Dijkstra, Gianluca Fossati, Tim L Jansen, Charles A Dinarello, Mihai G Netea, Leo A B Joosten
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Acute gouty arthritis is caused by endogenously formed monosodium urate (MSU) crystals, which are potent activators of the NLRP3 inflammasome. However, to induce the release of active interleukin (IL)-1β, an additional stimulus is needed. Saturated long-chain free fatty acids (FFAs) can provide such a signal and stimulate transcription of pro-IL-1β. In contrast, the short-chain fatty acid butyrate possesses anti-inflammatory effects. One of the mechanisms involved is inhibition of histone deacetylases (HDACs). Here, we explored the effects of butyrate on MSU+FFA-induced cytokine production and its inhibition of specific HDACs. Methods Freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with MSU and palmitic acid (C16.0) in the presence or absence of butyrate or a synthetic HDAC inhibitor. Cytokine responses were measured with ELISA and quantitative PCR. HDAC activity was measured with fluorimetric assays. Results Butyrate decreased C16.0+MSU-induced production of IL-1β, IL-6, IL-8 and IL-1β mRNA in PBMCs from healthy donors. Similar results were obtained in PBMCs isolated from patients with gout. Butyrate specifically inhibited class I HDACs. The HDAC inhibitor, panobinostat and the potent HDAC inhibitor, ITF-B, also decreased ex vivo C16.0+MSU-induced IL-1β production. Conclusions In agreement with the reported low inhibitory potency of butyrate, a high concentration was needed for cytokine suppression, whereas synthetic HDAC inhibitors showed potent anti-inflammatory effects at nanomolar concentrations. These novel HDAC inhibitors could be effective in the treatment of acute gout. Moreover, the use of specific HDAC inhibitors could even improve the efficacy and reduce any potential adverse effects.
Large serrated tongue and gastrointestinal bleeding
Authors: A. Rehman, W. L. Peterson, J. P. Ahluwalia
Journal: Gut (2010)

A 60-year-old man with history of diabetes mellitus, chronic renal insufficiency, hypertension and multiple myeloma diagnosed 1 year ago presented with new onset crampy abdominal pain and tarry black stools. He had been receiving treatment with Bortezomib. His vital signs were normal except for the blood pressure that was 146/82 mm Hg. Physical examination revealed a thick, serrated tongue with very prominent impression of teeth (panel A), mild lower abdominal tenderness without any rebound and melenic stool in the rectum. Laboratory studies showed a haemoglobin of 10 g/dl, serum creatinine …
Strategies for reducing inequalities and improving developmental outcomes for young children in low-income and middle-income countries
Authors: Patrice L Engle, Lia CH Fernald, Harold Alderman, Jere Behrman, Chloe O'Gara, Aisha Yousafzai, Meena Cabral de Mello, Melissa Hidrobo, Nurper Ulkuer, Ilgi Ertem, Selim Iltus
Journal: The Lancet (2011)
Gabapentin Treatment for Alcohol Dependence
Authors: Barbara J. Mason, Susan Quello, Vivian Goodell, Farhad Shadan, Mark Kyle, Adnan Begovic
Journal: JAMA Internal Medicine (2013)

Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling.Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups.Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.clinicaltrials.gov Identifier: NCT00391716.
Are ultrasound and magnetic resonance imaging of value in assessment of Achilles tendon disorders? A two year prospective study
Authors: K M Khan, B B Forster, J Robinson, Y Cheong, L Louis, L Maclean, J E Taunton
Journal: British Journal of Sports Medicine (2003)

To (a) compare ultrasound (US; including grey scale and colour and power Doppler) and magnetic resonance imaging (MRI; with high resolution and fat saturation sequences) with a clinical yardstick in the evaluation of chronic Achilles tendinopathy, and (b) examine whether either imaging method predicted 12 and 24 month clinical outcome.Forty five patients with symptoms in 57 Achilles tendons were diagnosed with tendinopathy by an experienced sports medicine doctor. All patients underwent US examination (12 MHz probe) with colour and power Doppler, and 25 consecutive patients also underwent MRI with high resolution T1 weighted and STIR sequences.US identified abnormal morphology in 37 of the 57 symptomatic tendons (65%) and normal morphology in 19 of 28 asymptomatic tendons (68%). Baseline US findings did not predict 12 month clinical outcome. The addition of colour and power Doppler did not improve the diagnostic performance of US. MRI identified abnormal morphology in 19 of 34 symptomatic tendons (56%) and normal morphology in 15 of 16 asymptomatic tendons (94%). Lesser grades of MR signal abnormality at baseline were associated with better clinical status at 12 month follow up.US and MRI show only moderate correlation with clinical assessment of chronic Achilles tendinopathy. Graded MRI appearance was associated with clinical outcome but US was not.
The Plasma Disappearance, Excretion, and Tissue Distribution of Cobalt60 Labelled Vitamin B12 in Normal Subjects and Patients with Chronic Myelogenous Leukemia
Authors: Aaron Miller, Howard F. Corbus, John F. Sullivan
Journal: Journal of Clinical Investigation (1957)

The serum concentration of vitamin B12 is in- creased in chronic myelogenous leukemia, and there is an associated increase in the in vitro binding of vitamin B12 by such sera (1, 2).On the other hand, the vitamin B12 concentration in the white cells and tissues in chronic myelogenous leu- kemia is not elevated (2).Mollin, Pitney, Baker, and Bradley (3) have demonstrated a delayed disappearance of cobalt58 labelled vitamin B12 from the plasma of patients with chronic myelogenous leukemia using an intravenous dose of 1.5 micro- grams.It was the purpose of this study to meas- ure plasma disappearance, tissue distribution, and excretion of a 4-microgram intravenous dose of cobalt60 labelled vitamin B12 in normal subjects and patients with chronic myelogenous leukemia.In vitro experiments would indicate that this dose exceeds the binding capacity of normal serum by about four fold, but is within the total binding ca- pacity of chronic myelogenous leukemia serum (1, 2,4).Using a 4-microgram dose, a clear-cut differen- tiation could be made between normal controls and patients with chronic myelogenous leukemia. METHODS A. Clinical materialThe subjects chosen for normal controls in this study were hospitalized patients convalescing from cerebro- vascular accidents.Two to four months had elapsed since the onset of hemiparesis.All were asymptomatic save for residual paralysis, and none had evidence of anemia, renal disease, liver disease, congestive heart failure or infection.The diagnosis of chronic myelogenous leu- kemia was well established in eight patients.At the time of study, four patients had received no anti-leukemic therapy, and four had received some form of anti-leukemic therapy from three weeks to six months previously.Also studied were two patients with myeloid metaplasia, one patient with chronic lymphatic leukemia, one patient with Laennec's cirrhosis with ascites and two postoperative patients with common bile duct drainage.B. Experimental plan * Plasma volume was determined by the Evans blue technique.
Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: a multicentre cohort study
Authors: K. S. Boparai, E. M. H. Mathus-Vliegen, J. J. Koornstra, F. M. Nagengast, M. van Leerdam, C. J. M. van Noesel, M. Houben, A. Cats, L. P. van Hest, P. Fockens, E. Dekker
Journal: Gut (2009)

<h3>Background and aims</h3> Patients with hyperplastic polyposis syndrome (HPS) receive endoscopic surveillance to prevent malignant progression of polyps. However, the optimal treatment and surveillance protocol for these patients is unknown. The aim of this study was to describe the clinical and pathological features of a large HPS cohort during multiple years of endoscopic surveillance. <h3>Methods</h3> Databases were searched for patients with HPS, who were analysed retrospectively. Endoscopy reports and histopathology reports were collected to evaluate frequency of endoscopic surveillance and to obtain information regarding polyp and the presence of colorectal cancer (CRC). <h3>Results</h3> In 77 patients with HPS, 1984 polyps were identified during a mean follow-up period of 5.6 years (range: 0.5–26.6). In 27 (35%) patients CRC was detected of which 22 (28.5%) at initial endoscopy. CRC was detected during surveillance in five patients (cumulative incidence: 6.5%) after a median follow-up time of 1.3 years and a median interval of 11 months. Of these interval CRCs, 4/5 were detected in diminutive serrated polyps (range: 4–16 mm). The cumulative risk of CRC under surveillance was 7% at 5 years. At multivariate logistic regression, an increasing number of hyperplastic polyps (OR 1.05, p=0.013) and serrated adenomas (OR 1.09, p=0.048) was significantly associated with CRC presence. <h3>Conclusions</h3> HPS patients undergoing endoscopic surveillance have an increased CRC risk. The number of serrated polyps is positively correlated with the presence of CRC in HPS, thus supporting a 'serrated pathway' to CRC. To prevent malignant progression, adequate detection and removal of all polyps seems advisable. If this is not feasible, surgical resection should be considered.
Defective autophagosome trafficking contributes to impaired autophagic flux in coronary arterial myocytes lacking CD38 gene
Authors: Yang Zhang, Ming Xu, Min Xia, Xiang Li, Krishna M. Boini, Mi Wang, Erich Gulbins, Paul H. Ratz, Pin-Lan Li
Journal: Cardiovascular Research (2014)

Autophagic flux is an important process during autophagy maturation in smooth muscle cells. However, the molecular mechanisms underlying autophagic flux in these cells are largely unknown. Here, we revealed a previously undefined role of CD38, an enzyme that metabolizes NADP(+) into NAADP, in the regulation of autophagic flux in coronary arterial myocytes (CAMs).In vivo CD38 gene knockout mice (CD38(-/-)) fed the high-fat Western diet showed increased accumulation of autophagosomes in coronary arterial media compared with that in wild-type (CD38(+/+)) mice, suggesting that CD38 gene deletion results in a defective autophagic process in CAMs of coronary arteries. In primary cultured CAMs, CD38 gene deletion markedly enhanced 7-ketocholesterol (7-Ket, an atherogenic stimulus and autophagy inducer)-induced accumulation of autophagosomes and increased expression of an autophagic marker, LC3B. However, no difference in autophagosome formation was observed between CD38(+/+) and CD38(-/-) CAMs when autophagic flux was blocked, which indicates that CD38 regulates autophagic flux rather than induction of autophagosome formation. Further, 7-Ket-induced formation of autophagolysosomes was markedly attenuated in CD38(-/-) CAMs compared with CD38(+/+) CAMs. Mechanistically, CD38 gene deletion markedly inhibited 7-Ket-induced dynein activation and autophagosome trafficking, which were associated with attenuated lysosomal Ca(2+) release. Importantly, coronary arterial smooth muscle from CD38(-/-) mice fed the Western diet exhibited phenotypic changes towards a more dedifferentiated state with abnormal extracellular matrix metabolism.Taken together, these results suggest that CD38 plays a critical role in autophagosome trafficking and fusion with lysosomes, thus controlling autophagic flux in CAMs under atherogenic stimulation.
CONSTRUCTION OF AN OXYGEN CHAMBER FOR THE TREATMENT OF PNEUMONIA
Authors: William C. Stadie
Journal: The Journal of Experimental Medicine (1922)

1. The construction of an oxygen chamber is given. This chamber can be quickly filled with oxygen to any concentration up to 65 per cent and maintained at the desired concentration for an indefinite time. 2. The construction of ventilating system, cooling device, carbon dioxide remover, automatic oxygen analyzer, and filling and maintenance devices is given. 3. The chamber is designed so that pneumonia patients with anoxemia may be placed in it and breathe an atmosphere containing 40 to 60 per cent of oxygen. 4. The chamber is easy of ingress and egress, is economical in cost of operation, and comfortably accomodates patient and attendants so that adequate nursing and medical attention can be given at all times.
Studies in laboratory animals to assess the safety of anti-inflammatory agents in acute porphyria.
Authors: K E McColl, G G Thompson, M R Moore
Journal: Annals of the Rheumatic Diseases (1987)

Over the past decade, the treatment of rheumatoid arthritis has been revolutionised by the development of therapies targeted at molecules involved in driving the inflammatory response. This review briefly summarises the established uses of biologic therapies in rheumatoid disease, and outlines other diseases in rheumatology and other fields where biologic agents are finding a role.
Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin – Microbubble scaffold
Authors: Thai-Yen Ling, Yen-Liang Liu, Yung-Kang Huang, Sing-Yi Gu, Hung-Kuan Chen, Choa-Chi Ho, Po-Nien Tsao, Yi-Chung Tung, Huei-Wen Chen, Chiung-Hsiang Cheng, Keng-Hui Lin, Feng-Huei Lin
Journal: Biomaterials (2014)
HTLV-I and -II
Authors: S. Gerald Sandler
Journal: JAMA (1986)

In the June 13 issue ofThe Journal, M. Robert-Guroff et al<sup>1</sup>reported antibody prevalences of 9% for human T-cell lymphotropic virus (HTLV) type I, 18% for HTLV-II, and 41% for HTLV-III in drug abusers in New York. Of concern is the known association of HTLV-I and adult T-cell leukemia (ATL), raising the possibility that this report of serological findings may be the forewarning of serious clinical events yet to come. Although HTLV-I is endemic in some areas of Japan, the Caribbean, and Africa, both HTLV-I infection and ATL are rare in the United States.<sup>2,3</sup>In Kyushu, an endemic area in Japan, a recent study revealed that 100% of 18 patients with ATL had HTLV-I antibodies, compared with 16% HTLV-I seropositivity in 604 apparently healthy adults.<sup>2</sup>Other studies of healthy populations in Japan indicate that high rates of HTLV-I infection are restricted geographically, with prevalences ranging from