tbuckley/cabot-search huggingface dataset:
Monitoring is vital for government's end of life care strategy to be successful
Authors: L. Hitchen
Journal: BMJ (2008)

Parkinson9s disease (PD) is characterized by the progressive loss of select neuronal populations, but the prodeath genes mediating the neurodegenerative processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a stress-induced gene with proapoptotic activity that was previously described as highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA) cellular model of PD. Here, we report that Trib3 immunostaining is elevated in dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD patients. Trib3 protein is also upregulated in cellular models of PD, including neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6-OHDA, 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>), or α-synuclein fibrils (αSYN). In the toxin models, Trib3 induction is substantially mediated by the transcription factors CHOP and ATF4. Trib3 overexpression is sufficient to promote neuronal death; conversely, Trib3 knockdown protects neuronal PC12 cells as well as ventral midbrain dopaminergic neurons from 6-OHDA, MPP<sup>+</sup>, or αSYN. Mechanism studies revealed that Trib3 physically interacts with Parkin, a prosurvival protein whose loss of function is associated with PD. Elevated Trib3 reduces Parkin expression in cultured cells; and in the SNpc of PD patients, Parkin levels are reduced in a subset of dopaminergic neurons expressing high levels of Trib3. Loss of Parkin at least partially mediates the prodeath actions of Trib3 in that Parkin knockdown in cellular PD models abolishes the protective effect of Trib3 downregulation. Together, these findings identify Trib3 and its regulatory pathways as potential targets to suppress the progression of neuron death and degeneration in PD. <b>SIGNIFICANCE STATEMENT</b> Parkinson9s disease (PD) is the most common neurodegenerative movement disorder. Current treatments ameliorate symptoms, but not the underlying neuronal death. Understanding the core neurodegenerative processes in PD is a prerequisite for identifying new therapeutic targets and, ultimately, curing this disease. Here, we describe a novel pathway involving the proapoptotic protein Trib3 in neuronal death associated with PD. These findings are supported by data from multiple cellular models of PD and by immunostaining of postmortem PD brains. Upstream, Trib3 is induced by the transcription factors ATF4 and CHOP; and downstream, Trib3 interferes with the PD-associated prosurvival protein Parkin to mediate death. These findings establish this new pathway as a potential and promising therapeutic target for treatment of PD.
Counsellors in English and Welsh general practices: their nature and distribution.
Authors: B Sibbald, J Addington-Hall, D Brenneman, P Freeling
Journal: BMJ (1993)

OBJECTIVE--To establish the prevalence of counselling services in English and Welsh general practices and factors associated with their distribution; to describe qualifications, working arrangements, and case mix of "counsellors." DESIGN--Postal questionnaire and telephone interview survey of a sample of about one in 20 general practitioners in England and Wales. SETTING--English and Welsh general practices. SUBJECTS--1880 general practitioners of whom 1542 (82%) completed questionnaires. MAIN OUTCOME MEASURES--Prevalence and distribution of practice counselling services; counsellors9 qualifications and funding; types of patients referred. RESULTS--586 counsellors were distributed among 484 of the 1542 practices. Three types of counsellor predominated: community psychiatric nurses (187); "practice counsellors" (145); and clinical psychologists (95). Practice characteristics which independently predicted the presence of a counsellor were for community psychiatric nurses four or more partners (odds = 1.72, 95% confidence interval 1.18 to 2.26); for practice counsellors stress clinic (odds = 2.22; 1.83 to 2.61), training practice (odds = 1.70; 1.24 to 2.16), and health region (chi 2 = 55.94; df = 14; p &lt; 0.001); and for clinical psychologists list size of &gt; or = 10,500 (odds = 1.79; 1.09 to 2.49), training practice (odds = 1.78; 1.31 to 2.25), health region (chi 2 = 48.31; df = 14; p &lt; 0.001). 197 counsellors had training in counselling. The qualifications of 85 were unknown to the general practitioner. The principal source of funding was the district health authority for community psychiatric nurses (150) and clinical psychologists (58) and the family health services authority for practice counsellors (76). All counsellors were referred a wide range of problems. CONCLUSIONS--Counselling services are wide-spread in general practice, but a high proportion of counsellors lack qualifications, and many may be referred problems outside their knowledge.
EPIDEMIC OF STREPTOCOCCUS PNEUMONIA AND EMPYEMA AT CAMP DODGE, IOWA
Authors: JOSEPH L. MILLER
Journal: JAMA (1918)

From Sept. 20, 1917, until May 10, 1918, 675 patients, whose cases were diagnosed as lobar pneumonia, have entered the base hospital at Camp Dodge, Iowa. This does not include a limited number of cases diagnosed clinically as bronchopneumonia. At necropsy, however, not infrequently it was found that, in reality, we were dealing with a confluent bronchopneumonia which was localized chiefly or entirely in a single lobe. Inasmuch, however, as these cases, if necropsy had not been performed, would have been placed on record as lobar pneumonia, they have been so considered in this discussion. Although measles was quite prevalent throughout the entire winter, pneumonia as a complication was very infrequent; only since about May 1 has pneumonia as a complication of measles reached any considerable number, and this period is not connected with the epidemic of streptococcus pneumonia, which at the time mentioned was on the wane. The ordinary
Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris
Authors: W. Lew, E. Lee, J.G. Krueger
Journal: British Journal of Dermatology (2004)

Type 1 T cells are hypothesized to be central in the immunopathogenesis of psoriasis. Through elaboration of interferon (IFN)-gamma, type 1 T cells regulate the expression of many 'downstream' inflammatory genes, including an array of chemokines that regulate leucocyte trafficking and activation in skin lesions. Accordingly, disease progression and/or severity might be controlled by the degree to which differing cytokines and chemokines are overexpressed in focal skin regions. To examine this possibility, we studied two forms of chronic psoriasis vulgaris that differ significantly in overall severity and progression: small plaque (SP) psoriasis occurring in Korean patients, and large plaque (LP) psoriasis occurring in North American patients.To characterize LP and SP psoriasis vulgaris with respect to expression of proinflammatory genes that define the type 1 T-cell axis in skin lesions [genes encoding interleukin (IL)-12, IFN-gamma, and IFN-gamma-regulated chemokines or inflammatory mediators].Total cellular RNA of skin samples from groups of patients with LP or SP psoriasis was analysed by quantitative reverse transcription-polymerase chain reaction (TaqMan analysis) to compare the differences in mRNA expression of genes related to the IFN-gamma pathway.The mRNA expression of keratin 16, CD25, IFN-gamma, IL-12 p40, signal transducer and activator of transcription-1, inducible nitric oxide synthase, IL-8, macrophage inflammatory protein-3alpha, monocyte chemoattractant protein-1, S100A12, IFN-gamma-inducible protein of 10 kDa, IFN-inducible T-cell alpha-chemoattractant and monokine induced by IFN-gamma was increased in the lesions of both LP psoriasis and SP psoriasis. However, IL-18 mRNA expression was significantly different in the lesions of LP psoriasis in comparison with those of SP psoriasis.The results indicate that proinflammatory type 1 genes regulated by IFN-gamma are similarly increased in both SP and LP psoriasis, but a potential difference in IL-18 exists between these disease forms. The consistent activation of this set of genes argues for a central role of IFN-gamma as a molecular regulator of inflammation in these distinct subtypes of psoriasis vulgaris. In contrast, disease extent/severity must be controlled by yet other factors.
Testicular Germ-Cell Neoplasms: Recent Advances in Diagnosis and Therapy
Authors: TOM ANDERSON
Journal: Annals of Internal Medicine (1979)

The diagnosis and treatment of testicular neoplasms have been facilitated by identification of the tumor-associated proteins alpha-fetoprotein and human chorionic gonadotropin. These circulating tumor markers, present in 85% to 90% of patients with nonseminomatous testicular cancer, reflect tumor presence and reliably indicate response to therapy. Alpha-fetoprotein is produced by embryonal carcinoma and yolk-sac tumors; human chorionic gonadotropin is produced by syncytiotrophoblastic giant cells and the syncytiotrophoblastic component of choriocarcinoma. Refinements in staging techniques and definitions have improved prognostication. Effective therapy for seminoma (cure rate, greater than 90%), early-stage (stage I, stage IIN1-2) testicular carcinoma (cure rate, 65% to 87%), and advanced (stage IIN3-4, stage III) testicular carcinoma (complete remission rate, 50% to 74%) has been shown in clinical trials. Adjuvant chemotherapy/radiotherapy trials for limited stages of testicular carcinoma, and further experience with intensive chemotherapy-based trials for advanced stages may further improve the prognosis for all testicular germ-cell neoplasms.
IMMEDIATE VERSUS DELAYED PERCUTANEOUS CORONARY INTERVENTION FOR PATIENTS WITH NON-ST SEGMENT ELEVATION-ACUTE CORONARY SYNDROME: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Naveen Rajpurohit, Nadish Garg, Abhishek Choudhary, Kul B. Aggarwal, Kevin C. Dellsperger, Martin Alpert
Journal: Journal of the American College of Cardiology (2011)
Cancer of the Larynx
Authors: William P. Rogers, Charles Reynolds, Masao Yatsuhashi
Journal: New England Journal of Medicine (1966)

CANCERS of the larynx comprise 20 per cent of malignant lesions of the head and neck.1 Over 90 per cent are of the squamous-cell type, and they occur in a male-to-female ratio of nearly 10:1. The median age at the time of detection is sixty years. Although the cancers arise in an area in which over 90 per cent of them can be seen and biopsied by simple laryngoscopy 85 per cent of patients have persistent symptoms for four months before the diagnosis is made.1 AnatomyFor anatomic and pathological reasons, the entire laryngeal unit from the epiglottis at the . . .
Reproductive Anthropology: Descent Through Woman
Authors: T. Keith Edwards
Journal: JAMA (1982)

Reading this book is like listening to a resolutions committee at a large medical convention bring in an endless and tiresome resolution. You know the kind I mean: where the resolutions committee chairman reads off six to ten "whereas" clauses before arriving at the point of the resolution. After completing each chapter, the reader is in the position of having heard one more whereas clause from the author. We keep hoping that he will eventually get to the point, but he never does. In addition to this disconcerting, verbose wandering through obstetric history, Dr Gebbie bows to present-day militant feminism by referring to the human race as "wan." This appears to be a newly coined word combining the first letter of woman with the last two letters of man, creating a new word that is simply distracting to the reader. The title of the first chapter, "In the Very Beginning,"
CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy
Authors: Joseph M. Tuscano, Jason Kato, David Pearson, Chengyi Xiong, Laura Newell, Yunpeng Ma, David R. Gandara, Robert T. O'Donnell
Journal: Cancer Research (2012)

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets.
William Carlos Williams Commemorative Issue
Authors: John Stone
Journal: JAMA (1985)

Whatever other designations our age may deserve, it seems to me an age of<i>biography</i>. As a glance at published titles will attest, there is a passion for details of how the famous have lived their lives and made their contributions (or<i>not</i>made them, as the case may be). It's as though our disparate generations have together agreed with Emerson that, "There is properly no history; only biography." Moreover, our age has not only the taste for biography, but also the technology to record it: on tape, on film, and, most accessibly (at least for the present), in words. It must have been in this spirit that the editors of the<i>Journal of the Medical Society of New Jersey</i>decided to publish an entire issue in honor of a native son, the physicianwriter William Carlos Williams (1883 to 1963). The issue was conceived to celebrate the centennial of his
Decreased plasma fibrinolysis in patients with rheumatoid arthritis.
Authors: J J Belch, B McArdle, R Madhok, K McLaughlin, H A Capell, C D Forbes, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1984)

We have investigated the fibrinolytic status of 56 patients with rheumatoid arthritis (RA). Plasma fibrinogen and plasminogen were significantly elevated. Levels of these two substrates, along with alpha 2 macroglobulin and antithrombin III correlated with disease activity. Plasminogen activator (PA) activity was decreased in patients with severe disease. Twelve patients were given stanozolol, a fibrinolytic enhancing agent, for two months as a test for endothelial production of plasminogen activator. This caused a significant increase in blood plasminogen and PA activity. Five patients received a two-week course of stanozolol with joint aspiration before and after. Joint plasminogen levels were increased. We suggest that inadequate fibrinolysis occurs in RA, and that this may contribute to some of the pathological features of the disease. It is possible to stimulate both blood and joint fibrinolysis by stanozolol. A more prolonged increase in plasminogen activator activity might decrease joint fibrin deposition, and stanozolol should be investigated as a therapeutic agent in RA.
Anaerobic axillary abscess.
Authors: R D Leach, S J Eykyn, I Phillips, B Corrin, E A Taylor
Journal: BMJ (1979)

Fifty-two patients with axillary abscesses were seen during two years. Staphylococcus aureus was isolated from 34, anaerobic bacteria from 12, and skin flora from five; in one case the pus was sterile. Seven patients with hidradenitis suppurativa had recurrent infection with abscess formation, which was bilateral in three. Anaerobes were isolated in five of these cases and skin flora alone in two. Anaerobes are secondary invaders in this condition, and histological examination shows that the primary abnormality is obstruction of pilosebaceous follicles and apocrine glands, associated with keratin plugging of the follicles. Chemotherapy offers little hope of cure, although metronidazole removes the offensive smell of the discharge. Radical surgery is usually indicated.
Medical Students in the Philippines
Authors: Reuben C. Balagot
Journal: JAMA (1965)

To the Editor:—  It is a little difficult to accept some of Dr. Bowers' observations, his possibly preconceived notions, and surely outmoded ideological cliches which, he believes, contribute to the mold of the Filipino character ( JAMA  191 : 119-123 [Jan 11] 1965). For instance, I am sure Dr. Bowers means waves of immigrants from Indonesia instead of Indochina . The cacique, or absentee landlord, has become politically intolerable. Usury, if at all rampant, is subject to severe and punitive antiusury laws.  Powerful influences which help pattern the medical student's decisions and actions, eg, family domination and provincialism, have been eroded to a great degree by the disrupting impact of World War II. The extensive exposure to GIs during this period to the present has destroyed provincialism.  Nevertheless, Dr. Bowers' observation of the student's limited ability to use the English language may be right. This limitation is probably more from a verbal aspect
A Noninvasive Technique for the Determination of Velocity of Circumferential Fiber Shortening in Man
Authors: John A. Poraskos, William Grossman, Stephen Saltz, James E. Dalen, Lewis Dexter
Journal: Circulation Research (1971)

Velocity of circumferential fiber shortening (V as determined by analysis of left ventricular cineangiocardiograms has been proposed as a measure of left ventricular myocardial contractility. In this study, a noninvasive ultrasonic technique was used to measure the rate of shortening of the left ventricular internal minor axis throughout ejection in 61 patients. These measurements permitted calculation of mean Vcr. In 23 patients with normal left ventricular function, mean V CF averaged 1.45 ± 0.08 circumferences/sec (mean SE). Tn contrast, mean V in 38 patients with impaired left ventricular function was significantly depressed (0.91 ±0.09 circumferences/see, P &lt;0.001). In 17 patients, adequate resolution of septal and posterior wall thicknesses permitted measurement of midwali radius at 50-msec intervals throughout the cardiac cycle. These measurements permitted computation of instantaneous and peak V Values for peak V CF at the midwall were generally similar to those observed for mean V at the internal axis. In patients with normal left ventricular function, peak V CF averaged 1.58 ± 0.23 circumferences/sec. This study has demonstrated the feasibility of measuring the velocity of left ventricular circumferential fiber shortening in man by a noninvasive method. Initial studies indicate that this approach may prove useful in the detection and serial evaluation of left ventricular performance in patients with heart disease.
Abstract 3694: The mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase as an inhibitory target for cancer therapeutics
Authors: Athanasios Paschos, Pierre Laflamme, Gurmit Singh
Journal: Cancer Research (2010)

Abstract The hypoxic and glycolytic environment of malignant cells facilitates high levels of reactive oxygen species (ROS) production. Breast, ovarian and prostate cancer etiology is associated with the ROS production, which are thought to play an important role in regulating the cancers cell growth, survival and metastasis. A potent and major cellular, however functional limited characterized source of ROS, is the mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (GPD2). GPD2 is an essential component of the glycerol-3-phosphate shuttle and necessarily expressed in all tissues. In several cancer cell lines, GPD2 is highly expressed and we estimated it accounts for up to 70% of the total ROS production within the prostate cancer cell line PC3. In this study we have utilized this knowledge, to complete a cell-based high throughput-screening (HTS) assay, aimed to identify small molecule inhibitors of the GPD2 dependent ROS formation in PC3 cell lines. We employed the amplex red hydrogen peroxidase detection assay and adapted it to the HTS format. 133 inhibitory compounds from the Canadian Compound Collection were identified to reduce the ROS production activity within the PC3 cells. In order to validate these hits and to determine their mode of action, we PCR amplified GPD2 form PC3-cell cDNA and purified recombinant human GPD2 from a bacterial overproducing strain to homogeneity by employing Strep-tactin affinity-chromatography. The heterologously expressed enzyme, devoid of its mitochondrial target sequence, displayed glycerol-3-phosphate dependent resazurin, dichlorophenolindophenol, as well as tetrazole/phenazine methosulfate oxidoreductase activity. Follow up enzymatic assays of the primary HTS hits with the artificial electron acceptors identified several GPD2 activity specific inhibitors. Subsequent concentration response studies of the HTS derived inhibitors elucidated their in vitro half maximal inhibitory concentration at the range of 10 μM. In order to map GPD2's ROS production site and determine the inhibitor binding sites within the enzyme, we bioinformatically derived the proteins tertiary structure. Considering that GPD2 dependent ROS formation may drive the prostate cancer proliferation, we aim by exploiting the results of this work to generate novel lead molecules as promising potential anti-proliferating cancer drug candidates. (This work was supported by a grant from the Canadian Institutes of Health Research to Gurmit Singh) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3694.
Diagnostic usefulness of testing for anti-HBc IgM in acute hepatitis B
Authors: Karen L. Lindsay, Anne J. Nizze, Ronald Koretz, Gary Gitnick
Journal: Hepatology (1986)

Numerous tests to detect anti-HBc IgM have been developed and shown to have different degrees of sensitivity and specificity. One of these assays, Corzyme-M (Abbott Laboratories, North Chicago, Ill.), recently became commercially available. The present study was undertaken to evaluate the clinical utility of this anti-HBc IgM test in establishing the diagnosis of acute hepatitis B using sera from a group of 42 prospectively followed individuals who had been exposed to hepatitis B virus. The Corzyme-M test was highly sensitive in detecting recent hepatitis B virus infection. All 30 patients with symptomatic and 12 with asymptomatic acute hepatitis B virus infection developed anti-HBc IgM. However, the timing of sample testing relative to onset of symptoms in symptomatic patients was important, inasmuch as 2 of 23 patients were negative for anti-HBc IgM early in the symptomatic period, although all were HBsAg positive. The duration of anti-HBc IgM positivity after acute infection was variable, ranging from 2 to 134 weeks. In 14% of patients, anti-HBc IgM remained detectable for more than 1 year. From the data, recommendations are given regarding the usefulness of anti-HBc IgM testing in the diagnosis of acute hepatitis B virus infection.