tbuckley/cabot-search huggingface dataset:
Clinical spectrum of myelophthisis in cancer patients
Authors: Stephen N. Makoni, Damian A. Laber
Journal: American Journal of Hematology (2004)

Myelophthisis is a form of bone marrow failure due to replacement of hematopoietic tissue by abnormal tissue, most commonly metastatic carcinomas. This results in extramedullary hematopoiesis, typically in the spleen leading to premature release of hematopoietic cells into the circulation. Peripheral blood findings may include nucleated red blood cells, tear drop forms, giant platelets, and immature leukocytes. This is called a leukoerythroblastic picture. The first case demonstrates acute myelophthisis as a presentation of pancreatic cancer. The second case is of extramedullary hematopoiesis as a manifestation of widely metastatic melanoma. The presence of a leukoerythroblastic peripheral blood picture should serve as a valuable clue about a possible underlying malignancy. This late presentation of advanced cancer may now be rarely seen because of early diagnosis and more effective therapies.
Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes
Authors: Chiara Zuccato, Marzia Tartari, Andrea Crotti, Donato Goffredo, Marta Valenza, Luciano Conti, Tiziana Cataudella, Blair R Leavitt, Michael R Hayden, Tõnis Timmusk, Dorotea Rigamonti, Elena Cattaneo
Journal: Nature Genetics (2003)
Use of diazepam in treatment of severe convulsive status epilepticus.
Authors: M. J. Parsonage, J. W. Norris
Journal: BMJ (1967)

Urinary White Cell Excretion-Lindsay et al. MEDICALJOUNAL 85postoperative day, and it is unlikely that this would explain the marked sex difference.It is highly unlikely that over 60% of apparently normal women had latent urinary tract infection, but perhaps the changes we have observed are in some way related to the unknown cause underlying the increased suscep- tibility of the female to urinary tract infection. SummarySemi-quantitative urinary white cell counts were performed in 198 patients before and after surgery.A significant rise in white cell excretion rates was found in 61% of the females but in only 11 % of the males.The results were confirmed in a further group of patients by means of fully quantitative cell counts, and bacterial counting showed that this pyuria was often associated with significant bacteriuria.The possible significance of these findings is discussed.
Impairment of chemokine and cytokine production in patients with HIV related Pneumocystis jerovici pneumonia
Authors: D Israel-Biet
Journal: Thorax (2004)

Pneumocystis jerovici pneumonia (PJP) remains a frequent opportunistic infection in HIV infected patients which markedly upregulates HIV replication by mechanisms so far poorly elucidated. PJP triggers the production of proinflammatory mediators with activating effects on HIV. However, anti-inflammatory factors with inhibiting effects on HIV are normally produced in parallel. We postulated that an imbalance of mediators normally controlling HIV replication could underlie its marked increase during PJP.The production of tumour necrosis factor alpha (TNFalpha), interleukins IL-6 and IL-10, and beta-chemokine by bronchoalveolar lavage (BAL) cells recovered from HIV infected patients with and without PJP was compared. The pulmonary viral load was determined and correlations with cytokine and chemokine production were examined.TNFalpha and IL-6 release was similar in patients with and without PJP but IL-10 and beta-chemokine release was markedly lower in the PJP group (IL-10: p<10(-2), RANTES, MIP-1alpha and MIP-1beta: p<0.001). The pulmonary viral load was markedly higher in patients with PJP (p<0.001) and correlated negatively with levels of MIP-1alpha, RANTES and IL-10 in BAL fluid cells (p<0.05).Pulmonary IL-10 and beta-chemokine production is markedly defective in HIV infected patients with PJP, while pulmonary TNFalpha and IL-6 levels are normal. The resulting excess of these latter factors, which are known to upregulate HIV replication, might contribute to the increase in pulmonary viral load and to the more rapid HIV disease progression observed in patients with PJP.
Skeletal muscle peroxisome proliferator- activated receptor-gamma expression in obesity and non- insulin-dependent diabetes mellitus.
Authors: Y T Kruszynska, R Mukherjee, L Jow, S Dana, J R Paterniti, J M Olefsky
Journal: Journal of Clinical Investigation (1998)

The two isoforms of peroxisome proliferator-activated receptor-gamma (PPARgamma1 and PPARgamma2), are ligand-activated transcription factors that are the intracellular targets of a new class of insulin sensitizing agents, the thiazolidinediones. The observation that thiazolidinediones enhance skeletal muscle insulin sensitivity in obesity and in patients with non-insulin-dependent diabetes mellitus (NIDDM), by activating PPARgamma, and possibly by inducing its expression, suggests that PPARgamma expression in skeletal muscle plays a key role in determining tissue sensitivity to insulin, and that PPARgamma expression may be decreased in insulin resistant subjects. We used a sensitive ribonuclease protection assay, that permits simultaneous measurement of the two isoforms, to examine the effects of obesity and NIDDM, and the effects of insulin, on skeletal muscle levels of PPARgamma1 and PPARgamma2 mRNA. We studied seven patients with NIDDM (body mass index, 32+/-1 kg/m2), seven lean (24+/-1 kg/m2), and six obese (36+/-1 kg/m2) normal subjects. Biopsies from the vastus lateralis muscle were taken before and after a 5-h hyperinsulinemic (80 mU/m2 per minute) euglycemic clamp. The obese controls and NIDDM patients were insulin resistant with glucose disposal rates during the last 30 min of the clamp that were 67 and 31%, respectively, of those found in the lean controls. PPARgamma1, but not PPARgamma2 mRNA was detected in skeletal muscle at 10-15% of the level found in adipose tissue. No difference was found in PPARgamma1 levels between the three groups, and there was no change in PPARgamma1 levels after 5 h of hyperinsulinemia. In obese subjects, PPARgamma1 correlated with clamp glucose disposal rates (r = 0.92, P < 0.01). In the lean and NIDDM patients, muscle PPARgamma1 levels correlated with percentage body fat (r = 0.76 and r = 0.82, respectively, both P < 0.05) but not with body mass index. In conclusion: (a) skeletal muscle PPARgamma1 expression does not differ between normal and diabetic subjects, and is not induced by short-term hyperinsulinemia; (b) skeletal muscle PPARgamma1 expression was higher in subjects whose percent body fat exceeded 25%, and this may be a compensatory phenomenon in an attempt to maintain normal insulin sensitivity.
CHOLESTEROL METABOLISM IN THE MACROPHAGE
Authors: Zena Werb, Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1971)

Macrophage membrane cholesterol is present in two subcellular cholesterol pools, a rapidly exchanging compartment comprising about two-thirds of the total cholesterol, and a slowly exchanging compartment comprising one-third of the total. The morphological identification of the kinetically distinguishable pools proceeded by alteration of each compartment. Trypsin treatment markedly decreased the rate of cholesterol exchange without removing cholesterol from the membrane. Recovery of normal exchange rates took more than 7 hr and required protein synthesis. This suggested that a plasma membrane receptor is involved in positioning of lipoproteins for exchange, and is consistent with the plasma membrane localization of the rapidly exchanging compartment. Extensive pinocytosis by nondegradable dextran, dextran sulfate, or sucrose resulted in the accumulation of many secondary lysosomes, thus increasing the relative proportion of intracellular membranes. The measurable granule membrane area, cholesterol content, phospholipid content, and the relative size of the slowly exchanging cholesterol compartment all increased. The amount of intracellular membrane altered by extensive phagocytosis of latex particles also increased the size of the slowly exchanging cholesterol compartment. This suggested that the slowly exchanging pool of cholesterol represented the intracellular membranes primarily of lysosomal origin. Rabbit alveolar macrophages and thioglycollate-stimulated peritoneal macrophages contain many secondary lysosomes as a result of multiple bouts of in vivo phagocytosis and pinocytosis. In both of these cells the fast and slow pools are equal in size. The increased cholesterol content was attributable to the increase in the relative size of the slowly exchanging compartment. L-cells and melanoma cells also exchange their cholesterol with that of serum lipoproteins. Both cells contain few cholesterol-rich intracellular membranes, and had lower cellular cholesterol contents. In these cells the slowly exchanging pool was a minor contribution to cell cholesterol. Studies with these cells provided further evidence for the lysosomal membrane and plasma membrane localization of the slowly and rapidly exchanging cholesterol compartments.
Dutch may relent over euthanasia prosecutions
Authors: T. Sheldon
Journal: BMJ (1996)

Dutch government ministers are considering moves to stop doctors facing criminal charges if they perform euthanasia. Euthanasia is currently illegal with a maximum jail sentence of 12 years. At the moment, doctors who carry out euthanasia must report their actions, and only escape prosecution if legal officials accept that guidelines have been met. Now justice minister Winnie Sorgdrager has said that changing the law to include a medical exception is an “attractive idea.” This would require setting up a committee …
PD08-08: Preclinical Efficacy of the Combination of Met and Src Family Kinase Inhibitors in Triple-Negative Breast Cancer.
Authors: EM Gartner, EMH Kim, L Choi, J Boerner
Journal: Cancer Research (2011)

Abstract Background: Epidermal growth factor receptor (EGFR), although overexpressed in almost 60% of all triple-negative breast cancers, has yet to be identified as an effective therapeutic target for the treatment of the disease. We have previously shown in cell culture models of triple-negative breast cancer that primary resistance to EGFR tyrosine kinase inhibitors through ligand-independent phosphorylation can be overcome by co-inhibiting EGFR with either Met or Src family kinases (SFKs). We also demonstrated that inhibiting Met kinase activity reduced EGFR and c-Src phosphorylation and inhibiting SFK reduced EGFR phosphorylation. Taken together, these data suggest that EGFR, Met and SFKs regulate the activity of each other through transphosphorylation. This process of transphosphorylation, or crosstalk, allows for the continued activation of key signaling proteins required for proliferation and transformation. Here we demonstrate that inhibiting both Met and SFKs decreases cell viability and eliminates the need for inhibition of EGFR tyrosine kinase activity, as the autophosphorylation sites of EGFR were lost with the combination treatment. Methods: Seven triple-negative (SUM102, SUM149, SUM229, SUM1315, BT20, BT549, MDA-MB-231), two HER2+ (SUM190 and SKBr3), and two ER/PR+ (MCF7 and T47D) breast cancer cell lines were used to test the efficacy of the combination of Met and SFK inhibitors, Arq-197 and dasatinib, respectively. Cell viability after drug treatment was assessed by MTT assays. IC50 values were calculated and drug synergy calculations were performed. Transphosphorylation was measured by immunoblotting using phospho-specific antibodies. Apoptosis was characterized by immunoblotting. Results: All seven triple-negative breast cancer cell lines demonstrated decreased cell viability with the combination of Arq-197 and dasatinib when compared with either drug alone. In contrast, none of the HER2+ or ER/PR+ breast cancer cell lines had any additional loss of viability with the combination treatment. We found that the interactions between Arq-197 and dasatinib were synergistic in several of the breast cancer cell lines. Specifically, in one such cell line (BT20), the combinatorial index values were less than 1.0. Interestingly, in this cell line, the tyrosine phosphorylation levels on residues 1068 and 992 of EGFR were significantly altered with the combination treatment and activation of apoptotic proteins, including PARP, occurred. Conclusions: These data demonstrate that two tyrosine kinases, known to be downstream of EGFR activation, interact to promote resistance to EGFR inhibitors. However, inhibiting both Met and SFKs was sufficient to decrease cell viability and stimulate apoptosis in triple-negative breast cancer cells. Further studies to validate the relevance of these findings are ongoing. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-08.
Valproic Acid in Epilepsy
Authors: Wulfred Berman
Journal: JAMA (1980)

To the Editor.—  It is interesting to read inThe Journalthat Livingston et al (241:1892, 1979) found valproic acid to be  little or no benefit in grand mal, psychomotor, or myoclonic epilepsy of older children. Our experience in a group of 46 mentally retarded patients, ranging in age from 2 to 57 years and receiving valproic acid in dosages of 15 to 75 mg/kg/day in a period of from two to 16 months, is different but fortunately encouraging. In all patients valproic acid was added to the existing anticonvulsant regimen, and the dosage was increased gradually until seizure control was obtained, the medication was considered ineffective, or signs of toxic reaction appeared.  The patients had intractable seizures and were refractory to the standard anticonvulsant medication, whether administered singly or in different combinations. The types of epilepsy were as follows: generalized tonic-clonic seizures (grand mal), 30 patients; generalized tonic-clonic
Narp and NP1 Form Heterocomplexes that Function in Developmental and Activity-Dependent Synaptic Plasticity
Authors: Desheng Xu, Carsten Hopf, Radhika Reddy, Richard W. Cho, Liping Guo, Anthony Lanahan, Ronald S. Petralia, Robert J. Wenthold, Richard J. O'Brien, Paul Worley
Journal: Neuron (2003)
Strontium 85 Scintimetry in Ankylosing Spondylitis
Authors: Nitranjan Singh Ranawat
Journal: JAMA (1972)

Strontium 85 step-scan scintimetry of the sacroiliac joints and spine was performed in 19 patients with established or suspected ankylosing spondylitis two weeks after intravenous injection of 100 microcuries of strontium nitrate Sr 85. In completely ankylosed sacroiliac joints and spine, scintimetry values were normal, indicating the disease was clinically arrested. Localized high uptake was observed in several patients, corresponding with areas of complaint. Tomograms of these areas demonstrated destructive changes of vertebral bodies. Uptake of strontium 85 was high in cases with early roentgenographic changes of the sacroiliac joints and minimal spinal involvement. Observations were similar in two patients in whom ankylosing spondylitis was suspected clinically. This indicated new bone formation, suggesting activity of the disease not yet seen on roentgenograms. The method is potentially valuable for establishing early diagnosis when used in conjunction with conventional clinical and radiologic techniques.
Sharks Still Intrigue Cancer Researchers
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Sharks Still Intrigue Cancer Researchers Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Pages 1000–1002, https://doi.org/10.1093/jnci/84.13.1000-a Published: 01 July 1992
Black Women Receive Less Mammography Even with Similar Use of Primary Care
Authors: Risa B. Burns
Journal: Annals of Internal Medicine (1996)

Background: Black women with breast cancer have a decreased 5-year survival rate in comparison with white women, possibly because of less frequent use of mammography. Having a regular provider or source of health care is the most important determinant of mammography use. Objective: To examine whether the difference in mammography use between elderly black women and elderly white women is related to the number of visits made to a primary care physician. Design: Retrospective review of 1990 Health Care Financing Administration billing files (Medicare part B) from 10 states. Setting: Outpatient mammography services in 10 states. Participants: Black women and white women, 65 years of age and older, residing in one of the 10 states. Measurements: Any mammogram. Predictors included race, number of visits to a primary care physician (0, 1, 2, or 3 or more), median income of ZIP code of residence (a surrogate measure of income), and state. Results: The following are findings from Georgia; similar results were found in each state studied. The mean age of the 335 680 women was 75 years; 20% were black. Sixty-eight percent of the black women and 69% of the white women made at least one visit to a primary care physician. Overall, 14% of the women had had mammography; black women had mammography less often than white women (9% compared with 15%). At each primary care visit level (1, 2, or 3 or more visits), black women had mammography less often than white women (1 visit, 7% compared with 15%; 2 visits, 12% compared with 21%; and 3 or more visits, 12% compared with 20%). Even among women who had made at least one visit to a primary care physician, a deficit for blacks occurred in each income quintile (lowest quintile, 13% compared with 20%; low, 10% compared with 18%; middle, 12% compared with 18%; high, 10% compared with 19%; and highest, 12% compared with 22%) and in each state (in Georgia, for example, the percentages were 14% compared with 21%). An age-, income-, and state-adjusted logistic model predicting mammography use for 2.9 million white women in all 10 states shows the powerful effect of primary care use on mammography (odds ratios for 1, 2, and 3 or more visits were, respectively, 2.73 [95% CI, 2.70 to 2.77]; 3.98 [CI, 3.93 to 4.03]; and 4.62 [CI, 4.58 to 4.67]). The same model fit to 250 000 black women shows a lesser effect (analogous odds ratios were 1.77 [CI, 1.67 to 1.87]; 2.49 [CI, 2.36 to 2.63]; and 3.15 [CI, 3.04 to 3.25]). Conclusions: Among older women, mammography is used less often for blacks than for whites. More frequent use of mammography is associated with more visits to a primary care physician in both groups, but the deficit for black women persists at each income level and in each state, even after primary care use is considered. Primary care visits are less likely to "boost" mammography use for black women than for white women.
Molecular Pathways: Regulation and Targeting of Kinetochore–Microtubule Attachment in Cancer
Authors: Jacob A. Herman, Chad M. Toledo, James M. Olson, Jennifer G. DeLuca, Patrick J. Paddison
Journal: Clinical Cancer Research (2014)

Kinetochores are large protein structures assembled on centromeric DNA during mitosis that bind to microtubules of the mitotic spindle to orchestrate and power chromosome movements. Deregulation of kinetochore-microtubule (KT-MT) attachments has been implicated in driving chromosome instability and cancer evolution; however, the nature and source of KT-MT attachment defects in cancer cells remain largely unknown. Here, we highlight recent findings suggesting that oncogene-driven changes in kinetochore regulation occur in glioblastoma multiforme (GBM) and possibly other cancers exhibiting chromosome instability, giving rise to novel therapeutic opportunities. In particular, we consider the GLE2p-binding sequence domains of BubR1 and the newly discovered BuGZ, two kinetochore-associated proteins, as candidate therapeutic targets for GBM.
Immigration rules hit potential GP registrars Labour promises power to all GPs Review body report 1996 Who will give medical advice?
Authors: L. Beecham
Journal: BMJ (1996)

# Immigration rules hit potential GP registrars {#article-title-2}

Overseas doctors from countries outside the European Economic Area (EEA) who want to train in general practice in Britain may face immigration restrictions, which may lead to their being unable to complete their training. Overseas doctors working as general practice registrars must hold training and work experience scheme work permits, and a condition of these is that the holder must leave Britain at the end of the agreed period. A transfer to ordinary employment in Britain is not allowed. The permits have to be applied for by the potential employer—that is, the trainer—through the Department for Education and Employment.

Family health services authorities are prohibited from reimbursing the salary of any general practice registrar who is unable to continue to practise in Britain. Any overseas nationals wanting to work as registrars should, therefore, have an alternative source of funding for their salaries and related costs, such as their own government.

The position is different for overseas doctors from outside the EEA who do their postgraduate training in hospitals. They should …
Abstract 2906: Preclinical systems to study the biodistribution of nanoparticle delivery in pancreatic ductal adenocarcinoma
Authors: Eric A. Collisson, Jonathan Zuckerman, Donghui Wang, Paul Phojanakong, Aaron B. Gale, Chung Hang J. Choi, Byron Hann, Frank McCormick, Mark Davis
Journal: Cancer Research (2012)

Abstract Pancreatic Ductal Adenocarcinoma (PDA) is a deadly disease, with no effective available treatment. Primary chemoresistance is common and has been attributed to the hypovascularity characteristic of the disease and the dense desmoplastic response that accompanies virtually every case of PDA. Effectively delivering therapeutic anticancer agents to PDA cells is therefore a specific, difficult and understudied problem in PDA that must be resolved for successful treatments to emerge. With the goal of eventually delivering drug payloads via nanoparticles (NP), we used well-defined mouse models of the disease to iteratively test NP distribution to both the cancerous and normal pancreas. Minimal deposition was observed in normal pancreas after intravenous or intraperitoneal administration of a variously sized (25nm or 40nm) NP. Surprisingly, abundant NP deposition was seen in both syngenic xenografted and autochthonous KPC models of PDA. NP deposition tended to be greater with IP administration and was enriched in stoma rich tumor regions. These findings have encouraging ramifications for delivery of depot or novel (e.g. siRNA, radiopharmaceutical, etc.) agents in this deadly disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2906. doi:1538-7445.AM2012-2906