tbuckley/cabot-search huggingface dataset:
Recommended Prostate-Specific Antigen Testing Intervals for the Detection of Curable Prostate Cancer
Authors: H. Ballentine Carter
Journal: JAMA (1997)

To evaluate prostate-specific antigen (PSA) testing intervals that maintain the detection of curable cancer and reduce unnecessary testing.Historical prospective study of serial PSA measurements at 2- and 4-year intervals from frozen serum samples of 40 men who eventually developed prostate cancer and 272 men without prostate cancer who were participants in a prospective aging study (Gerontology Research Center of the National Institute on Aging, the Baltimore Longitudinal Study of Aging) and the case series of 389 consecutive men treated surgically for nonpalpable prostate cancer.Probability of a PSA conversion to 4.1 to 5.0 ng/mL and to greater than 5.0 ng/mL at 2 and 4 years and probability of detecting curable prostate cancer by age and PSA level.When the pretreatment PSA level was less than or equal to 4.0 ng/mL, nonpalpable prostate cancers were highly likely (34/36, 94%) to be curable (organ-confined or capsular penetration with Gleason score < 7 and negative margins), and the majority (25/36, 69%) were small cancers (confined tumor < or = 0.5 cm3 with no Gleason pattern 4 or 5). When the pretreatment PSA level was greater than 4.0 ng/mL and less than or equal to 5.0 ng/mL, cancers were highly likely to be curable (32/36, 89%), and a minority were small cancers (12/36, 33%). When the pretreatment PSA level was greater than 5.0 ng/mL, 96 (30%) of 317 cancers were noncurable. The PSA conversion (for cancer cases) to a level at which cure is less likely (> 5.0 ng/mL) is rare (0%) after 2 or 4 years when the initial PSA is less than 2.0 ng/mL. PSA conversion to a range at which cancers are likely to be curable and less likely to be small (4.1-5.0 ng/mL) is rare after 2 years (0%-4%) when the baseline PSA level is less than 2.0 ng/mL but common when the baseline PSA level is between 2.1 and 3.0 ng/mL (27%) or 3.1 and 4.0 ng/mL (36%).These data suggest that for men with no cancer suspected on digital rectal examination, a PSA level of 4.0 to 5.0 ng/mL is an acceptable range for maintaining the detection of curable prostate cancer and a 2-year PSA testing interval is not likely to miss a curable prostate cancer when the initial PSA level is less than 2.0 ng/mL. Recognizing that 70% of a screened population between the ages of 50 years and 70 years have PSA levels less than 2.0 ng/mL, elimination of annual PSA testing for these men would result in large health care cost savings.
Twelve Versus Six Months of Clopidogrel to Reduce Major Cardiac Events in Patients Undergoing γ-Radiation Therapy for In-Stent Restenosis
Authors: Ron Waksman, Andrew E. Ajani, Ellen Pinnow, Edouard Cheneau, Laurent Leborgne, Regina Dieble, Anh B. Bui, Lowell F. Satler, Augusto D. Pichard, Kenneth K. Kent, Joseph Lindsay
Journal: Circulation (2002)

Background— Intracoronary γ-radiation reduces recurrent in-stent restenosis (ISR). Late thrombosis was attenuated with 6 months of aspirin and clopidogrel. We aimed to find out whether 12 months of aspirin plus clopidogrel is superior to a strategy of 6 months after radiation therapy for patients with ISR. Methods and Results— One hundred twenty consecutive patients with diffuse ISR in native coronaries and vein grafts with lesions &lt;80 mm in length underwent PTCA, laser ablation, or rotational atherectomy. Additional stents were placed in 39 patients (33%). After the intervention, a ribbon with different trains of radioactive 192 Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 12 months and followed up clinically. The cardiac clinical event rates at 15 months were compared with the γ-treated (n=120) patients of the WRIST PLUS study (only 6 months of antiplatelet therapy). Whereas the late thrombosis rates were similar (3.3% for the group given 12 months of antiplatelet therapy versus 4.2% for the group given 6 months, P =0.72), the group treated with 12 months of antiplatelet therapy had a rate of 21% for major adverse cardiac events and 20% for target-lesion revascularization compared with 36% ( P =0.01) and 35% ( P =0.009), respectively, in patients who were treated with only 6 months of clopidogrel. Conclusions— Twelve months of clopidogrel is superior to 6 months in reducing overall major cardiac events and revascularization rates at 15 months for patients with ISR treated with γ-radiation. At least 12 months of clopidogrel therapy should be recommended for patients undergoing radiation therapy for ISR.
Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.
Authors: A D'Andrea, M Rengaraju, N M Valiante, J Chehimi, M Kubin, M Aste, S H Chan, M Kobayashi, D Young, E Nickbarg
Journal: The Journal of Experimental Medicine (1992)

Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35. NKSF/IL-12 has multiple effects on T and NK cells and was originally identified and purified from the supernatant fluid of Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cell lines. We have produced a panel of monoclonal antibodies against both chains of NKSF/IL-12. Some of these antibodies have neutralizing activity, and several combinations of them have been used to establish sensitive radioimmunoassays detecting the free p40 chain, the free p35 chain, or the p70 heterodimer. Using these reagents, we have determined that most EBV-transformed human B lymphoblastoid cell lines constitutively produce low levels of the p70 heterodimer and an excess of the free p40 chain, whereas Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived cell lines produce neither. Production of both p40 and p70 is increased several-fold upon stimulation of the EBV-transformed cell lines with phorbol diesters. The ability of supernatant fluids from unstimulated and phorbol diester-stimulated cell lines to induce interferon gamma (IFN-gamma) production from T and NK cells, one of the effects of NKSF/IL-12, parallels the levels of production of the p70 heterodimer, known to be the biologically active form of NKSF/IL-12. Staphylococcus aureus Cowan I strain (SAC) and other stimuli induce accumulation of p40 mRNA and production of both p40 and p70 by peripheral blood mononuclear cells (PBMC). The producer cells appear to include both adherent cells and nonadherent lymphocytes, possibly B cells. The supernatant fluids from SAC-stimulated PBMC mediate the typical functions of NKSF/IL-12 (i.e., IFN-gamma induction, mitogenic effects on T/NK blasts, enhancement of NK cell cytotoxicity) at concentrations of p70 similar to those at which recombinant NKSF/IL-12 mediates the same functions. Moreover, these activities are significantly inhibited by anti-NKSF/IL-12 antibodies. The neutralizing anti-NKSF/IL-12 antibodies also inhibit 85% of the IFN-gamma production in response to SAC, an NKSF/IL-12 inducer, and approximately 50% of the IFN-gamma production in response to non-NKSF/IL-12-inducers such as IL-2, phytohemagglutinin, and anti-CD3 antibodies. These results indicate that induced or constitutively produced NKSF/IL-12 has a major role in facilitating IFN-gamma production by peripheral blood lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
The horse race to language understanding: FLMP was first out of the gate, and has yet to be overtaken
Authors: Dominic W. Massaro
Journal: Behavioral and Brain Sciences (2000)

Our long-standing hypothesis has been that feedforward information flow is sufficient for speech perception, reading, and sentence (syntactic and semantic) processing more generally. We are encouraged by the target article's argument for the same hypothesis, but caution that more precise quantitative predictions will be necessary to advance the field.
Effect of meal on portal hemodynamics in healthy humans and in patients with chronic liver disease
Authors: Stefano Gaiani, Luigi Bolondi, Silvia Li Bassi, Vittorio Santi, Gianni Zironi, Luigi Barbara
Journal: Hepatology (1989)

The effect of a standard Italian meal on portal hemodynamics was evaluated in 12 normal subjects, in 11 patients with chronic active hepatitis and in 11 patients with liver cirrhosis using duplex Doppler ultrasound, which allows a noninvasive assessment of portal blood flow. In the fasting state, the portal vein caliber was significantly higher in patients with liver cirrhosis than in normal subjects and patients with chronic active hepatitis, whereas the mean flow velocity in the portal vein was significantly lower in this group. Basal flow volume of the portal vein was greater in patients with liver cirrhosis than in normal subjects and patients with chronic active hepatitis. Sixty minutes after the standard meal, we observed both in normal subjects and in patients with chronic active hepatitis a significant increase of mean caliber, mean velocity and flow volume in the portal vein, whereas in patients with liver cirrhosis, these parameters remained almost unchanged. In addition, the examination of individual patterns showed that flow velocity and flow volume in the portal vein decreased in some cirrhotic patients after the meal. This behavior is probably related to the hypertensive state in the splanchnic venous bed and diversion of splanchnic blood flow into spontaneous portosystemic collaterals.
Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinase activity and Casein Kinase II inhibition as a potential treatment option
Authors: Stefan M Willems, Yvonne M Schrage, Inge H Briaire-de Bruijn, Karoly Szuhai, Pancras CW Hogendoorn, Judith VMG Bovée
Journal: Molecular Cancer (2010)

Abstract Background Myxoid liposarcoma is a relatively common malignant soft tissue tumor, characterized by a (12;16) translocation resulting in a FUS-DDIT3 fusion gene playing a pivotal role in its tumorigenesis. Treatment options in patients with inoperable or metastatic myxoid liposarcoma are relatively poor though being developed and new hope is growing. Results Using kinome profiling and subsequent pathway analysis in two cell lines and four primary cultures of myxoid liposarcomas, all of which demonstrated a FUS-DDIT3 fusion gene including one new fusion type, we aimed at identifying new molecular targets for systemic treatment. Protein phosphorylation by activated kinases was verified by Western Blot and cell viability was measured before and after treatment of the myxoid liposarcoma cells with kinase inhibitors. We found kinases associated with the atypical nuclear factor-kappaB and Src pathways to be the most active in myxoid liposarcoma. Inhibition of Src by the small molecule tyrosine kinase inhibitor dasatinib showed only a mild effect on cell viability of myxoid liposarcoma cells. In contrast, inhibition of the nuclear factor-kappaB pathway, which is regulated by the FUS-DDIT3 fusion product, in myxoid liposarcoma cells using casein kinase 2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) showed a significant decrease in cell viability, decreased phosphorylation of nuclear factor-kappaB pathway proteins, and caspase 3 mediated apoptosis. Combination of dasatinib and TBB showed an enhanced effect. Conclusion Kinases associated with activation of the atypical nuclear factor-kappaB and the Src pathways are the most active in myxoid liposarcoma in vitro and inhibition of nuclear factor-kappaB pathway activation by inhibiting casein kinase 2 using TBB, of which the effect is enhanced by Src inhibition using dasatinib, offers new potential therapeutic strategies for myxoid liposarcoma patients with advanced disease.
Occupational Health and Safety Regulation in the Coal Mining Industry: Public Health at the Workplace
Authors: James L. Weeks
Journal: Annual Review of Public Health (1991)

The strategy for preventing occupational disease and injury in the coal mining industry employs several elements. Standards are set and enforced; technical assistance, research, and development are provided; and surveillance is conducted. Compensation for black lung is a vivid reminder of the consequences of failure to prevent disease. And, workers are represented by a union that encourages active participation in all aspects of this strategy. There are significant problems in each of these elements. Regulatory reform threatens to weaken many standards, there is a decline in government research budgets, surveillance is not well monitored, and compensation for black lung is significantly more difficult to obtain now than in the past. Moreover, the conservative governments of the past decade are not friendly towards unions. Nevertheless, the fundamental structure of disease and injury prevention remains intact and, more importantly, it has a historical record of success. The Mine Safety and Health Act provided for a wide array of basic public health measures to prevent occupational disease and injury in the mining industry. These measures have been effective in reducing both risk of fatal injury and exposure to respirable coal mine dust. They are also associated with temporary declines in productivity. In recent years, however, productivity has increased, while risk of fatal injury and exposure to respirable dust have declined. At individual mines, productivity with longwall mining methods appear to be associated with increases in exposure to respirable dust. These trends are not inconsistent with similar trends following implementation of regulations by OSHA. When OSHA promulgated regulations to control exposure to vinyl chloride monomer, enforcement of the standard promoted significant efficiencies in vinyl chloride production (5). Similarly, when OSHA promulgated its standard regulating exposure to cotton dust, this effort provoked modernization in the cotton textile industry (14). It is not inevitable that occupational health and safety regulations are associated with negative economic performance. On the contrary, in some instances, public health on the job and productivity are complementary.
Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase
Authors: Suzana Hadjur, Karen Ung, Louis Wadsworth, James Dimmick, Evica Rajcan-Separovic, Richard W. Scott, Manuel Buchwald, Frank R. Jirik
Journal: Blood (2001)
Differences in Stroke Subtypes Between Black and White Patients With Stroke
Authors: Hugh S. Markus, Usman Khan, Jonathan Birns, Andrew Evans, Lalit Kalra, Anthony G. Rudd, Charles D.A. Wolfe, Paula Jerrard-Dunne
Journal: Circulation (2007)

Determining whether the distribution of stroke subtypes differs between ethnic groups is important in understanding the mechanisms of the increased stroke incidence in black patients.In this study, 600 black and 600 white patients with stroke were prospectively and consecutively recruited to determine differences in stroke subtypes. The pathophysiological Trial of Org 10172 (TOAST) classification was used and compared with a clinical (Oxfordshire Community Stroke Project) subtype classification. Stroke subtypes were determined by one investigator by review of original imaging. Black patients with stroke were significantly younger and had higher prevalences of hypertension, diabetes, and obesity. They were less likely to be smokers and had lower prevalences of myocardial infarction and atrial fibrillation. In the black patients, 33% of stroke was due to cerebral small vessel disease compared with 14% in the white stroke cohort (odds ratio, 2.94; 95% confidence interval, 1.97 to 4.39; P<0.001, controlling for age, gender, cardiovascular risk factors, and social class). The black stroke cohort had less large vessel atherosclerosis (odds ratio, 0.49; 95% confidence interval, 0.29 to 0.82; P=0.007) and cardioembolic disease (odds ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002). Using a classification based on clinical syndrome alone gave a higher estimate of the frequency of small vessel disease stroke, particularly in white patients.A relative excess of small vessel disease was observed in black patients with stroke compared with an excess of extracranial atherosclerosis and cardioembolic stroke in white patients with stroke that was independent of conventional risk factors and social class. Whether these excesses are due to differences in genetic susceptibility or as-yet undetermined differences in environmental risk remains to be determined.
Fractures in Chronic Arthritis
Authors: G. J. Baer
Journal: Annals of the Rheumatic Diseases (1941)

THE incidence of fractures in chronic arthritis, the rate of healing, and the complications following fractures have not been recorded in modern medical literature.A review of the literature from 1900 to 1940 makes no mention of this subject.The 1,625 case records of arthritis at the Robert Breck Brigham Hospital were reviewed to determine the frequency of fractures, the rate of healing, the setiology, and the effect upon the systemic and local disease processes.The case records examined included the different types of disease in all accepted classifications.Fractures are among the less common complications of arthritis.They occurred 21 times, or in 1-2 per cent. of the cases examined.Dislocations, on the other hand, are common.It is frequently difficult to differentiate a fracture from "disintegration " at the bone ends due to atrophy and cystic degeneration.In the roentgenogram one frequently can see a fracture line at the bone ends where disintegration has taken place.Should such disintegrations be considered as fractures, the incidence of fractures in chronic arthritis would be increased statistically.Such " infractions," as they have been described by Knaggs,l have not been classified as fractures in this survey.A fracture to be so classified had to satisfy the criteria commonly *
Anabolic steroid accelerated multicompartment syndrome following trauma
Authors: H Bahia, A Platt, N B Hart, P Baguley
Journal: British Journal of Sports Medicine (2000)

The case is reported of a 23 year old male body builder who was involved in a road traffic accident after taking anabolic steroids. The resulting trauma caused a severe life threatening acute multicompartment syndrome resulting in the need for urgent multiple fasciotomies.
Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells
Authors: Wen-Pin Cheng, Bao-Wei Wang, Shih-Chung Chen, Hang Chang, Kou-Gi Shyu
Journal: Cardiovascular Research (2011)

The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cyclic stretch enhances PUMA expression in VSMCs undergoing apoptosis. Human VSMCs grown on a Flexcell I flexible membrane base were stretched via vacuum to 20% of elongation at a frequency of 1 Hz. An in vivo model of volume overload with aorta-caval shunt and pressure overload with aortic banding in adult rats was used to study PUMA expression. Cyclic stretch markedly enhanced PUMA protein and gene expression after stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125 and interferon-γ (IFN-γ) antibody 30 min before stretch inhibited PUMA expression. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1 (IRF-1). SP600125, JNK small interfering RNA, and IFN-γ antibody attenuated the DNA binding activity induced by stretch. PUMA-Mut plasmid, SP600125, and IRF-1 antibody attenuated the promoter activity. Stretch increased secretion of IFN-γ from VSMCs, and conditioned media from stretched VSMCs increased PUMA protein expression. The in vivo model of aorta-caval shunt and aortic banding also showed increased PUMA protein expression in the aorta. Cyclic mechanical stretch increases PUMA expression in cultured human VSMCs. The PUMA expression induced by stretch is mediated by IFN-γ, JNK, and IRF-1 pathways. These findings suggest that PUMA is an important mediator in VSMC apoptosis induced by stretch.
DNA minor groove binders as potential antitumor and antimicrobial agents
Authors: Pier Giovanni Baraldi, Andrea Bovero, Francesca Fruttarolo, Delia Preti, Mojgan Aghazadeh Tabrizi, Maria Giovanna Pavani, Romeo Romagnoli
Journal: Medicinal Research Reviews (2004)

DNA minor groove binders constitute an important class of derivatives in anticancer therapy. Some of these compounds form noncovalent complexes with DNA (e.g., distamycin A, Hoechst 33258, and pentamidine) while others DNA-binding compounds (such as CC-1065) cause cleavages in the DNA backbone. In this article, we have reviewed the minor groove binders currently in preclinical evaluation in the last years. Diarylamidines such as DAPI, berenil, and pentamidine; bis-benzimidazoles such as Hoechst 33258; ecteinascidins, pyrrololo [2,1-c]-[1,4]-benzodiazepines (PBDs), CC-1065, and distamycins are the classes discussed in this review article. A special section has been dedicated to hybrid molecules resulted by the combination of two minor groove binders, especially for derivatives of naturally occurring antitumor agents, such as anthramycin or the alkylating unit of the antibiotic CC-1065, and distamycin frames.
Aphasia, prefrontal dysfunction, and the use of word-order strategies
Authors: Herman H. H. J. Kolk, Robert J. Hartsuiker
Journal: Behavioral and Brain Sciences (1999)

Caplan &amp; Waters's neuropsychological evidence for two types of verbal working memory rests entirely on a very restricted definition of “syntactic complexity,” one in terms of word order. This opens the possibility that the dissociation they observe relates to the differential use of word-order strategies rather than to the structure of verbal working memory.
Pandemic influenza preparedness in the Asia–Pacific region
Authors: Richard Coker, Sandra Mounier-Jack
Journal: The Lancet (2006)

Concerns are mounting that the threat of another influenza pandemic will become a reality and that the epicentre of the outbreak could be the Asia-Pacific region. We assessed the documents that some Asia-Pacific countries have published as part of preparedness planning for an outbreak of influenza in people. Regional approaches were polarised. Thailand, China, and Vietnam had set out a strategic vision to strengthen future capacity in preparedness planning. By contrast, Hong Kong, Australia, and New Zealand took a strategic approach aimed mainly at harnessing available resources or preparing for the deployment of resources such as stockpiled antiviral agents and vaccines. The plans of Hong Kong, Australia, and New Zealand compared favourably with the best European plans. The plans of resource-poor countries addressed some issues that were largely neglected by most European plans. Other countries (including those that do not yet have plans) could benefit from analysis of the strengths and weaknesses of the plans drawn up by countries in the region and in Europe.
Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation
Authors: Jan Storek, Ansamma Joseph, German Espino, Monja A. Dawson, Daniel C. Douek, Keith M. Sullivan, Mary E. D. Flowers, Paul Martin, George Mathioudakis, Richard A. Nash, Rainer Storb, Frederick R. Appelbaum, David G. Maloney
Journal: Blood (2001)