tbuckley/cabot-search huggingface dataset:
The Microsomal Triglyceride Transfer Protein Gene-493T Variant Lowers Cholesterol But Increases the Risk of Coronary Heart Disease
Authors: Helena Ledmyr, Alex D. McMahon, Ewa Ehrenborg, Lars B. Nielsen, Matt Neville, Hans Lithell, Peter W. MacFarlane, Christopher J. Packard, Fredrik Karpe
Journal: Circulation (2004)

Background— The microsomal triglyceride transfer protein (MTP) transfers lipids into apolipoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. The T-variant of a functional polymorphism in the MTP promoter, MTP-493G/T, has been associated with reduced low-density lipoprotein cholesterol concentrations. We hypothesize that this polymorphism impacts on coronary heart disease (CHD) risk. Methods and Results— The effect of the polymorphism was therefore tested in the West of Scotland Coronary Prevention Study biobank (580 cases and 1160 controls). MTP-493T carrier status was associated with significantly increased risk of CHD despite a small reduction in total cholesterol. Compared with the genotypic group with the lowest event rate (MTP-493GG, pravastatin treatment), the respective odds ratios (95% confidence interval) in the placebo group for CHD events were: GG, 1.23 (0.92 to 1.63); GT, 1.53 (1.12 to 2.08); and TT, 2.78 (1.53 to 5.05), suggestive of a gene-dose effect. The excess risk for CHD of the MTP-493T-variant was eliminated by pravastatin treatment. The Uppsala Longitudinal Study of Adult Men (ULSAM), which is a 20-year follow-up study of CHD, was used as an independent confirmatory database. These unexpected findings prompted the investigation of non-plasma lipid factors that could associate the MTP gene with CHD risk. In a limited number of subjects (n=18), heart muscle biopsies showed a MTP-493T genotype-specific depression of MTP mRNA expression. Conclusion— The MTP-493T variant confers an increased risk of CHD that is unrelated to plasma lipids and lipoproteins, but eliminated by pravastatin treatment. A direct effect of the MTP polymorphism on myocardial lipid metabolism and vulnerability upon ischemic damage cannot be excluded.
Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile
Authors: Bruno Paiva, Teresa Paino, Jose-Maria Sayagues, Mercedes Garayoa, Laura San-Segundo, Montserrat Martín, Ines Mota, María-Luz Sanchez, Paloma Bárcena, Irene Aires-Mejia, Luis Corchete, Cristina Jimenez, Ramon Garcia-Sanz, Norma C. Gutierrez, Enrique M. Ocio, Maria-Victoria Mateos, Maria-Belen Vidriales, Alberto Orfao, Jesús F. San Miguel
Journal: Blood (2013)
Adjuvant-specific regulation of long-term antibody responses by ZBTB20
Authors: Yinan Wang, Deepta Bhattacharya
Journal: The Journal of Experimental Medicine (2014)

The duration of antibody production by long-lived plasma cells varies with the type of immunization, but the basis for these differences is unknown. We demonstrate that plasma cells formed in response to the same immunogen engage distinct survival programs depending on the adjuvant. After alum-adjuvanted immunization, antigen-specific bone marrow plasma cells deficient in the transcription factor ZBTB20 failed to accumulate over time, leading to a progressive loss of antibody production relative to wild-type controls. Fetal liver reconstitution experiments demonstrated that the requirement for ZBTB20 was B cell intrinsic. No defects were observed in germinal center numbers, affinity maturation, or plasma cell formation or proliferation in ZBTB20-deficient chimeras. However, ZBTB20-deficient plasma cells expressed reduced levels of MCL1 relative to wild-type controls, and transgenic expression of BCL2 increased serum antibody titers. These data indicate a role for ZBTB20 in promoting survival in plasma cells. Strikingly, adjuvants that activate TLR2 and TLR4 restored long-term antibody production in ZBTB20-deficient chimeras through the induction of compensatory survival programs in plasma cells. Thus, distinct lifespans are imprinted in plasma cells as they are formed, depending on the primary activation conditions. The durability of vaccines may accordingly be improved through the selection of appropriate adjuvants.
Hereditary Coproporphyria
Authors: BIRGITTA HAEGER-ARONSEN
Journal: Annals of Internal Medicine (1968)

Hereditary coproporphyria is described in a Swedish family. The proband, a 13-year-old girl, presented with an acute episode of abdominal pain precipitated by barbiturates given for epileptic seizures. Porphyrin investigations demonstrated porphyrin precursors and coproporphyrin III in the urine and coproporphyrin III in the feces, while later, when the patient was in remission, the urinary precursors returned to normal values. Studies of the proband's 39 maternal relatives revealed 13 persons with latent hereditary coproporphyria. The inheritance pattern strongly suggests that hereditary coproporphyria is transmitted as a non-sex-linked mendelian dominant. A hypothesis relating the disease to a structural defect in the mitochondrion is given.
What Is the Optimal Blood Pressure in Patients After Acute Coronary Syndromes?
Authors: Sripal Bangalore, Jie Qin, Sarah Sloan, Sabina A. Murphy, Christopher P. Cannon
Journal: Circulation (2010)

Background— Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes. Methods and Results— We evaluated 4162 patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization. The relationship between BP (systolic or diastolic) followed a J- or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density lipoprotein cholesterol. A nonlinear Cox proportional hazards model showed a nadir of 136/85 mm Hg (range 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic) at which the incidence of primary outcome was lowest. The curve was relatively flat for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg. Conclusions— After acute coronary syndrome, a J- or U-shaped curve association existed between BP and the risk of future cardiovascular events, with lowest event rates in the BP range of approximately 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic and a relatively flat curve for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg, which suggests that too low of a pressure (especially &lt;110/70 mm Hg) may be dangerous. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00382460.
Metastatic Hepatic Lesions Are Detected Better by Delayed Imaging With Prolonged Emission Time
Authors: Yen-Kung Chen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2005)

Dual-phase PET images, a combination of early and late images, was used to determine if the observed lesion was fixed and to calculate changes in standard uptake value from early to late results. Thus, dual-phase PET images were used for distinguishing malignant from benign lesions. In addition, dual phase may enhance lesions in highly suspected regions and may be useful for small-sized cancer and low cell-density cancer. Importantly, the FDG PET images showed a significant increase in the tumor-to-background contrast and hence detected more foci in the delayed phase with prolonged emission time.
Reaction products of ozone: a review.
Authors: W H Glaze
Journal: Environmental Health Perspectives (1986)

The reaction products of ozone that form during the oxidation of compounds found in aqueous media are reviewed. Reaction products of ozone are well documented only for a limited number of substrates, and mechanistic information is quite rare. Decomposition of ozone during its reactions, sometimes induced by matrix impurities or by the by-products of the reactions, will generate highly reactive hydroxyl radicals. Thus, even reactions occurring at pH less than 7 may have radical character. More complete destruction of organic substrates may be enhanced by using catalysts, such as ultraviolet radiation or hydrogen peroxide, to accelerate radical formation. However, complete mineralization is generally not practical economically, so partially oxidized by-products can be expected under typical treatment conditions. Ozone by-products tend to be oxygenated compounds that are usually, but not always, more biodegradable and less toxic than xenobiotic precursors. Of particular interest are hydroperoxide by-products, which may have escaped detection because of their lability, and unsaturated aldehydes. Inorganic by-products tend to be in high oxidation states, which in some cases (e.g., some metallic elements) may lead to enhanced removal by flocculation and sedimentation. In other cases oxidation may lead to formation of reactive species such as hypobromous acid from bromide ion or permanganate from manganous ion. In general, more research is required before a valid assessment of the risks of ozone by-products can be made.
The PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events
Authors: Kiran Bhaskar, Megan Miller, Alexandra Chludzinski, Karl Herrup, Michael Zagorski, Bruce T Lamb
Journal: Molecular Neurodegeneration (2009)

Accumulating evidence suggests that neurons prone to degeneration in Alzheimer's Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein (APP) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (Abeta) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble Abeta species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic primary cortical neurons to Abeta oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and induction of CCEs in a concentration dependent manner. Retraction of neuronal processes correlated with the induction of CCEs and the Abeta monomer or Abeta fibrils showed only minimal effects. In addition, we provide evidence that induction of neuronal CCEs are autonomous to primary neurons cultured from the R1.40 mice. Finally, our results also demonstrate that Abeta oligomer treated neurons exhibit elevated levels of activated Akt and mTOR (mammalian Target Of Rapamycin) and that PI3K, Akt or mTOR inhibitors blocked Abeta oligomer-induced neuronal CCEs. Taken together, these results demonstrate that Abeta oligomer-based induction of neuronal CCEs involve the PI3K-Akt-mTOR pathway.
Risk of Sudden Infant Death Syndrome after Immunization with the Diphtheria–Tetanus–Pertussis Vaccine
Authors: Marie R. Griffin, Wayne A. Ray, John R. Livengood, William Schaffner
Journal: New England Journal of Medicine (1988)

To evaluate recent immunization against diphtheria, tetanus, and pertussis (DTP) as a possible risk factor for sudden infant death syndrome (SIDS), we studied the rates of SIDS after the administration of DTP vaccine in a cohort of 129,834 children who were born in four urban Tennessee counties during the period from 1974 through 1984. All the children received at least one DTP immunization in the first year of life at county health-department clinics or from Medicaid providers. Computerized immunization records from these sources were linked with Tennessee birth and death certificates to establish the cohort, ascertain the timing of immunization, and identify cases of SIDS. These children represented 42 percent of the births in the four counties. Among these children, 204 deaths occurred at the ages of 29 to 365 days; 109 deaths were classified as due to SIDS. We estimated the risk of SIDS according to the length of time, up to 30 days, since DTP immunization and compared it with the risk 31 days or more after immunization to calculate the relative risk. With control for age, the relative risk from 0 to 3 days after DTP immunization was 0.18 (95 percent confidence interval, 0.04 to 0.8); from 4 to 7 days, 0.17 (95 percent confidence interval, 0.04 to 0.7); from 8 to 14 days, 0.75 (95 percent confidence interval, 0.4 to 1.5); and from 15 to 30 days, 1.0 (95 percent confidence interval, 0.6 to 1.6). A multivariate analysis in which we controlled for age, sex, race, year, birth weight, and Medicaid enrollment, produced similar results. We conclude that in this large population of children there was no increase in the risk of SIDS after immunization with the DTP vaccine. (N Engl J Med 1988; 319:618–23.)
Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy.
Authors: P Dieppe, J Cushnaghan, P Young, J Kirwan
Journal: Annals of the Rheumatic Diseases (1993)

To test the hypothesis that bone scintigraphy will predict the outcome of osteoarthritis (OA) of the knee joint.Ninety four patients (65 women, 29 men; mean age 64.2 years) with established OA of one or both knee joints were examined in 1986, when radiographs and bone scan images (early and late phase) were also obtained. The patients were recalled, re-examined, and had further radiographs taken in 1991. Paired entry and outcome radiographs were read by a single observer, blinded to date order and other data. Scan findings and other entry variables were related to outcome. Progression of OA of the knee was defined as an operation on the knee or a decrease in the tibiofemoral joint space of 2 mm or more.Over the five year study period 10 patients died and nine were lost to follow up. Fifteen had an operation on one or both knees (22 knees). Of the remaining 120 knees (60 patients) analysed radiographically, 14 (12%) had progressed in the manner defined. Of 32 knees with severe scan abnormalities, 28 (88%) showed progression, whereas none of the 55 knees with no scan abnormality at entry progressed. The strong negative predictive power of scintigraphy could not be accounted for by disease severity or any combination of entry variables. Pain severity predicted a subsequent operation, but age, sex, symptom duration, and obesity had no predictive value.Scintigraphy predicts subsequent loss of joint space in patients with established OA of the knee joint. This is the first description of a powerful predictor of change in this disease. The finding suggests that the activity of the subchondral bone may determine loss of cartilage.
Skiing lacerations. Preventability by the use of ski brakes
Authors: T. G. Colmey
Journal: JAMA (1980)

Analysis of all ski injuries recorded at Vail, Colo, during the 1973-1974 season showed that 178 injuries occurred in which the skier was lacerated by his own ski. This represented approximately one out of every ten ski injuries—a ratio that remained constant during the six seasons from 1972 through 1978. Frequently these lacerations occurred about the head and face and were cosmetically serious in nature. It is believed that such injuries are largely preventable. The use of ski brakes as an alternative to runaway straps could appreciably lower the incidence of these injuries. (<i>JAMA</i>244:1699-1700, 1980)
Estrogens and the Menopause
Authors: Nathan Kase
Journal: JAMA (1974)

The climacteric woman faces a variety of clinical problems that are thought to be associated with the decline in estrogen production and function that follows the menopause. These include osteoporosis, arteriosclerosis, mucous membrane deterioration, disorders of the skin and genitourinary system, as well as psychological difficulties. When one considers that at the time of the 1970 census, of the 104 million women in the United States 27 million were 50 years old or more—and each woman at age 50 has an expectation of living an additional 28 years—the magnitude of the public health challenge that the menopause presents can be appreciated. In reaction to this challenge and despite the fact that the mechanisms by which the disorders of aging relate (if at all) to waning estrogen are either unknown, uncertain, or disputed, the use of empiric estrogen "replacement" therapy has been advocated to relieve or retard some or all of
Dendritic cells in the arterial wall express C1q: potential significance in atherogenesis
Authors: W Cao
Journal: Cardiovascular Research (2003)

Dendritic cells (DCs) accumulate in atherosclerotic lesions but their characteristics and their role in atherogenesis are poorly understood. C1q, an element of the first component of complement, is expressed by interdigitating dendritic cells and follicular dendritic cells in the spleen. It has been suggested that C1q is involved in capturing immune complexes in the lymphoid tissue. Immune complexes are also detected in atherosclerotic lesions. The present study investigated whether C1q is expressed by DCs in the arterial wall. Because DCs accumulating within atherosclerotic lesions might originate from monocytes that infiltrate the intima from very early stages of atherosclerosis, C1q expression was also examined in monocyte-derived DCs in vitro.Specimens of the aorta, carotid, mammary, popliteal and tibial arteries were obtained during operation. Expression of C1q in the arterial wall was studied by immunohistochemistry. The nature of cells expressing C1q was studied in sections double stained with antibodies to C1q and cell type specific markers including CD1a and S-100 (for identification of DCs), CD68 (macrophages), CD3 (T-cells), von Willebrand factor (endothelial cells), and smooth muscle alpha-actin (smooth muscle cells). In vitro, DCs were differentiated from human peripheral blood monocytes using GM-CSF and IL-4. Peripheral blood monocytes were differentiated to macrophages using M-CSF. The expression of C1q in monocytes and in vitro monocyte-derived DCs and macrophages was determined by RT-PCR, Western blotting, immunofluorescence microscopy and flow cytometry.In all the arterial specimens studied, DCs expressing C1q were detected. C1q was also found in macrophages, macrophage foam cells and in neovascular endothelial cells in atherosclerotic lesions, but no C1q expression was detected in T-cells and smooth muscle cells. In vitro analysis demonstrated that monocyte-derived DCs and macrophages express C1q but no C1q was detected in monocytes.C1q is expressed by DCs residing in the arterial wall as well as by monocyte-derived DCs in vitro. Expression of C1q occurs during differentiation of monocytes to DCs and macrophages and might be important in binding and trapping immune complexes in atherosclerotic lesions.
SEROLOGICAL REACTIVITY OF HYDROLYTIC PRODUCTS FROM SILK
Authors: K. Landsteiner
Journal: The Journal of Experimental Medicine (1942)

The foregoing experiments show that products of the hydrolysis of silk that consist of peptides having, from amino nitrogen determinations, molecular weights from about 600 to 1000 were capable of inhibiting the reactions of precipitin sera for silk. From the results it may reasonably be inferred that silk fibroin contains determinant structures not larger than the peptides examined, which probably consist of not more than 8 to 12 amino acids. That similar relations may obtain with other proteins is not improbable in view of results previously reported with dialyzable split products.
What is an "n-of-1" trial?
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers assessed the effectiveness of “n-of-1” trials for the short term choice of drugs for osteoarthritis. The efficacy of sustained release paracetamol was compared with celecoxib in the management of symptoms associated with osteoarthritis. A series of double blind randomised n-of-1 controlled trials using a double dummy design was performed. The intervention was sustained release paracetamol (two 665 mg tablets, three times a day), or celecoxib (200 mg daily, or 200 mg twice a day for those who were already using this dose). Each treatment regimen was taken for two weeks, administered for three treatment cycles. The primary outcome measures included pain, stiffness, and functional limitation scores; preferred treatment; and adverse effects.1

Participants were eligible if they had osteoarthritis in multiple sites, with pain for at least one month. In addition, their pain was severe enough to warrant consideration of the long term use of celecoxib, but the efficacy of this drug was in doubt. In total, 59 patients were recruited, with 41 completing an n-of-1 trial. It was reported that 33 of the 41 patients could not identify a difference between sustained release paracetamol and celecoxib in terms of overall symptom relief. Of the eight patients who were able to identify differences, seven reported better relief with celecoxib and one with sustained release paracetamol. It was concluded that n-of-1 trials …
Death certification in general practice: review of records.
Authors: D A Black, S J Jachuck
Journal: BMJ (1984)

The records of death that had been certified by general practitioners in one practice over 18 years were assessed in the light of the recent joint publications of the Royal College of Physicians and the Royal College of Pathologists. Over this period roughly 30% of the deaths in the practice population occurred outside hospital and a total of 262 certificates were issued. A review of 262 counterfoils of records of death certification showed that 12 counterfoils (4.6%) had no age and sex mentioned, and three counterfoils did not describe the place of death. The average age at death outside hospital was 71.6 years--the age of women being 75.1 years compared with that of men of 68.2 years. Only 2% of patients had had a necropsy. The common causes of death stated in the certificates were: cardiovascular 41%, carcinoma 35%, respiratory 15%, and stroke 8%. All contributory causes are also mentioned. Ninety seven per cent of the patients were seen after death by the doctors in the practice and 68% had been seen in the two days preceding death. We emphasise the importance of keeping accurate records of deaths in general practice for audit and research as well as for planning services for terminally ill and recently bereaved patients.
456 Safety, pharmacokinetics and pharmacodynamic results of higher doses of albuferon in a phase single and double dose-escalation study in treatment experienced subjects with chronic hepatitis C
Authors: V. Balan, M. Sulkowski, D. Nelson, G. Everson, R. Dickson, L. Lambiase, A. Post, R. Redfield, R. Wiesner, J. Recta, B. Osborn, L. Novello, W. Freimuth, M. Subramanian
Journal: Journal of Hepatology (2004)