tbuckley/cabot-search huggingface dataset:
Effect of renal vasodilatation on the distribution of cortical blood flow in the kidney of the dog
Authors: Jay H. Stein, Thomas F. Ferris, James E. Huprich, Timothy C. Smith, Richard W. Osgood
Journal: Journal of Clinical Investigation (1971)

Studies were performed to evaluate the validity of using the radioactive microsphere technique to measure regional blood flow in the renal cortex. A technique was developed in which the renal cortex was divided into four equal zones, and the fractional and absolute distribution of blood flow in these zones was determined. It was consistently found that approximately 70% of the renal blood flow was distributed to the two outer cortical zones with the remaining 30% going to the two inner cortical zones. In addition, there was a reproducible pattern of distribution of blood flow in different areas of the same kidney after a single injection of microspheres and in the same area of the kidney after multiple injections of microspheres. Using this method, the distribution of renal blood flow was determined before and during the intrarenal administration of either acetylcholine (40 mug/min) or bradykinin (5 mug/min). Both agents decreased the per cent of blood flow to outer cortical zone 1, caused no change in zone 2, and increased the fractional blood flow in inner cortical zones 3 and 4. When this data was evaluated in terms of total blood flow, there was no change in zone 1, an increase in zone 2 commensurate with the change in total blood flow, and a marked increase in inner cortical zones 3 and 4 which accounted for 60 and 65% of the increase in total blood flow during acetylcholine and bradykinin administration, respectively.Therefore, the natriuresis of renal vasodilatation is associated with a redistribution to inner cortical nephrons.
The protease inhibitor, N-acetyl-L-leucyl-L-leucyl-leucyl-L-norleucinal, decreases the pool of major histocompatibility complex class I-binding peptides and inhibits peptide trimming in the endoplasmic reticulum.
Authors: E A Hughes, B Ortmann, M Surman, P Cresswell
Journal: The Journal of Experimental Medicine (1996)

N-acetyl-L-leucyl-L-leucyl-L-norleucinal, (LLnL), which inhibits proteasomes in addition to other proteases, was found to prolong the association of major histocompatibility complex class I molecules with the transporters associated with antigen processing (TAP), and to slow their transport out of the endoplasmic reticulum (ER). LLnL induced a reversible accumulation of ubiquitinated proteins and changed the spectrum of peptides bound by class I molecules. These effects can probably be attributed to proteasome inhibition. Unexpectedly, in the TAP-deficient cell line .174, the rate of intracellular transport of human histocompatibility leukocyte antigen (HLA) A2 was also reduced by LLnL, and the generation of most HLA-A2-associated signal sequence peptides was inhibited. The inhibition of HLA-A2 transport in .174 cells was found to be less sensitive to LLnL than in wild-type cells, and a similar difference was found for a second protease inhibitor, benzyloxycarbonyl-L-leucyl-L-leucyl-L-phenylalanilal. These data suggest that under some conditions such inhibitors can block trimming of peptides by an ER peptidase in addition to inhibiting cytosolic peptide generation.
Effects of time and height on behavior of emissions.
Authors: I Van der Hoven
Journal: Environmental Health Perspectives (1975)

The effect of the two parameters is reviewed. Variability with time is discussed in relation to stability and other atmospheric conditions. The magnitude of ground level concentrations from elevated release is discussed as an interaction between rate of emission release, physical height of stack, and thermal conditions. The point is made that plant effluent rates have increased in proportion to stack height.
C-reactive protein in juvenile chronic arthritis: an indicator of disease activity and possibly amyloidosis.
Authors: M Gwyther, H Schwarz, A Howard, B M Ansell
Journal: Annals of the Rheumatic Diseases (1982)

C-reactive protein (CRP) was found to be particularly high early in the course of those cases of juvenile chronic arthritis (JCA) with a systemic onset, the mean level being 12 mg/dl (120 mg/l). It was also raised in cases with a polyarticular onset, mean level 6 mg/dl, while in cases with a pauciarticular onset it was associated with only a modest increase up to 1.5 mg/dl (15 mg/l). At the onset of disease there was a good correlation with the erythrocyte sedimentation rate (ESR). Regression of systemic disease was associated with a steady fall in C-reactive protein, but those patients who developed amyloidosis within 5 years from onset had persistently high values until cytotoxic therapy was introduced. Patients who developed amyloidosis later tended to have high CRP levels in the months or even years before diagnosis. In a few patients with polyarthritis the CRP appeared to reflect severe disease more closely than their relatively low ESR.
Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b-8 assembly
Authors: ER Podack, J Tschoop, HJ Muller-Eberhard
Journal: The Journal of Experimental Medicine (1982)

Evidence has been presented suggesting that during assembly of the membrane attack complex (MAC) of complement, the C5b-8 complex induces polymerization of C9. The C9 polymer was detected by sodium dodecyl sulfate (SDS) gel electrophoresis of MAC isolated from complement-lysed erythrocytes. It resembled the previously described polymerized C9 (poly C9) produced from isolated monomeric C9 by prolonged incubation at 37 degrees C in that it was resistant to dissociation by SDS and reducing agents and had an apparent molecular weight of approximately 1.1 million. The presence of poly C9 in the MAC was further supported by the expression of identical neoantigens by the MAC and poly C9 and by the high C9 content of the MAC relative to its other constituents. Isolated C8 in solution was found to have a single C9-binding site. In mixture, the two proteins formed a reversible equimolar complex that had a sedimentation coefficient of 10.5S. In contrast, a single, cell-bound C5b-8 complex was found to bind up to 12-15 C9 molecules and clusters of C5b- 8 bound 6-8 C9 molecules per C8 molecule. In either case, typical ultrastructural membrane lesions were observed, suggesting that the membrane lesion is identical with the tubular poly C9 consisting of 12-16 C9 molecules, and that the MAC can have either the composition (C5b-8)polyC9 or (CSb-8)(2)polyC9. When C9 input was restricted so that the molar C9/C8 ratio was less than or equal to 3, C9-induced aggregates of C5b-8 were observed but virtually no circular membrane lesions were found. We suggest, therefore, that C9, at low dosage, causes cross-linking of multiple C5b-8 complexes within the target membrane and that, at high dosage, C9 is polymerized by C5b-8 to form a transmembrane channel within the MAC assembly. It is primarily the C9 polymer that evokes the ultrastructural image of the MAC or of membrane lesions caused by complement.
Natural Human Plasmacytoid Dendritic Cells Induce Antigen-Specific T-Cell Responses in Melanoma Patients
Authors: Jurjen Tel, Erik H.J.G. Aarntzen, Tetsuro Baba, Gerty Schreibelt, Barbara M. Schulte, Daniel Benitez-Ribas, Otto C. Boerman, Sandra Croockewit, Wim J.G. Oyen, Michelle van Rossum, Gregor Winkels, Pierre G. Coulie, Cornelis J.A. Punt, Carl G. Figdor, I. Jolanda M. de Vries
Journal: Cancer Research (2013)

Vaccination against cancer by using dendritic cells has for more than a decade been based on dendritic cells generated ex vivo from monocytes or CD34(+) progenitors. Here, we report on the first clinical study of therapeutic vaccination against cancer using naturally occurring plasmacytoid dendritic cells (pDC). Fifteen patients with metastatic melanoma received intranodal injections of pDCs activated and loaded with tumor antigen-associated peptides ex vivo. In vivo imaging showed that administered pDCs migrated and distributed over multiple lymph nodes. Several patients mounted antivaccine CD4(+) and CD8(+) T-cell responses. Despite the limited number of administered pDCs, an IFN signature was observed after each vaccination. These results indicate that vaccination with naturally occurring pDC is feasible with minimal toxicity and that in patients with metastatic melanoma, it induces favorable immune responses.
Usefulness of the Initial Noninvasive Imaging Study to Predict the Adverse Outcomes in the Medical Treatment of Acute Type A Aortic Intramural Hematoma
Authors: Jong-Min Song, Hyun-Sook Kim, Jae-Kwan Song, Duk-Hyun Kang, Myeong-Ki Hong, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park, Tae-Hwan Lim, Meong-Gun Song
Journal: Circulation (2003)

There have been contradictory reports about the outcomes of medically treated patients with type A aortic intramural hematoma (AIH), and it is not certain if the initial noninvasive imaging studies can provide any useful predictors for the adverse outcomes.Imaging studies and clinical outcomes of 25 consecutive patients with type A AIH who initially received medical treatment were analyzed retrospectively. Adverse outcomes (death, surgery, and development of dissection) occurred in 9 patients (group A), whereas the other 16 patients showed an uneventful course (group B). The hematoma thickness (14+/-4 versus 8+/-4 mm, P<0.005) and hematoma area (988+/-316 versus 555+/-352 mm2, P<0.01) in the imaging study performed <or=48 hours after onset of initial symptoms were significantly larger in group A; maximal aortic diameter (53+/-6 versus 48+/-8 mm, P=0.10) and aortic cross-sectional area (2247+/-501 versus 1809+/-626 mm2, P=0.09) were also somewhat larger in group A. The hematoma thickness was the only independent predictor for the adverse outcomes by stepwise multiple logistic regression analysis (odds ratio 1.41, 95% confidence interval 1.07 to 1.86, P<0.05). Hematoma thickness >or=11 mm predicted the adverse outcomes with sensitivity 89% and specificity 69%. No one with hemodynamically stable initial condition and the hematoma thickness <11 mm experienced the adverse outcomes.Noninvasive imaging study provides important prognostic information in the medical treatment of acute type A AIH, and initial hematoma thickness seems to be the best index for predicting adverse clinical outcome.
The integrin VLA-2 binds echovirus 1 and extracellular matrix ligands by different mechanisms.
Authors: J M Bergelson, B M Chan, R W Finberg, M E Hemler
Journal: Journal of Clinical Investigation (1993)

The integrin VLA-2 mediates cell adhesion to collagen and laminin and also functions as a virus receptor, mediating cell surface attachment and infection by a human pathogen, echovirus 1. To determine whether extracellular matrix proteins and virus interact with VLA-2 in the same manner, we carried out a detailed comparison of these two functions and found that they differed markedly in six different respects. In contrast to the ECM/VLA-2 interaction, echovirus 1 binding did not discriminate between functional forms of VLA-2, showed a different pattern of inhibition by anti-beta1 and -alpha 2 antibodies, was not stimulated by phorbol esters, was not activated by beta 1 antibodies that stimulate ECM binding, was not inhibited by any particular divalent cation, and most notably was not inhibited by EDTA. These striking differences were found both with intact cells expressing VLA-2 and with solubilized VLA-2, suggesting that VLA-2 interacts with these different ligands by markedly different mechanisms, and probably at different functional sites. In addition, alterations in the alpha 2 cytoplasmic domain that had marked effects on cellular responses to collagen and laminin had no effect on virus internalization and cell killing. Thus VLA-2-mediated events that occur after receptor occupancy by extracellular matrix proteins also appear to be distinct from those that occur after receptor interaction with virus.
High frequency of the MAGE-1 gene expression in hepatocellular carcinoma
Authors: N Yamashita
Journal: Hepatology (1996)

The MAGE-1 gene, originally isolated from a human melanoma cell line, directs the expression of a potential tumor-rejection antigen, MZ2-E. This antigen is recognized by autologous cytotoxic T lymphocytes in association with a major histocompatibility complex class I molecule (HLA-A1), and has provided a basis for specific immunotherapy for melanoma patients. Here we show a high frequency of expression of the MAGE-1 gene in hepatocellular carcinoma (HCC). We examined the expression of the MAGE-1 gene in cell lines originated from hepatoma cells and in tumor and nontumor tissues of livers with HCC by reverse-transcription polymerase chain reaction (RT-PCR) and subsequent Southern blotting. MAGE-1 messenger RNA (mRNA) was expressed in three of four HCC cell lines (75%) and in 16 of 20 (80%) resected HCCs though none was detected in nontumor tissues. The high frequency expression of MAGE-1 gene in HCCs suggests the possibility as a target for tumor- specific immunotherapy for HCC patients. (Hepatology 1996 Dec;24(6):1437-40)
Twice daily beclomethasone dipropionate administered with a concentrated aerosol inhaler: efficacy and patient compliance.
Authors: M J Smith, M E Hodson
Journal: Thorax (1986)

The efficacy of twice daily inhaled beclomethasone dipropionate administered by a concentrated aerosol inhaler (one puff twice daily-500 micrograms/day) has been compared with that of treatment four times daily with a standard dose inhaler (two puffs four times daily-400 micrograms/day) in 21 patients with stable asthma. Double placebo inhalers were used in a randomised crossover fashion during two four week treatment periods. Mean peak expiratory flow (PEF), mean symptom scores, and number of extra salbutamol inhalations required were not significantly different between the two treatment periods. Local side effects were more common during treatment with the four times daily active preparation; overt oropharyngeal candidiasis, however, was not found in either group during the study. On completion of the crossover study patients were transferred to the twice daily regimen. At the three month follow up all patients had remained stable and the outpatient PEF was significantly higher (mean 382 (SD 26)l min-1) than at entry into the trial (mean 345 (24)l min-1) (p less than 0.05). Twice daily beclomethasone administered by a concentrated aerosol inhaler appears to be as effective as the standard four times daily regimen in controlling stable asthma.
Thyroid Hypofunction After Exposure to Fallout From a Hydrogen Bomb Explosion
Authors: P. Reed Larsen
Journal: JAMA (1982)

Thyroid function was evaluated in the Marshallese who were accidentally exposed to fallout-containing radioiodine isotopes in 1954. Measurements of thyrotrophin (TSH, thyroid-stimulating hormone) levels and free thyroxine (T4) index (FT4I) have revealed that, among 86 persons exposed on Rongelap and Ailingnae atolls, 14 have shown evidence of thyroid hypofunction. This was first noted in some individuals about ten years after exposure. Only two of these showed clinical evidence of hypothyroidism. The most marked TSH elevations were noted in nine persons exposed when younger than 6 years, with estimated doses to the thyroid from 390 to 2,100 rad. Most of this group subsequently had surgery for removal of thyroid nodules. The remaining five cases have been noted more recently among 36 surviving adults exposed at an older age who showed no other detectable thyroid abnormalities. This group had received estimated thyroid doses ranging from 135 to 335 rad and showed modest elevation of serum TSH levels (6 to 9 μU/mL) and a slightly subnormal FT<sub>4</sub>I. No abnormalities were found in persons on Utirik who received substantially less radiation, and hypothyroidism was present in less than 1% of the control, unexposed Marshallese. The high prevalence of a thyroid hypofunction in these persons indicates that this condition, as well as thyroid nodularity, can be a delayed complication of exposure to early fallout from a nuclear explosion. The fact that a significant fraction of the radiation to the thyroid was from short-lived radioiodine isotopes (<sup>132</sup>I,<sup>133</sup>I,<sup>135</sup>I), as opposed to<sup>131</sup>I, may account for the severity of the thyroid damage. (<i>JAMA</i>1982;247:1571-1575)
Emergence of Sex Differences in Prevalence of High Systolic Blood Pressure
Authors: Kaberi Dasgupta, Jennifer O’Loughlin, Shunfu Chen, Igor Karp, Gilles Paradis, Johanne Tremblay, Pavel Hamet, Louise Pilote
Journal: Circulation (2006)

High systolic blood pressure (SBP) occurs more frequently both among men and boys than among women and girls. No longitudinal study has investigated whether the impact of SBP determinants differ according to sex in youth.Between 1999 and 2005, an adolescent cohort (n=1267) completed a questionnaire survey and underwent biannual blood pressure and anthropometric assessment (grades 7, 9, and 11). Boys accounted for approximately 50% of those with high SBP at grade 7 and 9 assessments but 67% of those with high SBP at the grade 11 assessment. As computed through a generalized estimating equations logistic regression model (sex, age, sex and age interaction term, overweight, physical activity, sedentary behavior, heart rate, household income, tobacco use, and 4 language categories), the likelihood of high SBP values among boys compared with girls was 1.29 (95% CI, 0.77 to 2.16) in grade 7, 1.98 (95% CI, 1.35 to 2.93) in grade 9, and 2.74 (95% CI, 1.52 to 4.94) in grade 11. Although there was a significant interaction between sex and age, interaction terms of sex with overweight, sedentary behavior, and physical activity were not statistically significant. Overweight (odds ratio [OR], 2.63; 95% CI, 1.76 to 3.92) and sedentary behavior (OR, 1.17 for increment of 5 hours weekly; 95% CI 1.04 to 1.33) demonstrated positive associations with high SBP values. Physical activity was inversely associated with the presence of high SBP (OR, 0.92 for increment of 5 activities in 7 days; 95% CI, 0.84 to 1.00).Boys are more likely than girls to develop high SBP as they approach adulthood. Even among overweight adolescents, reducing sedentary behavior and increasing physical activity may lower the risk of high SBP.
Pus, deoxyribonucleic acid, and sputum viscosity.
Authors: R Picot, I Das, L Reid
Journal: Thorax (1978)

On 100 sputum specimens selected from patients suffering from chronic bronchitis, bronchiectasis, asthma, and cystic fibrosis total deoxyribonucleic acid (DNA) content has been related to macroscopic type, to total dry weight yield, and to the apparent viscosity of the secretion at 1350 s-1: since DNA may be present, either as fibres or within cells, in one-third of the specimens the contribution of each form to the apparent viscosity was assessed. The effect on sputum viscosity of the addition of DNA in vitro has also been studied. Whereas between mucoid, mucopurulent, and purulent macroscopic types a significant difference in total DNA and dry weight yield has been found, viscosity was not significantly correlated with purulence. Similarly, the concentration of either cells or fibres correlated significantly with total DNA but not with viscosity. The in vitro addition of DNA to sputum caused a significant increase in its viscosity, and reasons for the differences between the iv vivo and in vitro effect are discussed. Certain constituents of purulent sputum tend to increase viscosity and others to reduce it, and the influence of these varies in the several diseases studied.
Targets of antibodies against Plasmodium falciparum–infected erythrocytes in malaria immunity
Authors: Jo-Anne Chan, Katherine B. Howell, Linda Reiling, Ricardo Ataide, Claire L. Mackintosh, Freya J.I. Fowkes, Michaela Petter, Joanne M. Chesson, Christine Langer, George M. Warimwe, Michael F. Duffy, Stephen J. Rogerson, Peter C. Bull, Alan F. Cowman, Kevin Marsh, James G. Beeson
Journal: Journal of Clinical Investigation (2012)

Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.
Effect of Dehydroepiandrosterone and the Antiestrogen EM-800 on Growth of Human ZR-75-1 Breast Cancer Xenografts
Authors: Steeve Couillard, Claude Labrie, Alain Bélanger, Bernard Candas, Frédéric Pouliot, Fernand Labrie
Journal: JNCI Journal of the National Cancer Institute (1998)

In the mammary gland, androgens are formed from the precursor steroid dehydroepiandrosterone (DHEA). Clinical evidence indicates that androgens have inhibitory effects on breast cancer. Estrogens, on the other hand, stimulate the development and growth of breast cancer. We studied the effect of DHEA alone or in combination with the newly described pure antiestrogen EM-800 on the growth of subcutaneous tumor xenografts formed by the human breast cancer cell line ZR-75-1 in ovariectomized nude mice.Immediately after ovariectomy, mice received daily subcutaneous injections of 0.5 microg estrone (E1) (an estrogenic hormone). EM-800 (15, 50, or 100 microg) was given orally once daily. DHEA was administered percutaneously twice daily (total dose of 0.3, 1.0, or 3.0 mg) to the dorsal skin either alone or in combination with a 15-microg daily oral dose of EM-800. Changes in tumor size in response to the treatments (in relation to measurements made on the first day of treatment) were assessed periodically. At the end of the experiments, tumors were dissected and weighed.A 9.4-fold increase in tumor size in 9.5 months was observed in ovariectomized mice receiving E1 alone. Administration of 15, 50, or 100 microg EM-800 in E1-supplemented mice led to inhibitions of 87.5%, 93.5%, and 94.0% in tumor size, respectively. DHEA, on the other hand, at doses of 0.3, 1.0, or 3.0 mg inhibited terminal tumor size by 50.4%, 76.8%, and 80.0%, respectively. Comparable inhibitions in tumor size were obtained with a daily 15-microg oral dose of EM-800 with or without different doses of percutaneous DHEA.DHEA and EM-800 independently suppressed the growth of E1-stimulated ZR-75-1 xenograft tumors in nude mice. Administration of DHEA at the defined doses did not alter the inhibitory effect of EM-800.