tbuckley/cabot-search huggingface dataset:
Serum levels of NG, NG-dimethyl-L-arginine, a potential endogenous nitric oxide inhibitor in dialysis patients.
Authors: B Anderstam, K Katzarski, J Bergström
Journal: Journal of the American Society of Nephrology (1997)

Nitric oxide (NO) is involved in blood pressure regulation, and its synthesis is inhibited by methylarginines. It has been hypothesized that one of these, asymmetrical dimethylarginine (ADMA), may contribute to dialysis-associated hypertension because it accumulates in the plasma of hemodialysis (HD) patients in a concentration high enough (4 mumol/L) to inhibit NO synthesis in experimental model systems. A precolumn HPLC technique was used to quantify methylarginines (ADMA and symmetrical dimethylarginine [SDMA]) in plasma from HD patients before and after dialysis, from continuous ambulatory peritoneal dialysis (CAPD) patients, and from healthy subjects. Plasma ADMA concentrations were 0.59 +/- 0.22 (SD) mumol/L in HD patients predialysis (n = 19) and 0.70 +/- 0.27 mumol/L in CAPD patients (n = 11), versus about half of the concentration in control subjects (0.36 +/- 0.08 mumol/L, n = 7). The concentrations of SDMA (not an inhibitor of NO formation) were approximately four to five times the ADMA concentrations in both HD and CAPD patients, in contrast to a ratio of 1:1 in the control subjects. Methylarginine concentrations were reduced by 23% and 40% postdialysis, as calculated from ADMA and SDMA values, respectively. No significant correlations were observed between ADMA concentrations, on the one had, and blood pressure, creatinine and dialysis dose (Kt/V urea), on the other hand. It is concluded that plasma levels of ADMA are considerably lower than those reported earlier in patients treated with HD and also below the levels that hitherto have been thought to have clinical relevance. The role of ADMA in inhibiting NO in dialysis-associated hypertension is questioned.
Regional differences in sensitization to Ambrosia in Croatian children
Authors: Ivana Banic, Ana Vecenaj, Adrijana Miletic Gospic, Marija Perica, Jelena Zivkovic, Davor Plavec, Ante Cvitkovic, Renata Peternel, Nenad Peris, Mirjana Turkalj
Journal: European Respiratory Journal (2014)

Introduction : FP7 project ATOPICA ( Atopic diseases in changing climate, land use and air quality ) supported by EU Grant agreement NO: CP 282687 explores the combined pan-European impact of changes in climate, land use and air pollution on allergen pollen-induced diseases.   Aims and objectives:  To determine the prevalence and future incidence in allergy to Ambrosia in children from different exposure sites.   Methods:  Cohort of 3590 children, aged 4-10 years, was recruited from 3 regions of Croatia differing in Ambrosia pollen concentrations: Slavonia with the highest, Zagreb area with middle and Dalmatia with the lowest. Each participant underwent skin prick test (SPT) to the standard set of aeroallergens. Pollen concentrations and air quality data were gathered from authorized institutions.   Results:  A total of 369 children were sensitized to Ambrosia pollen. Prevalence of Ambrosia sensitization was 14.84 % in Zagreb area, 14.26 % in Slavonia and 1.52 % in Dalmatia. Analysis of sensitization in two age groups (4-6 and 7-10 years) reveals higher prevalence of Ambrosia, birch and D. pteronyssinus sensitization as well as double sensitization (birch and Ambrosia) in older age group for all 3 regions. Sensitization to above allergens was more prevalent in male participants. After two pollen seasons of follow-up, de novo sensitized children were recorded: 2.88% in Zagreb area, 2,73% in Slavonia and 0,00% in Dalmatia. De novo sensitization was more prevalent in older age group.   Conclusions:  Region of Slavonia measures highest Ambrosia pollen concentrations and also most de novo sensitized children, which leads to assumption that sensitization rates are primary correlated to exposure levels to Ambrosia pollen.
Induced Resistance in Normal Mice and Growth Enhancement in Tumor-Bearing Mice by Inoculation With Syngeneic Hybrid Cells23
Authors: Toshio Dei, Takehiko Tachibana
Journal: JNCI Journal of the National Cancer Institute (1980)

Primary tumor cells (MCT) induced in an inbred C3H mouse by 3-methylcholanthrene were fused with 8-azagua-nine-resistant L-cells with the use of UV-irradiated HVJ (Sendai virus). Two types of hybrid cell clones showing different behavior in culture were obtained. Both hybrid cell lines expressed H-2k antigen, tumor cell antigen, and L-cell antigen. These hybrid cells failed to produce tumors in normal C3H mice after ip or sc inoculations of as many as 106 cells. Normal C3H mice pretreated with the inocula of viable hybrid cells showed specific resistance to the challenge of parental MCT cells. In the Winn test, the effector activity was observed in immune lymphoid spleen cells and was not lost by passage through a nylon fiber column, but was abrogated by treatment with anti-Thy-1.2 antiserum and complement. However, inoculation of these hybrid cells in syngeneic mice bearing MCT cells enhanced tumor growth. In these mice with enhanced tumor growth, generation of cytotoxic T-cells was also observed in the spleen; in sera, however, free cytotoxic antibodies to tumor cell surface antigens and antigen-antibody complexes existed at higher concentration than in sera of tumor bearers. Sera from mice with tumor enhancement interfered with in vitro cellular cytotoxicity at the level of both target cells and immune spleen cells. Therefore, the inoculation of viable hybrid cells seemed to preferentially stimulate cellular immunity in normal mice but accelerated the humoral response and subsequently enhanced tumor growth in tumor-bearing mice.
Postoperative Nausea is Relieved by Acupressure
Authors: G Barsoum, E P Perry, I A Fraser
Journal: Journal of the Royal Society of Medicine (1990)

One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.
Abstract 389: Human Cardiac Sympathetic Nerves Switch the Neurotransmitter Property from Catecholaminergic to Cholinergic in Patients with Severe Heart Failure
Authors: Hideaki Kanazawa, Masaki Ieda, Kensuke Kimura, Takahide Arai, Haruko Manabe, Tokuhiro Kimura, Yasunori Okada, Hatsue Ueda, Keiichi Fukuda
Journal: Circulation (2008)

[Background] Congestive heart failure (CHF) is characterized by activation of the sympathetic nervous system (SNS) with depletion of norepinephrine (NE) stores, which was initially considered to be the result of excess NE secretion and the loss of noradrenergic nerve terminals. Recent studies however have revealed that it is caused by down regulation of NE synthesis and re-uptake, although the molecular mechanism of down regulation of the sympathetic neuronal function remains unknown. We recently found in an animal model of CHF that the cardiac SNS switches the neurotransmitter property from catecholaminergic to cholinergic, mediated by cytokines LIF and CT-1 secreted from failing myocardium. This study was designed to investigate whether or not this cholinergic transdifferentiation of cardiac SNS occurs in patients with CHF. [Methods &amp; Results] (1) We analyzed 8 samples from patients who died of non-cardiac causes obtained at autopsy (control group), and 8 samples from patients with CHF (CHF group). Five of them died of CHF, and 3 were obtained from native hearts of transplant recipients. (2) The heart weight was significantly higher in the CHF group. (3) The gross morphology of the cardiac SNS did not differ between the two groups. HE and Masson trichrome staining showed disorganized cardiomyocytes and interstitial fibrosis in CHF. (4) Immunostaining for tyrosine hydroxylase (TH, sympathetic nerve marker) revealed that the epicardial nerve bundles and stellate ganglia of the control group had a predominance of TH + nerves, whereas those of CHF group were significantly decreased. (5) Immunostaining for choline transporter (CHT, cholinergic neuron marker) revealed that CHT + neurons were markedly increased in the epicardial nerve bundles of CHF hearts compared with the control group. Some nerves co-expressed both TH and CHT markers. (6) Immunostaining for choline acetyl transferase (ChAT, a cholinergic neuron marker) revealed that stellate ganglia had a lot of ChAT + neurons compared with the control. (7) Nissl staining showed that there was no difference between the two groups in neuron number in the stellate ganglia. [Conclusions] These results indicated that in patients with CHF the cardiac sympathetic nerves also had cholinergic nerve properties.
Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.
Authors: L J Laubenstein, R L Krigel, C M Odajnyk, K B Hymes, A Friedman-Kien, J C Wernz, F M Muggia
Journal: Journal of Clinical Oncology (1984)

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.
Tumor imaging and therapy with activatable cell penetrating peptides
Authors: Aguilera A. Todd, Emilia S. Olson, Tao Jiang, Ed H. Wong, Quyen Nguyen, Mariam Scadeng, Lesley Ellies, Roger Y. Tsien
Journal: Clinical Cancer Research (2006)

B27   To develop an amplifying mechanism to accumulate imaging and therapeutic agents, we have synthesized and tested novel peptide-based agents that are substrates for matrix metalloproteinases (MMPs), proteases highly expressed in the tumor microenvironment. These agents concatenate a payload (e.g. optical (Cy5), magnetic (Gd-DOTA), or radioactive ( 99m Tc(CO) 3 ) contrast agents, or doxorubicin as a chemotherapeutic), a poly-D-arginine cell-penetrating peptide, an MMP-cleavable linker, a poly-D-glutamate inhibitory sequence, and a macromolecular carrier to modulate pharmacokinetics. Protease-mediated cleavage of the linker separates the payload plus polycationic cell-penetrating peptide from the inhibitory polyanion, allowing uptake onto and into cells. These agents have given promising results in isolated cells, 3-D cultures of MDA-MB-231 tumor cells, and slices from resected human squamous cell carcinomas. We have now begun tests on two standard murine models, nude mice bearing xenografts of HT1080 human fibrosarcoma cells and transgenic mice that develop mammary tumors due to mouse mammary tumor virus driving expression of polyoma middle T oncoprotein. After intravenous injection of the probes, we obtain serial images with far-red epifluorescence, T 1 -weighted MRI, or planar scintigraphy, and harvest post-mortem tissues to quantify cargo uptake. With standard cytotoxicity assays and optical fluorescence of doxorubicin we can develop and optimize delivery of therapeutic peptides to tumor cells in tissue culture and eventually murine models.Optical imaging of Cy5-labeled probes with albumin or dextran carriers gave up to 4:1 contrast for primary tumors over neighboring normal regions in MMTV-PyMT mice, and even higher contrast in lymph nodes containing tumor metastases, both peaking around 24-48 hr after injection. MRI of Gd-DOTA-labeled probes also highlighted metastatic lymph nodes. However,  99m Tc-labeled agents conjugated to albumin, 70KDa-dextran, or generation-5 PAMAM dendrimers deposited radioactivity to a much greater extent in the liver (12-18% ID/g), kidney, and spleen than in the xenografted tumors (up to 3% ID/g for the albumin-conjugate). Precleaved and uncleaved doxorubicin peptides imaged by confocal microscopy reveal differential uptake and subcellular localization over time in culture. These optical data can corroborate therapeutic potential when combined with cytotoxicity analysis.This contrast mechanism offers enzymatic amplification and could provide a general alternative to antibody targeting. Combined imaging and therapeutic cargoes could offer personalized therapy.
Measurement Methodology: What Does Blood Pressure Mean in the PARTAGE Study?—Reply
Authors: Athanase Benetos, Patrick Rossignol
Journal: JAMA Internal Medicine (2015)

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A single dose of a specific serinoprotease inhibitor attenuated the protease-antiprotease imbalance in an experimental model of emphysema
Authors: Clarice R. Olivo, Juliana D. Lourenço, Luana Neves, Francine Almeida, Carla M. Prado, Iolanda C.L. Tibério, Aparecida Tanaka, Sergio Sasaki, Milton A. Martins, Fernanda D.T.Q.S. Lopes
Journal: European Respiratory Journal (2012)

We showed that a single dose of specific serinoprotease inhibitor in mice attenuated parenchymal destruction with an improvement in lung function in emphysema. Objectives: To study the possible effects of this inhibitor in pathological mechanisms that contribute to emphysema. Methods: Mice were submitted to either a nasal instillation of porcine pancreatic elastase (PPE) or saline (S) and 1h after, animals received a second nasal instillation of either a protease inhibitor (r-BmTIA, 35.54pmol) or vehicle (VE). After 21 days,we evaluated the number of macrophages (MAC) and cells expressing metalloproteinase 12 (MMP12) to assess the protease-antiprotease imbalance. We quantified caspase-3 to evaluate apoptosis and expression of 8-isoprostane as a marker of oxidative stress. Results: We observed an increase in MAC in groups that received PPE and only PPE-VE group showed higher values of MMP-12. There were no differences between groups when we analyzed caspase-3 and 8-isoprostane.

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Conclusions: Although this inhibitor treatment has not diminished the macrophages in animals that received PPE, it reduced MMP-12 positive cells, suggesting that the improvement in parenchyma destruction and in lung function occured due to attenuation in protease-antiprotease imbalance.Supported by FAPESP, LIMHC-FMUSP, Brazil.
In Vivo Growth Advantage of the MOPC-315 Mouse Myeloma Over Its Immunoselected Variants
Authors: Kristian Hannestad, Ming-Shian Kao, Richard G. Lynch, Herman N. Eisen
Journal: JNCI Journal of the National Cancer Institute (1977)

Myeloma cells of the "wild type" that produce complete immunoglobulin molecules and those of the more usual variant type that display only one kind of chain [either light (L) or heavy (H)] were cocultivated ip and sc in syngeneic BALB/c mice. With each of six deliberately selected variants, a progressive increase in the proportion of wild-type cells was observed; the rate of change suggested that these variants had an approximately 10% slower growth rate than that of the wild-type tumor. In contrast, a variant that arose spontaneously overgrew the wild-type cells. The results may account for a) the stable capacity of most wild-type tumors to produce complete immunoglobulin molecules (L- plus H-chains) over many years, even though they frequently generate variant cells that produce only L- or only H-chains; and b) the occasional spontaneous change of myeloma cell populations from predominantly wild-type to variant cells.
Effects of tobacco smoke on respiratory epithelial clearance of DTPA and on lung histology in rats
Authors: M Mordelet-Dambrine, G Leguern-Stanislas, TC Chinet, L Barritault, J Chretien, GJ Huchon
Journal: European Respiratory Journal (1991)

The respiratory epithelial clearance of 99mTc-(DTPA) diethylenetriamine penta-acetate (RC-DTPA) was measured in rats before and after sham or cigarette smoke exposures. RC-DTPA was increased by cigarette smoke exposure (p less than 0.001); the amount and duration of the exposure had no significant effect. In smoker animals, the number of bronchoalveolar macrophages was decreased after one or five smoke exposures a day for one day (p less than 0.001) and the number of bronchoalveolar neutrophils was increased after five exposures a day for ten days (p less than 0.001). No abnormality was found in the lung parenchyma on light microscopy. We conclude that in rats RC-DTPA is increased by exposure to tobacco smoke, whatever the amount and duration of exposure; however, no gross parenchymal lung abnormality explains the increase in RC-DTPA.
Anaerobic Glycolysis and Patterns of Glycolytic Intermediates During Liver Carcinogenesis and in Hepatoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G. Gaja, F. Cajone, M. E. Ferrero, A. Bernelli-Zazzera
Journal: JNCI Journal of the National Cancer Institute (1970)

A short incubation period in oxygen, which increased the rate of anaerobic glycolysis in normal tissue slices but failed to affect the glycolysis of various types of tumors and embryonic tissues, stimulated anaerobic glycolysis in 5123 Morris hepatoma. During treatment with p-dimethylaminoazobenzene (DAB), which was accompanied by an increase in the basal glycolytic rate and in glycogen breakdown, glycolytic stimulation was always detectable in liver slices from treated animals, but it occurred at a reduced extent, not correlated with the duration of the treatment. Glycolytic stimulation disappeared suddenly in well-developed, DAB-induced hepatomas. Changes in the concentration pattern of glycolytic intermediates, particularly fructose diphosphate, triose phosphate, α-glycerolphosphate, and 3-phosphoglycerate, supported the view that hepatoma glycolysis was not restrained at the steps which, in the normal homologous tissue, limit the metabolic flow after the level of triose phosphates and which are affected by previous exposure to oxygen. The pattern of glycolytfc intermediates in DAB-fed rats was consistent with the fact that glycolytic stimulation, though reduced, was still present. The high basal glycolysis in these rats depended on factors other than those responsible for the glycolytic stimulation in normal liver. The results are discussed in relation to the mechanism that regulates trlose phosphate utilization during anaerobic glycolysis.
High-dose thiotepa with autologous bone marrow transplantation for metastatic malignant melanoma: results of phase I and II studies of the North American Bone Marrow Transplantation Group.
Authors: S N Wolff, R H Herzig, J W Fay, C F LeMaistre, D Frei-Lahr, J Lowder, B Bolwell, L Giannone, G P Herzig
Journal: Journal of Clinical Oncology (1989)

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.