gebhart/patrepeval huggingface dataset:
Antidromic vasodilatation and the migraine mechanism (2011)

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of 'antidromic vasodilatation' as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical-pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine.
Experimental Renal Failure and Iron Overload: A Histomorphometric Study in Rat Tibia (2005)

Renal failure (RF) is a serious disease of relatively high incidence, known to cause bone alterations. RF patients frequently suffer anemia, which is usually treated with iron. Given that iron overload inhibits bone formation, the aim of the present study was to evaluate the effect of iron on the subchondral bone of rat tibiae, using a model of renal failure. Male Wistar rats were subjected to experimental nephrectomy in order to induce renal failure and to iron overload by daily intraperitoneal injections of 88 mg/kg body weight of iron-dextran for 16 days. Tetracyclines were injected intraperitoneally to evaluate dynamic parameters of bone. Undecalcified histological sections of the tibiae were obtained. Serum urea, creatinine, and paratohormone (PTH) levels were evaluated 30 days after the onset of the experiment. Static and dynamic histomorphometric measurements were performed. Iron overload modified the response of the animals with renal failure: a reduction in bone forming activity compatible with adynamic bone disease and a decrease in peritrabecular fibrosis were observed. Our results suggest that iron is yet one more factor involved in the imbalance in bone metabolism typically found in renal failure patients treated with iron, rendering diagnosis and treatment of bone disease in these patients more complex.
Discovery of Selective Aminothiazole Aurora Kinase Inhibitors (2008)

Aurora family kinases regulate important events during mitosis including centrosome maturation and separation, mitotic spindle assembly, and chromosome segregation. Misregulation of Aurora kinases due to genetic amplification and protein overexpression results in aneuploidy and may contribute to tumorigenesis. Here we report the discovery of new small molecule aminothiazole inhibitors of Aurora kinases with exceptional kinase selectivity and report a 1.7 A cocrystal structure with the Aurora B:INCENP complex from Xenopus laevis. The compounds recapitulate the hallmarks of Aurora kinase inhibition, including decreased histone H3 serine 10 phosphorylation, failure to complete cytokinesis, and endoreduplication.
The role of genes domesticated from LTR retrotransposons and retroviruses in mammals (2012)

The acquisition of multiple genes from long terminal repeat (LTR) retrotransposons occurred in mammals. Genes belonging to a sushi-ichi-related retrotransposon homologs (SIRH) family emerged around the time of the establishment of two viviparous mammalian groups, marsupials and eutherians. These genes encode proteins that are homologous to a retrotransposon Gag capsid protein and sometimes also have a Pol-like region. We previously demonstrated that PEG10 (SIRH1) and PEG11/RTL1 (SIRH2) play essential but different roles in placental development. PEG10 is conserved in both the marsupials and the eutherians, while PEG11/RTL1 is a eutherian-specific gene, suggesting that these two domesticated genes were deeply involved in the evolution of mammals via the establishment of the viviparous reproduction system. In this review, we introduce the roles of PEG10 and PEG11/RTL1 in mammalian development and evolution, and summarize the other genes domesticated from LTR retrotransposons and endogenous retroviruses (ERVs) in mammals. We also point out the importance of DNA methylation in inactivating and neutralizing the integrated retrotransposons and ERVs in the process of domestication.
High Efficiency Retroviral-Mediated Gene Transduction into CD34 + Cells Purified from Peripheral Blood of Breast Cancer Patients Primed with Chemotherapy and Granulocyte-Macrophage Colony-Stimulating Factor (1994)

The hematopoietic system has been one of the major targets for designing human gene therapy protocols. In the present system, we have transduced LNL6, one of the most commonly used retroviral vectors in gene therapy, into purified CD34+ cells from peripheral blood of patients primed with chemotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). Purification of CD34+ cells was achieved by incubation with a murine anti-CD34 monoclonal antibody (9C5), and subsequently with paramagnetic microspheres (Dynal) coated with sheep anti-mouse IgG1 (Fc). The CD34+ cells were released from the beads by treatment with chymopapain. Flow cytometry analysis using the anti-CD34 antibody HPCA-2-FITC targeted at another epitope of CD34 showed that 78-97.5% of the cells thus purified were CD34+. After retroviral-mediated gene transfer, polymerase chain reaction (PCR) analysis revealed that 67-100% of the hematopoietic colonies contained the marker gene neo, indicating that CD34+ cells purified by immunomagnetic microsphere method from peripheral mononuclear cells primed with hematopoietic growth factors are highly susceptible to retroviral-mediated gene transfer. The expression of neo as determined by reverse transcription (RT)-PCR appeared to be unstable and not persistent. Taken together, our data suggest that LNL6 is a suitable vector for gene marking of hematopoietic progenitors but not for gene therapy protocols based on persistent gene expression.
Protective immunity to HIV-1 in SCID/beige mice reconstituted with peripheral blood lymphocytes of exposed but uninfected individuals (1996)

Immunodeficiency typically appears many years after initial HIV infection. This long, essentially asymptomatic period contributes to the transmission of HIV in human populations. In rare instances, clearance of HIV-1 infection has been observed, particularly in infants. There are also reports of individuals who have been frequently exposed to HIV-1 but remain seronegative for the virus, and it has been hypothesized that these individuals are resistant to infection by HIV-1. However, little is known about the mechanism of immune clearance or protection against HIV-1 in these high-risk individuals because it is difficult to directly demonstrate in vivo protective immunity. Although most of these high-risk individuals show an HIV-1-specific cell-mediated immune response using in vitro assays, their peripheral blood lymphocytes (PBLs) are still susceptible to HIV infection in tissue culture. To study this further in vivo, we have established a humanized SCID mouse infection model whereby T-, B-, and natural killer-cell defective SCID/beige mice that have been reconstituted with normal human PBLs can be infected with HIV-1. When the SCID/beige mice were reconstituted with PBLs from two different multiply exposed HIV-1 seronegative individuals, the mice showed resistance to infection by two strains of HIV-1 (macrophage tropic and T cell tropic), although the same PBLs were easily infected in vitro. Mice reconstituted with PBLs from non-HIV-exposed controls were readily infected. When the same reconstituted mice were depleted of human CD8 T cells, however, they became susceptible to HIV-1 infection, indicating that the in vivo protection required CD8 T cells. This provides clear experimental evidence that some multiply exposed, HIV-1-negative individuals have in vivo protective immunity that is CD8 T cell-dependent. Understanding the mechanism of such protective immunity is critical to the design and testing of effective prophylactic vaccines and immunotherapeutic regimens.
Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. (1992)

Analysis of genomic organization and expression of platelet-derived growth factor receptors (PDGFR) and epidermal growth factor receptor (EGFR) in human malignant gliomas showed amplification and overexpression of both receptors in distinct subsets of tumors. Amplification of the alpha PDGFR was detected in 4 of 50 glioblastomas (8%). EGFR was amplified in 9 of the 50 tumors (18%). Western blot analysis showed elevated expression of alpha PDGFR and EGFR proteins in 4 (24%) and 3 (18%), respectively, of 17 tumor specimens analyzed. Increased production of alpha PDGFR as well as EGFR proteins was observed in the presence or absence of gene amplification. Three of the 4 tumors with elevated levels of alpha PDGFR also overexpressed the beta PDGFR, which was present as a single copy gene in all 50 tumors analyzed. Our findings suggest that the amplification and/or overexpression either of EGFR or of the alpha PDGFR along with the coordinate overexpression of the beta PDGFR can contribute to the malignant phenotype of distinct subsets of human glioblastoma.
Cost analysis serves many purposes. (1998)

This article discusses the utility of performing cost analysis of family planning (FP) personnel resources by relying on a system analysis framework in developing countries. A study of a national provider that distributes 16% of all FP services in Mexico found that more efficient use of staff would increase the number of clients served. Nurses and doctors worked slightly more than 6 hours/day, and 38% of a nurse's time and 47% of a physician's time was spent in meetings, administrative duties, unoccupied work time, and personal time. The Mexican government proposed increasing the work day to 8 hours and increasing to 66% the portion of the work day spent on direct client activity. With this change, services would increase from 1.5 million couple-years of protection (CYP) to 1.8 million CYP in 2010, without additional staff, and CYP cost would decline. CYP costs could potentially be reduced by increasing the number of contraceptive units provided per visit and switching from a 1-month- to a 3-month-duration injectable contraceptive. A Bangladesh study found that CYP costs could be reduced by eliminating absenteeism and increasing work time/day by 1 hour. Cost studies can address specific human resource issues. A study in Thailand found that Norplant was more expensive per CYP than injectables and the IUD, and Norplant acceptors were willing to switch to other effective modern methods. The Thai government decided to target Norplant to a few target groups. Staff time use evaluations can be conducted by requiring staff to record their time or by having clients maintain records of staff time on their health cards. The time-motion study, which involves direct observations of how staff spend their time, is costly but avoids estimation error. A CEMOPLAF study in Ecuador found that 1 visit detected almost as many health problems as 4 visits. Some studies examine cost savings related to other services.
Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of camptothecin derivatives bearing five-membered heterocycle containing 10-substituents. (1998)

A series of new camptothecin derivatives bearing certain five-membered heterocycles was synthesized and evaluated for in vitro cytotoxic activity. The cytotoxicity results show that camptothecin derivatives bearing pyrrole and thiophene rings were more potent than camptothecin, whereas those bearing furan were less active than camptothecin. Agarose gel electrophoresis shows different inhibitory activities of the camptothecin analogs towards topoisomerase I DNA cleavage. The pyrrole-containing compounds inhibit topoisomerase I DNA cleavage more strongly than camptothecin, but the thiophene and furan compounds do not show any inhibitory activities for DNA cleavage functions of topoisomerase I. Polyacrylamide gel sequencing electrophoresis shows that the pyrrole compounds induce single-strand breaks after incubating with a labeled DNA fragment. The results suggest that the pyrrole compounds fit the compound-enzyme-DNA complex better than camptothecin and the other analogs.
Microarray-in-a-Tube for Detection of Multiple Viruses (2006)

The microarray-in-a-tube system is a rapid, labor-saving tool for multiple virus detection with several advantages, such as convenience, prevention of cross-contamination of the PCR products, and potential for multiple-gene detection.
A Microfluidic Device for Conducting Gas-Liquid-Solid Hydrogenation Reactions (2004)

We have developed an efficient system for triphase reactions using a microchannel reactor. Using this system, we conducted hydrogenation reactions that proceeded smoothly to afford the desired products quantitatively within 2 minutes for a variety of substrates. The system could also be applied to deprotection reactions. We could achieve an effective interaction between hydrogen, substrates, and a palladium catalyst using extremely large interfacial areas and the short path required for molecular diffusion in the very narrow channel space. This concept could be extended to other multiphase reactions that use gas-phase reagents such as oxygen and carbon dioxide.
Characterization of Conductivity Changes During High-Frequency Irreversible Electroporation for Treatment Planning (2017)

The treatment planning method developed in this study can be translated to H-FIRE treatments of different widths and for different tissue types.
Linear invariant systems (2007)

We formulate in a simple fashion the concept of invariance for a linear
system. We show that one must define what we call an associated Hermitian which commutes with the
system function. We show that it is this Hermitian operator that defines the
invariance and also determines the appropriate transform and other connections
between input and output relations.
Urinary prostaglandins. Identification and origin. (1975)

Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.
Detection and Quantification of Transgenes in Grains by Multiplex and Real-Time PCR (2002)

Multiplex PCR reactions were developed for detecting simultaneously the CryIA(b) and pat genes from events 176, MON810, BT11, and T25 of transgenic maize, using only two pairs of primers, one for the CryIA(b) gene and the other for the pat gene. The Roundup Ready soybean can be precisely detected by a multiplex PCR reaction using known primers, amplifying fragments of the NOS and the epsps sequences simultaneously. Transgenic events such as Roundup Ready soybean and GA21 maize, among others, can be quantified by real-time PCR using a pair of primers and a probe specifically designed for annealing to the NOS ending region. As an alternative to amplifying an endogenous gene, the addition of a foreign gene in a percentage equal to the required level of detection, in a parallel reaction, is proposed. The use of hexane to homogenize large flour samples is suggested.
Antineoplastic Activity of Cannabinoids2 (1975)

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).
Immunobiological activities of synthetic lipid A analogs and related compounds as compared with those of bacterial lipopolysaccharide, re-glycolipid, lipid A, and muramyl dipeptide (1983)

Thirteen acylated and phosphorylated derivatives of beta-1,6-linked glucosamine disaccharide (lipid A analogs), which were synthesized after the structural model of Salmonella-type lipid A, and seven similar derivatives of glucosamine monosaccharide (lipid A-related compounds) were studied for their immunobiological activities. These included mitogenicity and polyclonal B cell activation enhancement of migration of monocytes and polymorphonuclear leukocytes derived from human peripheral blood, stimulation of guinea pig peritoneal macrophages, activation of human complement, and stimulation of serum antibody production and induction of delayed-type hypersensitivity against ovalbumin in guinea pigs. Comparisons were made with lipid A, RE-glycolipid, lipopolysaccharide of natural sources, and a well-known synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine. Some of the lipid A analogs were found to manifest the mitogenic, polyclonal B cell-activating macrophage-stimulating, complement-activating, and immunostimulating activities, although the observed activities were generally far less than those of natural products in intensity and efficiency. Other immunobiological effects exhibited by most of the synthetic lipid A analogs were the enhancement of migration of monocytes and polymorphonuclear leukocytes. It is premature to draw definite conclusions on structure-activity relationships, since a few compounds which were active in some assay systems were scarcely active in other assays. However, an indisputable fact was that beta-1,6-glucosamine disaccharide 1 alpha,4'-diphosphate, which carries two amide-bound (R)-3-hydroxytetradecanoyl and three ester-bound tetradecanoyl residues, and thus has the structure most closely resembling natural lipid A among test compounds in this study, was definitely active in all of the present assay systems. However, its potency was generally much less than natural products. Some of glucosamine monosaccharide derivatives, especially N-(R)-3-[(R)-3-hydroxytetradecanoyloxy]tetradecanoyl glucosamine, also exerted all of the in vitro activities described above. This fact suggests that a glucosamine disaccharide structure may not necessarily be a prerequisite as far as the in vitro immunobiological activities tested are concerned.
Temporal profile of CREB phosphorylation after focal ischemia in rat brain (1999)

The phosphorylation of cAMP response element binding protein (CREB) in the rat brain was examined immunohistochemically at 3.5 h, 12 h, 24 h and 48 h of recirculation after focal ischemia induced by occlusion of the middle cerebral artery for 1.5 h. Brain sections were stained with affinity purified anti-phosphorylated CREB antibody. The ischemic core revealed a significant, but transient increase in number of phosphorylated CREB-positive cells at 3.5 h of recirculation, followed by a rapid decrease during the subsequent period. In the peri-ischemia area, the number of phosphorylated CREB-positive cells showed a more marked increase as compared to that in the ischemic core at 3.5 h of recirculation, and the increase continued until 48 h of recirculation with a tendency for gradual decline. Persistent enhancement of CREB phosphorylation may thus be closely related to the neuronal viability and neuroprotective mechanisms, whereas rapid disappearance of CREB phosphorylation may clearly precede neuronal death.
Breast cancer--new aspects of tumor biology: are calcitriol and cyclooxygenase-2 possible targets for breast cancer? (2014)

Up until now there have been many advances in treatment options for breast cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are still many more that warrant further exploration. Two of these targets might be the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid to prostaglandins, and calcitriol [1,25(OH)2D3] which is the biologically active form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown antiproliferative and prodifferentiation, as well as pro-apoptotic effects in different malignancies in vitro and in vivo, and the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor suppressor activity. Furthermore, the combination ofcalcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2 inhibitors, acting synergistically to achieve significant cell growth inhibition in prostate cancer. Some epidemiological studies suggest that vitamin D confers a moderate benefit against breast cancer while most epidemiological studies presume that NSAIDs confer the same. Nevertheless there is growing body of evidence that COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date, clinical trials have been conducted in patients with different malignancies using treatment strategies including COX-2 inhibitors and calcitriol and are showing partially encouraging results. The goal of this review is to shed light on the association between the prostaglandin as well as vitamin D metabolism relating to the incidence and therapy of breast cancers. Moreover, this review will also highlight potential treatment options, as well as extract any existing interactions between the two metabolisms.