gebhart/patrepeval huggingface dataset:
Biomechanics of the aging spine. (2006)

Experimental studies indicate age and degeneration affect spinal biomechanics. In vitro biomechanical experimentation is used to validate finite element cervical spine models. A high percentage of experimental studies have utilized older specimens. Computer models based on these experimental studies may not accurately represent the normal population. Younger full-column and C5-C6 motion segments were tested under pure sagittal plane moments. A review of literature was conducted, and results from previous studies were compared to present data to determine whether age was an influencing factor in spinal biomechanics. Findings indicate younger specimens under equivalent pure moment loading magnitudes underwent greater ranges of motion between 0.5 and 2.5 Nm. Based on these preliminary findings, validation of finite element modeling to ensure biofidelity should consider age as a factor that may affect biomechanics.
Over‐expression of FoxM1 stimulates cyclin B1 expression (2001)

FoxM1 (previously named WIN, HFH-11 or Trident) is a Forkhead box (Fox) transcription factor widely expressed in proliferating cells. Various findings, including a recent analysis of FoxM1 knockout mice, suggest that FoxM1 is required for normal S-M coupling during cell cycle progression. To study the regulatory role of FoxM1 and its downstream regulatory targets, three stably transfected HeLa lines that display doxycycline (dox)-inducible FoxM1 expression were established. Over-expression of FoxM1 by dox induction facilitates growth recovery from serum starvation. Quantitation of cyclin B1 and D1 levels using flow cytometric, Western and Northern analyses reveals that elevated FoxM1 levels lead to stimulation of cyclin B1 but not cyclin D1 expression. Transient reporter assays in the dox-inducible lines and upon co-transfection with a constitutive FoxM1 expression plasmid suggest that FoxM1 can activate the cyclin B1 promoter.
Thrombokinetics in man (1969)

Platelet production, distribution, and destruction have been quantitated in normal man and in selected patients with platelet disorders. In most instances, total production as calculated from the megakaryocyte mass agreed with production estimated from platelet turnover. In patients with megaloblastosis, a discrepancy between these two measurements indicated the presence of ineffective thrombopoiesis. Thrombopoiesis was regulated by (a) alterations in megakaryocyte number, and (b) changes in megakaryocyte volume (produced by changes in endomitosis). The volume-endomitosis changes were closely related to the peripheral platelet count and were a useful indicator of thrombopoietic stimulus. Thrombocytopenic disorders have been classified on the basis of the disturbed physiology into disorders of (a) production (hypoproliferative or ineffective), (b) distribution (splenic pooling), or (c) destruction (immune or consumptive). Less than a twofold increase in platelet production in the presence of significant thrombocytopenia was taken to represent impaired proliferation. Thrombocytosis was classified as reactive or autonomous. Reactive thrombocytosis was consistently associated with a mean megakaryocyte volume and endomitosis less than normal but appropriate for the elevated circulating platelet count. In contrast, the average megakaryocyte volume and nuclear number were always greater than normal in thrombocythemia findings indicating autonomy.
Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor (1997)

In order to reduce the extrahepatic side-effects of antiviral nucleoside analogues in the treatment of chronic viral hepatitis, these drugs are conjugated with galactosyl-terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor present in large amounts and high affinity only on these cells. Within hepatocytes the conjugates are delivered to lysosomes where enzymes split the bond between the carrier and the drug, allowing the latter to become concentrated in the liver. The validity of this chemotherapeutic strategy has been endorsed by a clinical study. Adenine arabinoside monophosphate (ara-AMP), conjugated with lactosaminated human serum albumin (L-HSA) and administered to hepatitis B virus (HBV)-infected patients for 28 days, exerted an antiviral activity to the same extent as the free drug without producing any clinical side-effects, including the severe neurotoxicity caused by the free drug. Preclinical studies are now underway with conjugates obtained using lactosaminated poly-L-lysine (Lac-poly(Lys)) as the hepatotropic carrier. These new conjugates have some advantages over those prepared with L-HSA: they can be administered by the intramuscular route; they are obtained entirely by chemical synthesis, thus eliminating the problems involved in the use of haemoderivatives; they have a heavy drug load, which permits administration of smaller quantities of conjugate that are more easily digested in lysosomes; and they enable higher quantities of drug to be introduced into hepatocytes. The results of the experiments with two Lac-poly(Lys) conjugates, one with ara-AMP and one with ribavirin, are reported in this review.
A Convergent Synthetic Platform for Single-Nanoparticle Combination Cancer Therapy: Ratiometric Loading and Controlled Release of Cisplatin, Doxorubicin, and Camptothecin (2014)

The synthesis of polymer therapeutics capable of controlled loading and synchronized release of multiple therapeutic agents remains a formidable challenge in drug delivery and synthetic polymer chemistry. Herein, we report the synthesis of polymer nanoparticles (NPs) that carry precise molar ratios of doxorubicin, camptothecin, and cisplatin. To our knowledge, this work provides the first example of orthogonally triggered release of three drugs from single NPs. The highly convergent synthetic approach opens the door to new NP-based combination therapies for cancer.
A depropargylation-triggered fluorescence “turn-on” probe for the detection of Pd2+ based on a bispropargylamine–rhodamine conjugate (2013)

A bis-propargyl-appended rhodamine B-based receptor BPRB has been synthesised that exhibits pronounced fluorescence enhancement in the presence of Pd2+ ions. The addition of Pd2+ enhanced the fluorescence intensity of BPRB by 113-fold (Φf = 0.37) and BPRB was found to exhibit high selectivity towards Pd2+ compared to a range of other metal ions. The enhancement of fluorescence was triggered by spirolactam ring opening followed by depropargylation of BPRB in the presence of Pd2+, as evidenced by FTIR and NMR analyses. BPRB was able to detect Pd0 without the addition of a reducing agent, and the emission intensity of BPRB–Pd0 was almost identical to that of BPRB–Pd2+; however, a rapid fluorescence response was observed in the presence of PPh3. To explore the efficiency of the rhodamine unit, a bispropargyl derivative of cyclohexane (BPCH) was synthesised and the fluorescence response towards Pd2+ was examined and compared with BPRB, revealing that the rhodamine unit enhanced the fluorescence intensity by 500-fold. The fluorescence images of BPRB and BPRB–Pd2+ samples indicate that BPRB could be useful for imaging Pd2+ in living cells.
Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds (1994)

Cartilage implants which could potentially be used to resurface damaged joints were created using rabbit articular chondrocytes and synthetic, biodegradable polymer scaffolds. Cells were serially passaged and then cultured in vitro on fibrous polyglycolic acid (PGA) scaffolds. Cell-PGA constructs were implanted in vivo as allografts to repair 3-mm diameter, full thickness defects in the knee joints of adult rabbits, and cartilage repair was assessed histologically over 6 months. In vitro, chondrocytes proliferated on PGA and regenerated cartilaginous matrix. Collagen and glycosaminoglycan (GAG) represented 20 to 8% of the implant dry weight (dw), respectively, at the time of in vivo implantation; the remainder was PGA and unspecified components. Implants based on passaged chondrocytes had 1.7-times as much GAG and 2.6-times as much collagen as those based on primary chondrocytes. In vivo, cartilaginous repair tissue was observed after implantation of PGA both with and without cultured chondrocytes. Six month repair was qualitatively better for cell-PGA allografts than for PGA alone, with respect to: 1) surface smoothness, 2) columnar alignment of chondrocytes, 3) spatially uniform GAG distribution, 4) reconstitution of the subchondral plate, and 5) bonding of the repair tissue to the underlying bone. These pilot studies demonstrate that it is feasible to use cell-polymer allografts for joint resurfacing in vivo.
Human lung tryptase. Purification and characterization. (1984)

Human lung tryptase, a mast cell-derived trypsin-like serine protease, has been isolated from whole human lung tissue obtained at autopsy. Increased yields from this purification process have allowed extensive characterization of the enzyme. One of the critical steps in the purification scheme is the use of a linear heparin gradient to elute active material from cellulose phosphate. Gel filtration studies in 1.0 M NaCl yielded an apparent Mr = 135,000, and subsequent electrophoresis on sodium dodecyl sulfate-polyacrylamide gels demonstrated the presence of two active species with apparent Mr = 30,900 and 31,600. Enzymatic activity was sensitive to NaCl concentrations above 0.05 M and was only 50% in 0.15 M NaCl, decreasing to 18% in 0.6 M NaCl. The effects of synthetic and natural inhibitors have also been studied, confirming the enzyme's trypsin-like characteristics and demonstrating that naturally occurring serum inhibitors are incapable of diminishing its activity. A complete amino acid analysis showed a high tryptophan content. Lastly, antisera to human lung tryptase have been generated, and the immunological identity of active fractions has been investigated as well as the localization of the enzyme to the mast cell granule by immunohistochemical staining.
Structure-Based Design of a Highly Selective Catalytic Site-Directed Inhibitor of Ser/Thr Protein Phosphatase 2B (Calcineurin) (2003)

Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transductions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1,5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.
CD11b+ macrophages that infiltrate human epidermis after in vivo ultraviolet exposure potently produce IL-10 and represent the major secretory source of epidermal IL-10 protein. (1994)

Because activated human macrophages can be potent sources of IL-10, and because immunosuppressive tolerance-inducing macrophages populate the skin after UV exposure, we determined whether IL-10 is induced after UV exposure of human skin and whether it is related to the immigrating macrophages. Keratomes were obtained from control skin or from skin obtained 72 h after a single exposure to four minimal erythemal doses of UVB. Quantitative reverse-transcriptase PCR on total RNA extracted immediately from skin keratomes showed that IL-10 mRNA was elevated in UV-exposed skin. Epidermal cell suspensions from non-UV-exposed keratomes (C-EC) and UV-exposed keratomes (UV-EC) were fractionated by sequential immunobead selection. IL-10 mRNA was reproducibly 200- to 400-fold higher in CD11b+ UV-EC (macrophages) relative to CD11b- UV-EC (keratinocytes). IL-10 mRNA was not detected in C-EC that contained the CD1a+ population (Langerhans cells) nor in CD1a- C-EC keratinocytes from normal skin. As determined by ELISA, CD11b+ UV-EC IL-10 cell-associated protein was fivefold higher than that of CD11b- UV-EC; this was confirmed by flow cytometric visualization of IL-10 protein in permeabilized cells. CD11b+ UV-EC macrophages secreted IL-10 protein into the supernatant at a level of 333 +/- 51 pg/10(6) cells, whereas UV-EC keratinocytes did not secrete detectable levels of IL-10 (n = 3), although UV did induce low levels of IL-10 mRNA and cell-associated protein in keratinocytes. Therefore, although human keratinocytes accumulate intracellular IL-10 after in vivo UV exposure, the most potent production and secretion of IL-10 in the epidermis seems to be that of UV-induced macrophages. Skin-infiltrating macrophage secretion of such a potent immunoregulatory cytokine may account for the delayed immunosuppressive environment of sunburned skin and the altered APC activity of the infiltrating macrophages.
Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anesthesia in cesarean section. (2011)

All three drugs maintained hemodynamics within 20 percent of the baseline values on intravenous administration.
The role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis (2014)

Statistically relevant expression changes for MMPs, laminins, collagens, and chemokines, which are components of the extracellular matrix and inflammation process, may be considered as a molecular biomarker for early prediction. Further studies are necessary to determine and understand the molecular mechanisms that underlie OSCC metastasis.
Pyridoxine deficiency: new approaches in immunosuppression and chemotherapy (1997)

Pyridoxine deficiency leads to impairment of immune responses. It appears that the basic derangement is the decreased rate of production of one-carbon units necessary for the synthesis of nucleic acids. The key factor is a pyridoxine enzyme, serine hydroxymethyltransferase. This enzyme is very low in resting lymphocytes but increases significantly under the influence of antigenic or mitogenic stimuli, thus supplying the increased demand for nucleic acid synthesis during an immune response. Serine hydroxymethyltransferase activity is depressed by deoxypyridoxine, a potent antagonist of pyridoxal phosphate, and also by known immunosuppressive or antiproliferative agents. The combination of these agents is additive. Our results lead us to suggest the following medical applications: (a) combination of deoxypyridoxine with immunosuppressive or chemotherapeutic drugs may be effective in cases of immunosuppressive therapy or organ transplantation, (b) the development of special agents directed against the serine hydroxymethyltransferase apoprotein may prove to be a valuable medical tool, since this enzyme presents an excellent target for chemotherapy, (c) lymphocytes of individual patients could be used to design tailor-made specific immunosuppressive or chemotherapeutic treatment, and (d) the serine hydroxymethyltransferase activity of lymphocyte culture presents an excellent indicator for the evaluation of potency of immunosuppressive, chemotherapeutic or genotoxic compounds in a simple and rapid test.
SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH (2010)

Many studies estimate that chromosomal mosaicism within the cleavage-stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism has been overestimated due to technical inconsistency rather than the biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques. Thirteen arrested cleavage-stage embryos were studied. Each was biopsied into individual cells (n = 160). The cells from each embryo were randomized into two groups. Those destined for FISH-based aneuploidy screening (n = 75) were fixed, one cell per slide. Cells for SNP microarray-based aneuploidy screening (n = 85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P = 0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (31%) than by FISH (100%) (P = 0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2 +/- 0.2) than microarray (1.3 +/- 0.2) (P < 0.0001). This is the first prospective, randomized, blinded and paired comparison between microarray and FISH-based aneuploidy screening. SNP microarray-based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. These results also suggest that FISH technology may overestimate the contribution of mitotic error to the origin of aneuploidy at the cleavage stage of human embryogenesis.
Cigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells: Implication in mucin over-expression (2011)

Excessive mucus is a hallmark of chronic obstructive pulmonary disease (COPD). There is an emerging interest in the role of TGF-β signaling in the initiation and progression of COPD. Growth differentiation factor 15 (GDF15) is a divergent member of TGF-β superfamily. However, whether cigarette smoke induces airway epithelial GDF15 production and its functions in the airways have not been revealed. Therefore, we first analyzed GDF15 protein expression in airway epithelium of human COPD smokers versus normal non-smokers. We then examined the regulation and function of GDF15 in human airway epithelial cells in response to cigarette smoke exposure. We found increased GDF15 protein expression in airway epithelium (mainly in ciliated cells) of human COPD smokers compared with normal non-smokers. Furthermore, cigarette smoke exposure consistently up-regulated GDF15 expression in human airway epithelial cells. Moreover, GDF15 was shown to play a critical role in cigarette smoke-induced airway epithelial MUC5AC expression. Lastly, activation of phosphoinositide 3-kinase (PI3K) pathway was largely responsible for GDF15-induced airway epithelial MUC5AC expression. Our findings indicate that human airway epithelial cells can produce GDF15 during cigarette smoke exposure, which subsequently activates PI3K pathway to promote mucin (e.g. MUC5AC) expression. This highlights a novel role of GDF15 in regulating airway mucosal immunity (e.g. mucin) in cigarette smoke-exposed lungs.
Reconstitution photoactive yellow protein from apoprotein and p‐coumaric acid derivatives (1995)

We report reconstitution of photoactive yellow protein (PYP) from apoPYP and p-coumaric acid derivatives. The addition of p-coumaric acid to the apoPYP sample did not result in the recovery of PYP. In contrast, yellow products were obtained by the addition of p-coumaryl thiophenyl ester or p-coumaric anhydride to the apoPYP sample, the absorption spectra of which were indistinguishable from the spectrum of intact PYP. Our findings provide strong evidence that PYP has the p-coumaryl chromophore. This reconstitution technique opens the way for further biophysical studies of PYP using artificial chromophore analogs.
Adaptive shaping of femtosecond pulses (1998)

Summary form only given. We generalize the adaptive approach for pulse compression to adaptively shape completely uncharacterized femtosecond pulses into desired waveforms. In this approach, the input pulses are modified iteratively according to a feedback signal derived from a measurement of the output pulses. Consequently, the adaptive approach removes the need for characterization of the input pulses, and is applicable in cases where the pulses undergo slow variations in time. The experimental setup for adaptive pulse shaping uses a programmable 4-f pulse shaper, an intensity cross-correlation arrangement, and a computer. The computer was used for calculating the feedback signal, derived from the crosscorrelation measurement.
Warfarin Causes Rapid Calcification of the Elastic Lamellae in Rat Arteries and Heart Valves (1998)

High doses of warfarin cause focal calcification of the elastic lamellae in the media of major arteries and in aortic heart valves in the rat. Aortic calcification was first seen after 2 weeks of warfarin treatment and progressively increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the highly focal calcification of major arteries could be seen on radiographs and by visual inspection of the artery. The calcification of arteries induced by warfarin is similar to that seen in the matrix Gla protein (MGP)-deficient mouse, which suggests that warfarin induces artery calcification by inhibiting gamma-carboxylation of MGP and thereby inactivating the putative calcification-inhibitory activity of the protein. Warfarin treatment markedly increased the levels of MGP mRNA and protein in calcifying arteries and decreased the level of MGP in serum. Warfarin treatment did not affect bone growth, overall weight gain, or serum calcium and phosphorus levels, and, because of the concurrent administration of vitamin K, prothrombin times and hematocrits were normal. The results indicate that the improved warfarin plus vitamin K treatment protocol developed in this study should provide a useful model to investigate the role of MGP in preventing calcification of arteries and heart valves.
Biodegradable, Endosome Disruptive, and Cationic Network-type Polymer as a Highly Efficient and Nontoxic Gene Delivery Carrier (2002)

The success of gene therapy is largely dependent on the delivery vector system. Efficient transfection and nontoxicity are two of the most important requirements of an ideal gene delivery vector. To generate both an efficient and nontoxic vector, we rationally constructed polymeric vectors to have simultaneous multiple functions, i.e., controlled degradation, an endosome disruptive function, and positive charges. Remarkably, the transfection efficiency of network poly(amino ester) (n-PAE) synthesized in this manner was comparable to that of polyethylenimine (PEI), one of the most efficient polymeric gene delivery vectors reported to date. However, there was a marked difference in cytotoxicity between the polymers. The majority of PEI-transfected cells were granulated and dead, whereas most of the cells transfected with n-PAE were viable and healthy. Successive events of efficient endosome escape of n-PAE/DNA polyplex and n-PAE biodegradation should result in high transfection efficiency and favorable cell viability response. The n-PAE-mediated transfection was also very efficient in the presence of serum. These data show that the approach we applied is a very appropriate way of making an ideal gene delivery carrier.