UNLABELLED: BACKGROUND AND OBJECTIVES The goal of this study was to evaluate the analgesic effects of intrathecal versus epidural methylprednisolone acetate (MPA) in patients with intractable postherpetic neuralgia (PHN). METHODS: We studied 25 patients with a duration of PHN of more than 1 year. The patients were randomly allocated to one of two groups: an intrathecal group (n = 13) and an epidural group (n = 12). Sixty milligrams of MPA was administered either into the intrathecal or the epidural space four times at 1-week intervals depending on the treatment group. Continuous and lancinating pain and allodynia were evaluated by a physician unaware of group assignment with a 10-cm visual analogue scale before treatment, at the end of treatment, and 1 and 24 weeks after treatment. In addition, cerebrospinal fluid (CSF) was obtained for measurement of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha before and 1 week after treatment. RESULTS: We found marked alleviation of continuous and lancinating pain and allodynia in the intrathecal group (P < .001). The improvements were much greater in the intrathecal group than in the epidural group at all time points after the end of treatment (P < .005). IL-8 in the CSF decreased significantly in the intrathecal group as compared to the epidural group at the l-week time point (P < .01), whereas the other cytokines were undetectable. CONCLUSIONS: Our results suggest the effectiveness of intrathecal as compared to epidural MPA for relieving the pain and allodynia associated with PHN. Also, our findings, together with the decrease in IL-8, may indicate that intrathecal MPA improves analgesia by decreasing an ongoing inflammatory reaction in the CSF.

Aged↗

PubMedDate not supplied

Modulation of Wnt signaling by Axin and Axil.

The Wnt signaling pathway is conserved in various species from worms to mammals, and plays important roles in development, cellular proliferation, and differentiation. The molecular mechanisms by which the Wnt signal regulates cellular functions are becoming increasingly well understood. Wnt stabilizes cytoplasmic beta-catenin, which stimulates the expression of genes including c-myc, c-jun, fra-1, and cyclin D1. Axin and its homolog Axil, newly recognized as components of the Wnt signaling pathway, negatively regulate this pathway. Other components of the Wnt signaling pathway, including Dvl, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, and adenomatous polyposis coli (APC), interact with Axin, and the phosphorylation and stability of beta-catenin are regulated in the Axin complex. Axil has similar functions to Axin. Thus, Axin and Axil act as scaffold proteins in the Wnt signaling pathway, thereby modulating the Wnt-dependent cellular functions.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Synthesis of poly(ethylene oxide) with heterobifunctional reactive groups at its terminals by an anionic initiator.

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Anions↗

PubMedDate not supplied

Temperature-responsive bioconjugates. 3. Antibody-poly (N-isopropylacrylamide) conjugates for temperature-modulated precipitations and affinity bioseparations.

Immunoglobulin G (IgG) has been modified by poly(N-isopropylacrylamide) (PIPAAm) to create a novel bioconjugate which exhibits reversible phase transition behavior at 32 degrees C in aqueous media. A terminal carboxyl group introduced into PIPAAm molecule by polymerization of IPAAm with 3-mercaptopropionic acid was used for conjugation to IgG via coupling reaction of activated ester with protein amino group. These conjugates exhibited rapid response to changes in solution temperature and significant phase separation above a critical solution temperature corresponding to that for the original PIPAAm. These conjugates bound to antigen quantitatively in aqueous system, and antigen-bound complex also demonstrated phase separation and precipitation above a critical temperature. Precipitate was reversibly redissolved in cold buffer. Though particular conjugate which includes 12 molecules of PIPAAm with 6,100 molecular weight suppressed more than 95% of Fc-dependent binding with protein A, it retained approximately 60% of original specific antigen binding activity. It was manifested that polymer content of conjugate was 20-30 wt% for the case of 6,100 molecular weight of PIPAAm to demonstrate specific antigen binding activity most effectively and to reduce Fc-dependent binding with protein A. IgG-PIPAAm conjugates were soluble in water and formed antigen-bound complex in homogeneous solution system below a critical temperature. These conjugates were separated from solution and other solutes corresponding to PIPAAm nature and scarcely bound to antigen above a critical temperature. It is revealed that temperature-responsive PIPAAm conjugated to biomolecule operated as a switching molecule. These phenomena are attractive for not only reversible bioreactors and protein separations but also carrier substrate to localize biomolecules such as drugs, peptides and hormones in a living body.

3-Mercaptopropionic Acid↗

PubMedDate not supplied

Effect of molecular architecture of poly(N-isopropylacrylamide)-trypsin conjugates on their solution and enzymatic properties.

Polymer-enzyme hybrid conjugates modified by a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), have been synthesized. We have investigated the molecular architecture of PIPAAm-enzyme conjugates by preparing two types of PIPAAm-trypsin conjugates, wherein PIPAAm chains are attached by either single-end or multipoint chemistry. A semitelechelic co-oligomer (IDc) was attached to trypsin by single-point conjugation (IDc-trypsin). A copolymer (PIDAAc) consisting of acrylic acid and IPAAm randomly linked in polymer chains was attached to trypsin using multipoint conjugation (PIDAAc-trypsin). Both conjugates exhibited reversible temperature-responsive phase separation. The IDc-trypsin conjugate exhibited phase separation at the same temperature as pure IDc, due to the highly mobile free polymer end group which remains sensitive to small temperature changes. The PIDAAc-trypsin conjugate precipitated at higher temperatures than pure PIDAAc, whose movement was restricted by multiple binding points. Enzyme stability in solution was improved after introduction of PIPAAm chains, which prevented autolysis attributed to conjugate steric hindrance. Stability under repeated temperature cycling was also dependent on the architecture of conjugates; the IDc-trypsin conjugate was more stable than the PIDAAc-trypsin. As a consequence, single-end conjugation of polymer to enzyme provides novel bioconjugate with novel functionality attributed to attached polymer while retaining native biological function with high stability.

Acrylic Resins↗

PubMedDate not supplied

Reverse gyrase--a topoisomerase which introduces positive superhelical turns into DNA.

An enzymatic activity which converts closed circular DNA into a positively supercoiled form is present in cellular extracts of Sulfolobus, an acidothermophilic archaebacterium. This novel enzyme is a type II DNA topoisomerase and is active only at temperatures greater than 55 degrees C, in the presence of ATP and Mg2+.

DNA Topoisomerases, Type I↗

PubMedDate not supplied

Novel three-way translocation t(5;8;21) in acute myeloblastic leukemia (M2) with chloroma.

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Bone Marrow Cells↗

PubMedDate not supplied

Weekly carboplatin and paclitaxel is safe, active, and well tolerated in recurrent ovarian cancer cases of Japanese women previously treated with cisplatin-containing multidrug chemotherapy.

The safety and efficacy of weekly carboplatin and paclitaxel administration in recurrent ovarian cancers after platinum-containing multidrug chemotherapy were tested. Japanese patients who achieved complete response with surgery and adjuvant platinum-based chemotherapy and who had a recurrence after at least 6 months were included in the case - control study. Twenty-seven cases received the weekly TJ (WTJ) regime (cohort 1: T = 80 mg/m(2), J = AUC 2, median course = 13, range = 3-26) and 41 received other regimens [cohort 2: CAP = 37, monthly TJ (MTJ) = 4]. Toxicity profile, response rate, therapeutic index (TI), and survival were analyzed. Neutropenia, thrombocytopenia, and peripheral neuropathy (grades 3 and 4) in cohorts 1 and 2 were 1.7% and 90%, 5.1% and 14.3%, and 0% and 4.8%, respectively. Response rates were 77.8% and . Thus, TI of the two cohorts was 3.9 and 1.9, respectively. The median survival of cohort 1 was 48.3 months (95% CI 11.5-85.0) whereas that of cohort 2 was 17.8 months (95% CI 5.3-30.3, P < 0.005). WTJ has better toxicity profile and TI than monthly platinum-based multidrug regimens for recurrent ovarian cancers in Japanese women. As second-line treatment of ovarian cancer should primarily provide high TI, WTJ regimen appears a better candidate, but its long-term survival benefit should be tested against MTJ.

Adenocarcinoma↗