Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4

The availability of an analgesic compound devoid of the side effects associated with the commonly used opioid and nonsteroidal antiinflammatory drugs would be useful during the perioperative period. Although adenosine has analgesic and anesthetic-sparing properties, it also produces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardiovascular or respiratory depression. This preliminary study investigated the effects of a novel adenosine kinase-inhibiting drug, GP683, on the minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GP683 dose regimens (or the solvent) by intravenous infusion on separate occasions according to a cross-over study design. After determining the baseline desflurane MAC value, GP683 was infused at 75, 150, or 300 microg x kg(-1) x min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 microg x kg(-1) x min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-180 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals before, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, respectively. In addition, there was good correlation between the decrease in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by the highest infusion rate of GP683, adjustments in the desflurane concentration to an equi-MAC value resulted in normalization of the MAP values. Furthermore, GP683 produced no changes in heart rate. In conclusion, the adenosine kinase-inhibiting drug, GP683, produced dose-dependent decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. IMPLICATIONS: An investigational drug (GP683) that can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular system.     

Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules

We investigated retrospectively 132 cases of open wedge high tibial osteotomy using an external fixation device, concentrating on the rate of neurological complications. One group of patients underwent surgery according to the conventional technique (n = 89). The rate of transient neurological complications was 15.7%; 7 months after surgery the rate of persistent deficits was 12.4%. For the second group (n = 43) a modified surgical technique was used that lowered the complication rate significantly (transient deficits 14%, persistent deficits 4.7%). In the modified technique the osteotomy is not performed in the conventional way using an oscillating saw but through consecutive drill holes of increasing diameter followed by osteoclasis. The lower complication rate in the second group is mainly due to the less extensive approach that leads to a smaller number of postoperative tibialis anterior syndromes (type B lesion). No differences were found with type C lesions (extension deficit of D1). No complete peroneal nerve palsy (type A) occurred in either group. We conclude that the reduction of neurological complications in group 2 is related to the less extensive approach of the proposed technique.     

Fiber-optic devices for local area network application

Recent developments on fiber-optic devices are reviewed from the local area network (LAN) application viewpoint. Future technical trends are also discussed, along with current research activities. In local area network systems, low device cost and easy maintenance or maintenance-free devices are especially required. Light sources and photodetectors suitable for the systems are described. InGaAsP/InP light emitting diodes can cover a broad application field, up to a gigabits per second super high-speed network region. Optical passive devices, which include branching couplers, switches and connectors, are mentioned as essential components. Compact transmitter/receiver module technology is a key factor in realizing optical-fiber local area network systems. An example of 200-Mbit/s transmitter/receiver module is reported.     

Use of a YAP1 overexpression cassette conferring specific resistance to cerulenin and cycloheximide as an efficient selectable marker in the yeast Saccharomyces cerevisiae.

Drug-resistance markers for yeast transformation are useful because they can be applied to strains without auxotrophic mutations. However, they are susceptible to technical difficulties, namely lower transformation efficiency and the appearance of drug-resistant mutants without the marker. To avoid these problems, we have constructed a phosphoglycerate kinase (PGK) promoter-driven YAP1 expression cassette, called PGKp-YAP1. Yeast cells containing PGKp-YAP1 were resistant to cycloheximide, a protein synthesis inhibitor, and also to cerulenin, a fatty acid synthesis inhibitor, but not to other drugs tested. The transformation efficiency of PGKp-YAP1 using cerulenin selection was comparable to that using a URA3 auxotrophic marker when low concentrations of cerulenin were used. Non-transformed drug-resistant colonies did appear on the low-concentration cerulenin plates. However, these non-transformed colonies could easily be identified, based on their cycloheximide sensitivity and/or their resistance to aureobasidin A to which the transformants were sensitive. Therefore, the dual drug resistance of PGKp-YAP1 could be used as an effective selection for PGKp-YAP1 recipient cells. The PGKp-YAP1 marker was used to disrupt the LYS2 gene and to transform an industrial yeast strain, indicating that this marker can be used for efficient and reliable gene manipulations in any Saccharomyces cerevisiae strain.     

Using precise data sets on farming and pesticide properties to verify a diffuse pollution hydrological model for predicting pesticide concentration.

Verification of a diffuse pollution model involves comparing results actually observed with those predicted by precise model inputs. Acquisition of precise model inputs is, however, problematic. In particular, when the target catchment is large and substantial estimation uncertainty exists, not only model verification but also prediction is difficult. Therefore, in this study, rice-farming data were collected for all paddy fields from all farmers in a catchment and pesticide adsorption and degradation rates in paddy field soil samples were measured to obtain precise model inputs. The model inputs successfully verified the model's capability to predict pesticide concentrations in river water. Sensitivity analyses of the model inputs elucidated the processes significantly affecting pesticide runoff from rice farms. Pesticide adsorption and degradation rates of the soil did not significantly affect pesticide concentrations, although pesticide discharge to river water accounted for less than 50% of the total quantity of pesticide applied to fields, possibly owing to pesticide adsorption and degradation. The timing of increases in pesticide concentrations in river water was affected mostly by the farming schedule, including the time of pesticide application and irrigation, and secondarily by rainfall events.     

Left ventricular regional systolic motion in patients with right ventricular pressure overload

The highly reactive and cytotoxic hydroxyl radical (OH) was found by electrochemical detection to be produced in reactions involving hydrogen peroxide (H2O2) and the nitric oxide (NO) donor diethylamine- NO complex. Using aromatic hydroxylation of salicylate as a specific indicator of OH, three salicylate hydroxylation products were identified; catechol, 2,3- and 2,5-dihydroxybenzoic acid. Four additional compounds were detected but not identified. The interactions of H2O2 and NO represent a biologically feasible reaction mechanism that can account for OH-induced damage in cellular environments where transition metal ions are unavailable for participation in the superoxide-mediated Fenton reaction. The ability of the NO/H2O2 complex to generate OH independently of iron or other transition metals provides a new focus for studies concerned with the origin of tissue-specific damage caused by oxygen-derived species.     

Studies on relationship between activity and electron density on carbonyl oxygen in sex pheromone mimics of the American cockroach,part XI

From the relationship between structures of the 2-substituents of verbanyl analogs and their sex pheromone activities to the American cockroach, electron density of the carbonyl oxygen atom in the substituent, as estimated by the [¹⁷O]NMR chemical shift, was estimated to be an important factor which influenced the activity, in addition to length of the substituent and the position of the carbonyl group. (+)-Verbanyl methylcarbonate (XX), possessing the highest electron density on the carbonyl oxygen atom, showed the strongest activity among the analogs.For Part X, see Manabe et al., 1983. J. Chem. Ecol. 9:533–549.     

Thermal shock resistance of flat plastic integrated circuit packages

Flat packages (FPs) were formed from epoxy molding compounds with various physical properties using a transfer molding machine. The compounds were prepared by changing kinds and amounts of additives and addition methods. The thermal shock test was carried out by the following procedures. The plastic package was soaked alternately in liquid nitrogen (?196°) and in liquid solder (200°) in the cycle of 140s. The median life to crack initiation was defined to be the cycles when half of the specimens exhibited crack initiation. According to linear fracture mechanics, the following expression was obtained relating the median life N, thermal stress σ_t, and strength σ_b; N = C/σ·(σ_b/σ_t)^m. We found the linear relation between logarithm of Nσ and logarithm of σ_b/σ_t for various packages, and estimated the values of C and m as 5 × 10⁴ MPa² and 5.5, respectively. The value of m was the same as that obtained for a dual-in-line package.