The therapeutic effects of the peptidyl-prolyl cis/trans isomerase Pin1 inhibitor juglone on animal-model experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no satisfactory treatment for this disease. Pin1 is the only known peptidyl-prolyl cis/trans isomerase (PPIase) that is involved in many cellular processes, including immune responses. Numerous studies have shown that juglone effectively inhibits Pin1 activity. However, the effect of Pin1 inhibitor juglone on autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), remain incomplete. So the present study aimed to explore the therapeutic effects of the Pin1 inhibitor juglone on EAE. EAE was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG)35-55 and treatment with juglone. The health status of EAE was observed and inflammation explored using pathological analysis. The impact of juglone on immune cells was further examined using intracellular staining and flow cytometry. The results demonstrated that juglone ameliorates EAE and reduces inflammation and demyelination in the CNS. The study also found that juglone suppresses pathogenic Th1 and Th17 cells and the expression of CD83 and MHCII on dendritic cells in EAE. In addition, juglone ameliorates EAE. Pin1 inhibitors therefore hold great promise for autoimmune disease and MS therapy.

Gas Sensing Properties of Epitaxial LaBaCo2O5.5+δ Thin Films.

Chemical reactivity and stability of highly epitaxial mixed-conductive LaBaCo2O5.5+δ (LBCO) thin films on (001) LaAlO3 (LAO) single-crystalline substrates, fabricated by using pulsed laser deposition system, were systematically investigated. Microstructure studies from x-ray diffraction indicate that the films are c-axis oriented with the interface relationship of [100]LBCO//[100]LAO and (001)LBCO//(001)LAO. LBCO thin films can detect the ethanol vapor concentration as low as 10 ppm and the response of LBCO thin film to various ethanol vapor concentrations is very reliable and reproducible with the switch between air and ethanol vapor. Moreover, the fast response of the LBCO thin film, as the p-type gas sensor, is better than some n-type oxide semiconductor thin films and comparable with some nanorods and nanowires. These findings indicate that the LBCO thin films have great potential for the development of gas sensors in reducing/oxidizing environments.

Use of asymmetric somatic hybridization for transfer of the bacterial blight resistance trait from Oryza meyeriana L. to O. sativa L. ssp. japonica.

Bacterial blight is one of the major diseases affecting rice productivity. To improve the resistance of cultivated rice to bacterial blight, we introduced a bacterial blight resistance trait from Oryza meyeriana, a wild rice species, into an elite japonica rice cultivar (Dalixiang) using asymmetric somatic hybridization. One hundred and thirty-two independent lines were regenerated. The hybrid plants possessed several morphological features of the donor species, O. meyeriana. Random amplified polymorphic DNA analysis revealed that hybrid plants exhibited banding patterns derived from their parental genotypes. For the majority of the hybrids, resistance to bacterial blight pathogens was intermediate to that observed for O. meyeriana and O. sativa (cv. Dalixiang). Four of the hybrid lines exhibited a high bacterial blight resistance, but it was less than that observed for O. meyeriana. These results demonstrate that O. meyeriana can be used as a good genetic source for improving bacterial blight resistance in commercial rice cultivars through asymmetric somatic hybridization.

The use of alprostadil sterile powder in a home self-injection study of Asian men with erectile dysfunction.

This study evaluated the individual optimal dose of alprostadil in the office setting that could be used as the basis for effective home self-injection therapy. The study included 150 Asian men with erectile dysfunction (ED). The mean age of study participants was 48.3 years (range, 21 to 74 years), and the mean duration of ED was 3.6 years. The most common cause of ED was venogenic (24%), psychogenic (21%), arteriogenic (13%), neurogenic (0.7%), or a combination of these (41%). An optimal response was seen in 72% of patients (n = 108) in the office and 96% of patients (n = 100) at home. The mean +/- SD office dose of alprostadil was 19.4 +/- 12.8 micrograms versus 18.0 +/- 12.2 micrograms at home. More than half of the patients (57% in an office setting and 53% at home) achieved an optimal response at a dose between 5 and 15 micrograms. By the 20-micrograms dose, 82% of patients had achieved an optimal dose at home compared with 70% of patients in the office. An optimal response was seen at the same dose in the office and home in 75% of patients; the dose at home decreased from the office dose for 16% of the patients and increased for 9%. There were 24 patients who experienced adverse events: penile pain after injection (18 patients), cold sweating (2 patients), pediculosis (1 patient), broken leg (1 patient), ankle pain (1 patient), and prolonged erection (1 patient). One patient discontinued the study because of penile pain. Alprostadil sterile powder offered safe and effective treatment of ED for home self-injection therapy. Once an optimal dose response had been established in the physician's office, further home adjustments were needed in 25% of patients. Penile pain, usually mild, was the most common, possibly related adverse effect reported.

Intranigral administration of D2 dopamine receptor antisense oligodeoxynucleotides establishes a role for nigrostriatal D2 autoreceptors in the motor actions of cocaine.

Dopamine D2 autoreceptors found on nigrostriatal dopaminergic neurons are thought to inhibit dopamine release, tyrosine hydroxylase activation, and spontaneous firing rate. It is likely that these receptors play an important role in moderating the behavioral response to cocaine, but the lack of potent selective autoreceptor ligands has made it difficult to assess this contribution. We have developed an antisense phosphorothioate oligodeoxynucleotide (ODN) against D2 receptor mRNA, which was used to reduce levels of D2 receptors in vitro and in vivo. Unilateral administration of antisense ODN, via intracerebral cannula, into the substantia nigra of rats for several days caused dramatic contralateral rotational behavior in response to a subcutaneous injection of cocaine. This effect was maximal by 10 min after injection of cocaine and lasted for > 30 min; without cocaine, no spontaneous rotational behavior was noted. In striatal slices, the potency of sulpiride, a D2 antagonist, in enhancing electrically stimulated dopamine release was significantly reduced on the antisense-treated side; this is consistent with a decrease in the striatal D2 autoreceptor population. As measured by quantitative autoradiography, administration of antisense ODN caused a loss of approximately 40% of nigral D2 receptor [125I]iodosulpride binding, compared with the untreated side. In vitro, treatment of WERI-27 retinoblastoma cells with D2 antisense ODN at a concentration of 1 microM reduced D2 receptor levels by 57% after 3 days. The robustness of cocaine-induced rotation and the impaired ability of sulpiride to enhance dopamine release from slices suggest that nigrostriatal D2 autoreceptors play a direct role in reducing the motor response to cocaine administration. Furthermore, the absence of spontaneous rotation in antisense ODN-treated animals suggests that autoreceptor effects are masked by compensatory mechanisms during normal behavior.

Study on neutrophil enzymes in atopic disease.

Neutrophils (PMN) from 20 patients with atopic disease (atopy), the parents of 8 of the patients and 10 normal controls were studied by light-microscopic cytochemistry. The results revealed that myeloperoxidase (MPO) and acid phosphatase (ACP) activities in PMN in all cases significantly decreased and alkaline phosphatase activity was normal. Parents or parent of 7 of those patients had PMN enzyme deficiency similar to that of the patients. The results indicated that a primary combined and partial deficiency of MPO and ACP in PMN azurophilic granule existed in atopy. It is postulated that the deficiency led to reduction of PMN bactericidal power and delay of bactericidal action. Foreign bodies which were partially degraded could possess antigenic property. This is believed to be the important cytobiological mechanism of the tendency toward infections and formation of sensitive antigen in atopy.

Partial azurophilic granule deficiency. Report of 2 cases with ultrastructural and light-and-electron-microscopic cytochemical observation.

The neutrophils in 2 patients with atopic disease were studied. Ultrastructurally, a number of abnormal azurophilic granules (AG) with low electron-density (Case 1) and secondary lysosomes with "myelinoid membranes" figures (Case 2) were found. Myeloperoxidase (MPO) and acid phosphatase activity were detected by light cytochemical techniques, and showed significantly low values. The deficiency of MPO and abnormal distribution of AG were also demonstrated by electron microscopic cytochemical technique. The neutrophils from the parents revealed changes similar to the patients. This study suggests that since genetic partial deficiency of neutrophil AG enzymes existed, the phagocytosed substances were only partially degraded, leading to accumulation of substances with antigenicity, and became trigger event of atopic disease.

Stress protein synthesis and accumulation after traumatic injury of crayfish CNS.

By several days after a crush injury of crayfish CNS, the wound site heals. Changes in protein synthesis and accumulation occur at the lesion site and nearby. During the first few hours, synthesis of 35, 70, 90, and 150 kDa proteins is induced in the injured tissue. By one day, the relative amounts of 70-90 kDa proteins increase dramatically, particularly at the crush site and adjacent to it. The 70 kDa proteins, which are related to mammalian stress proteins (SPs), remain elevated for at least one month in the traumatized region or nearby. The crushed tissue contains an SP70 isoform not present in its uncrushed counterpart. These biochemical changes may reflect the cellular changes that accompany wound healing and/or a cellular stress response to compensate for the lesion. Since similar adaptations occur in the mammalian CNS, they may represent a phylogenetically conserved attempt to retard or repair CNS tissue deterioration.

Stress protein synthesis by crayfish CNS tissue in vitro.

Some crustacean axons remain functional for months after injury. This unusual property may require stress proteins synthesized by those neurons or provided to them by glial cells. To begin to explore this hypothesis, we examined the conditions that stimulated stress protein synthesis by crayfish CNS tissue in vitro. Incubation for 1-15 h with arsenite or at temperatures about 15 degrees C higher than the acclimation temperature of 20 degrees C induced transient expression of several stress proteins. The heat stress response was blocked by Actinomycin D, suggesting that synthesis of new mRNA was required. In addition, the major crayfish 66 kD stress protein and its mRNA had sequence identities with the 70 kD stress proteins of mammals. Since the crayfish stress response has much in common with that of other organisms, the unique advantages of the crayfish nervous system can be used to study the impact of stress proteins on glial and neuronal function.

[Extracorporeal shockwave lithotripsy and ureteroscopic lithotripsy for ureteral stones. A comparative study].

From June 1987 to December 1988, 212 cases of ureteral calculi were treated with ESWL and ureteroscopic lithotripsy (URSL) respectively. The lithotriptic success rates of ESWL for upper, mid and distal ureteric stones were 100.0%, 100.0% and 93.4% respectively as compared with 62.5%, 85.7% and 93.7% of URSL. ESWL for upper and mid ureteral stones was obviously superior to URSL (P less than 0.001). The incidence rate of complications of ESWL was lower than that of URSL (P less than 0.05). In the 212 cases, urinary extravasation caused by ureteral injury occurred in 4 cases treated by URSL. We suggest that ESWL should be the first treatment of choice for ureteral calculi and URSL is not recommended for the treatment of upper ureteral calculi, but it may be used as an adjunctive method.

Evaluation of fluorescent leprosy antibody absorption test versus enzyme-linked immunosorbent assay with phenolic glycolipid 1 and their use in immuno-epidemiological studies on leprosy.

We systematically conducted comparative studies on the validity, reliability and practicality of FLA-ABS.T/PGI-ELISA in large samples. Namely, 284 leprosy patients, 20 tuberculosis patients, 172 normal controls (from nonendemic area of leprosy), 425 leprosy household contacts (HC) and 2573 random samples from the general population (RS) were involved. The results indicated that FLA-ABS.T/PGI-ELISA are highly sensitive and specific for detecting antibodies against M. leprae. Their Youden's indexes (YI) are greater than 90%, and the positive predicative and negative values are 90%. The test results agreed with immuno-epidemiological studies: 1. The positive rates using FLA-ABS.T/PGI-ELISA increased gradually from TT to LL leprosy patients (in HC, the positive rates of PGI-ELISA were much higher in contacts of multibacillary patients than in contacts of paucibacillary patients); 2. The positive rates detected by FLA-ABS.T were identical to those of PGI-ELISA both in HC and in RS; 3. Among RS, the positive rates detected by FLA-ABS. T/PGI-ELISA were similar in each district and were in concordance with the general prevalence rates. Thus, both FLA-ABS.T and PGI-ELISA are useful tests in diagnosing leprosy and detecting subclinical infection with M. leprae. However, because the PGI-ELISA is simple, it will be more practical than FLA-ABS.T in the future. The authors emphasize that the methodology of obtaining dried blood from ear lobes is important for the immuno-epidemiological study of leprosy on a large scale.