Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A.

In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.     

GLUCOCORTICOID-UNRESPONSIVE FEVER IN A PATIENT WITH WEBER-CHRISTIAN DISEASE

SUMMARY Weber-Christian disease, a disease of unknown aetiology, is characterised by relapsing febrile episodes and systemic panniculitis. Glucocorticoid therapy is often useful during acute phases of the disease. This report describes a patient in whom hyperpyrexia did not respond to high-dose glucocorticoid treatment, yet did respond to a non-steroidal anti-inflammatory drug (NSAID).     

Clinical features of patients with mild systemic lupus erythematosus.

Clinical features of 16 patients with mild systemic lupus erythematosus (SLE) were compared with those of 21 control patients with moderate or severe disease. Age at the time of diagnosis of SLE was higher in mild disease group. The incidence of the coexistence of Sj?gren's syndrome (SS) at the time of diagnosis of SLE was higher in patients who later developed mild disease. Anti-Sm antibody and decreased levels of C3, C4, and CH50 occurred less frequently in patients with mild disease. SLE patients with the coexistence of SS at the time of diagnosis of SLE may represent a subset with a benign prognosis.     

Measurement of quality of life in rheumatoid arthritis]

This study was designed to explore the health status or quality of life (QOL) in 366 patients with rheumatoid arthritis in Japan. Physical, social, and emotional functions of the patients, namely the QOL, were measured by the modified health assessment questionnaire, the quality of well-being score, and the face scale, respectively. These functions were also evaluated by the new methods using visual analogue scales. The longer the duration of rheumatoid arthritis, the worse the QOL measures in these patients. A similar result was observed in the relationship between the stage classification of progression of rheumatoid arthritis and the QOL measures. In contrast, the traditional medical process measures, such as Lansbury activity index, sedimentation rate, and serum CRP concentration did not correlate with the duration of the disease. We conclude that the QOL measures in this study are useful for evaluation of the functional status and well-being of patients with rheumatoid arthritis. However, the clinical usefulness of these measures for evaluation of effectiveness and/or side effects of anti-rheumatic drugs still remains unknown.     

Memory impairment associated with a dysfunction of the hippocampal cholinergic system induced by prenatal and neonatal exposures to bisphenol-A

One of the most common chemicals that behaves as an endocrine disruptor is the compound 4,4′-isopronylidenediphenol, called bisphenol-A. In the previous study, we reported that exposure to bisphenol-A induced the abnormality of dopamine receptor functions in the mouse limbic area, resulting in a supersensitivity of drugs of abuse-induced pharmacological actions. The present study was undertaken to investigate whether prenatal and neonatal exposures to bisphenol-A could alter other behavioral abnormalities such as anxiogenic behavior, motor learning behavior, or memory. In the present study, adult female mice were chronically treated with bisphenol-A-admixed powder food from mating to weaning. All experiments were performed using male pups. Here we found that prenatal and neonatal exposures to bisphenol-A failed to induce anxiogenic effects and motor-learning impairment using the light-dark test, elevated plus maze test, and rota-rod test. On the other hand, we found that prenatal and neonatal exposures to bisphenol-A induced the memory impairment using the step-through passive avoidance test. Immunohistochemical study showed the dramatic reduction in choline acetyltransferase-like immunoreactivity, which is a marker of acetylcholine (ACh) production, in the hippocampus of mice prenatally and neonatally exposed to bisphenol-A. These results suggest that chronic exposures to bisphenol-A could induce the memory impairment associated with the reduction in ACh production in the hippocampus.     

Differential distribution of estrogen receptor (ER)-alpha and ER-beta in the midbrain raphe nuclei and periaqueductal gray in male mouse: Predominant role of ER-beta in midbrain serotonergic systems

We examined the distribution of estrogen receptor (ER)-alpha and ER-beta immunoreactive (ir) cells in the dorsal (DRN) and median/paramedian (MPRN) raphe nuclei in male mice. ER-alpha ir neurons were scattered across the three subdivisions (ventral, dorsal, and lateral) of the DRN and the MPRN. Robust ER-beta ir cells were observed throughout the raphe nuclei, and were particularly abundant in the ventral and dorsal subdivisions of the DRN. Using dual-label immunocytochemistry for ER-alpha or ER-beta with tryptophan hydroxylase (TPH), the rate-limiting enzyme for 5-hydroxytryptamine (5-HT) synthesis, over 90% of ER-beta ir cells exhibited TPH-ir in all DRN subdivisions, whereas only 23% of ER-alpha ir cells contained TPH. Comparisons of ER-alpha knockout (alphaERKO) as well as ER-beta knockout (betaERKO) mice with their respective wild-type (WT) littermates revealed that gene disruption of either ER-alpha or ER-beta did not affect the other ER subtype expression in the raphe nuclei. In situ hybridization histochemistry revealed that there was a small but statistically significant decrease in TPH mRNA expression in the ventral DRN subdivision in betaERKO mice compared with betaWT mice, whereas TPH mRNA levels were not affected in alphaERKO mice. These findings support a hypothesis that ER-beta activation may contribute to the estrogenic regulation of neuroendocrine and behavioral functions, in part, by acting directly on 5-HT neurons in the raphe nuclei in male mice.     

The superiority of water-diluted 0.25% to neat 1% lidocaine for trigger-point injections in myofascial pain syndrome: a prospective, randomized, double-blinded trial

Trigger-point injection with a mixture of commercially available 1% lidocaine in sterile distilled water at a ratio of 1:3 compared with 1% lidocaine alone resulted in better efficacy and less injection pain. This simple procedure may be suitable for treatments of a wide range of myofascial pain syndromes.     

Discrepancy between E-cadherin protein expression and morphology in human gastric carcinoma cells

BACKGROUND/AIMS: The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. The purpose of this study is to examine the effect of E-cadherin on morphogenesis of MKN28 human gastric carcinoma cell line in the course of E-cadherin antisense S-oligodeoxynucleotide (ODN) treatment. METHODOLOGY: The effect of E-cadherin antisense or random S-ODN treatment on cell growth, morphology in monolayer culture, and E-cadherin protein expression of MKN28 cells were evaluated. Further, immunohistochemical examination was performed. RESULTS: Cell growth under 3-microM and 6-microM E-cadherin antisense S-ODN treatment did not differ from that under random S-ODN treatment. Although the expression of E-cadherin was decreased assuredly at the time of 6 days after 3-microM E-cadherin antisense S-ODN treatment by immunohistochemical examination, cell-cell adhesion was still observed until Day 10 after the treatment. On Day 15, the cells lost the cell-cell adhesion and showed the detachment and intercellular slits at least. Expression of the insoluble fraction of E-cadherin protein decreased in E-cadherin antisense S-ODN treatment cells at 6 days. CONCLUSIONS: In this study, we demonstrated that discrepancy between E-cadherin protein expression and morphology exists in MKN28 cells treated with E-cadherin antisense S-ODN treatment.     

Crystal structures of two tropinone reductases: Different reaction stereospecificities in the same protein fold

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-Å resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.