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.     

GABAB receptor transduction mechanisms, and cross-talk between protein kinases A and C, in GABAergic terminals synapsing onto neurons of the rat nucleus basalis of Meynert

The transduction mechanisms underlying presynaptic GABA_B receptor-mediated inhibition of transmitter release have been characterized for a variety of synapses in the central nervous system (CNS). These studies have suggested a range of transduction mechanisms, including a role for second messengers such as protein kinases A (PKA) and C (PKC). In the present study, we have examined the intracellular signalling pathways underlying baclofen-induced inhibition of GABA release from terminals synapsing onto rat basalis of Meynert neurons using patch-clamp recordings. Baclofen, a selective GABA_B receptor agonist, reversibly decreased both evoked and spontaneous, miniature, GABAergic inhibitory postsynaptic currents (eIPSCs and mIPSCs, respectively). Such baclofen actions were completely abolished by CGP55845A, a selective GABA_B receptor antagonist, and by staurosporine, a non-selective PKA and PKC inhibitor. The mIPSC frequency was still decreased by baclofen even in the presence of 4 AP, a K⁺ channel blocker, and Cd²⁺, a voltage-dependent calcium channel blocker. Pharmacological activation or inhibition of PKC activity affected basal GABA release and mildly affected the response to baclofen. Inhibition of the cAMP/PKA cascade also affected basal GABA release and, in a subset of neurons, occluded the effects of baclofen, suggesting that the GABA_B receptor-mediated inhibitory action on GABA release was mediated via decreases in PKA activity. In addition, PKA inhibition occluded the effects of PKC modulation on both basal GABA release and on the response to baclofen. Our results characterize the transduction pathway of baclofen at these nucleus basalis of Maynert (nBM) synapses and show, for the first time, some cross-talk between the cAMP/PKA and PKC pathways in mammalian presynaptic nerve terminals.     

A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK-432 for advanced and recurrent gastric carcinoma

BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432 (FLPO therapy) was devised for the treatment of patients with advanced and recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every other day. Thirty patients completed 59 courses of treatment consisting of 2 weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response rate was 40%, with 1 complete response and 11 partial responses observed. All twelve patients responded after 1 course of treatment. The response rate differed depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in the lung, and 100.0% with skin metastases. The most frequently observed toxicity was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required treatment interruption because of the grade 3 toxicity of diarrhea. The median survival time was 198 days overall, 242 days for responders and 125 days for non-responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the treatment of advanced and recurrent gastric carcinoma.     

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.     

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.     

A case of systemic lupus erythematosus complicated by Nocardia farcinica]

We report a patient with systemic lupus erythematosus (SLE) complicated with nocardiosis. This case is very important that the complication of nocardiosis in SLE is very rare and the treatment to both SLE and nocardiosis is very difficult. A twenty-one-year old female was admitted to our hospital because of thoracic empyema and active lupus nephritis. Her medical history revealed that the diagnose of SLE was made when she was 18 with lymphocytopenia, proteinuria, positive antinuclear antibodies, and high titer of antibodies to native DNA. She was treated with prednisolne 60 mg daily and became better. Proteinuria appeared again in September 1995 and she was admitted to the former hospital. Renal biopsy proved diffuse proliferative glomeluronephritis (WHO IVb). She was treated with 1 g per day of methylprednisolone for 3 days and succeeded with 60 mg day of prednisolone. In early November she developed left chest pain and fever and chest X-ray demonstrated left pleural effusion. Antibiotics, antituberculosis, and antifungal therapy failed to subside her pleuritis and it turned to empyema. Then she was transferred to our hospital for further treatment. Nocardia farcinica was detected from the aspirated pleural fluid obtained at the former hospital. Drainage and intrathoracic impenem injection were effective. While long usage of minocycline was continued for the nocardiosis, 500 mg of cyclophosphamide pulse therapy to lupus nephritis was administrated. Two weeks later a new pulmonary lesion with left chest pain and liver abscess developed. Administration of trimethoprim-sulfamethoxazole subsided the nocardiosis. She was discharged with 1 g per day of proteinuria the prescribed 13 mg per day of prednisolone and continuous TMP-SMZ intake for nocardial infection. When immunosuppressive therapy must be given to the immunocompromised host, a more potent therapy must be added to avoid infection.