This was a multicenter study of rituximab, a chimeric monoclonal immunoglobulin G antibody directed against CD20, for the treatment of refractory autoimmune bullous diseases (pemphigus and pemphigoid). Ten patients (three with pemphigus vulgaris, six with pemphigus foliaceus and one with bullous pemphigoid) were treated with a single cycle of rituximab (four weekly infusions at a dose of 375 mg/m2 of body surface area). The primary end‐points were the number of serious adverse events and rate of complete remission at 40 weeks. Five patients (50%) achieved complete remission with minimal therapy (defined as no active lesions with lower doses of systemic corticosteroids compared to that with prednisolone 10 mg/day). Improvements in clinical scores (Pemphigus Disease Area Index) and decreases in autoantibody titers in the sera were observed in the four pemphigus patients who failed to achieve complete remission. This suggests that rituximab was effective in nine of 10 cases. Two serious adverse events (Pneumocystis carinii pneumonia and septic shock due to infectious arthritis) were observed and adequately treated with hospitalization. CD19‐positive B lymphocytes in the peripheral blood decreased on day 29 following rituximab treatment, and remained at low levels throughout the observation period (280 days). Our results confirmed the efficacy of rituximab therapy for refractory autoimmune bullous diseases in Japan.
The effects of mono(2-ethylhexyl) phthalate (MEHP) on 21-day-old C57Bl/6N mice and their Sertoli cell cultures were studied. Mice were given a single dose of 800 mg/kg MEHP by oral gavage and sacrificed 24 h later. At the same time, testes were harvested from another batch of mice for Sertoli cell cultures. Cultures were subsequently exposed to 0, 1, and 100 nmol/ml MEHP for 0, 3, 6, 12, and 24 h. An antivimentin antibody was used to detect intermediate filament changes in Sertoli cells. Meanwhile, detection of preapoptotic signals and presence of apoptotic cells were done using annexin V-FITC (fluorescein isothiocyanate) and TUNEL (deoxynucleotidyltransferase-mediated dUTP nick end labeling) analyses, respectively. In vivo results showed a correlation between the increase in TUNEL-positive cells and the vimentin disruption in treated mice. Toluidine blue staining of the Sertoli cell cultures showed the increased number and size of vacuoles in Sertoli cell cytoplasm. Vimentin immunohistochemistry showed gradual disappearance of vimentin in Sertoli cell cultures as time and dose increased. Some Sertoli cells were found to be annexin V-FITC positive, but no TUNEL-positive cells were found. Taken together, these results show that the appearance of vacuoles and the vimentin disappearance caused by MEHP in the Sertoli cells are related with each other and can be observed in relation to time. This can be used as an indicator of the loss of mechanical support for spermatogenic cells, which in the end causes apoptosis of spermatogenic cells.
Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that clinicopathologically resembles breast cancer. The prognosis of metastatic EMPD is poor. Although several chemotherapies have been tried, the effects are temporary; better drugs and combinations are required.
In the present study, we retrospectively analyze the efficacy and safety of combination of cisplatin, epirubicin, and paclitaxel in five metastatic EMPD cases. The efficacy was better than that for previously reported regimens: 80% partial responses, including two patients who were refractory to taxane‐ and/or platinum‐based regimens. In terms of safety, four patients who were able to continue treatment exhibited acceptable tolerability.
This is the first regimen to combine taxane and anthracycline. When treating breast cancer, anthracycline is regarded as the key cytotoxic agent, and anthracycline in combination with taxane constitutes a key chemotherapeutic regimen. Given our results, we speculate both drugs are critical chemotherapeutic agents for the treatment of metastatic EMPD.
ABSTRACT:The aim of this study was to evaluate the effect of raising the rear end when replacing the prolapsed uterus in cows on the outcome and reproductive performance. A total of 76 cows with uterine prolapse were investigated, 10 of which had died before treatment. According to the posture, cows were divided into standing (Standing: n = 11) and recumbent (Recumbent: n = 55). Recumbent cows were subdivided randomly into lying (Lying: n = 24), lifting up using a cow-lift (Cow-lift: n = 18), and raising hind legs using a tractor (Raising: n = 13). Recovery rate after treatment of all cows was 60.6%. The recovery rate of Recumbent (52.7%) was significantly (P < 0.01) lower than Standing (100%). Among the recumbent cows, Lying showed the lowest recovery rate (37.5%), which was significantly lower than the recovery rate (64.5%) of the combined Cow-lift and Raising groups. The mean nonpregnant term of Raising (144 days) was significantly (P < 0.05) shorter than of Cow-lift (297 days). In conclusion, the method of replacing the uterus by raising the hind legs during treatment of uterine prolapse in cows could improve the recovery rate and breeding performance.
The effects of mono-(2-ethylhexyl) phthalate (MEHP), an active metabolite of di-(2-ethylhexyl) phthalate (DEHP), on prepubertal guinea pig testes in vitro were investigated. The testes of 35-day-old guinea pigs were surgically excised. They were seeded in a defined medium containing antibiotics and administered MEHP at concentrations of 1, 10, and 100 nmol/ml, respectively. The control groups were administered a similar volume of corn oil vehicle. The tissues were incubated for 3, 6, and 9 h. The specimens were collected at 3, 6, and 9 h after treatment. They were fixed in 4% paraformaldehyde or 5% glutaraldehyde. For quantitation of the apoptotic spermatogenic cells, the terminal dUTP nick end-labeling (TUNEL) staining was performed by light microscopy. Detachment and displacement of spermatogenic cells, thin seminiferous epithelia, and Sertoli cell vacuolization were observed. Maximal testicular damage was recognized at 100 nmol/ml and 9 h after MEHP treatment. The percentage (%) of apoptotic spermatogenic cells significantly increased at 3, 6, and 9 h after treatment, compared to the control groups. Because the loss of spermatogenic cells by MEHP treatment varies among species, the present study, using guinea pigs, was designed and conducted to obtain further information.
We report a patient with paraneoplastic pemphigus associated with a thymic tumour. Immunoblot study using affinity-purified gamma-catenin protein revealed that his serum recognized gamma-catenin (plakoglobin) in epidermal, thymic tumour and mouse bladder extracts.
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