Endothelin-1 within the corpus luteum during spontaneous luteolysis in the cow: local interaction with prostaglandin F2alpha and angiotensin II

It is generally accepted that endothelin-1 (ET-1) is involved in the regression of the corpus luteum (CL) in cows, but there are few in vivo data available on the local release of vasoconstrictors, including ET-1. Thus, we aimed to determine in detail the local secretion of ET-1, angiotensin II (Ang II) and prostaglandin F2alpha (PGF2alpha) within the CL during spontaneous luteolysis in the cow. To observe real-time dynamics of the releasing profile of CL-derived factors, a microdialysis system was surgically implanted in the CL on day 15 of the estrous cycle and continuously perfused with Ringer's solution. Local secretion of ET-1, Ang II and PGF2alpha increased immediately after the onset of luteolysis (the time point when progesterone release started to decrease within the CL) and was maintained at high levels. A positive relationship was observed in intra-luteal changes among ET-1, Ang II and PGF2alpha release. This is the first real-time and in vivo evidence that the secretion of ET-1 together with Ang II and PGF2alpha immediately increases within the CL after the onset of spontaneous luteolysis. Consequently, we suggest that the activation of a local positive feedback mechanism among ET-1, Ang II and PGF2alpha might play a functional role in the paracrine modulation of luteolytic cascade and, simultaneously, the elevated ET-1 with Ang II and PGF2alpha should induce a strong vasoconstriction, thereby reducing the blood supplying the CL during spontaneous luteolysis.     

False-positive CT and thallium-201 SPECT results in a patient with suspected lung cancer and mediastinal lymph node metastasis

We describe a patient with a final diagnosis of inflammatory change in which combined imaging results were strongly suggestive of lung cancer with mediastinal lymph node metastases. The patient, who was suspected of having a pulmonary lesion on chest radiography performed at a local hospital, was referred to our hospital. Contrast-enhanced computed tomography (CT) of the chest showed a small-sized opacity in the left upper lung and multiple mediastinal nodules. The largest mediastinal nodule, depicted at a pretracheal region, was 22 mm in size. Thallium-201 single photon emission computed tomography (SPECT) showed increased uptake in these lesions, which exhibited no remarkable washout of the tracer, supportive of the diagnosis of lung cancer with mediastinal lymph node metastasis. However, bronchoscopic and mediastinoscopic biopsy revealed no malignant cells or reactive lymph nodes, respectively. Therefore, no surgical procedure was performed after the biopsy. The patient has done well without evidence of malignancy for 21 months. Radiologists should be careful in the differential diagnosis of benign and malignant lesions even with combined imaging modalities.     

The hepatitis B virus X protein enhances AP-1 activation through interaction with Jab1

Hepatitis B virus X protein (HBx) has many cellular functions and is a major factor in hepatitis and hepatocellular carcinoma caused by HBV infection. A proteomic approach was used to search for HBx-interacting proteins in order to elucidate the molecular mechanism of hepatocarcinogenesis. HBx was attached to myc and flag tags (MEF tags) and expressed in 293T cells; the protein complex formed within the cells was purified and characterized by mass spectrometry. COP9 signalosome (CSN) subunits 3 and 4 were subsequently identified as HBx-interacting proteins. In addition, CSN subunit 5, Jun activation domain-binding protein 1 (Jab1), was shown to be a novel cellular target of HBx. In vivo and in vitro interactions between HBx and Jab1 were confirmed by standard immunoprecipitation and GST pull-down assays. An analysis of HBx deletion constructs showed that amino acids 30-125 of HBx were responsible for binding to Jab1. Confocal laser microscopy demonstrated that HBx was mainly localized in the cytoplasm, while Jab1 was found mainly in the nucleus and partially in the cytoplasm, and that the two proteins colocalized in the cytoplasm. The cotransfection of HBx and Jab1 resulted in substantial activator protein 1 (AP-1) activation and knockdown of endogenous Jab1 attenuated AP-1 activation caused by HBx. In addition, the coexpression of HBx and Jab1 potentiated phosphorylation of JNK, leading to the subsequent phosphorylation of c-Jun, whereas the level of c-Jun and JNK phosphorylation induced by HBx was decreased in Jab1 knockdown cells. These results suggest that the interaction between HBx and Jab1 enhances HBx-mediated AP-1 activation.     

Cytotoxicity and antigenicity of antimicrobial synthesized peptides derived from the beetle Allomyrina dichotoma defensin in mice

Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In addition, antigenicity of these peptides was studied by evaluating antibody responses in mice immunized with these peptides. The toxicity of peptide A toward mouse peritoneal cells was less than that of polymyxin B, when morphologically evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24 h. Interestingly, almost all of mice injected intravenously with these peptides at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or negligible anti-peptide A or B antibody production, although anti-KLH antibody was significantly produced. The results indicated that peptides A and B were less cytotoxic than polymyxin B and also had poor antigenicity to produce specific antibody in mice.     

Treatment of advanced prostatic carcinoma with cis-diamminedichloroplatinum

Chemotherapeutic effects of CDDP used as the main drug were studied in 20 patients with progressive prostatic cancer in stage C or D. On the average 208 mg of CDDP was given to the patients receiving chemotherapy without antiandrogen therapy (13 patients who showed resistance to hormone and an untreated new patient) and both ADM and IFM were also given to 3 of them. According to the criterion proposed by Shida and his coworkers, the chemotherapy without antiandrogen therapy was effective in 2 cases, relatively effective in 7 cases, and ineffective in 5 cases. The chemotherapy was effective for metastatic tumors of the lung in 2 out of 2 cases, but had no effect on tumors of the lymph node (1 case) and primary lesion of the tumors (14 cases). The chemotherapy improved acid phosphatase values in 5 out of 10 cases, alkaline phosphatase values in 3 out of 10 cases, dysuria in 4 out of 8 cases, nocturia in 1 out of 12 cases, residual urine in 5 out of 6 cases, lumbago in 6 out of 8 cases, and constitutional symptom in 6 out of 12 cases. The effect of the chemotherapy in combination with antiandrogen therapy was excellent in 4 and good in 2 of the 6 patients treated with castration + diethylstilbestrol diphosphate + CDDP + ADM +/- IFM. The chemotherapy with antiandrogen therapy had no effect on metastatic tumors of the bone (2 cases), but decreased the hardness and size of primary lesion in 6 out of 6 cases. Urethrography showed better changes in 6 out of 6 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinical study of urological examinations in uterus malignant tumors before treatment

Sixty six cases of uterus malignant tumors examined urologically before gynecologic treatment between 1980 and 1984 are reviewed retrospectively. The uterus lesion excluding 1 malignant mixed mesodermal tumor was cervical carcinoma in 55 cases and corpus carcinoma in 10 cases. Pathologically, 46 cases were squamous cell carcinoma, 10 were adenocarcinoma, 3 were squamous adenocarcinoma and 6 were unknown. Clinical staging according to classification of FIGO, was stage 0 in 3 cases, stage I in 23 cases, stage II in 28 cases, stage III in 3 cases, stage IV in 7 cases, and unknown in 2 cases. Only 4 cases (6.1%) had urological symptoms with no special relationship to the uterus lesion. Abnormal findings of urine tests were seen in 15 cases (22.7%). The incidence of hematuria and pyuria, which were seen in 12 and 10 cases, respectively, was high. Cystoscopic abnormality was revealed in 32 (51.6%) out of 62 cases. Protrusion of vesical wall was found in 11 cases (34.3%) and it was an important finding which showed a significant incidence. Edema was seen in 11 cases (34.3%). This was a sign of progression, and the observation on spread of lesion was important. Redness was seen in 3 cases (4.8%). It was considered to be the result of circulatory disturbance. At the same time observations on vascular change, edematous change etc. should be done in detail. Bleeding was seen in 1 case (1.6%), microscopic bleeding was seen more frequently than macroscopic bleeding. Abnormalities of ureteral orifice were significant only after other examinations were reviewed in addition to these signs. IVU was performed in 58 cases.(ABSTRACT TRUNCATED AT 250 WORDS)