The truncated C-terminal E2 (E2-TR) protein of bovine papillomavirus (BPV) type-1 is a transactivator that modulates transcription in vivo and in vitro in a manner distinct from the E2-TA and E8

The E2 open reading frame of bovine papillomavirus (BPV)-1 encodes a 410 amino acid (aa) transcriptional activator, E2-TA, and collinear polypeptides--E2-TR (243 aa) and E8^E2 (196 aa). E8^E2 and E2-TR share the DNA-binding domain of E2-TA, and both have been defined as transcriptional repressors. Although purified E2-TR and E8^E2 proteins specifically bound E2 sites with similar affinities, only the E2-TR stimulated transcription. Here we show that E2-TR trans-activates E2-dependent promoters 5 to 10-fold in cooperation with cellular factors and in a dose-dependent fashion in epithelial cells and fibroblasts of animal or human origin while E2-TA activated >100-fold and the E8^E2 had no effect. However, in contrast to E2-TA, E2-TR activated transcription from a promoter-proximal position. E2-TR also partially inhibited the BPV-1 P89 or heterologous promoters whereas E8^E2 led to complete repression. Thus, the BPV-1 E2-TR modulates viral gene expression in a manner distinct from other E2 proteins.

Severe obliterative bronchitis associated with Stevens-Johnson syndrome.

We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation. Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO(2) increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease.

Cellular factor YY1 downregulates the human papillomavirus 16 E6/E7 promoter, P97, in vivo and in vitro from a negative element overlapping the transcription-initiation site.

Cellular factors that bind to cis sequences in the human papillomavirus 16 (HPV-16) upstream regulatory region (URR) positively and negatively regulate the viral E6 and E7 oncogene promoter, P97. DNase I footprinting has revealed the binding of cellular proteins to two previously undetected cis elements overlapping and 3' of the transcription-initiation site of the P97 promoter. Mutations within homologous motifs found in both of these cis elements abolished their negative function in vivo and the binding of the same cellular complex in vitro. This factor was identified as YY1 by complex mobility and binding specificity in comparison with vaccinia virus-expressed, purified recombinant YY1 protein and by antigenic reactivity with YY1 antisera. Cis mutations in the 'initiator' YY1 site activated the P97 promoter in vivo and in vitro. P97 was also activated threefold in vitro by depletion of endogenous YY1 with wild-type, but not mutant, YY1 oligonucleotides from the IgH kappa E3' enhancer. Furthermore, increasing concentrations of exogenous, purified recombinant YY1 repressed wild-type P97 transcript levels by up to threefold, but did not influence the P97 promoter mutated in the 'initiator' YY1 site. Thus, the promoter-proximal YY1 site was not necessary for correct transcription initiation at the P97 promoter, but was found to be required for downregulation of P97 transcription in vivo and in vitro. In contrast to other viral and cellular promoters, where YY1 is thought to function as a positive transcription-'initiator' factor, HPV-16 P97 transcription is downregulated by YY1 from a critical motif overlapping the transcription start site.

Delayed postpartum hemorrhage due to cesarean scar dehiscence.

CASE REPORT: A 28-year-old woman presented with massive postpartum hemorrhage. Laparotomy revealed a cesarean scar dehiscence due to wound infection. CONCLUSION: Although postpartum hemorrhage due to cesarean scar dehiscence is an unusual complication, practitioners should add dehiscence to their differential diagnoses.

[A case of cT0N2M0 small cell lung cancer with Lambert-Eaton myasthenic syndrome].

We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of muscle weakness was admitted to our hospital. Although his chest radiograph on admission showed no abnormal findings, CT scanning detected a mediastinal lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission tomography (FDG-PET) revealed increased accumulation in the same portion in the mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings (waning and waxing phenomenon in response to low-and high-frequency repetitive stimulation, respectively) in combination with the increased serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody. Subsequent histopathological diagnosis by mediastinoscopic resection of a paraaortic lymph node was small cell carcinoma. No distant metastasis was detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti-VGCC antibody titers followed by marked improvement of neurological dysfunction (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a loss of waning phenomenon) was observed. A close relationship between reduction of the antibody titers and improvement of neurological symptoms after the therapy was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC antibody titer in the serum is important for evaluating the efficacy of chemotherapy for LEMS associated with SCLC.

[Effect of glycyrrhizin on anti-tuberculosis drug-induced hepatitis].

In cases in which hepatotoxicity developed during anti-tuberculosis chemotherapy, the rapid recovery of liver function is essential for the completion of the anti-tuberculosis chemotherapy protocol. Glycyrrhizin (Stronger Neo-Minophagen C: SNMC) is widely used in Japan for the treatment of patients with drug eruption or chronic hepatitis. However, a consensus on the clinical effects of glycyrrhizin for the treatment of anti-tuberculosis drug-induced hepatitis has not yet been reached. We studied 24 cases who showed abnormal liver function test results while undergoing anti-tuberculosis chemotherapy and who were treated with or without glycyrrhizin. We then compared recovery periods of liver function among both groups. The time required for liver function normalization in the patients who received glycyrrhizin (SNMC, 40 ml daily, intravenously) was 15.1 +/- 4.5 days and the time required for normalization in the non-glycyrrhizin group was 15.2 +/- 5.2 days. The difference was not significant and the fact indicated that glycyrrhizin is not useful for the treatment of anti-tuberculosis drug-induced hepatitis.