For the purpose of examining the Topoisomerase II (Topo II) activity in human kidney cancer cells, we performed experiments with using DNA unknotting method. This method check relative Topo II activity with its conversion of knotted form P4 phage DNA to unknotted form. Our preliminary results demonstrate remarkable activity of Topo II with specific conversion of knotted form P4 DNA to unknotted form in human kidney cancer cells, YCR and ACHN. Moreover, addition of etoposide to the same experiment suppressed Topo II activity in a dose dependent manner. Our results suggest that kidney cancer has a certain amount of Topo II, a target for etoposide. We believe this method is useful to measure Topo II activity in cancer cells and to estimate chemotherapeutic potential of Topo II inhibitors including etoposide in human kidney cancers.
Measurement of cerebral blood flow (CBF) and computed tomography (CT) cisternography were performed in 37 patients with a tentative diagnosis of normal pressure hydrocephalus (NPH) to predict their surgical outcome. The mean CBF of the whole brain was measured quantitatively by single photon emission computed tomography with technetium-99m-hexamethylpropylene amine oxime before surgery. The results of CT cisternography were classified into four patterns: type I, no ventricular stasis at 24 hours; type II, no ventricular stasis with delayed clearance of cerebral blush; type III, persistent ventricular stasis with prominent cerebral blush; type IV, persistent ventricular stasis with diminished cerebral blush and/or asymmetrical filling of the sylvian fissures. The mean CBF was significantly lower than that of age-matched controls (p < 0.005). Patients with a favorable outcome had a significantly higher mean CBF than patients with an unfavorable outcome (p < 0.005). Patients with the type I pattern did not respond to shunting. Some patients with type II and III patterns responded to shunting but improvement was unsatisfactory. Patients with type IV pattern responded well to shunting, and those with a mean CBF of 35 ml/100 g/min or over achieved a favorable outcome. The combination of CBF measurement and CT cisternography can improve the prediction of surgical outcome in patients with suspected NPH.
Abstract Purpose Spontaneous pneumomediastinum, supposedly attributed to air leakage from the respiratory tract, is a common complication of interstitial lung disease often resulting in mediastinal widening. However, several cases of pneumomediastinum without mediastinal widening have been observed. This study aimed to investigate the cause of pneumomediastinum in patients without mediastinal widening. Patients and methods This study included 41 patients diagnosed with pneumomediastinum using computed tomography (CT) between July 2011 and September 2021 at Yokohama Minamikyosai Hospital; they had undergone a previous CT showing no gas density. Based on a comparison with previous CT images, the patients were classified into two groups: without mediastinal widening and with mediastinal widening. Results Of the 41 patients, 13 and 28 had pneumomediastinum without and with mediastinal widening, respectively. There were no significant differences in the sex, age, body mass index, or pneumomediastinum distribution between the two groups. However, the rate of weight loss per month was significantly higher in the group without mediastinal widening than in that with mediastinal widening. No significant differences were observed in the respiratory function test results between the two groups; however, 11 of the 13 patients had restrictive disorders. Pulmonary disease in this group included idiopathic pulmonary fibrosis (n = 6) and interstitial lung disease with collagen disease (n = 4). Pneumomediastinum occurred during periods of weight loss in all the patients excluding two patients without data. Conclusion Pneumomediastinum without mediastinal widening occurs during rapid weight loss and is often associated with restrictive lung disorders. The negative pressure attributed to the decreased plasticity of the lungs, which complements the space where the mediastinal fat has disappeared, is presumably the cause of pneumomediastinum. This pathophysiology is different from that of conventional pneumomediastinum attributed to increased intrapleural space pressure; thus, we propose to name the abovementioned pathophysiology negative pressure pneumomediastinum.
Primary malignant melanoma of the lung (PML) is extremely rare. No precursor lesions of PML have been identified, and little is known about the genetic mutations associated with the disease. Typically, 15-20% of malignant melanomas possess NRAS gene mutations, but no cases of NRAS-mutated PML have been reported in the English literature. We present a case of PML involving an NRAS mutation.Clinical summary A 74-year-old Japanese female presented with worsening dyspnea and was admitted to hospital. Computed tomography (CT) revealed a right lung (S10) mass and pleural dissemination. Cytology of the pleural effusion in the right lung was performed, and malignant melanoma or clear cell sarcoma was suspected. A dermatological examination and gallium scintigraphy were conducted to determine the primary tumor site, but no suspicious lesions, expect for the right lung mass, were found. After admission, CT showed complicating bilateral pneumonia, and an antibiotic drug was administered, but the pleural effusion got worse. About 2 weeks later, the patient died of respiratory failure and cardiac arrest. An autopsy was performed to determine the histological diagnosis. Autopsy findings A 26x15x20-mm black and pale yellow mass was found in the right lower lobe. Many disseminated nodules were found in the right lobe. The tumor had invaded the right diaphragm. Subcarinal lymph node metastasis was also detected. Immunohistochemically, the tumor cells exhibited positivity for S-100 and HMB45 staining. The patient was diagnosed with malignant melanoma. Sanger sequencing of the tumor detected an NRAS mutation.We found an NRAS D54N mutation in PML, which has not been reported previously anywhere in the world. Previous reports indicated that most cases of PML can be classified into the triple-wild-type, but BRAF mutation status was only analyzed in a few cases. We should analyze the mutation patterns of PML to determine whether any subtypes other than the triple-wild-type exist. PML might be a form of de novo cancer.