An efficient construction of conditionally replicating adenoviruses that target tumor cells with multiple factors.

Despite the enormous potential of conditionally replicating adenoviruses (CRAs), the time-consuming and laborious methods required to construct CRAs have hampered both the development of CRAs that can specifically target tumors with multiple factors (m-CRA) and the efficient analysis of diverse candidate CRAs. Here, we present a novel method for efficiently constructing diverse m-CRAs. Elements involving viral replication, therapeutic genes, and adenoviral backbones were separately introduced into three plasmids of P1, P2, and P3, respectively, which comprised different antibiotic resistant genes, different ori, and a single loxP (H) sequence. Independently constructed plasmids were combined at 100% accuracy by transformation with originally prepared Cre and specific antibiotics in specific Escherichia coli; transfection of the resulting P1+2+3 plasmids into 293 cells efficiently generated m-CRAs. Moreover, the simultaneous generation of diverse m-CRAs was achieved at 100% accuracy by handling diverse types of P1+2 and P3. Alternatively, co-transfection of P1+3 and P2 plasmids into Cre-expressing 293 cells directly generated m-CRA with therapeutic genes. Thus, our three-plasmid system, which allows unrestricted construction and efficient fusion of individual elements, should expedite the process of generating, modifying, and testing diverse m-CRAs for the development of the ideal m-CRA for tumor therapy.

Diabetic ketoacidosis associated with Guillain-Barré syndrome with autonomic dysfunction.

A 37-year-old woman was admitted in a comatose state, after exhibiting fever and diarrhea. Diabetic ketoacidosis was diagnosed due to an increased blood glucose level (672 mg/dl), metabolic acidosis, and positive urinary ketone bodies. On the fifth hospital day, despite recovery from the critical state of ketoacidosis, the patient suffered from dysphagia, hypesthesia and motor weakness, followed by respiratory failure. Cerebrospinal fluid analysis was suggestive of Guillain-Barre syndrome (GBS). Autonomic dysfunction was manifested as tachycardia and mild hypertension in the acute stage. Marked orthostatic hypotension persisted long after paresis was improved, indicating an atypical clinical course of GBS.

[Assessment of right ventricular function by magnetic resonance imaging of old myocardial infarction].

The usefulness of magnetic resonance imaging (MRI) for estimating right ventricular function and the influence of left ventricular dysfunction on the performance of the right ventricle were assessed in 43 patients with chronic myocardial infarction (MI) and 14 control subjects (N) using electrocardiography-gated MRI and cardiac catheterization. Patients with MI were divided into three groups according to the location of the coronary lesions; 22 patients with left coronary artery lesion (LCA group), 13 with right coronary artery lesion (RCA group), and 8 with both left and right coronary artery lesions (L+R group). The right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) were measured by Simpson's rule algorithm on transverse images of the right ventricle obtained at the end-systolic and end-diastolic phases. In 34 of the 43 patients, the same parameters of right ventricular function were calculated by the thermodilution method using a Swan-Ganz catheter with rapid response thermistor. Left ventricular ejection fraction (LVEF) and end-diastolic volume were determined from left ventriculography. The intraobserver reproducibility (11 cases, r = 0.97) and interobserver reproducibility (11 cases, r = 0.92) of RVEF measured by MRI were excellent. The RVEF and RVEDV determined from MRI were significantly correlated with those from the thermodilution method (RVEF: r = 0.56, RVEDV: r = 0.52). There was no difference in right ventricular end-diastolic volume index in any patient group. The RVEF was decreased in the L+R (41.0 +/- 4.5%, p < 0.01) and RCA (45.9 +/- 6.6%) groups, but there was no difference between the LCA (50.6 +/- 6.6%) and N (48.9 +/- 4.3%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of miliary tuberculosis with skull tuberculosis].

A 47-year old woman was admitted to our hospital with complaints of headache and right occipital swelling. Brain CT scan showed right occipital bone defect with a sequestrum and soft tissue swelling. T1 weighted MRI enhanced by GD-DTPA revealed several nodules. A right occipital craniotomy was performed. Subcutaneous pus and a well-circumscribed yellowish, firm mass which existed under the bone defect was extirpated. Pathologically, this mass was considered to be a tuberculoma and intracranial nodules were suspected to be cerebral tuberculosis. Anti-tuberculous therapy was started. Since her admission fecal occult blood continued and endoscopic examination with biopsy revealed sigmoid colon cancer. Sigmoidectomy was performed and she has been well during 1 year post-operative follow up. Although tuberculous disease are decreasing in number in our country, we must take into account of the existence of skull tuberculosis.

[Successful embolization of bronchial artery in racemose hemangioma].

A 74-year-old male was admitted to our hospital because of hemoptysis. Bronchoscopic examination showed a polypoid lesion in the right middle lobe bronchus. Biopsy of the polypoid lesion caused a massive bleeding. A massive hemoptysis of about 1,200 ml occurred again on the 13th day after biopsy, angiographic embolization of the right bronchial artery was performed successfully. Dilatation, convolution and hypervascularization of the right bronchial artery were observed, and anastomosis with pulmonary artery was seen. The diagnosis of primary racemose hemangioma of the bronchial artery was made. There was no recurrence of hemoptysis 3 years after the embolization procedure. Bronchial artery embolization is an effective method of treatment of hemoptysis due to racemose hemangioma.

[Long-term prognosis related to coronary risk factors, clinical characteristics of acute myocardial infarction and coronary angiographic findings in the elderly].

In order to clarify the characteristics of acute myocardial infarction in the elderly, we investigated the clinical profile and long-term prognosis of patients with myocardial infarction in the past 13 years. The early fatality rate (within 30 days after onset) in the relatively younger patients (less than 65 years old) was 8.8%, and in the older patients (greater than 65 years old) was 29.1%. The fatality rate was significantly higher in older than in younger patients. On coronary and left ventriculography, the older patients showed multi-vessel lesions with decreased ejection fraction and cardiac index. According to the cumulative survival curves related to the coronary risk factors, no significant differences were found with or without smoking or hypertension. However, the long-term prognosis of the patients with controllable hypercholesteremia was better than in uncontrollable patients less than 65 years old. No significant difference was found in patients with hypercholesteremia over age 65. The long-term prognosis of the patients with uncontrollable diabetes mellitus was worse than that of controllable diabetic patients.