Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats

Background  The purpose of this study was to achieve stomach-selective gene transfer in rats by our simple and novel administration method, which is gastric serosal surface instillation of naked plasmid DNA (pDNA). Methods  Naked pDNA encoding firefly luciferase as a reporter gene was instilled onto the gastric serosal surface in male Wistar rats. As controls, we performed intraperitoneal, intragastric and intravenous administration of naked pDNA. At appropriate time intervals, we measured luciferase activities in the stomach and other tissues. Results  Gene expression in the stomach 6 h after gastric serosal surface instillation of naked pDNA (5 μg) was significantly higher than that after using other administration methods. The present study is the first report on stomach-selective gene transfer following instillation of naked pDNA onto the gastric serosal surface in rats. Also, the gene expression level in the stomach 6 h after gastric serosal surface instillation of naked pDNA was markedly higher than that in other tissues. In a dose-dependent study, the gene expression level was saturated over 5 μg. Gene expression in the stomach was detected 3 h after gastric serosal surface instillation of naked pDNA. The gene expression level peaked 12–24 h after instillation of naked pDNA, then decreased to a level similar to 3 h at 48 h. Conclusions  Gastric serosal surface in stillation of naked pDNA can be a highly stomach-selective gene transfer method in rats.     

Prognosis of gastric carcinoma patients aged 85 years or older who underwent surgery or who received best supportive care only

Background

There is controversy regarding strategies for treating very elderly patients with gastric carcinoma. We aimed to assess survival after surgery in very elderly patients according to their clinical characteristics.

Methods

Gastric cancer patients aged ≥85 years were retrospectively reviewed. There were no significant differences in clinical characteristics between 58 patients with curative resection (OP group) and 32 patients with best supportive care alone (BSC group) in cancer stage IA–IIIC and with a performance status of 0–3.

Results

Overall survival (OS) was significantly better in the OP group than in the BSC group in females [hazard ratio (HR) 0.27, 95 % confidence interval (CI) 0.12–0.57, P < 0.001] but not in males (HR 0.71, 95 % CI 0.35–1.49, P = 0.35). OS was significantly better in the OP group in patients aged 85–89 years (HR 0.44, 95 % CI 0.25–0.78, P = 0.006) but not in patients aged ≥90 years (HR 0.47, 95 % CI 0.12–1.66, P = 0.24). OS was significantly better in the OP group in patients with stage IB–IIIC cancer (HR 0.29, 95 % CI 0.14–0.58, P < 0.001) but not in patients with stage IA cancer (HR 0.52, 95 % CI 0.21–1.27, P = 0.15).

Conclusions

Females, patients aged 85–89 years, and patients with stage IB–IIIC cancer had significantly better OS with surgery than without. For males, patients aged ≥90 years, or stage IA patients, the decision to perform surgery should be carefully made, and BSC might be an optimal strategy.     

Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer

Objectives

The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer.

Methods

We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups.

Results

Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p = 0.77), PFS (log-rank, p = 0.57), and OS rates (log-rank, p = 0.41) to definitive radiotherapy alone. The frequencies of acute grade 3–4 toxicities were similar between the two groups (24.2% versus 24.5%, p = 1.0), whereas the frequencies of grade 3–4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p = 0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3–4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97–5.99, p = 0.059).

Conclusions

Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer.     

Unilateral lung-selective gene transfer following the administration of naked plasmid DNA onto the pulmonary pleural surface in mice

The purpose of the present study was to examine unilateral lung-selective gene transfer following the administration of naked plasmid DNA (pDNA) onto the pulmonary pleural surface in mice. Naked pDNA was administered intravenously, intraperitoneally, and instilled onto the right pulmonary pleural surface. Four hours later, right pulmonary pleural surface instillation of naked pDNA resulted in high gene expression in the right lung. On the contrary, intravenous and intraperitoneal administration of naked pDNA resulted in no detectable gene expression. After instilling naked pDNA onto the right or left pulmonary pleural surface, gene expressions in the applied lung were significantly higher than those in the other lung and tissues. In addition, gene expressions were detected only in the intrathoracic tissues, not in the intraperitoneal tissues. Four hours after instillation of naked pDNA onto the right pulmonary pleural surface, gene expression in the right lung was the highest, and thereafter gene expression in the right lung decreased gradually. This novel gene transfer method is expected to be a safe and effective treatment against serious lung diseases.     

Spleen-selective gene transfer following the administration of naked plasmid DNA onto the spleen surface in mice

The purpose of present study was to examine spleen-selective gene transfer following the administration of naked plasmid DNA (pDNA) onto the spleen surface in mice. Gene expression in the spleen and other tissues was evaluated based on firefly luciferase activity. Six hours after spleen surface instillation of naked pDNA, high gene expression in the spleen was observed. On the contrary, intravenous and intraperitoneal administration of naked pDNA resulted in no detectable gene expression. After instilling naked pDNA onto the spleen surface, gene expression in the spleen was significantly higher than those in other tissues. Six hours after instillation of naked pDNA onto the spleen surface, gene expression in the spleen reached the peak value, and thereafter decreased gradually. By utilizing a glass-made diffusion cell that is able to limit the contact dimension between the spleen surface and naked pDNA solution administered, site-specific gene expression in the spleen was found. This novel gene transfer method is expected to be a safe and effective strategy for DNA vaccine against serious infectious diseases and cancers.     

Nosocomial infection by multidrug-resistant Pseudomonas Aeruginosa (MDRP) presumably spread a radiation technician

Isolated of multidrug resistance Pseudomonas aeruginosa (MDRP) that the receptivity pattern of the antimicrobial suscepti respectively resembled isolated from clinical specimens (sputum) in two patients of each internal medicine ward in Kitasato University East Hospital for two days from September 18 and 20, 2004. Both of bacteria were formed small colonies of a smooth-type on dollargalluskey improvement-type BTB agar plates, and the judgment of ClassB (metallo)-beta-lactamase by biochemical properties and disk diffusion method sodium mercaoto-acetic acid (SMA) was mutually corresponding. Moreover, it was same serotype C according to the serotype, and it was confirmed that it was the same bacterial strain from the molecular epidemiology analysis by Random amplified polymorphic DNA polymerase chain reaction (Random amplified polymorphic DNA polymerase chain reaction: RAPD). From the investigation of clinical backgrounds of two patients who isolated bacterial strains, September 18, 2004. 10 : 20 a.m., and 10 : 40 a.m., other chances that can become with contact infection in this hospital, except conducted X-Ray or roentgenograph of the chest and abdomen of Portable X-ray device continuously done by one radiation technician was not seen. Because it had turned out that a radiation technician who had taken charge had been neglecting the hand washing at the time of each X-Ray or roentgenograph, it was guessed the case with nosocomial infection by contact infection occurred via specific radiation technician.     

A sclerosant with astringent properties developed in China for oesophageal varices: Comparison with ethanolamine oleate and polidocanol

BACKGROUND: Xiao zhi ling (XZL), which consists of Chinese nutgalls and aluminium potassium sulphate, is used as a local injection for the treatment of internal haemorrhoids in China. It is also used for endoscopic sclerotherapy of oesophageal varices. To date, however, it has not been compared with other sclerosants with regard to its safety and efficacy. METHODS: In the present study, the effect on the endothelium and the haemolytic and thrombosing effects of XZL were compared with those of 5% ethanolamine oleate and 1% polidocanol, using an endothelial cell line and red blood cells taken from rats and the dorsal marginal ear vein of rabbits. In addition, XZL was injected into the area surrounding varices in rats and its efficacy was studied endoscopically and histologically. RESULTS: Xiao zhi ling reduced the size of varices in rats after causing severe damage in the injected region. Compared with the other two sclerosants, however, XZL had little effect on the endothelium and was the least haemolytic compound. Furthermore, XZL did not cause thrombosis in the injected vein of a rabbit. CONCLUSIONS: These results suggest that XZL is another type of sclerosant with astringent rather than detergent properties. This compound should be used to treat oesophageal varices by paravariceal injection in smaller doses than 5% ethanolamine oleate and 1% polidocanol.     

Clinical features of Sjögren’s syndrome associated with recurrent annular erythema

Our objective was to describe the clinical features of Sjögren’s syndrome (SS) with recurrent annular erythema which resembles subacute cutaneous lupus erythematosus (SCLE), and determine a possible association of anti-SS-A/Ro and/or SS-B/La antibody titers with the episodes of cutaneous manifestation. Recurrent annular erythema was observed in 4% (six patients; five females and one male) of our 143 patients diagnosed as primary SS. All the patients developed annular erythema on the facial area as their initial manifestation when they were between 21 and 31 years old. They had few subjective sicca symptoms, but both anti-SS-A/Ro and SS-B/La antibodies were positive and parotid sialography showed typical findings for SS (subclinical SS). Parotid gland swellings had developed in five of the patients during their follow-up periods, (3–12 years). In addition to the facial area, most patients repeated the cutaneous episodes on extremities and palmar, plantar or auricular areas. Skin biopsy was performed in three patients and the common findings were mononuclear cell infiltrations in the dermis with few epidermal changes. Transient leukopenia (four patients), low titers of anti-DNA antibodies (one patient) and chronic false-positive results of serological tests for syphilis (one patient) were observed. Two of our patients, therefore, temporarily fulfilled four items of the ARA classification criteria for systemic lupus erythematosus (SLE), if their facial erythema was considered as malar rash. Serum antibodies to 52 kDa SS-A/Ro peptides (80%) were more frequently detected in the five patients examined by enzyme-linked immunosorbent assays (ELISA), compared with those to 60 kDa SS-A/Ro peptides (40%). Furthermore, we could serially determine serum anti-SS-A/Ro and SS-B/La antibody titers in three patients by using ELISA for 3 or 4 years. Annular erythema usually developed when the antibody titers became relatively high and disappeared after the treatment with oral prednisolone which suppressed the antibody titers. We could observe five pregnancies in our three patients and all the patients developed annular erythema during their pregnant periods. Their five infants, however, were free from any complications such as neonatal lupus erythematosus and congenital heart block. We conclude that annular erythema is a rare manifestation of SS and develops in relatively young patients who are subclinical for sicca symptoms. The cutaneous episodes seemed to relate with anti-SS-A/Ro and/or SS-B/La antibody titers. Some of the erythema observed in SS patients may belong to SCLE, but they do not usually develop typical SLE. The possibility that SS may be more frequent in the SCLE patients remains to be determined.