Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes.

Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN.     

Crohn's ileocolitis with initially superimposed cytomegalovirus infection, resembling intestinal tuberculosis]

We describe a case of 41-year-old Japanese man with Crohn's ileocolitis and cytomegalovirus infection, confirmed by histology of ileal ulcers. Although his colonoscopic and radiological features resembled those of intestinal tuberculosis, granulomas of typical Crohn's disease were evident on histology of biopsy specimens taken from the duodenum and colon. The lesions remain unchanged even after 1.5 years by oral administration of salazosulphapyridine 3g daily.     

Solitary fibrous tumor of the inguinal region

Solitary fibrous tumors (SFT) have recently been established to be of mesenchymal origin. Although there are numerous reports of SFTs arising from the pleura, reports of the tumor arising from extrapleural sites are comparatively rare [Fletcher CDM, Unni K, Mertens F (eds) World Health Organization classification of tumors, pathology & genetics, tumors of soft tissue and bone. IARC Press, Lyon, pp 86–901, 2002]. We report a case of SFT arising in the inguinal region.     

Successful embolization of a large superior gluteal artery pseudoaneurysm emerging during anticoagulant therapy

Gross hemorrhage is the most serious complication of anticoagulant therapy. We report the discovery and treatment of a large pseudoaneurysm of the superior gluteal artery in one patient who had been receiving oral anticoagulant therapy. We diagnosed the pseudoaneurysm by contrast-enhanced computed tomography, and embolized the artery with stainless steel coils. The exact cause of the pseudoaneurysm remains unclear, however, minor trauma appears most likely.     

Detection of Platelet Antibody Using Rosette Technique with Anti-IgG Antibody-Coated Polyacrylamide Gel

Abstract. Paraformaldehyde-fixed platelets from normal donors were used for detection of antibody to platelet by in vitro sensitization (indirect method) utilizing rabbit anti-human IgG heavy chain specific antibody-coated polyacrylamide gels (Immunobeads). The sensitized platelets formed rosettes with Immunobeads and the positive rosette count was over 30%, while control showed less than 8% when normal sera were used. This method was also applicable for detecting antibody-sensitized platelets in vivo (direct method) in patients with autoimmune thrombocytopenia. This method is simple, rapid and reproducible for clinical use. Direct and indirect immunofluorescent antibody tests and a blocking test with anti-human serum also supported the results of Immunobead rosetting technique.     

Pigmented squamous cell carcinoma of the uterine cervix.

A 57-year-old female presented with an abnormal Pap smear. Colposcopic examination of the cervix revealed white mucosa with erosion and several areas of black pigmentation. After a colposcopically directed biopsy and loop conization, radical hysterectomy and bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy were performed. Pathological examination disclosed an invasive squamous cell carcinoma admixed with many dendritic melanocytes. Melanin granules were present within the melanocytes and tumor cells. Although similar tumors have been reported in other sites, this is the first report to our knowledge of a pigmented squamous cell carcinoma of the uterine cervix.     

Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system.

Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.     

Effect of allocating attention to aversive events on cardiovascular responses and event-related potentials in a dual-task paradigm.

This study investigated the effect of the allocation of attentional resources on event-related potentials (ERPs) and cardiovascular responses during a dual-task situation in which an avoidance task and a reward task were coupled. For the avoidance task, subjects were able to avoid an aversive shock that followed a target tone by pressing a button. For the reward task, subjects were asked to detect the direction of an arrowhead presented on the display screen and were rewarded for rapid, accurate reaction times. The 31 participants were divided into two groups based on their subjective impression of attention distribution between the avoidance and the reward task. Participants in the first group were motivated more by the avoidance task (AVD; n=18), whereas those in the second group were motivated more by the reward task (RWD; n=13). The ERPs to non-target and target tones, ECG, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed in the dual-task situation. The results indicated that the amplitudes of N1 to target and non-target tones, and of N2 to the target tone were larger in the avoidance (AVD) group than they were in the reward (RWD) group. The AVD group had higher blood pressure than did the RWD group during the aversive periods. However, there were no significant group differences in the mean RTs for avoidance and reward tasks, and participants in both groups reported similar subjective evaluations of their mental workloads. The results suggest a vigilant coping strategy that selectively focus attention to threatening information as illustrated by N1 and N2 changes may intensify psychophysiological arousal under stress.