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To identify ARIX gene and PHOX2B gene polymorphisms in patients with congenital superior oblique muscle palsy, 3 exons of the ARIX gene and PHOX2B gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 31 patients with congenital superior oblique muscle palsy and in 54 normal individuals. A family with a father and one daughter each having congenital superior oblique muscle palsy was also included in this study. Eleven patients with congenital superior oblique muscle palsy had heterozygous nucleotide changes in the ARIX gene, including 4 patients reported on previously. One patient with atrophy of the superior oblique muscle had a new change of T-4G in the promoter region of the ARIX gene. The other 6 patients had a heterozygous nucleotide change of G153A in the 5'-untranslated region (UTR) of the exon 1 of the ARIX gene. These nucleotide changes of the ARIX gene, taken together, had a significant association with congenital superior oblique muscle palsy(P = 0.0022). One patient and 5 patients had heterozygous nucleotide changes of A1106 C and A1121 C in exon 3 of the PHOX2B gene, respectively, while these changes were absent in the normal individuals. Two patients had both the G153A change in the 5'-UTR of exon 1 of the ARIX gene and the A1121 C change in exon 3 of the PHOX2B gene. In conclusion, the polymorphisms of the ARIX gene and PHOX2B gene may be genetic risk factors for the development of congenital superior oblique muscle palsy.

The purpose of this study was to evaluate the outcomes for out-of-hospital cardiac arrest (OHCA) and cardiopulmonary resuscitation (CPR) in the city of Okayama, Japan, during a 1-year period after the reorganization of defibrillation by Emergency Life-Saving Technicians (ELSTs) with standing orders of CPR. The data were collected prospectively according to an Utstein style between June 1, 2003 and May 31, 2004; OHCA was confirmed in 363 patients. Cardiac arrest of presumed cardiac etiology (179) was witnessed by a bystander in 62 (34.6%) cases. Of this group, ventricular fibrillation (VF) was documented in 20 cases (32.3%), and 1 patient (5%) was discharged alive without severe neurological disability. This outcome is average in Japan, but it is quite low level compared with Western countries because there is less VF in Japan. The Utstein style revealed that we must try to detect VF before the rhythm changes and to provide defibrillation as soon as possible in order to improve outcomes. Further research will be required to accurately evaluate OHCA in Okayama city.

We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications.

We report herein a unique, previously unreported, successful outcome for a patient untreated for a tumor affecting a femoral neck considered as painless osteoid osteoma. The lesion was detected by chance at examination for groin injury. Diagnosis was based on the plain radiography, bone scan, and computed tomography. The results of the full blood examination were normal. Neither pharmacomedical nor surgical treatments were given. Two years later, radiological resolution of the lesion was revealed. The patient was observed between 1995 and 2002. We conclude that painless osteoid osteoma should be included in the differential diagnosis of asymptomatic femoral neck lesions. Our case suggests that osteoid osteoma has a tendency to regress over time and that conservative management appears to be a reliable option.

This study focused on the effects of different intervals between sessions of a hypercholesterolemia education class on post-intervention outcomes. The same comprehensive group-programme contents on hypercholesterolemia were delivered either monthly (for 6 months) or twice-monthly (for 3 months) by the same teaching professionals in a community setting. The twice-monthly programme included 46 participants (male/female = 7/39, average age: 65.8 years)and the monthly programme consisted of 48(male/female = 9/39, age: 66.4). At the beginning of the study, all subjects belonged to the 'contemplation' stage of diet and exercise habits within the Transtheoretical Model of Change. The stage-matched intervention helped many participants move to the 'action ' stage by 6 months after the last session, especially in the twice-monthly group. The change rate of exercise from the 'contemplation' stage to the 'action' stage was significantly higher in the twice-monthly group (76.1 percent) than in the monthly (54.2 percent ). In both monthly and twice-monthly formats, participants' satisfaction and understanding levels at the end of the programme were high, but were significantly higher in the twice-monthly group. Through favorable lifestyles and higher levels of satisfaction and learning, the twice-monthly format may produce more positive results in cholesterol management than the monthly format, as the shorter period of time makes the programme more intensive.

Epstein-Barr virus (EBV) is usually maintained in an asymptomatic and latent form by the host immune system, and primarily by EBV-specific cytotoxic T cells (CTLs). However, EBV has been linked to several refractory diseases such as EBV-associated hemophagocytic syndrome(EBV-AHS) and chronic active EBV infection (CAEBV). In these ectopic diseases, EBV infects T/NK cells, causing severe immunodeficiency with a very high EBV load. In recent years, the laboratory procedure to assess these types of EBV infections has been improved. In particular, real-time polymerase chain reaction (PCR) has been used to quantify the EBV load, and the MHC: peptide tetramer assay has been used to quantitate EBV-specific CTLs; these tests have been employed for the management of the illnesses associated with EBV infection. Here, we have reviewed the recent progress in the clinical application of these assays. The pathogenesis of EBV-infected T/NK cells, and the host immune response to infection, including the roles carried out by innate immunity and inflammatory cytokines, are likely to be revealed in the future.

Oridonin, an active component isolated from Rabdosia rubescences, has been reported to have antitumor effects. In this study, we compared the signal transduction pathways between TNFalpha-and oridonin-induced L929 cell death. Oridonin and TNFalpha initiated apoptotic morphologic changes, but DNA fragmentation was found in TNFalpha-treated L929 cells but not in oridonin-treated ones. The pan-caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk) augmented oridonin-and TNFalpha-induced cell death. However, the caspase-9 inhibitor (z-LEHD-fmk) only increased oridonin-induced L929 cell death. Moreover, poly (ADPribose) polymerase (PARP) was cleaved in oridonin-treated L929 cells but not in the TNFalpha-treated groups, and the caspase-3 inhibitor (z-DEVD-fmk) failed to inhibit PARP cleavage. These results showed that only oridonin-induced L929 cell death required PARP degradation in a caspase-3 independent manner. In addition, oridonin increased the ratio of Bax/Bcl-2 protein expression, but TNFalpha did not. TNFalpha induced p38 and ERK activation, whereas oridonin triggered only ERK activation. We also investigated the effect of oridonin on intracellular TNFalpha expression, and found that oridonin augmented endogenous pro-TNFalpha expression and its upstream protein IkB phosphorylation. These results indicated that although oridonin promoted endogenous pro-TNFalpha expression, a great difference existed between the signal pathways through which TNFalpha-and oridonin-induced cell death.

We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's augmentation of TNFalpha-induced L929 cell death and found this mechanism differs from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929 cells as measured by an agarose gel electrophoresis and lactate dehydrogenase(LDH)activity based assay. Mitochondrial permeability transition (MPT) inhibitor (cyclosporine A) effectively inhibited z-VAD-fmk-augmented cell death. In addition, z-VAD-fmk plus TNFalpha increased Bax expression without affecting Bcl-2 and cytochrome expression. Western-blot analysis showed that z-VAD-fmk plus TNFalpha caused persistent JNK activation and ERK inactivation. Poly(ADP-ribose) polymerase (PARP) inhibitor (DPQ) effectively reversed the cell death which was augmented by z-VAD-fmk, and z-VAD-fmk plus TNFalpha also caused PARP cleavage to an 85 KDa fragment. These results indicate that in the presence of TNFalpha, z-VAD-fmk further augments cell death which requires the mitochondrial permeability transition and the JNK activation. However, we did not detect the changes in cytochrome c expression and the participation of caspase-9 in this process, suggesting that there might exist an unknown signal pathway(s) from the mitochondria to the downstream protein PARP, which is cleaved in a caspase-independent manner.

In recent years, the results of some studies have revealed the possible potential role of several infectious agents in the inflammatory mechanism of atherosclerosis. The detection of specific antibodies against microorganisms such as and as well as Chlamydia pneumoniae and cytomegalovirus as well as antibodies directed to heat shock proteins in the sera of atherosclerotic patients and the presence of genomic material in atheromatous plaques all provide evidence supporting the presumptive role of infectious agents in atherosclerosis. There are some findings that can be accepted as clues for the possible involvement of Mycobacterium tuberculosis in atherosclerosis. These consist of the presence of high levels of mycobacterial heat shock protein 65 in atherosclerotic patients, and in animal studies, the detection of atherosclerotic changes in the vascular wall of animals vaccinated with recombinant heat shock protein 65, and Mycobacterium tuberculosis containing heat shock protein 65. The probable proatherogenic effect of the specific immune response to BCG-associated heat shock protein was also suggested. The mycobacterium cell wall contains a phospholipid, phosphatidylinositol, which was shown to have a procoagulant effect similar to that of a cytomegalovirus possessing phosphatidylserine, another phospholipid showing a procoagulant effect. These data suggest that Mycobacterium tuberculosis may also be involved in the pathogenesis of atherosclerosis.

An unusual case is described in which an abdominal wall and thigh abscess was an initial symptom of ascending colon cancer. A 76-year-old woman was referred to our hospital for investigation of fever and abdominal and thigh swelling. Computed tomography revealed a right abdominal wall, retroperitoneal, psoas and thigh abscess formation suspected to be caused by colon perforation. Due to the patient's poor general condition, local drainage of the abscess was performed on the following day of hospitalization. Histological examination of necrotic tissues removed form the retroperitoneal cavity demonstrated adenocarcinoma of the colon. The patient subsequently underwent right hemicolectomy with lymph nodal dissection after 19 days of the drainage procedure and was transferred to another hospital on the 49th day following the second surgery.

We report on 64 patients who did not achieve erections adequate for satisfactory sexual intercourse from among a total of 243 patients who were prescribed PDE5 inhibitors for erectile dysfunction (ED). Intracavernous injection (ICI) of PGE was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE1 in 1 ml saline was performed and the responses evaluated. Forty-nine out of 64 (77 percent ) cases responded to 20 mcg of PGE1. Forty mcg of PGE was injected into the 15 non-responding cases, and 9 patients responded favorably. The overall effective rate was 58/64 (91 percent ). No major adverse effects were observed.

We describe a novel method for immunofluorescent detection of multiple antigens in a single paraffin-embedded tissue section. We hypothesized that if fluorescent dyes are resistant to heat treatment, then thermal inactivation of immunoglobulins during antigen detection procedures might make it possible to use multicolor immunofluorescence detection even if the primary antibodies are from the same species. We found that several fluorescent dyes, including fluorescein isothiocyanate (FITC), Cy3 and Cy5, were resistant to heating at 90 degrees Celsius for 15 min, whereas the antigenicities of the primary antibodies were lost completely. This novel method, which uses heat treatment between staining steps, has great advantages for multicolor immunofluorescence because unlabeled primary antibodies from the same species can be used. Therefore, by using this method not only 3 unlabeled mouse monoclonal antibodies but also 3 unlabeled rabbit antisera can be used as primary antibodies for multicolor immunofluorescence.

A 67-year-old male visited his physician because of a 2-month history of cough and sputum. An abnormal shadow at the left upper mediastinum on chest x-ray film was detected, and the patient was referred to our department for further examination. Chest x-ray film revealed a round shadow at the left upper posterior mediastinum. Computed tomography(CT)revealed a uniform iso density mass about 4 cm in diameter, with a well-defined border. After the intravenous contrast administration, a slight peripheral enhancement was seen around the mass. On magnetic resonance imaging, the mass was hypointense in T1-weighting and hyperintense in T2-weighting. The contrast pattern was the same as that observed in the CT scan. On sagittal and coronal sections, the mass was adjacent to the aortic arch. Although a benign tumor was mostly suspected based on imaging findings, a malignant tumor was also possible. Accordingly, we resected this mass with video-assisted thoracoscopy. Findings at operation were a cystic mass. The pathological findings were compatible with benign parathyroid cyst, which was suspected to be the cystic degeneration of a parathyroid adenoma.

The nuclear matrix is an operationally defined nuclear skeletal structure that is believed to be involved in many nuclear functions including DNA replication, transcription, repair, and prem RNA processing/transport. Until relatively recently, the nuclear matrix was thought to be a rigid and static structure, but it is now thought to be dynamic. This paradigm shift was based in part on the tracking of the intranuclear movement of proteins tagged with fluorochromes. In this review, we attempt to redefine the nuclear matrix in light of recent findings and describe some useful techniques for the dynamic analysis of nuclear function.

Changes in brain vascularity in adult rats during adaptation to chronic normobaric hypoxia with or without elevated CO(2) were morphometrically investigated. Immunohistochemistry with anti-rat endothelial cell antigen (RECA-1) antibody was carried out for the vascular analysis. After the rats were subjected to hypoxia for 2 to 8 weeks (wks)(10 percent O(2) in N(2)), the total area of blood vessels was measured in 6 brain regions. After 2 wks of hypoxia, the blood vessel area was found to be significantly increased in the frontal cortex, striatum, hippocampus, thalamus, cerebellum, and medulla oblongata, by 44% , 96% , 65% , 50% , 102% and 97% , respectively. The ratio of large vessels with an area > 500 micro m(2) was also increased in all brain regions. Hypoxic adaptation in brain vascularity did not change during 8 wks of hypoxia, and the hypoxia-induced levels measured in the vasculature returned to control levels 2 wks after the termination of hypoxia in areas of the brain other than the cortex and thalamus. In addition, hypoxia-induced changes in terms of the total vascular area and vessel size distribution were significantly inhibited by the elevation in CO(2), whereas chronic hypercapnia without hypoxia had no effect on brain vascularity. These findings suggested that adaptations in brain vascularity in response to hypoxia are rapidly induced, and there are regional differences in the reversibility of such vascular changes. Carbon dioxide is a potent suppressor of hypoxia-induced vascular changes, and may play an important role in vascular remodeling during the process of adaptation to chronic hypoxia.

Macrophages and microglia are implicated in spinal cord injury, but their precise role is not clear. In the present study, activation of these cells was examined in a spinal cord injury model using 2 different antibodies against ED1 clone and ionized calcium binding adaptor molecule 1 (Iba1). Activation was observed at 1, 4, 8, and 12 weeks after contusion injury and was compared with sham operated controls. Our results indicate that activation could be observed in both the dorsal funiculus and the ventral white matter area in the spinal cord at 5 mm rostral to the epicenter of injury. For both cells, there was a gradual increase in activation from 1-4 weeks, followed by down-regulation for up to 12 weeks. As a result, we could stain macrophages by ED1 and microglia by Iba1. We concluded that macrophages may play a role in the phagocytosis of denatured dendrites after spinal cord injury, while microglia may have some cooperative functions, as they were found scattered near the macrophages.

Primary aorto-enteric fistula (PAEF)is a serious complication of abdominal aortic aneurysm(AAA). We report a patient with PAEF associated with inflammatory AAA who underwent emergent surgery. A 52-year-old male presented with recurrent hematemesis. A computer tomography scan showed a sealed rupture of the AAA adjacent to the duodenum. At surgery, a coin-sized PAEF was noted. The aorta was replaced with a Dacron graft in situ . Histological examination revealed the characteristics of an inflammatory AAA. The postoperative course was uneventful, and there has been no evidence of infection during a follow-up period of 3 years. We discuss the etiologic and surgical considerations regarding this unusual entity.

The effects of irradiation on different cell compartments in the submandibular gland were analyzed in adult C57BL/6 mice exposed to X-ray irradiation and followed up for 10 days. Apoptosis was quantified using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling method (TUNEL). Cell proliferation was detected using immunohistochemistry for proliferating cell nuclear antigen (PCNA). Radiation-induced apoptosis occurred rapidly, reaching a maximum 3 days post-irradiation. The percentage of apoptotic cells increased with the irradiation dose. At day 1 post-irradiation, cell proliferation was significantly reduced in comparison to sham-irradiated controls. After post-irradiation arrest of the cell cycle, proliferation increased in all gland compartments, reaching a maximum at day 6 post-irradiation. The proliferation response corresponded to the dose of irradiation. We suggest that the reason for gland dysfunction could be the coexistence of high apoptotic and proliferative activity in the irradiated gland.

To determine the characteristic curve of the radiographic screen/film systems in a short focal spot-film distance, the inverse square sensitometric method was modified by changing the radiation intensity with two kinds of filters. The characteristic curves obtained in the two exposure series with these two kinds of filters were overlapped to obtain a complete one. The characteristic curve thus obtained was almost the same as the one obtained by the original inverse square sensitometric method. The accuracy of the characteristic curves obtained by the modified method was well-reflected in the clinical radiographs.

Twenty-five patients with intractable asthma had swimming training in a hot spring pool for 3 months. The subjects were divided into three groups according to their clinical symptoms and ages. Changes of ventilatory function during swimming training were observed in in each group. The ventilatory function test revealed that free swimming training in a hot spring pool for 30 min did not induce bronchoconstriction in any of the groups. The values of ventilatory parameters such as FEV 1.0%, %PEFR, %V50 and %V25 were improved after the 3-month swimming training. The improvement of ventilatory parameters, especially %MMF, %V50 and %V25, by the training was most remarkable in the type II asthma group. The percent increase in %MMF, %V50 and %V25 was highest in patients more than 61 years of age, and higher in patients aged 40 to 60 years than in younger patients.