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The authors conducted a study on children undergoing treatment at major school refusal treatment centers in Hiroshima Prefecture. On the whole, school refusal in the prefecture was found to peak between 13 and 14 years of age. By age group, the main reason for school refusal in elementary school group was parent-child relationship with separation anxiety. Given additional problems such as neglect at home and complicated social situations in their schools, junior high school students were found to present diverse symptoms from introversion and self-analysis to extroversion, neglect of studies, and delinquency. Among high school students, there were more cases suffering withdrawal and schizophrenia spectrum disorders. The major task regarding treatment seems to lie in how to treat complex cases combining different problems. We summarized herein the studies we have carried out and propose a model for a network therapy system based on functional liaisons between treatment centers. With this system, a child psychiatric medical facility plays the part of a liaison center for the overall network system.

We compared the thin-section CT findings of 11 intrapulmonary lymph nodes with pathological findings and evaluated the possibility of CT scan differential diagnosis from pulmonary metastatic nodules. First, we retrospectively reviewed CT scan and pathological findings of intrapulmonary lymph nodes. The median size of these nodules was 6.2 mm. The nodules appeared round (n=3) or angular (n=8) in shape with a sharp border, and they were found below the level of the carina. The median distance from the nearest pleural surface was 4.6 mm, and 3 of the 11 nodules were attached to the pleura. On thin-section CT scan, linear densities extending from the intrapulmonary lymph nodes were frequently visualized, and were pathologically proven to be ectatic lymphoid channels. We then compared the thin-section CT findings of 8 metastatic nodules less than 1 cm in diameter with those of the 11 intrapulmonary lymph nodes. The median size of these nodules was 6.8 mm, and the median distance from the nearest pleural surface was 16 mm. All nodules appeared round in shape. None of the nodules had linear densities extending from the nodules. The linear densities on thin-section CT scan may be the most useful characteristic of intrapulmonary lymph nodes, when differential diagnosis from metastatic nodules is necessary.

To elucidate the mechanism by which hyperbaric oxygen (HBO2) induces electrical discharge, changes in the extracellular concentrations of GABA and glutamate were measured every 5 min using a microdialysis technique in rats during a period of exposure to HBO2 (5 atm abs). Electrical discharge was observed at 28 +/- 4 min after the onset of exposure. Though the extracellular concentrations of glutamate remained unchanged, the extracellular GABA concentrations (pre-exposure level, 0.026 +/- 0.005 microM in dialysate) began to decrease 15 min after the onset of exposure and reached their lowest level (74 +/- 14%, 0.019 +/- 0.004 microM) at the time of appearance of the discharge. There was a close logistic relationship between extracellular GABA concentrations and the discharge incidence, and the extracellular concentrations of GABA causing electrical discharge in 50% of the animals were estimated to be 80% of the pre-exposure level. These results suggest a possible mechanism that HBO2 exposure-induced discharge is caused by the decrease in extracellular concentration of GABA.

Sneddon's syndrome is characterized by livedo reticularis and cerebrovascular lesions. We report the cases of women (mean age, 36.2 +/- 8.1 years) diagnosed with Sneddon's syndrome based on the presence of livedo reticularis and characteristic cerebrovascular findings. Seven of these patients had cerebral infarcts on cranial computed tomography scan. Antiphospholipid antibodies were positive in 6 of these cases. Three cases had abnormal levels of antithrombin III. Analyses of chromosome 6 revealed no abnormalities. In 3 of the cases, investigation of the pedigrees revealed autosomal dominant traits. Two cases had epilepsy, and 3 had migraine. One case with migraine also had myasthenia gravis. In addition, we detected inferior altudinal hemianopia in 2 cases, cognitive functional disorder in 3 and depression in 2. Based on these findings, the entire vascular, haematologic, neurologic, and dermatologic systems should be evaluated in patients diagnosed with Sneddon's syndrome.

Rheumatoid arthritis (RA) is often associated with deformities of the feet, and foot pain often arises in the talonavicular joint of patients with RA. The object of this study was to assess the relationship between magnetic resonance imaging (MRI) findings of the talonavicular joint and walking ability. The subjects were 35 RA patients (10 feet in 5 males and 56 feet in 30 females) aged 34-87 years (mean: 70 years +/- 12.1), with a disease duration from 1-54 years (mean: 14 years +/- 12.1). MRI findings were classified as follows: Grade 1, almost normal; Grade 2, early articular destruction; Grade 3, moderate articular destruction; Grade 4, severe articular destruction; and Grade 5, bony ankylosis dislocation. Walking ability was classified into one of 9 categories ranging from normal gait to bedridden status according to the system of Fujibayashi. As the grade of MRI images became higher the walking ability decreased, and these parameters showed a correlation by Spearman's rank correlation coefficient analysis (P = 0.003). Thus, in the present cohort group of patients with RA, the deterioration of walking ability increased with the severity of destruction of the talonavicular joint.

We studied the differentiation of thyroid nodules using fine-needle aspiration biopsy (FNA) and Tl-201 scintigraphy quantitative analysis. One-hundred and thirty-one thyroid nodules were examined: 83 follicular lesions (58 benign and 25 malignant lesions) and 48 non-follicular lesions (8 benign and 40 malignant lesions). During Tl-201 scintigraphy examinations, an early and a delayed image were acquired 10 and 120 min after an intravenous injection, respectively. The T/N ratio (counts of nodular lesion/counts of contralateral normal thyroid tissue) of each image was calculated quantitatively. We assessed the ability of the Tl-201 scintigraphy and of the FNA analysis to differentiate benign and malignant lesions and determined the cut-off levels for the assays. For the follicular lesions, the area under the ROC (Receiver Operating Characteristic) curve (Az) for the Tl-201 scintigraphy data was greater than that for the FNA data. For the non-follicular lesions, the Az for the FNA data was greater than that for the Tl-201 scintigraphy data. We set cut-off levels at 1.370 for follicular lesions, and 1.070 for non-follicular lesions. The sensitivity and specificity were 76% and 82.7% for follicular lesions, and 90% and 87.5% for non-follicular lesions, respectively. The overall accuracy of the analysis was 84.0%.

Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.

A 34-year-old woman was admitted to our emergency room with a high fever, abdominal pain, dyspnea and confusion. High fever and abdominal pain had first occured after a cystocele operation 5 months earlier. Later, congestive heart failure with mural thrombus formation, peripheral polyneuropathy and ischemic cerebrovascular accident were identified in clinical follow-ups, and multiple arterial and venous thromboses were seen on cranial and abdominal magnetic resonance imaging angiography. The patient's symptoms improved with anticoagulant treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG levels was diagnosed, and ischemic peripheral polyneuropathy with axonal degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome, elevated anticardiolipin antibodies appear to be the most common acquired blood protein defect causing thrombosis. Disseminated vascular thrombosis in catastrophic antiphospholipid syndrome can result in multiorgan failure with increased morbidity and mortality. It rarely occurs secondary to various infections as in the case of our patient, who suffered postoperative intraabdominal infection. It is important to note that peripheral nervous system involvement is rare in antiphospholipid syndrome.

To clarify the incidence, background, and progress of hepatic infarction following interventional procedures, cases of hepatic infarction following interventional procedures at our department during the last decade were identified by reviewing the clinical records of 1982 abdominal angiography and interventional procedures and records of abdominal CT. Nine episodes (0.5%) in 8 patients were identified as hepatic infarction following an interventional procedure. Five episodes were preceded by embolization of the hepatic or celiac artery at emergency angiography for postoperative bleeding with hemorrhagic shock. Three episodes followed the elected interventional procedure for hepatocellular carcinoma, and the remaining episode occurred after 12 months of chemoinfusion through an indwelling catheter in the hepatic artery and portal vein. Hepatic arterial occlusion in all episodes and portal venous flow abnormality in 5 episodes were observed on angiography. Four patients whose liver function was initially impaired died of hepatic infarction, although the extent of the disease on CT did not appear to be related to the mortality. Multiple risk factors, including arterial insufficiency, were observed in each patient. The incidence of hepatic infarction following interventional procedures in this series was low but sometimes fatal, and occurred most frequently in emergency embolization in hemorrhagic shock.

Brugada syndrome is increasingly being recognized in clinical medicine. What started as an electrocardiographic curiosity has become an important focus of attention for individuals working in the different disciplines related to sudden cardiac death, from basic scientists to clinical cardiac electrophysiologists. In just 12 years, since the description of the disease, clinically relevant information is continuously being provided to physicians to help protect the individuals with Brugada syndrome to the best of our ability. And this information has been gathered thanks to the effort of hundreds of basic scientists, physicians and patients who continue to give their time, effort and data to help understand how the electrocardiographic pattern may cause sudden cardiac death. There are still many unanswered questions, both at the clinical and basic field. However, with the further collection of data, the longer follow-up and the continued interest from the basic science world we will have the necessary tools to the successful unraveling of the disease.

We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.

We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

Because of the many superficial similarities between the immune system and the central nervous system, it has long been speculated that somatic DNA recombination is, like the immune system, involved in brain development and function. To examine whether or not the V(D)J recombination signals of the immune system work in an in vitro neural differentiation model, the P19 mouse embryonal carcinoma cell line was transfected with a reporter gene that is designed, when rearranged, to express bacterial beta-galactosidase, which was previously reported to exhibit somatic DNA recombination in the transgenic mouse brain. The cloned cells were then induced into neural cells by retinoic acid treatment. This neural induction treatment resulted in the cloning of a P19 cell line that showed a high incidence of beta-galactosidase-positive cells. Most of these beta-galactosidase-positive cells were immunocytochemically identified as either neurons, neuroepithelial cells, or astrocytes. The 5'-end sequences of the beta-galactosidase transcripts expressed in the induced cells were analyzed, and sequences were found that seemed to reflect DNA rearrangement through re-integration of the reporter gene into the host genome. However, the V(D)J recombination signals did not work in the in vitro model. These results suggested that DNA rearrangement activity though integration increased during neural differentiation of P19 cells.

Staphylococci have been confirmed to form biofilms on various biomaterials. The purpose of this study was to investigate biofilm formation among methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with urinary tract infection (UTI) and to assess the relationship between biofilm-forming capacities and virulence determinants/clinical background. Over a 12-year period from 1990 through 2001, a total of 109 MRSA isolates were collected from patients (one isolate per patient) with UTI at the urology ward of Okayama University Hospital. We used the in vitro microtiter plate assay to quantify biofilm formation. We then investigated the presence of several virulence determinants by polymerase chain reaction assay and found eight determinants (tst, sec, hla, hlb, fnbA, clfA, icaA, and agrII) to be predominant among these isolates. Enhanced biofilm formation was confirmed in hla-, hlb-, and fnbA-positive MRSA isolates, both individually and in combination. Upon review of the associated medical records, we concluded that the biofilm-forming capacities of MRSA isolates from catheter-related cases were significantly greater than those from catheter-unrelated cases. The percentage of hla-, hlb-, and fnbA-positive isolates was higher among MRSA isolates from catheter-related cases than those from catheter-unrelated cases. Our studies suggest that MRSA colonization and infection of the urinary tract may be promoted by hla, hlb, and fnbA gene products.

Epstein-Barr virus (EBV), or human herpesvirus 4 (HHV-4), infects the vast majority of adults worldwide, and establishes both nonproductive (latent) and productive (lytic) infections. Host immune responses directed against both the lytic and latent cycle-associated EBV antigens induce a diversity of clinical symptoms in patients with chronic active EBV infections who usually contain an oligoclonal pool of EBV-infected lymphocyte subsets in their blood. Episomal EBV genes in the latent infection utilize an array of evasion strategies from host immune responses: the minimized expression of EBV antigens targeted by host cytotoxic T lymphocytes (CTLs), the down-regulation of cell adhesion molecule expression, and the release of virokines to inhibit the host CTLs. The oncogenic role of latent EBV infection is not yet fully understood, but latent membrane proteins (LMPs) expressed during the latency cycle have essential biological properties leading to cellular gene expression and immortalization, and EBV-encoded gene products such as viral interleukin-10 (vIL-10) and bcl-2 homologue function to survive the EBV-infected cells. The subsequent oncogenic DNA damage may lead to the development of neoplasms. EBV-associated NK/T cell lymphoproliferative disorders are prevalent in Asia, but quite rare in Western countries. The genetic immunological background, therefore, is closely linked to the development of EBV-associated neoplasms.

FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.

Muscle power in the lower extremities and body sway were measured in 57 healthy young women volunteers in their 20's. Body sway was measured with a stabilimeter for 30 sec during two-leg standing, and for 10 sec during one-leg standing with the eyes open or closed, alternating between right and left legs (5 times each). The measured parameters of body sway were locus length per time unit, locus length per environmental area, environmental area, rectangle area, root mean square area, and the ratio of sway with eyes closed to sway with eyes open. Knee flexor and extensor power and toe flexor and abductor power were the measures representing lower extremity muscle power. The increase in sway with the eyes closed was more marked during one-leg standing than two-leg standing, as expected. We found that 36 of 57 subjects (62%) were unable to maintain one-leg standing with their eyes closed, and this failure correlated with marked body sway (P = 0.0086). Many subjects had one leg that was classified as stable and the other leg classified as unstable. Clearly, testing of both legs alternately with eyes closed is necessary to measure the full range of sway in subjects. Lower extremity muscle power did not appear to be the dominant factor in maintaining balance in these young subjects.

Protein transduction therapy using poly-arginine peptide can deliver the biologically active proteins. A previous study showed that 11 poly-arginine fused p53 protein (11R-p53) effectively penetrated across the plasma membrane and inhibited the proliferation of oral cancer cells. However, the intracellular half-life of the delivered protein was less than 36 h. Previous studies also showed that 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite, induces the stabilization of the wild-type p53 protein in human cancer cells posttranscriptionally. In the present study, we examined whether 2-ME induced the stabilization of 11R-p53 and had an inhibitory effect on the proliferation of oral cancer cells. The application of 2-ME significantly enhanced the inhibitory effect of 11R-p53 on the proliferation of oral cancer cells. However, 2-ME had no effect on the intracellular half-life of 11R-p53 in oral cancer cells. Of interest is the finding that 2-ME suppressed the transcriptional activity of NFkappaB, which has an important role in tumorigenesis, but did not affect p53 transcriptional activity. These results suggest that 2-ME synergistically enhances the 11R-p53-induced inhibition of the proliferation of oral cancer cells through the suppression of NFkB transcription.

A 68-year-old Japanese man with a history of linitis plastica carcinoma of the stomach and subsequent gastrectomy 8 years previously presented with lower abdominal pain. Radiological and endoscopic examinations showed multiple submucosal nodular lesions similar to Crohn's disease in the ileocecal area. A firm diagnosis could not be made after initial multiple biopsies. Finally, a submucosal biopsy revealed adenocarcinoma. The ileocecal lesion was diagnosed as a recurrence because of the histological findings, which included mucosal preservation, a similarity with the histologic type of stomach carcinoma, and atypical immunoreactivity for primary colon carcinoma; the lesion was negative for both cytokeratin 7 and cytokeratin 20. In cases where metastatic carcinoma of the colon is suspected, we recommend early consideration of a submucosal biopsy.

Ureteroscopy has evolved in many aspects, particularly in the flexibility and size of ureteroscopes. We have developed a new detachable access sheath to make ureteroscopic procedures more straight-forward and to reduce possible damage to delicate instruments used in the procedure.