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We explored the effectiveness of loxoprofen sodium (loxoprofen), which is the most common non-steroidal anti-inflammatory drug (NSAID) in Japan, for patients with benign prostatic hyperplasia (BPH) complaining of nocturia. A total of 93 BPH patients aged 49-84 years were enrolled in the study. These patients had received standard drug therapy with alpha1-blocker for BPH, followed by anticholinergic drugs, hypnotics, tricyclic antidepressants, and/or antiduretic hormone, but they still complained about 2 or more episodes of nocturia. They each took a single 60-mg tablet of loxoprofen prior to sleeping at night for 14 days in addition to their BPH treatments. The effects were assessed by questionnaire before and after treatment as excellent (nocturia disappeared or decreased by 2 or more voids/night), improved (nocturia decreased by 1 void/night), unchanged, or worsened (nocturia increased). Nocturia improved or disappeared in 74.2% of patients: excellent, improved, unchanged, and worsened results were obtained in 37.6%, 36.6%, 21.5%, and 4.3% of patients, respectively. The effects were better in patients whose baseline nocturia was > 2 times than in those with a lesser frequency at enrollment (P = 0.04). Loxoprofen can be an effective and useful treatment option for patients with BPH complaining of refractory nocturia.

Pressure distribution patterns of the seating interface on the multi-cell air cushion (ROHO High Profile) of 36 adults with spinal cord injury (SCI) (Neurological level Th3 -L1) were measured at different air pressure levels by a pressure mat measurement system. Stress distribution relative to the inflated air pressure in the air cushion on the patients' wheelchairs was analyzed to determine the appropriate inflated air pressure of the cushion for patients. The maximum pressure points in all subjects were at the areas of the ischial tuberosities (82 to 347 mmHg). The optimal reduction in interface pressure at the ischial tuberosities was obtained just before bottoming out. The cushion air pressure at that point was between 17 and 42 mmHg, and correlated well to body weight (r = 0.495, P = 0.0021). In contrast, the maximum pressure levels did not correlate to body weight or the Body Mass Index (BMI). Pressure at the ischial area could be reduced, but not eliminated, by adjusting the air pressure. The maximum pressure levels seemed to be related to the shape of the buttocks, especially the amount of soft tissue, and exceeded the defined threshold for pressure ulcers (> 80 g/cm2).

Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin, and hemoglobin itself, are associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been demonstrated to be involved in the mechanism of seizures induced by iron ions in the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS are responsible for the induction for peroxidation of neural lipids, i.e., an injury of neuronal membranes, and also could induce disorders in the excitatory and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent the epileptogenic focus formation, or to attenuate seizure activities in the iron-injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate, adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic discharge in the iron-injected rat brain.

Hepatocyte growth factor (HGF) is a multifunctional factor implicated in tissue regeneration, wound healing, and angiogenesis. HGF was initially thought to be liver-specific, but it has become clear that HGF acts on alveolar type II cells and bronchial epithelial cells. This study was conducted to determine the role of HGF in pulmonary ischemia in a rat model. The first increase of the plasma HGF level was noted 30 min after pulmonary ischemia, and reached a peak at 12 h. Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) revealed that the HGF messenger RNA (mRNA) expression in the injured left lung was markedly increased at 1, 6, and 12 h after pulmonary ischemia (P < 0.05). The interleukin-1beta (IL-1beta) mRNA expression, one of the inflammatory cytokines which induces HGF expression, was markedly increased at 1 h in the injured left lung (P = 0.0007). Therefore, we considered that HGF might be mainly induced by paracrine mechanisms in pulmonary ischemia. In conclusion, we have shown that the expression of HGF was induced in pulmonary ischemia, and may be a useful biological marker for the early diagnosis.

We retrospectively evaluated the subjective and objective treatment results of transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH) and explored the difference in effectiveness between 30- and 60-min single treatments. From June 1997 through March 2003, 58 men with BPH underwent TUMT using the Targis device. Twenty-seven and 31 patients each received a single treatment of 60 or 30 min, respectively. Evaluations after treatment included a clinical determination of the International Prostate Symptom Score, urodynamic assessments by peak flow rate, and magnetic resonance imaging (MRI). In the 60-min treatment, the symptom score improved significantly, from 17.9 to 9.5 after 2 months. Similarly, there was a significant improvement in peak flow rate, from 6.7 to 11.2 ml/sec after 2 months. In the 30-min treatment, the symptom score also improved significantly, from 18.4 to 13.4 after 2 weeks. Similarly, there was a significant improvement in the peak flow rate, from 6.4 to 11.7 ml/sec after 1 month. MRI imaging showed necrosis of the prostate gland 2 weeks after either treatment. These results demonstrated that both the 60-min and the 30-min treatments were effective for patients with BPH. Moreover, the 30-min treatment led to quicker improvement than the 60-min treatment. Thus, a 30-min TUMT protocol is considered recommendable for this treatment.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.

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.

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.

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.

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.

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.

Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.

Sera from 84 patients with chronic liver disease [CLD] (74 chronic active) and from 53 blood donors were tested immunochemically for anti-liver cell membrane antibody (LMAb). LMAb to rat liver tested by an indirect immunofluorescent technique was positive in 53.3% of CLD patients with positive HB surface antibody (HBsAb) and 40.0% of HBsAb positive blood donors. Pepsin digestion of the sera indicated that the binding between liver cell membrane and IgG was at the Fc site on the immunoglobulin. The sera with positive LMAb from HBsAb positive blood donors had elevated Clq-binding activity (Clq-BA). The LMAb to rat liver was a macro-molecular IgG (19-22S IgG) when assayed by Sephadex G-200 column chromatography and 5-40% sucrose density gradient ultracentrifugation. The results suggest that the LMAb in serum from a patient with chronic active liver disease may be an immune complex which consists of various antigens such as HB virus and its antibodies in serum.

The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment.

Fifteen cases of keratoconjunctivitis sicca (KCS) of unknown etiology were treated with soft contact lenses for the purpose of their bandage effects and moisuture supply. A soft contact lens was worn on one of the eyes of each case but not on the other to compare its effectiveness. New opthalmic drops or contact lens wearers were dropped in both eyes. Furthermore, the KCS-index was worked out on the basis of the complaints of 23 patients of KCS of unknouwn etiology. The indexes before and after treatment were compared. Corneal objective findings were improved in all the eyes wearing soft contact lensen for along period, and seven stopped wearing them although corneal objective findings were much better, because they had some troubles with handlings were much better, because they had some troubles with handling the lenses, because they had lost rhem, or because their visual acuity decreased while wearing the lenses. Forlong term wearing the flattest lenses should be used in the beginning and changed gradually to lenses of greater curvature which are better able to keep their centering. Then immediately after successful fitting, the lenses should be given appropriate refractive power. The new ophthalmic drops for soft contact lens wearers were very much effective as artificial tears to both eyes with and without sofy contact lenses. KCS-indexes were numerical values relating to patients subjective symptoms. KSC-indexes improves by an average of +6.4±7.5 after treatment. On the other hand, KCS-indexes improved by +10.7±7.9 in the group that succeeded in wearing SCL for a long period, and by +7.6±2.1 even in the group that failed.

Human leukemic B-cell (BALL-1), T-cell (TALL-1) and null-cell (NALL-1) lines have been established from three patients with acute lymphoblastic leukemia (ALL). To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7) cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage.

Myxofibroma is a rare tumor. Three cases of myxofibroma, each of which developed at the right mandibular ramus, mandibular anterior tooth region, are presented. Myxofibroma developing in the mandibular ramus region is rare, and there has been only one case reported so far in Japan.

Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.