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A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent.This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events.Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed.EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos.Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Background We examined the relationship between the improved physical activity by early rehabilitation and the duration of hospitalization among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Thirteen allo-HSCT patients with myeloablative conditioning regimens (group A) and 13 patients with nonmyeloablative conditioning regimens (group B) were assessed retrospectively in this study. All patients received physical exercise immediately after neutrophil engraftment at the class 10,000 bioclean room (class 10,000). The mean daily steps at class 10,000 were measured as a substitute for the amount of physical activity, and the duration of hospitalization as one of the clinical outcomes. Results The degree of physical activity showed a negative correlation with the duration of hospitalization in group A (r = −.71; P = .0071), regardless of complications such as acute graft-versus-host disease, infections, and cytomegalovirus reactivation. However, there was no significant association in group B (r = .09; P = .77). Conclusion The improved physical activity through early rehabilitation may be an independent, favorable prognostic factor for allo-HSCT patients with myeloablative conditioning regimens.

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics. These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection.

Summary Background The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch–scratch response on the pathology of AD has not been precisely elucidated. Objectives To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv-NC mice), which are known to be an animal model for human AD. Methods Capsaicin-sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap-NC mice), and the development of spontaneous dermatitis in the Cap-NC mice was compared chronologically with that in Conv-NC mice. Results Scratching behaviour was almost completely prevented in Cap-NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap-NC mice were lower than those in Conv-NC mice. Immunological studies showed that the capability of spleen T cells to produce both T-helper (Th) 1 (interferon-γ) and Th2 [interleukin (IL)-5 and IL-13] cytokines was diminished in Cap-NC mice. Furthermore, serum levels of IL-18 were approximately twice higher in Conv-NC mice than in Cap-NC mice. Conclusions These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch-associated scratching behaviour is an effective treatment for AD.

To examine the frequency of congenital infection by Neospora caninum, BALB/c mice were inoculated intraperitoneally with tachyzoites of N. caninum either during pregnancy (Group 1) or 4 weeks or more before pregnancy (Group 2). Further, the mice inoculated during pregnancy were bred at 4 weeks or more after delivery to form Group 3. Congenital transmission was observed in 76% of the neonates of the mice in Group 1 and in 50% of the neonates of the mice in Group 2. Interestingly, congenital transmission was observed in 86% of the neonates from Group 3. These results suggest that chronically-infected BALB/c mice efficiently transmit N. caninum infection to their offspring.

Antibodies against Cryptosporidium parvum in the saliva and sera of three calves experimentally infected with this parasite were examined by an indirect immunofluorescence antibody test and immunoblotting. Salivary anti-C. parvum IgA antibody appeared on day 12 post-challenge and had a tendency to increase transiently between days 15 and 30 post-challenge. Salivary anti-C. parvum IgG antibody levels showed a gradual increase along with the change in IgA antibody levels during the infection. In contrast, serum anti-C. parvum IgA antibody levels showed only a slight increase between days 15 and 30 post-challenge. Serum anti-C. parvum IgG antibody levels rose on day 12 post-challenge and one calf maintained relatively high level up to the end of the experiment. In immunoblotting, an antigen with a molecular mass of 15 kDa was found to react strongly to salivary IgA antibody and a 27 kDa antigen to react to serum IgG antibody.

S. Azuma, DVM, Department of Veterinary Clinical Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan S. Tanabe, DVM, PhD, Y. Uzuka, DVM, PhD, T. Sarashina, DVM, PhD, Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, Y. Kobayashi, DVM, PhD, H. Furuoka, DVM, PhD, T. Matsui, DVM, PhD, Laboratory of Veterinary Pathology, Department of Pathobiological Science, Obihiro University of Agriculture and Veterinary Medicine, 2-11 Inada, Obihiro, Hokkaido 080-8555, Japan T. Oomachi, DVM, PhD, Patholab, 7-333-12-405 Sagamidai, Sagamihara, Kanagawa 228-0821, Japan

Background Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. Patients and methods Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45–80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23–43 fractions (median, 33 fractions). Results At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6–73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. Conclusions Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Background Inoperable patients with lymph node metastasis from extramammary Paget's disease (EMPD) have limited curative treatment options. Objective The aim of this study was to review the efficacy and toxicity of radiation therapy for lymph node metastasis from EMPD. Methods Eight EMPD patients with pelvic and inguinal lymph node metastasis, representing a total of 43 metastatic lymph nodes, underwent radiation therapy. Of these eight patients, two received radiation therapy as an initial treatment for EMPD and six for recurrence only in the lymph nodes after they had undergone surgery. Total doses of 45–61.2 Gy (median, 59.4 Gy) were delivered to metastatic lymph nodes in 25–34 fractions (median, 33 fractions). Results Of the 43 metastatic lymph nodes in the eight patients, all but one had no progression at the median follow-up time of 22 months. The 2-year local control rates were 86% in all patients and 98% in all metastatic lymph nodes, respectively. No therapy-related toxicities of grade 3 or greater were observed. Conclusion Radiation therapy is effective and safe, and appears to offer a curative treatment option for lymph node metastasis from EMPD.

Clinical anxiety disorders are associated with white matter hyperintensities and diffusion abnormalities measured using diffusion tensor imaging. However, it is not known if this association extends into individuals with mild anxious symptoms without formal diagnosis, in those who are older, or in those who have atherosclerosis. The current study explores whether white matter integrity and/or organization significantly associates with anxious symptoms in older adults with and without atherosclerosis.We recruited older adults (ages 55-90 years); 35 with clinically diagnosed atherosclerotic vascular disease (AVD) and 22 without AVD. Anxious symptoms were measured using the validated Symptom Checklist-90-Revised. Fractional anisotropy (FA), a proxy for white matter organization and health, was measured in the white matter globally, by lobe, and in several smaller regions of interest suggested by the literature. Partial correlations between anxious symptoms and FA were calculated, controlling for significant covariates.Participants with and without AVD did not differ in severity of anxious symptom endorsement. There was a unique inverse relationship between white matter health and anxious symptoms in the AVD participants, but not in healthy comparisons. Significant relationships were observed in the superior longitudinal fasciculus (r = -0.476, df = 32, p = 0.004), as well as the cingulum bundle, the frontal lobes, and the parietal lobes.Anxiety symptoms uniquely correlated with low FA in older adults with atherosclerosis. These findings may have implications for future research on the topic of anxiety in aging and vascular disease and warrant replication.

Atherosclerotic vascular disease (AVD) is endemic to the developed world, with known negative outcomes for cognition and brain health. The effects of AVD on the white matter fibers of the brain have not yet been studied using diffusion tensor imaging (DTI). This study examined differences in fractional anisotropy (FA) between AVD and healthy comparison (HC) participants, and described the regional patterns of FA in each group. AVD participants were hypothesized to have lower FA than HC participants, indicating abnormalities in white matter health or organization. 1.5 tesla diffusion tensor imaging was performed in 35 AVD and 22 HC participants. Mean FA measures were calculated for the white matter of the whole brain, as well for individual lobes. Globally and in every brain region measured except the temporal lobes, there were significant effects of group where AVD participants had lower FA values than their HC counterparts. Group differences in FA remained significant when controlled for white matter hyperintensity (WMH) volume, suggesting that FA detects white matter abnormality above and beyond what is measurable using the older WMH technique. These findings suggest a likely neural substrate underlying the changes in cognition and mood reported in atherosclerotic vascular disease patients.

The function and/or morphological features of the vomeronasal olfactory system remain unclear in aquatic animals, although the system appeared first in urodeles based on phylogenic data. We examined the lectin binding patterns in the olfactory bulb of a semi-aquatic urodele, the Japanese red-bellied newt, Cynops pyrrhogaster, using 22 different lectins. Eleven of the lectins showed specific binding to the nerve fibres and glomeruli in the olfactory bulb. Among these, Wheat germ agglutinin, pokeweed and peanut agglutinin preferentially bound the main olfactory bulb, reflecting variation in the expression of glycoconjugates between the main and accessory olfactory bulbs. By contrast, the types of lectins bound to the Cynops olfactory bulb were considerably different from those reported in other urodele families. These results suggest a histochemical distinction between the main and accessory olfactory bulbs, and that glycoconjugate expression may differ significantly among urodele families.

The effect of several vitamin K homologs on plasma vitamin K concentration was determined to assess their potential as a vitamin K supplement for adult horses. Sixteen Thoroughbred horses consisting of 8 mares and 8 geldings, aged 8.4 ± 3.6 yr and weighing 520.8 ± 36.1 kg, were allocated to 4 groups (n = 4). Each group was given phylloquinone, menaquinone-4, or menadione at 58 µmol/d, or no vitamin K supplement for 7 d. Plasma samples were collected before feeding, and 2, 4, and 8 h after feeding on d 7, and plasma concentrations of phylloquinone and menaquinone-4 were determined. Plasma phylloquinone concentration was greater in the phylloquinone group than in the other groups (P0.001). The phylloquinone concentration quadratically increased (P0.001) after feeding in the phylloquinone group but no changes in the plasma phylloquinone concentration were observed after feeding in the other groups. Plasma menaquinone-4 concentration was greater (P0.001) in the menadione group than the other groups, including the menaquinone-4 group. Menaquinone-4 concentration did not change (P = 0.192) after feeding in each group. Menaquinone-4 has been considered the most potent vitamin K homolog for bone metabolism; therefore, the present experiment indicates that menadione is a good source of vitamin K for bone health in horses because it is the only vitamin K homolog that increased the plasma concentrations of menaquinone-4.

Summary We report two patients who developed benign plasmacytosis with multiple skin lesions. The cases were characterized by hyperplasia of mature plasma cells, and polyclonal hypergammaglobulinaemia. One patient had hyperplasia of mature plasma cells not only in the skin, but also extensively in lymph nodes and the retroperitoneal areas around the ureters. The other had plasma cell hyperplasia limited to the skin. Extensive investigations failed to reveal any clinical or laboratory evidence suggesting the presence of any underlying disease accompanying the hypergammaglobulinaemia and/or plasma cell proliferation, such as chronic infectious disease, collagen disease or other chronic inflammatory disorder. Clinically and histologically, the first patient showed features compatible with a diagnosis of systemic plasmacytosis and the second with a diagnosis of cutaneous plasmacytosis. Significant serum interleukin-6 (IL-6) levels were detected in both patients, suggesting that IL-6 may be involved in the pathogenesis of these conditions.

The present study reports for the first time, the in vivo wound healing potential of Punica granatum L. peels. A 5% (w/w) methanolic extract based-ointment was formulated and evaluated for its wound healing in guinea pigs. The ointment was applied in vivo on the paravertebral area of twelve excised wounded models once a day for 10 consecutive days. The ointment significantly enhanced the wound contraction and the period of epithelialization as assessed by the mechanical (contraction rate, tensile strength), the biochemical (increasing of collagen, DNA and proteins synthesis) and the histopathological characteristics. Such investigation was encouraged by the efficiency of the methanolic extract as antimicrobial and antioxidant. Indeed, the extract showed antioxidant activity as strong as natural and synthetic compounds (Trolox, BHA, Quercetin). Furthermore, the extract exhibited significant antibacterial and antifungal activity against almost all tested bacteria: Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae, Salmonella anatum, Salmonella typhimurium, Streptococcus pneumoniae, and fungi Candida albicans, Candida glabrata, Trichopyton rubrum and Aspergillus niger. The formulated ointment might well find use as skin repair agent without hazard to human health based on these results and on the fact that it has been well established that the extracts of pomegranate used in conditions similar to those applied by traditional medicine, showed no toxic effects.

In order to conduct fast screening of passengers with infections such as severe acute respiratory syndrome (SARS) or pandemic influenza at a quarantine depot, we developed a non-contact screening system with self-produced program to conduct a human screening within five seconds, via a linear discriminant function from non-contact derived variables, i.e. palmer pulse derived from a laser Doppler blood-flow meter, respiration rate determined by a 10-GHz microwave radar, and facial temperature measured by thermography. The system evaluation was conducted on seven healthy male subjects (23 +/- 1 years). In order to achieve a pseudo-infection condition, the subjects maintained an ergometer exercise load (100 W, 10 minutes). Before (normal condition) and after (pseudo-infection condition) exercise, a significant linear discriminant function (p0.001) was determined to distinguish pseudo-infection condition from normal condition (Mahalanobis D-square = 20.3, classification error rate5%). The proposed system appears promising for future application in fast screening of infection at a quarantine depot.

Background Patients with gastric cancer who have positive cytologic results for cancer cells in peritoneal washings (CY1) have poor outcomes, even in the absence of other distant metastases. A standard treatment for such patients remains to be established. Methods We conducted a phase II trial with the 2-year survival rate as the primary endpoint. Patients who had gastric cancer with CY1 status but no other residual disease received postoperative chemotherapy with S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) at a daily dose of 80 mg/m2 for 4 weeks, followed by 2 weeks of rest. This cycle was continued until disease progression or intolerable adverse events. D2 dissection was the recommended surgical procedure; splenectomy could be omitted at the discretion of the surgeon. Accrual of 50 patients was planned, and a 2-year survival rate of more than 36% was needed to exceed the historical control. Results Forty-eight patients were enrolled, among whom 47 were assessable for survival and 46 for adverse reactions. Median overall survival was 705 days, and progression-free survival was 376 days. The 2-year survival rate was 47%. Median time to treatment failure was 288 days. Neutropenia was the commonest ≥grade 3 toxicity (6 patients), and anorexia was the most frequent ≥grade 2 non-hematologic toxicity (10 patients). Conclusions Gastrectomy followed by S-1 monotherapy resulted in survival that surpassed historical data and can serve as an active control treatment for future trials in patients who have gastric cancer with CY1 status in the Far East.

Adult neural stem and progenitor cells (NSPCs) are important autologous transplantation tools in regenerative medicine, as they can secrete factors that protect the ischemic brain. We investigated whether adult NSPCs genetically modified to secrete more glial cell line-derived neurotrophic factor (GDNF) could protect against transient ischemia in rats. NSPCs were harvested from the subventricular zone of adult Wistar rats and cultured for 3 weeks in the presence of epidermal growth factor. The NSPCs were treated with fibre-mutant Arg-Gly-Asp adenovirus containing the GDNF gene (NSPC-GDNF) or enhanced green fluorescent protein (EGFP) gene (NSPC-EGFP; control group). In one experiment, cultured cells were transplanted into the right ischemic boundary zone of Wistar rat brains. One week later, animals underwent 90 min of intraluminal right middle cerebral artery occlusion followed by magnetic resonance imaging and behavioural tests. The NSPC-GDNF group had higher behavioural scores and lesser infarct volume than did controls at 1, 7 and 28 days postocclusion. In the second experiment, we transplanted NSPCs 3 h after ischemic insult. Compared to controls, rats receiving NSPC-GDNF had decreased infarct volume and better behavioural assessments at 7 days post-transplant. Animals were killed on day 7 and brains were collected for GDNF ELISA and morphological assessment. Compared to controls, more GDNF was secreted, more NSPC-GDNF cells migrated toward the ischemic core and more NSPC-GDNF cells expressed immature neuronal marker. Moreover, the NSPC-GDNF group showed more effective inhibition of microglial invasion and apoptosis. These findings suggest that NSPC-GDNF may be useful in treatment of cerebral ischemia.

Seven cases suffered from a chest trauma (stab wound in 6 and impalement injury in 1) were emergently transferred to our hospital. Open thoracotomy was performed for the intolerable bleeding immediately after admission. Injured lung was treated by lobectomy in 1 patient, lingual segmentectomy in 2, lower basal segmentectomy in 2, partial resection in 4 and direct suture in 2. The penetrating trachea was carefully repaired by direct suture with additional midsternal thoracotomy. To accomplish appropriate partial resection of the injured lung, a metallic straight suction tube inserted into a pulmonary stab wound was retracted and a stapling instrument was applied underneath the suction tube. With the segmentectomy and the partial resection, the volume of the residual lung was maximally saved. As a result, all 7 patients were successfully alive.

To examine the possible age-related blood pressure (BP) deregulation in response to central hypervolemia, we measured spontaneous baroreflex sensitivity (SBRS), carotid arterial compliance (CC), and R-R interval coefficient of variation (RRICV) during basal and thermoneutral resting head-out-of-water immersion (HOWI) in 7 young (YG = 24.0 +/- 0.8 years) and 6 middle-aged/older (OL = 59.3 +/- 1.3 years) healthy men. Compared with basal conditions (YG = 19.6 +/- 4.0 vs OL = 6.1 +/- 1.5 ms/mmHg, P < 0.05), SBRS remained higher in YG than OL during rest HOWI (YG = 23.6 +/- 6.6 vs OL = 9.3 +/- 2.1 ms/mmHg, P < 0.05). The RRICV was significantly different between groups (YG = 6.5 +/- 1.4 vs OL = 2.8 +/- 0.4%, P < 0.05) under HOWI. The OL group had no increase in CC, but a significant increase in systolic BP (basal = 115.3 +/- 4.4 vs water = 129.3 +/- 5.3 mmHg, P < 0.05) under HOWI. In contrast, the YG group had a significant increase in CC (basal = 0.16 +/- 0.01 vs water = 0.17 +/- 0.02 mm(2)/mmHg, P < 0.05) with no changes in systolic BP. SBRS was positively related to CC (r = 0.58, P < 0.05 for basal vs r = 0.62, P < 0.05 for water). Our data suggest that age-related vagal dysfunction and reduced CC may be associated with SBRS differences between YG and OL groups, and with BP elevation during HOWI in healthy older men.

The association of aircraft noise exposure with cognitive performance was examined by means of a cross-sectional field survey. Two hundred thirty six children attending 10 primary schools around Heathrow Airport in west London were tested on reading comprehension, immediate/delayed recall and sustained attention. In order to obtain the information about their background, a questionnaire was delivered to the parents and 163 answers were collected. Logistic regression models were used to assess performance on the cognitive tests in relation to aircraft noise exposure at home and possible individual and school level confounding factors. A significant dose-response relationship was found between aircraft noise exposure at home and performance on memory tests of immediate/delayed recall. However there was no strong association with the other cognitive outcomes. These results suggest that aircraft noise exposure at home may affect children's memory.

Aim: Non-steroidal anti-inflammatory drug (NSAID) enteropathy is a cause of chronic blood and protein loss from the intestine. The aim of this investigation was to compare NSAID enteropathy with enteropathy not related to chronic NSAID use. Patients/Methods: During the period 1967–97, 12 cases of non-specific small intestinal multiple ulcers were laparotomised because of chronic and persistent blood loss for a prolonged period. The clinical features before and after surgery, and the small intestinal lesions, were compared between NSAID users and non-users. Results: Three patients were NSAID users and the other nine were not. Initial clinical manifestations, haemoglobin concentrations, serum protein values, and inflammatory reactions were similar in the two groups. In both groups there were multicentric stenoses in the small intestine. In those not using NSAIDs, the stenoses were accompanied by multiple, sharply demarcated small ulcers with minimal and non-specific chronic inflammatory infiltrates. The small intestinal ulcers in NSAID users showed linear and circumferential alignment. NSAID users were free from medication during the subsequent period of observation, whereas repeated laparotomy and medication were required in eight of the nine patients not using NSAIDs. Conclusion: There appears to be a chronic enteropathy, not related to the use of NSAIDs, in which non-specific multiple ulcers are found. This enteropathy may be a distinct entity that causes persistent blood and protein loss from the intestine.

To investigate the role of group III metabotropic glutamate receptors (mGluRs) in the globus pallidus (GP), whole-cell recordings were performed using rat brain slice preparations. Application of the group III mGluRs specific agonist l (+)-2-amino-4-phosphonobutyric acid ( l -AP4) suppressed the amplitude of striatal stimulation-induced IPSCs and internal capsule stimulation-induced EPSCs in most of the GP neurons that were capable of generating repetitive firing without spike accommodation. The suppression of IPSCs and EPSCs was accompanied by an increase in the paired-pulse ratio. The l -AP4 effects were antagonized by (R,S)-alpha-cyclopropyl-4-phosphophenylglycine, a blocker for group II/III mGluRs. l -AP4 reduced the frequency of mIPSCs and mEPSCs without changing their amplitude distribution. l -AP4 failed to change iontophoretic glutamate induced responses. These results suggest that the subthalamo-pallidal glutamatergic input might homo- and hetero-synaptically control GABAergic and glutamatergic transmission in the GP.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to enhance the symptoms of food-dependent exercise-induced anaphylaxis (1, 2). We report a rare case of wheat-induced anaphylaxis not related to exercise in which oral challenges with wheat and gluten-induced whole blood histamine release were enhanced by NSAIDs. A 59-year-old man was admitted to our hospital for investigation of recurrent food-induced anaphylaxis. He first developed urticaria after eating noodles at age 58. Since then he frequently had urticaria andoccasionally experienced anaphylaxis, including dyspnoea, wheezing, angioedema, and loss of consciousness after ingesting wheat, including noodles, bread, breaded cutlets, and tempura (Japanese deep-fried foods). It was determined that he had these episodes of anaphylaxis without exercise. Total IgE was 160 IU/ml. Skin-prick testing and specific IgEwere positive for wheat and gluten, the major allergen in wheat-induced allergy. To determine an elimination diet and to instruct the patient, open oral challenges were performed. Oral challenges with bread, noodles, cutlets, and tempura were all negative. However, when 30 mg of diclofenac sodium, an NSAID, was taken just before the challenge, he developed urticaria 1 h after eating noodles or tempura.He developed no symptoms after taking diclofenac sodium only. To clarify the effect of NSAIDs on wheat-induced anaphylaxis, we measured histamine release after in vitro exposure to gluten with or without tolmetin sodium, an NSAID, in this patient and a normal control subject. Heparinized whole blood samples were taken and incubated with gluten at concentrations ranging from 2.5 to 2500 lg/ml and with tolmetin sodium at concentrations ranging from 0.125 to 12.5 mg/ml for 30 min at 37 C. After centrifugation, histamine was measured in the cell-free supernatants by radioimmunoassay. Histamine release was found to be positive with gluten at the concentration of 2500 lg/ml in the patient. With tolmetin sodium at concentrations of 0.125 and 1.25 mg/ml, gluten-induced histamine release was not affected. However, tolmetin sodium at the concentration of 12.5 mg/ml enhanced the gluten-induced histamine release at all concentraions of gluten. Interestingly, tolmetin sodium enhanced histamine release even in the absence of gluten in the control subject as well as in the patient. Histamine release was not found in other conditions in the control subject. At follow-up 1 year after the discharge, he remained asymptomatic after strict elimination of wheat. The results of our in vitro study indicate that the induction of positive oral challenges with wheat after pretreatment with an NSAID is, at least partly, because of enhancement of histamine release. To our knowledge, this is the first report of wheatinduced anaphylaxis not related to exercise confirming thatNSAIDs enhance type I allergic reactions. Previous studies demonstrated that NSAIDs enhance in vitro histamine release induced by IgEor nonIgE-mediated mechanisms (3). In our study, histamine release was induced by tolmetin sodium even in the absence of allergen. In this regard, we speculate that the extent of enhancement of histamine releasemaydependon the type anddose of the NSAIDs as our patient developed no symptoms after taking diclofenac sodium only. We found that enhancement of the allergic symptoms induced by NSAIDs is not a specific phenomenon in fooddependent exercise-induced anaphylaxis, but can occur in other type I allergic diseases. Furthermore, pretreatment with NSAIDs under controlled conditions is useful for confirming the diagnosis of food-induced allergy when food challenge tests fail to induce positive reactions.

The expression of the messenger RNA of interleukin-12 (IL-12), interferon-γ, interleukin-4, interleukin-6, and interleukin-10 was examined by reverse-transcriptase polymerase chain reaction in peripheral blood lymphocytes of calves that were orally inoculated with Cryptosporidium parvum oocysts. In all of the calves, gene expression of interleukin-12, interleukin-6, and interferon-γ was observed at delivery and this expression was repressed within the next 24 h. In calves inoculated with C. parvum , mRNA expression of interleukin-12 and interferon-γ was noticed on day 3 post-inoculation (p.i.) and increased in the convalescent phase of the infection, whereas in non-inoculated calves no mRNA expression was detectable up to the end of the experiment. No mRNA expression of interleukin-4 or 6 was detected during the experiment. Our observations suggest that systemic Th1 type immune responses are induced in calves infected with C. parvum and may be available for evaluation of the control of the infection.

During water immersion bradycardia and increase in stroke volume induce by changing in hydrostatic pressure. We hypothesised that the cardiac alterations with immersion are associates with an increase in venous return from lower body. Because the venous return reflects volume of capacitance vein e.g, inferior vena cava. Therefore, we clarified the effects of water immersion on the size in left ventricle, aorta, and vena cava.

The cysteinyl leukotrienes (CysLT) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that two classes of receptors, named CysLT1 and CysLT2 receptor, exist. The former is sensitive to the CysLT1 antagonist currently used to treat asthma and allergic rhinitis. Recently, the cDNA for human CysLT1 and CysLT2 receptor have been cloned, making it now possible to study the gene expression of CysLTs receptors.We have used reverse transcription and polymerase chain reaction (RT-PCR) to study the gene expression of CysLT1 and CysLT2 receptor and in situ hybridization to determine the distribution of CysLT1 receptor mRNA in human nasal mucosa. In addition, the distribution of the CysLT1 receptor protein was studied by immunohistochemistry.Human turbinates were obtained after turbinectomy from six patients with nasal obstruction refractory to medical therapy. Total RNA was isolated from human nasal mucosa and both CysLT1 and CysLT2 receptor mRNA was detected in these tissues by using RT-PCR. For in situ hybridization study of human nasal mucosa, we used biotin-labelled oligonucleotides probes encoding human CysLT1 receptor cDNA. To identify the cells expressing the CysLT1 receptor protein, double immunostaining was performed by using anti-CysLT1 receptor antibody and monoclonal antileucocyte antibodies.RT-PCR analysis of total nasal RNA demonstrated the expression of both CysLT1 receptor and CysLT2 receptor mRNA. In situ hybridization indicated high levels of CysLT1 receptor hybridization in blood vessels and the interstitial cells, but a sparse signal in airway epithelium and submucosal glands. The immunohistochemical studies revealed that anti-CysLT1 receptor antibody labelled eosinophils, mast cells, macrophages, neutrophils and vascular endothelial cells in the nasal mucosa.The results may have an important clinical implication and also promote further investigation of the regulation of CysLT1 receptor in health and disease.

Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood.The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems.RBL-2H3 cells were directly stimulated with anti-rat FcepsilonRI alpha-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human FcepsilonRI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA).Cross-linking of FcepsilonRI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-FcepsilonRI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-FcepsilonRI mAb or by allergen in parallel.These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcepsilonRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.

Our case is a 50-year-old man with angina and chronic renal failure. He underwent double vessel MIDCAB (LITA-LAD and GEA-SVG-RCA). Postoperative course was uneventful and postoperative angiography revealed patent grafts. MIDCAB is thought to be effective for patients who have chronic renal failure, because they are able to resume hemodialysis in early postoperative period for controlling water and electolyte.

Hearing tests, primary and secondary, were conducted in two communities vicinal to Kadena US Air Base in Okinawa from May 1996 to July 1998. The noise exposure expressed in WECPNL as designated by the Defense Facilities Administration Agency ranged from 85 to 95 and above. A total of 2035 subjects aged between 25 and 69 years inclusive were considered eligible for inclusion in this study and among them 137 males and 206 females underwent the primary test. Before the test, subjects were asked about hearing difficulty, tinnitus, otological anamnesis and past experience of noise exposure at work and/or hobbies. The primary test was a pure tone audiometry using the ascending method of limits with 5 dB step at 7 test frequencies of 0.5 to 8 kHz. Forty individuals who were judged to have possible noise induced hearing loss were sent to Okinawa Chubu Hospital as subjects for the secondary test. The secondary test consisted of pure tone audiometry with 1 dB step at 9 test frequencies with the addition of 3 kHz and 6 kHz to the primary test frequencies, a Short Increment Sensitivity Index (SISI), test, tympanometry and audioscan audiometry. Based on test findings 12 subjects were considered to have noise induced hearing loss. The examiners interviewed the 12 subjects again to confirm that they had not experienced habitual or repeated intense noise exposure other than aircraft noise exposure around their homes. The geographical distribution of the subject's residences showed their proximity to the airfield, which strongly suggests that the cause of hearing loss may be exposure to aircraft noise from Kadena Air Base.

S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism.To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status.Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose.Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups.The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.

Changing pattern of asthma mortality rate for 100,000 population and number of asthma deaths between 0 to 19 years old since 1950 to 1999 was analyzed by the statistics of the Japan Ministry of Health and Welfare. Asthma mortality rate by the age group of 0-4 years old decreased almost smoothly after 1950 years and they were man 9.6, woman 8.2 for 1950 years, and almost became the smallest with the man 0.5, the woman 0.2 in 1999. The asthma mortality rates by age groups of 5-19 years old have decreased rapidly since 1997, though it increased, especially in men, in the 1960's and between 1980 middle and 1996. As for the asthma mortality in 1999, was 0.1, in the age group of 5-9 years old, 0.1, in 10-14 years old and 0.4, in 15-19 years old. The childhood asthma death of the Japanese decreases in spite of the increase in the recent prevalence rate with the asthma.

Osteopontin (OPN), secreted mainly from chondrocytes, is suggested to be involved in the ossification and remodeling of bone and also in regulation of cytokine profiles. We investigated whether patients with osteoarthritis (OA) and rheumatoid arthritis (RA) display autoimmunity against OPN.Recombinant human OPN (rhOPN) was prepared as a fusion protein with beta-galactosidase using E. coli. Serum samples from patients with OA or RA and from age matched healthy donors were tested for autoantibodies to rhOPN using ELISA and Western blotting. Reactivity of the same samples to purified native human OPN (nhOPN) was investigated by ELISA separately, to evaluate conformational epitopes.By ELISA, autoantibodies to rhOPN were found in one (0.95%) of 105 patients with OA and 2 (2.3%) of 88 patients with RA. These autoantibodies to rhOPN were confirmed by Western blotting. In contrast, 11 (9.5%) of 105 OA serum and 13 (15%) of 88 RA serum samples reacted to nhOPN. The anti-OPN positive RA patients showed high serum levels of rheumatoid factor and C-reactive protein and accelerated erythrocyte sedimentation rate compared to the anti-OPN negative group, although the differences did not achieve statistical significance.Our data showed that OPN is one of the autoantigens in OA and RA. Preferential recognition of nhOPN to rhOPN indicates that major epitope(s) of OPN would be conformational. Clinically, existence of the anti-OPN antibodies may be linked to disease severity in RA.

Isolated tricuspid regurgitation is rare. A 64-year-old man was admitted to our hospital with a complaining of shortness of breath and edema of lower extremities. Chest X-ray showed remarkable cardiomegaly (cardiothoracic ratio, 73%). Echocardiogram demonstrated severe tricuspid regurgitation and dilated right atrium. At operation, the tricuspid annulus was severely dilated about 7 cm in diameter, and all leaflets of tricuspid valve were intact. Prosthetic ring annuloplasty with a 32 mm Carpentier-Edwards ring was performed. Postoperative course was uneventful. Four weeks after operation he was discharged from the hospital and he is now leading a normal life. Careful follow up for long time is essential in this case.

A 28-year-old male, who was involved in an automobile accident 11 years previously, was diagnosed as having a chronic traumatic thoracic aneurysm. An enhanced computed tomographic scanning (CT) and three-dimensional CT demonstrated that a thoracic aortic aneurysm of 50 mm in the maximal axis was located at the aortic isthmus and dilated posteriorly. He underwent thoracic aorta graft replacement using Femoro-femoral partial bypass. The surgery was successful and the postoperative course was uneventful.

Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients not treated with corticosteroids. However, it is uncertain whether exhaled CO is related to severity of asthma. To study whether exhaled CO is related to severity of asthma in clinical courses, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 20 mild asthmatics treated with inhaled beta2-agonists alone, 20 moderate asthmatics treated with inhaled corticosteroids, and 15 stable asthmatics treated with high dose inhaled corticosteroids and oral corticosteroids once a month over 1 years. Exhaled CO concentrations were also measured in 16 unstable severe asthmatics who visited the hospital every 7 or 14 days for treatment with high dose inhaled corticosteroids and oral corticosteroids. The mean values of exhaled CO in severe asthma over 1 year were 6.7 +/- 9.5 p.p.m. (n = 31, mean +/- SD) and significantly higher than those of non-smoking control subjects (1.2 +/- 0.9 p.p.m., n = 20, P0.01). Exhaled CO concentrations in unstable severe asthmatics were significantly higher than those in stable severe asthmatics. However, exhaled CO concentrations in mild and moderate asthmatics did not differ significantly from those in non-smoking control subjects (P0.20). There was a significant relationship between the exhaled CO concentrations and forced expiratory volume in one second in all asthmatic patients. These findings suggest that exhaled CO concentrations may relate to the severity of asthma and measurements of exhaled CO concentrations may be a useful means of monitoring airway inflammation in asthma.

A 40-year-old man received blood transfusion in December 1998 because of gastric bleeding from a peptic ulcer. One month later, he developed febrile hemolytic anemia. Administration of high doses of glucocorticoid significantly reduced the hemolysis, but did not cure the disease. To investigate the cause of the hemolysis, the patient was transferred to our hospital in May 1999. Giemsa-stained peripheral blood smears showed Babesia parasites in the red blood cells (RBC), and PCR analysis confirmed the presence of Babesia microti DNA. The parasitemia disappeared hematologically after 2 weeks of quinine and clindamycin therapy. However, parasite DNA was still detectable in the RBC. Although treatment with oral atovaquone was given for 2 weeks, parasitemia and febrile hemolysis recurred within a month after the last treatment. Fortunately, complete remission was obtained after a second 12-week course of therapy with quinine and clindamycin. PCR analysis revealed asymptomatic Babesia infection in one of eight samples from the original blood donor. The initial steroid therapy given to the patient without an accurate diagnosis seemed to have delayed augmentation of the specific antibodies (IgG) against Babesia microti, thus prolonging the parasitemia after the initial acute stage of babesiosis.

Autumn crocus poisoning of cattle is characterized by severe diarrhea caused by alkaloid colchicine. Previously, we examined pathologically this poisoning in cattle and reported that enterotoxic lesions were closely associated with apoptosis. To examine enterotoxicity of autumn crocus more precisely, a reproductive study was performed using guinea pigs and mice, and pathological findings associated with autumn crocus poisoning were compared with those of colchicine. Each group of guinea pigs given the bulb of autumn crocus or colchicine exhibited severe diarrhea. Histopathological findings in intoxicated guinea pigs were entirely consistent with those in the autumn crocus-poisoned cattle. In contrast, each group of mice administered with the bulb or colchicine did not develop diarrhea. Our results confirmed that the toxicity of autumn crocus bulb is attributable to the toxicity of ingredient colchicine, and revealed that the guinea pig has high reproducibility of autumn crocus poisoning in cattle and colchicine poisoning in humans. It has been reported that the physiological mechanism of the apoptotic process for eliminating the enterocytes in the mouse and rat differs from that of the guinea pig, monkey, cattle and horse. Taking the observation that the former animals do not develop diarrhea, whereas the latter animals do so in the autumn crocus or colchicine poisoning into consideration, it would seem that the species-difference in enterotoxicity of autumn crocus may be closely associated with the physiological mechanism of eliminating the effete enterocytes.

Aiming at evaluating the utility of cefozopran (CZOP) against complicated urinary tract infections with the velocity of eradication of causal bacteria in early treatment and clinical efficacy by new criteria of UTIs, a comparative study was conducted using cefpirome (CPR) as the control drug. CZOP and CPR were administered by intravenous drip infusion at a dose of 1 g twice daily. The duration of treatment was for 5 days. The study method involved randomized assignment of the subjects to either group CZOP or group CPR. The results were as follows: 1. Of a total of 80 cases treated, 65 (CZOP group--32 cases, CPR group--33 cases) were evaluated for efficacy. 2. The overall clinical efficacy evaluation according to the criteria proposed by Japanese UTI Committee rated the CZOP group as 90.6% (29/32), and the CPR group as 90.9% (30/33), with no significant difference between the 2 groups. Clinical efficacy evaluated by attending physicians rated the CZOP group as 93.8% (30/32) and the CPR group as 90.9% (30/33). There was no significant difference between the 2 groups. 3. The efficacy rates to pyuria on day 2 were 26.7% and 0% for the CZOP group and the CPR group, respectively, indicating a higher efficacy rate for the former (p0.05). Those on after treatment were 59.4% and 54.5% for the CZOP group and the CPR group, respectively, with no significant difference between the 2 groups. 4. Regarding the bacteriological effect, the eradication rates of both groups were over 90% on day 1 and after treatment. There was no significant difference between the 2 groups. 5. Side effects occurred in 1 case (2.6%) out of 39 in the CZOP group and in 1 case (2.4%) out of 41 in the CPR group. Laboratory test value fluctuation was noted in 8 (20.5%) of 39 cases in the CZOP group and 11 (26.8%) of 41 cases in the CPR group. There was no significant difference between the 2 groups. The results indicate that CZOP achieves an early efficacy to pyuria, and is as useful as CPR against complicated urinary tract infections.

Plasma macrophage colony-stimulating factor(M-CSF) levels were determined during peripheral blood stem cell harvest and autologous stem cell transplantation(PBSCT). Plasma of 10 patients were analyzed by using ELISA system. The average peak values during PBSCT were quite higher than those during harvest(20,092 vs 1,681 pg/ml). Peak values were observed mainly around leukocyte nadir(Phase II) during harvest. On the other hand, they were detected just after pretreatment(Phase I) during PBSCT courses. Moreover, samples showing extremely high M-CSF values(Phase I) were associated with increase in serum LDH levels. These data suggest that plasma M-CSF in Phase I are mainly derived from chemotherapy-induced cellular damage during PBSCT courses, and there might be different mechanisms to raise M-CSF around the nadir of leukocytes. It is necessary to elucidate the biological meanings of M-CSF.

There is a large body of evidence that reactive oxygen species play a major role in the pathogenesis of ischaemic brain damage. On the other hand, it has recently been suggested that superoxide anions participate in the development of neuronal tolerance against lethal ischaemia following ischaemic preconditioning (PC). The present study aimed to examine whether or not the intravenous administration of human recombinant Cu/Zn superoxide dismutase (hr SOD) prior to PC would affect the subsequent development of neuronal tolerance. Animals were randomly assigned to the following three groups: group 1, sham PC treated with vehicle; group 2, PC treated with hr SOD and group 3, PC treated with vehicle. For PC, 10 min occlusion of the middle cerebral artery (MCA) by a modified intraluminal suture method was followed by 60 min recirculation and this procedure was successively repeated three times. The procedures were similar for sham PC except that the MCA was kept unoccluded. Just prior to PC or sham PC, a bolus of hr SOD (6 x 103 IU/2 ml/kg) was administered intravenously. Seventy-two hours thereafter, rats were subjected to lethal ischaemia, i.e. MCA occlusion for 100 min followed by recirculation for 48 h. The infarct area and volume were assessed with the 2,3,5-triphenyltetrazolium stain. A significant difference in the infarct volume was revealed between the sham PC/vehicle and the PC/vehicle groups (total and cortex P0.01; striatum P0.05), showing that PC induced a marked neuronal tolerance against lethal ischaemia. The infarct volume in the PC/SOD group was close to that in the sham PC/vehicle group, being significantly greater than that in the PC/vehicle group (total and cortex P0.01) and showing that the administration of hr SOD suppressed the development of neuronal tolerance induced by PC. In a parallel experiment, expression of 72-kDa heat-shock protein (hsp 72) at 72 h after PC was considerably reduced in rats treated with hr SOD compared with those treated with vehicle. These results suggest that superoxide anions intraluminally generated within cerebral microvessels participate in the development of neuronal tolerance as well as the induction of hsp 72 following PC.

A 71-year-old man presented with epigastralgia and tarry stool. Laboratory examination showed anemia (Hb 7.1 g/dl) due to hemorrhagic gastric ulcer and positive Coombs' test without features of hemolysis. Initial bone marrow smears disclosed normal granulocytes and megakaryocytes, but only erythroid hyperplasia with multinuclearity and megaloblastosis was identified. Cytogenetic studies revealed normal karyotype. Congenital dyserythropoietic anemia (CDA) type II was initially suspected. Serologically, however, acid hemolysis and anti-I * i tests were negative as were the results of another Coombs' test. The second bone marrow aspiration disclosed a marked decrease in multinucleated erythroblasts together with an increase in those that had internuclear chromatin bridges. Electron microscopy of bone marrow specimens demonstrated morphological features of CDA types I and II, thus yielding a final diagnosis of elderly dyserythropoietic anemia, which is similar to both CDA types. It was suggested that the reactive secretion of erythropoietin due to bleeding played a role in these pathologic changes.

application/pdf, A male 14-year-old Arab horse was pathologically diagnosed as equine motor neuron disease (EMND), which was kept as a breeding horse on a farm in Tokachi district of Hokkaido in Japan. On examination of the peripheral nerves, the most characteristic feature was Wallerian-type degeneration revealed by myelinoclasis associated with myelin ovoids which were sometimes infiltrated by macrophages. The other abnormalities were axonal swellings which were surrounded by thin myelin sheaths. Ultrastructurally, the axonal swelling was due to an accumulation of neurofilaments, and was accompanied by a thin and degenerating myelin sheaths. In teased nerve fiber preparations, the most conspicuous change was myelinoclasis represented by segmentation into myelin ovoids or balls. Occasionally, segmental demyelination and axonal degeneration characterized by multifocal axonal swelling were observed.

We studied, the rate and the affecting factor of ulcer healing of patients with gastric body ulcer treated by H2-receptor antagonist (H2-RA) and proton pump inhibitor (PPI). Gastric acidity was also examined using 24 hr pH monitoring. No difference was observed between the affecting factor of ulcer healing and healing rate (94.7% and 94.9%) among the patients treated by H2-RA or PPI. The average time below pH3 during treatment with H2-RA or PPI were 17.4 +/- 4.3 hr and 23.0 +/- 1.5 hr, respectively. Acid suppression was superior in PPI treated group than in H2-RA group. From these findings, we concluded that H2-RA had sufficient therapeutic efficacy in treating gastric body ulcer.

A boy with ocular type myasthenia gravis was reported. The therapeutic effect of pyridostigmine bromide and corticosteroid was insufficient. However, clinical symptoms disappeared rapidly after an influenza A virus infection. On a peripheral lymphocytes subsets analysis, the CD 3, CD 4 and CD 4/CD 45 RA positive lymphocytes increased with the therapy and decreased after the infection. By contrast, CD 19 positive lymphocytes decreased with the therapy and increased after the infection. These results suggested that influenza A may improve the clinical signs of myasthenia gravis, as is the improved case with measles.

Soy lecithin and soy oil are usually produced from the hexane extract of soybean. Some of the soybean proteins are included in the extract and are therefore present in small amounts in both soy lecithin and soy oil. The antigenicity of the proteins present in defatted soybean has been studied with respect to soybean allergy, but the antigenicity of those found in the extract is yet to be investigated.The antigenicity of soy lecithin and soy oil proteins with regard to soybean allergy were investigated.The proteins present in soy lecithin and soy oil were determined according to already established method and analysed by SDS-PAGE. The IgE- and IgG4-binding abilities of the soy lecithin proteins were investigated by immunoblotting with sera from 30 soybean-sensitive patients, including seven with a positive challenge test. Immunoblotting of soy oil proteins was performed with the sera from some of these patients.In 100 g of sample, the soy lecithin and soy oil contained 2.8 mg and 1.4-4.0 microg of proteins, respectively. The results of SDS-PAGE demonstrated the presence of only three proteins, with molecular weights of about 58-67 kDa in soy oil, and suggested that soy lecithin also contains these proteins. The soy lecithin also contained many proteins besides these. In the soy lecithin, the detection rate of only one protein, with a molecular weight of 31 kDa, by the serum IgE of patients was significantly different compared with controls (detection rate: 40%). The proteins with molecular weights of 58-67 kDa rarely bound to serum IgE. Only one of the patients who presented a positive challenge test had IgE antibodies to soy lecithin proteins. IgG4-binding proteins were found only rarely in soy lecithin. Neither the IgE nor the IgG4 present in the patients' sera reacted to any soy oil protein.Proteins present in soy lecithin and soy oil have little antigenicity with regard to soybean allergy.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.