Elevated serum eosinophil cationic protein and transforming growth factor-α levels in a patient with pemphigus vegetans.

Pemphigus vegetans (PVeg) is a rare variant of pemphigus, characterized by vegetating lesions mainly with antidesmoglein 3 antibodies. However, the pathomechanisms for PVeg is still unknown. We present a patient with PVeg mainly associated with antidesmocollin (Dsc)3 antibodies, who originally developed pemphigus foliaceus. Serum levels of eosinophil cationic protein and transforming growth factor (TGF)-α increased at the onset of PVeg in this patient. Thus, TGF-α might be involved in the formation of vegetating lesions in PVeg.

2D discontinuous piecewise linear map: Emergence of fashion cycles.

We consider a discrete-time version of the continuous-time fashion cycle model introduced in Matsuyama, 1992. Its dynamics are defined by a 2D discontinuous piecewise linear map depending on three parameters. In the parameter space of the map periodicity, regions associated with attracting cycles of different periods are organized in the period adding and period incrementing bifurcation structures. The boundaries of all the periodicity regions related to border collision bifurcations are obtained analytically in explicit form. We show the existence of several partially overlapping period incrementing structures, that is, a novelty for the considered class of maps. Moreover, we show that if the time-delay in the discrete time formulation of the model shrinks to zero, the number of period incrementing structures tends to infinity and the dynamics of the discrete time fashion cycle model converges to those of continuous-time fashion cycle model.

Amorphous nanosilica particles induce ROS generation in Langerhans cells.

Generation of total intracellular reactive oxygen species (ROS) was measured in XS52 cells, a Langerhans cell-like line, treated with different sized amorphous silica particles. The results suggested that exposure to amorphous nanosilica particles (nSPs) with a particle size of 70 nm induced a higher level of ROS generation than did exposure to micron-sized amorphous silica particles. This finding means that it is essential to examine the biological effects of ROS generated after exposure to nSPs, which will provide useful information for hazard identification as well as the design of safer nanomaterials.

Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab.

AIMS: To determine the level of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the plasma of patients with proliferative diabetic retinopathy before and after an intravitreal injection of bevacizumab. METHODS: Eleven patients with type 2 diabetes and control of 30 non-diabetic patients were studied. The 11 eyes of 11 patients received an injection of bevacizumab (1.25 mg). Samples of blood were collected just before the injection, and after 1 day, 7 days and 1 month. The concentrations of VEGF and PEDF in the plasma were measured by ELISA. RESULTS: The VEGF concentration before the injection was 114.0 pg/ml. It was significantly reduced to 9.7 pg/ml after 1 day, to 11.7 pg/ml after 7 days and to 25.9 pg/ml even after 1 month (p<0.001, p<0.001, p<0.001, respectively). The PEDF concentration before the injection was 7.2 microg/ml. It was significantly reduced to 5.8 microg/ml after 1 day, to 5.8 microg/ml after 7 days and to 6.3 microg/ml after 1 month (p<0.001, p<0.001, p>0.05, respectively). CONCLUSIONS: The decreased levels of blood VEGF after an intravitreal injection of bevacizumab indicate that bevacizumab enters the general circulation and may also affect the PEDF levels. Thus, we should carefully examine patients for systemic changes and the fellow eye after an intravitreal injection of bevacizumab.

Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells.

Amorphous silica nanoparticles (nSPs), are widely used in medicines, cosmetics and food. However, due to their reduced particle size they are suspected to pose new risks induced by changes in biological reactivity and kinetics, which differ from those of bulk materials. In a previous study, we showed that silica particles with a diameter of 70 nm penetrated the stratum corneum (SC) of mouse skin and were taken up by living cells such as keratinocytes and Langerhans cells. To clarify the relationship between particle size, distribution and cellular response, we have evaluated size-dependent intracellular localization and cytotoxicity of silica particles, using the mouse epidermal Langerhans cell line XS52. On treatment with silica particles of diameters 70, 300, and 1000 nm, cellular uptake and cytotoxicity increased with reduction in particle size. These results suggest that smaller sized silica particles induced greater cytotoxicity against Langerhans cells, which was correlated with the quantity of particle uptake into the cells.

Economic scale of utilization of radiation in medicine in Japan.

Economic scale of radioisotopes (RI) in Japan is studied in the field of medicine, agriculture and a part of industry. (1) RI is used during medical examination with economic scale by 1.7M$ (million dollars) in 1997 and 0.4M$ in 2005. (2) Economic scale of RI utilization in agriculture is 4M$ for R&D, 127M$ for environmental protection and 1M$ for chronology. RI usage in agriculture is increased five times due to needs at environmental technology lasted after the Kyoto protocol. (3) Indirect economic scale of RI ((85)Kr, (147)Pm, (90)Cr) usage in paper fabrication field in Japan for 2006 is 8432M$.

Influence of salivary macromolecules and fluoride on enamel lesion remineralization in vitro.

The aim of this study was to investigate the influence of salivary macromolecules on enamel lesion remineralization in the presence or absence of fluoride. Paraffin-stimulated whole saliva was centrifuged, and the supernatant was dialyzed in 1,000 molecular-weight cutoff dialysis tubes, first against a phosphate buffer and then against a mineral solution containing Ca and phosphate. Artificial subsurface lesions of human enamel, created in pH 4.5 acetate buffer, were remineralized for 28 days in 4 remineralizing solutions: group C--mineral solution as a control; group S--mineral solution + dialyzed saliva; group F--mineral solution + 1 ppm F; group SF--mineral solution + dialyzed saliva + 1 ppm F. Changes in relative mineral concentration in the lesions were assessed by transverse microradiography. The results showed statistically significant mineral gains in the lesion body in groups C (DeltaZ = 3,254 +/- 1,562% x microm) and SF (DeltaZ = 2,973 +/- 1,349% x microm), but not in groups S (DeltaZ = 5,192 +/- 1,863% x microm) and F (DeltaZ = 4,310 +/- 1,138% x microm) compared with the baseline group (DeltaZ = 5,414 +/- 461% x microm). It was also found that the mineral density at the surface layer in group F (75.0 +/- 15.7%) was greater than that in the baseline group (30.1 +/- 12.3%) with statistical significance, but not in group SF (39.9 +/- 16.5%). It was concluded that the macromolecules inhibited lesion remineralization fundamentally but that these molecules, in the presence of fluoride, seemed to play an important role in the continuation of remineralization by reducing mineral gains at the surface layer.

Generation of anti-tumour effector T cells from naïve T cells by stimulation with dendritic/tumour fusion cells.

Tumour-draining lymph node T cells are an excellent source of effector T cells that can be used in adoptive tumour immunotherapy because they have already been sensitized to tumour-associated antigens in vivo. However, such tumour-specific immune cells are not readily obtained from the host due to poor immunogenicity of tumours and reduced host immune responses. One obstacle in implementation of adoptive immunotherapy has been insufficient sensitization and expansion of tumour-specific effector cells. In this study, we aim to improve adoptive immunotherapy by generating anti-tumour effector T cells from naïve T lymphocytes. We attempted to achieve this by harnessing the advantages of dendritic cell (DC)-based anti-cancer vaccine strategies. Electrofusion was routinely employed to produce fusion cells with 30-40% efficiency by using the poorly immunogenic murine B16/F10 cell line, D5 cells, and DC generated from bone marrow cells. CD62L-positive T cells from spleens of naïve mice and the fusion cells were cocultured with a low concentration of IL-2. After 9 days of culture, the antigen-specific T cells were identified with an upregulation of CD25 and CD69 expression and a downregulation of CD62L expression. These cells secreted IFN-gamma upon stimulation with irradiated tumour cells. Moreover, when transferred into mice with 3-day established pulmonary metastases, these cells with coadministration of IL-2 exhibited anti-tumour efficacy. In contrast, naïve T cells cocultured with a mixture of unfused DC and irradiated tumour cells did not exhibit anti-tumour efficacy. Our strategy provides the basis for a new approach in adoptive T cell immunotherapy for cancer.

Projection patterns of lamina VIII commissural neurons in the lumbar spinal cord of the adult cat: an anterograde neural tracing study.

This study was designed to characterize the morphology of commissural axons, with the goal of revealing some of the organizing principles of their projections in the lumbosacral cord. Axons were labeled anterogradely with biotinylated-dextran amine which was injected in the left lamina VIII and the adjoining parts of lamina VII in the lumbar segments L5-L6 in seven cats. After 3-4 weeks, commissural axons were well labeled throughout lumbosacral segments L1-S2. After crossing the midline at the injection level, labeled axons traveled rostrally and/or caudally in the contralateral ventral and lateral funiculi giving off multiple axon collaterals. The trajectories of 34 single axons were traced in their entirety from their points of origin to their distal ends. Most of these axons were thin (proximal diameter <3.5 microm) and short (<30 mm), and gave off 6 to 32 axon collaterals at short intercollateral distances (mean <2 mm) in the lumbosacral enlargement. Some thicker axons (diameter >3.5 microm) ascended as far as the thoracic level; these supplied only four to six collaterals at long intercollateral intervals ( approximately 6.5 mm). All of the axons except one projected unilaterally. The axons as a whole terminated throughout the contralateral ventral horn. However, axons that traveled in different parts of the white matter had different characteristic terminal arborizations. The collaterals of axons that traveled in the ventral funiculus terminated preferentially in laminae VII-VIII, while those in the lateral funiculus terminated in lamina IX. Although the collateral branching patterns differed from one axon to another, collaterals arising from a particular axon usually exhibited similar patterns at different rostrocaudal levels. These uniform collateral termination patterns indicate that the morphology of each neuron might be specifically related to its function. This may allow future studies to identify different functional types of commissural neurons on the basis of much less extensive reconstructions.

Relative contribution of Ia inhibitory interneurones to inhibition of feline contralateral motoneurones evoked via commissural interneurones.

The aim of the study was to examine to what extent the crossed inhibition of hindlimb lumbar alpha-motoneurones is evoked via interneurones that mediate reciprocal inhibition between flexors and extensors (Ia inhibitory interneurones), and to what extent via other spinal interneurones. The crossed inhibition was evoked by reticulospinal and vestibulospinal tract fibres, stimulated in the contralateral medullary longitudinal fascicle and the lateral vestibular nucleus, respectively, or by group II muscle afferents in the contralateral quadriceps nerve. The components of the IPSPs recorded in motoneurones that were mediated by Ia inhibitory interneurones were identified by their depression following activation of Renshaw cells. Trisynaptic components of IPSPs of reticulospinal and vestibulospinal origin, and polysynaptic (but not trisynaptic) components of IPSPs from group II afferents were found to be depressed in the majority of the motoneurones, while disynaptic components, those due to direct actions of inhibitory commissural interneurones, were not depressed. These results indicate that the coordination of left and right hindlimb movements based on crossed inhibition from reticulospinal and vestibulospinal neurones, depends on the degree of activation of Ia inhibitory interneurones by muscle spindle afferents and on their inhibition by Renshaw cells. Our results also indicate that Ia inhibitory interneurones do not operate as last-order inhibitory interneurones in crossed trisynaptic pathways from group II afferents, even though they mediate inhibition evoked by interneurones in shared polysynaptic pathways of crossed flexor and extensor reflexes coactivated by group II and other high-threshold muscle, skin and joint afferents.

[Early and late results of combined valvular and coronary artery surgery].

A total of 42 patients with combined valvular and coronary artery surgery were examined to analyze risk factors for cardiac related events and late deaths. There were aortic valve disease in 26 patients and mitral valve disease in 16. Preoperatively, 14 patients (33%) had cardiac dysfunction (ejection fraction < or = 40%) and 10 patients (24%) were in New York Heart Association (NYHA) functional class IV. There was no operative death with 96% of early graft patency. There was 8 late deaths during 5.6 years of mean follow up. Actuarial survival rate was 86% and 64% after 5 and 10 years, respectively. Cardiac dysfunction was a significant independent predictor for late death. Cardiac related events occurred in 9 patients. Freedom from cardiac related events was 78% and 59% after 5 and 10 years, respectively. Cardiac dysfunction and mitral valve surgery were significant independent predictors for cardiac related events. Late result of combined mitral and coronary artery surgery was unfavorable in patients with cardiac dysfunction.

[Management for type A acute dissection].

From March 1998 to May 2002, we experienced 46 patients with type A acute dissection (AAD). Fifteen patients managed initially with conservative treatment because of intramular hematoma (IH, n = 10), broad cerebral infarction (n = 3), others (n = 2). One who diagnosed IH at admission progressed to AAD and underwent surgery. However his diagnosis of IH at admission was proved to be misdiagnosis retrospectively. In 8 of the remaining 9 patients, hematoma disappeared during the follow-up of 6 months to 1 year. In patients with broad cerebral infarction, 2 died early after admission and 1 discharged with hemiplegia. Thirty-two patients underwent surgery and 1 with preoperative broad cerebral infarction died 36 days after surgery. In the remaining 31 patients, 30 patients discharged ambulatory.

Medullary reticulospinal tract mediating a generalized motor inhibition in cats: III. Functional organization of spinal interneurons in the lower lumbar segments.

The previous report of intracellular recording of hindlimb motoneurons in decerebrate cats [ 511] has suggested that the following mechanisms are involved in a generalized motor inhibition induced by stimulating the medullary reticular formation. First, the motor inhibition, which was prominent in the late latency (30-80 ms), can be ascribed to the inhibitory effects in parallel to motoneurons and to interneuronal transmission in reflex pathways. Second, both a group of interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons mediate the late inhibitory effects upon the motoneurons. To substantiate the above mechanisms of motor inhibition we examined the medullary stimulus effects upon intracellular (n=55) and extracellular (n=136) activity of spinal interneurons recorded from the lower lumbar segments (L6-L7). Single pulses or stimulus trains (1-3) pulses, with a duration of 0.2 ms and intensity of 20-50 microA) applied to the medullary nucleus reticularis gigantocellularis evoked a mixture of excitatory and inhibitory effects with early (<20 ms) and late (>30 ms) latencies. The medullary stimulation excited 55 interneurons (28.8%) with a late latency. Thirty-nine of the cells, which included 10 Ib interneurons, were inhibited by volleys in flexor reflex afferents (FRAs). These cells were mainly located in lamina VII of Rexed. On the other hand, the late inhibitory effects were observed in 67 interneurons (35.1%), which included cells mediating reciprocal Ia inhibition, non-reciprocal group I (Ib) inhibition, recurrent inhibition and flexion reflexes. Intracellular recording revealed that the late inhibitory effects were due to inhibitory postsynaptic potentials with a peak latency of about 50 ms and a duration of 50-60 ms. The inhibitory effects were attenuated by volleys in FRAs. Neither excitatory nor inhibitory effects with a late latency were observed in 69 (36.1%) cells which were located in the intermediate region and dorsal horn. These results suggest the presence of a functional organization of the spinal cord with respect to the production of the generalized motor inhibition. Lamina VII interneurons that receive inhibition from volleys in FRAs possibly mediate the postsynaptic inhibition from the medullary reticular formation in parallel to motoneurons and to interneurons in reflex pathways.

Slowly developing perigraft seroma after a modified Blalock-Taussig shunt.

We report a 26-year-old patient with slowly developing perigraft seroma 15 years after a modified Blalock-Taussig shunt with an expanded polytetrafluorethylene graft. The mediastinal mass was first observed on a chest x-ray film 8 years after the shunt operation. The mass contained massive gelatinous or organic tissues with a severely calcified pseudocapsule, and it was adjacent to the calcified but functioning graft. No fluid collections were noted. The histological findings were compatible with a seroma. No recurrence was noted on last follow-up 1 year postoperatively.

Pulmonary venous obstruction requiring lobectomy for hemoptysis after a Glenn operation.

Right atrial isomerism is well known to be associated with anomalous pulmonary venous drainage and a potentially dangerous sequel to pulmonary venous obstruction, and is associated with high mortality. We report a 16-month-old girl with pulmonary venous obstruction requiring lobectomy for hemoptysis after a Glenn operation. Two years after surgery, she is doing well with 80% oxygen saturation and no further episodes of hemoptysis.

Environmentally benign formation of polymeric microspheres by rapid expansion of supercritical carbon dioxide solution with a nonsolvent.

A novel method is reported for forming polymer microparticles, which reduce atmospheric emissions of environmentally harmful volatile organic compounds such as toluene and xylene used as paint solvent in paint industry. The polymer microparticles have formed through rapid expansion from supercritical solution with a nonsolvent (RESS-N). Solubilization of poly(styrene)-b-(poly(methyl methacrylate)-co-poly (glycidyl methacrylate)) copolymer(PS-b-(PMMA-co-PGMA), MW = 5000, PS/PMMA/PGMA = 2/5/3), poly(ethylene glycol) (PEG, M. W = 4000), bisphenol A type epoxy resin (EP, MW = 3000), poly(methyl methacrylate) (PMMA; MW = 15000, 75000, 120000), and poly(oxyalkylene) alkylphenyl ether (MW = 4000) in carbon dioxide (CO2) was achieved with the use of small alcohols as cosolvents. The solubility of the PS-b-(PMMA-co-PGMA) is extremely low in either CO2 or ethanol but becomes 20 wt % in a mixture of the two. Because ethanol is a nonsolvent for the polymer, it can be used as a cosolvent in rapid expansion from supercritical solution to produce 1-3 microm particles that do not agglomerate. Obtained polymer particles by RESS-N were applied as powder coatings. The resulting coatings have a smooth and coherent film. The particle size distribution of microspheres was controlled by changing the polymer concentration, preexpansion pressure, temperature, and injection distance. The feed compositions were more effective than the other factors in controlling the particle size. The polymeric microparticles formed by RESS-N method can be utilized to make the thin coating film without anytoxic organic solvents and/or surfactants.

Postoperative evaluation of pylorus-preserving procedures compared with conventional distal gastrectomy for early gastric cancer.

We evaluated postoperative function in 98 patients who underwent surgery for early gastric cancer between 1995 and 1998 to compare the results of pylorus-preserving procedures to those of conventional distal gastrectomy with Billroth I (B-I). The pylorus-preserving procedures included endoscopic mucosal resection (EMR), performed in 12 patients; local resection (Local), performed in 14 patients; segmental resection (Seg), performed in 8 patients; and pylorus-preserving gastrectomy (PPG), performed in 19 patients. B-I was performed in 45 patients. The nutritional status and serum albumin (Alb) levels after PPG, the hemoglobin (Hb) levels after EMR, Local, and PPG, and the present/preoperative body weight ratios after EMR, Local, Seg, and PPG were superior to those after B-I. The time before oral intake was recommenced after EMR and Local, the volume of oral intake tolerated after EMR, Local, Seg, and PPG, and the postoperative hospital stay after EMR were all superior to those after B-I. Moreover, significantly fewer patients suffered reflux symptoms after EMR, Local, and PPG, abdominal fullness after EMR, and early dumping syndrome after EMR, Local, and PPG than after B-I. There was also less evidence of gastritis after EMR, Local, and PPG, and of bile reflux after EMR, Local, and PPG, than after B-I. These findings indicate that pylorus-preserving procedures may result in a better postoperative quality of life for selected patients with early gastric cancer.

Preparation and characterization of insulin-loaded acrylic hydrogels containing absorption enhancers.

The objectives of this study were to prepare insulin-loaded acrylic hydrogel formulations containing various absorption enhancers, to perform in vitro and in vivo characterization of these formulations, and to evaluate the factors which affecting insulin availability on rectal delivery of insulin using this hydrogel system. The acrylic block copolymer of methacrylic acid and methacrylate, Eudispert, was used to make the hydrogel formulations. As absorption enhancers, 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD), lauric acid (C12), or the sodium salt of C12 (C12Na), were incorporated into the hydrogels. In an in vitro release test, the release rate of insulin from the hydrogels decreased as the polymer concentration of the hydrogel increased. The addition of C12Na to the hydrogel further increased the insulin release rate, which was greater at higher concentrations of the enhancer. A portion of the C12Na was found to remain bound to the acrylic polymer in dissolution medium. Serum insulin levels were determined at various time points after the administration of insulin solution or insulin-loaded (50 units/kg body weight) Eudispert hydrogels containing 5% (w/w) of C12, C12Na, or DM-beta-CyD to in situ loops in various regions of the rat intestine. The most effective enhancement of insulin release was observed with formulations containing C12Na. The bioavailability of insulin from the hydrogels was lower than that from the insulin solutions. Hydrogel formulations containing 7% or 10% Eudispert remained in the rectum for 5 h after rectal administration. However, the 5% (w/w) C12Na solution stained with Evan's-blue had diffused out and the dye had reached the upper intestinal tract within 2 h. Finally, the rectal administration of insulin-loaded hydrogels, containing 4%, 7%, or 10% (w/w) Eudispert and 5% (w/w) of enhancer (C12, C12Na, or DM-beta-CyD) to normal rats was shown to decrease serum glucose concentrations. The greatest effect was found with insulin-loaded 7% (Eudispert) hydrogel containing C12Na which having cosiderable large insulin release rate and bioadhesive characteristics.