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Periodontal ligament (PDL) consists of different cell populations in various differentiation stages. In the present study, we isolated cell populations from rat molar PDL by sequential enzymatic digestion and characterized growth potential and mineralization activity of the PDL subpopulations (PDL-SP) to throw light on the mechanism of PDL remodeling and, in its turn, periodontal tissue regeneration. PDL attached to extracted rat molars was digested 2 mg/ml collagenase and 0.25% trypsin at 37 degrees C for 30 min. Then four consecutive digestions were performed for 20 min each in a fresh digestive solution. The solutions were centrifuged to collect released cells and 5 PDL subpopulations (30M-, 50M-, 70M-, 90M-and 110M-PDL-SP) were obtained. Light microscopic observation showed that about a half of PDL in width attached on the root surface of extracted teeth and 30M-PDL-SP was considered to contain cells mainly from middle portion of PDL. Scanning electron microscopic examination indicated that 110M-PDL-SP was enriched by root lining cementoblastic cells. 30M-PDL-SP showed a high level of proliferative activity. Although the growth potential of a subpopulation decreased in PDL-SP toward the root surface, 110M-PDL-SP had a high proliferative activity equivalent to that of 30M-PDL-SP. Analyses of alkaline phosphatase (ALP) and mineralization activities showed that higher activities in PDL-SP toward the surface of roots and that 110M-PDL-SP had the highest activity of ALP and the largest number of mineralization nodules. The present study shows as supposed by previous studies on cell kinetics in PDL that subpopulations with larger growth potential were generally located in the middle portion of PDL and those with higher mineralization activities toward the surface of the roots. It is suggested, however, that a possible pathway of PDL cell turnover may exist within the PDL-SP on the root surface in addition to the generally recognized pathway from the middle area of PDL to root surface.

This paper proposes optimal operational planning for a cogeneration system (CGS) using particle swarm optimization (PSO). CGS is usually connected to various facilities such as refrigerators, reservoirs, and cooling towers. In order to generate optimal operational planning for CGS, startup and shutdown status, and input values of the facilities for each control interval should be determined. The facilities may have nonlinear input-output characteristics. Therefore, the problem can be formulated as a mixed-integer nonlinear optimization problem (MINLP). PSO can be easily expanded to treat MINLP. The simple expansion of PSO for the optimal generation system operational planning problem is proposed and the proposed method is applied to typical CGS planning problems with promising results.

Surgical navigation systems (frameless stereotaxy) have been used in addition to or instead of fluoroscopy during transsphenoidal surgery. This study compares the intraoperative localization by an optical tracking system (Elekta Viewscope) with fluoroscopy. Viewscope and fluoroscope sagittal images were compared by the establishment of a Cartesian coordinate system based on anatomical landmarks and by the spatial localization of surgically relevant points for 20 patients. The Viewscope was found to have a total deviation of 3.0 ± 0.6 mm (mean ± SD) compared to fluoroscopy (p < 0.01). Much of the error resulted from the registration process, which according to the Viewscope software had an expected error of 3.1 ± 0.8 mm for this series of patients, and from the probe-to-system correlation (error of 1.0 ± 0.3 mm). Although frameless stereotactic systems give the surgeon useful trajectory data with three-dimensional visualizations, they remain somewhat inaccurate. The multiplanar abilities of the Viewscope provide an additional but not mandatory advantage to the simplicity and accuracy of fluoroscopy during this type of surgery.

Sawtooth oscillations have been observed in current-carrying helical plasmas by using electron-cyclotron-emission diagnostics in the Large Helical Device. The plasma current, which is driven by neutral beam injection, reduces the beta threshold of the sawtooth oscillation. When the central q value is increased due to the plasma current, the core region crashes, and, when it is decreased, the edge region crashes annularly. Observed rapid mixture of the plasma in the limited region suggests that these sawtooth crashes are reconnection phenomena. Unlike previous experiments, no precursor oscillation has been observed.

Human sweating is generally caused by thermal and mental stimuli. The former role is well known as a response for thermo regulation. The insensible perspiration may be generally controlled by the autonomic nervous system, and the responses due to mental and/or emotional stress by the sympathetic nervous system. As human sweating is directly concerned with some nervous systems, sweating may be a good indicator for the body reactions of feeling, surprise, emotional stress and etc. The measuring of sweat secretion and microscopic observation of active sweat glands can be presented the direct information of working of sympathetic nervous system and sudomotor. In the present report, we devised an instrumentation for the estimation of time lag of sweating [correction of seating] after physical stimuli. Variation of gravity during parabolic flights is a kind of physical stimulus. Iwase et al reported the changes of sympathetic outflow to muscle in humans during short periods of microgravity. We studied also the variation of number of active sweat glands under this condition for the evaluation of human sympathetic nervous system.

The purpose of this research is to develop methodology for generating large and complex neural networks. Especially, in this case, we adopt the methods to the organizational task in a multi-agent system. We propose the incremental evolution of weight modifiers for generating neural networks based on the GA. In this method, a chromosome contains only the instructions for making and modifying the weights in the base model of the neural network. In this generating process, because the GA holds only the instructions, the search space will be smaller than that of direct encoding methods. Concerning the architecture of the base model, we only determine the maximum number of neuron nodes. As an experiment for the proposed methods, we apply them to the organizational behavior generation in a multi-agent system. Throughout the experiments, the effectiveness of our proposed methods is shown.

Chemical agents represent a serious threat to the modern world. Among them, they stand out nerve agents because of its high lethality and dangerousness. They are typically organophosphate compounds, which act by inhibiting acetylcholinesterase, a key enzyme in the transmission of nerve impulses process. There are several forms of treatment for organophosphate poisoning, and pralidoxime (2-PAM) is the drug most used as reactivator of acetylcholinesterase. In this work, we developed the first three steps for the synthesis of 2-PAM, with the objective of obtaining data to calculate the kinetic parameters of these steps. These parameters may be used for the manufacture of 2-PAM in semi-pilot scale. Through the studies conducted it has been found that the preparation of the oxime has very rapid kinetics.

Summary form only given. We describe a micro deformation model of woven fabric deformation for computer animation. In simulating the woven fabric deformation, we do not deal with precise mechanical models. We have adopted the crimp theory proposed by Peirce, as the geometrical model of our model, using a surface model which represents threads constructing woven fabrics. The Bezier surface is chosen as the surface model because it allows for the representation of smooth and complex shapes by a few points, called the control points. Coordinates of the control points in three-dimensional space are determined by approximation using the geometric model. Since the control points correspond to the surface shape, the movement of the control points deform the geometrical model. In this paper, we use a simple trellis model which permits us to represent the anisotropy of the woven fabrics. The computer animation of the woven fabric deformation created by the proposed method are shown.

This paper describes an alternative method to generate convolution masks for edge detection. Values of the convolution masks depend on the relative position of the pixel being analyzed. As a result, only edges that fulfill a predetermined condition are detected and other edges are filtered. The method is then applied to shape detection of circular traffic signs.

A Phase I trial of irinotecan hydrochloride (CPT-11) was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with advanced neuroblastoma. Three children received 11 courses of CPT-11 administered as a 90-min i.v. infusion, daily for 3 days every 21 days. Doses ranged from 100 mg/m2 to 220 mg/m2. Two peaks in the total number of instances of diarrhea was observed, 25 stools at 3 days and 32 stools at 10 days. Myelosuppression was well controlled and of brief duration. One child achieved a clinical complete response (CR) and 2 had a partial response (PR). The MTD of CPT-11 administration was 180 mg/m2 for 3 days. These results indicate the usefulness of CPT-11 for the treatment of advanced neuroblastoma. Further investigation is necessary to establish its role in combination chemotherapeutic regimens.

Contralateral hematoma formation following acute subdural hematoma (ASDH) evacuation is a well-described complication. The most common type of contralateral hematoma is an epidural hematoma. Rarely, ASDH develops on the contralateral side. We report an elderly woman who presented with a post-traumatic ASDH and underwent ipsilateral hematoma evacuation by craniotomy and subsequently developed a contralateral ASDH. Because of the potential consequences of a delayed ASDH, there should be a low threshold for early post-operative imaging following ASDH evacuation, especially in elderly patients and those with additional associated intracranial injuries.

A case of retroperitoneal haematoma due to a ruptured microaneurysm of the posterior superior pancreaticoduodenal artery in a 61 year old man is described. Ultrasonography and computed tomography revealed cystic masses near the gall-bladder. Selective coeliac angiography disclosed a microaneurysm of the posterior superior pancreaticoduodenal artery. Surgical extirpation of the cystic masses was performed, and the histological finding was an encapsulated old haematoma.

Time-resolved soft X-ray photoelectron spectroscopy (PES) experiments were performed with time scales from picoseconds to nanoseconds to trace relaxation of surface photovoltage on the ZnO(0001) single crystal surface in real time. The band diagram of the surface has been obtained numerically using PES data, showing a depletion layer which extends to 1 μm. Temporal evolution of the photovoltage effect is well explained by a recombination process of a thermionic model, giving the photoexcited carrier lifetime of about 1 ps at the surface under the flat band condition. This lifetime agrees with a temporal range reported by the previous time-resolved optical experiments.

TS-1 is a novel oral formation of 5-fluorouracil, developed using tegafur and two biochemical modulations. We report the case of a patient with multiple lymph node metastases from gastric cancer that markedly responded to TS-1. A 70-year-old man suffering from hematemesis was admitted to our hospital. Computed tomography showed advanced gastric cancer with huge lymph node metastases. After non-curative operation, he received adjuvant chemotherapy with TS-1 for 12 weeks. CT revealed that almost complete reduction of the metastatic nodes was obtained. No serious adverse reactions were observed.

Since ginsenoside-Rg(3), one of the panaxadiol saponins isolated from the ginseng root, significantly inhibited the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the properties of ginsenoside-Rg(3) inhibition were investigated. Although ginsenoside-Rg(3) inhibited the secretion evoked by ACh in a concentration-dependent manner, it affected the secretion stimulated by high K(+) or veratridine, an activator of the voltage-sensitive Ca(2+) or Na(+) channels, only slightly. The ACh-induced Na(+) and Ca(2+) influxes into the cells were also reduced by ginsenoside-Rg(3). The inhibitory effect of this saponin on the secretion of catecholamines was not altered by increasing the external concentration of ACh or Ca(2+). The ACh-evoked secretion of catecholamines was completely restored in cells that were preincubated with 10 microM ginsenoside-Rg(3) and then incubated without the saponin, whereas secretion was not completely restored in cells that were preincubated with 30 microM of this compound. Above 30 microM ginsenoside-Rg(3) increased the fluorescence anisotropy of diphenylhexatriene in the cells. Furthermore, the inhibitory effect of ginsenoside-Rg(3) at 30 microM on the ACh-evoked secretion of catecholamines was dependent upon the preincubation time, but this was not the case at 10 microM. These results strongly suggest that ginsenoside-Rg(3) blocks the nicotinic ACh receptor-operated cation channels, inhibits Na(+) influx through the channels, and consequently reduces both Ca(2+) influx and catecholamine secretion in bovine adrenal chromaffin cells. In addition to this action, the ginsenoside at higher concentrations modulates the fluidity of the plasma membrane, which probably contributes to the observed reduction in the secretion of catecholamines.

To quantitatively describe the pharmacokinetics of valproic acid (VPA) in guinea pig serum (total [Cf+b] and free [Cf]), cerebrospinal fluid (CSF) [C]CSF and tears [C]T using a simple kinetic model, and to examine whether [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters.[Cf+b], [Cf], [C]CSF and [C]T were determined after bolus i.v. injection of 10 or 20 mg/kg VPA using GC/ECNCI/MS.[Cf+b] could be quantitatively described by a two compartment model with linear elimination kinetics. [Cf] was separately analyzed using multi-exponential equations. [C]CSF was analyzed using a simple kinetic model in which the CSF compartment is independently connected with the serum compartment by the apparent diffusion constants (KINCSF and KOUTCSF). [C]T was analyzed using the same simple kinetic model used for [C]CSF. The values of [C]CSF and [Cf] in the steady state can be represented by the following equations; [C]CSF = KINCSF/KOUTCSF x [Cf], [Cf] = KOUT/KINT x [C]T, and indicating that [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters.The measurement of [C]T which can be collected non-invasively and estimated the pharmacokinetic parameters for [Cf], [C]CSF, and [C]T might be a very useful method for TDM of VPA.

Metal-metal bonded Ru(3+)(mu-OR)(2)Ru(3+) and Ru(3.5+)(mu-OR)(2)Ru(3.5+) (R = CH(3) and CH(3)CH(2)) compounds with tetrachlorocatecholate (Cl(4)Cat) have been synthesized in the corresponding alcohol, MeOH and EtOH, from a nonbridged Ru(2+)-Ru(3+) compound, Na(3)[Ru(2)(Cl(4)Cat)(4)(THF)].3H(2)O.7THF (1). In alcohol solvents, compound 1 is continuously oxidized by oxygen to form Ru(3+)(mu-OR)(2)Ru(3+) and Ru(3.5+)(mu-OR)(2)Ru(3.5+) species. The presence of a characteristic countercation leads to selective isolation of either Ru(3+)(mu-OR)(2)Ru(3+) or Ru(3.5+)(mu-OR)(2)Ru(3.5+) as a stable adduct species. In methanol, Ph(4)PCl and dibenzo-18-crown-6-ether afford Ru(3+)(mu-OMe)(2)Ru(3+) species, [A](2)[Ru(2)(Cl(4)Cat)(4)(mu-OMe)(2)Na(2)(MeOH)(6)] ([A](+) = Ph(4)P(+) (2), [Na(dibenzo-18-crown-6)(H(2)O)(MeOH)](+) (3)), while benzo-15-crown-5-ether provides a Ru(3.5+)(mu-OMe)(2)Ru(3.5+) species, [Na(benzo-15-crown-5)(2)][Ru(2)(Cl(4)Cat)(4)(mu-OMe)(2)Na(2)(MeOH)(6)] (4). The air oxidation of 1 in a MeOH/EtOH mixed solvent (1:1 v/v) containing benzo-15-crown-5-ether provides a Ru(3.5+)(mu-OMe)(2)Ru(3.5+) species, [Na(benzo-15-crown-5)(H(2)O)][Ru(2)(Cl(4)Cat)(2)(mu-OMe)(2)Na(2)(EtOH)(2)(H(2)O)(2)(MeOH)(2)].(benzo-15-crown-5) (5). Similarly, the oxidation of 1 in ethanol with Ph(4)PCl provides a Ru(3.5+)(mu-OEt)(2)Ru(3.5+) species, (Ph(4)P)[Ru(2)(Cl(4)Cat)(4)(mu-OEt)(2)Na(2)(EtOH)(6)] (7). A selective formation of a Ru(3+)(mu-OEt)(2)Ru(3+) species, (Ph(4)P)(2)[Ru(2)(Cl(4)Cat)(4)(mu-OEt)(2)Na(2)(EtOH)(2)(H(2)O)(2)] (6), is found in the presence of pyrazine or 2,5-dimethylpyrazine. The crystal structures of these compounds, except 2 and 7, have been determined by X-ray crystallography, and all compounds have been characterized by several spectroscopic and magnetic investigations. The longer Ru-Ru bonds are found in the Ru(3+)(mu-OR)(2)Ru(3+) species (2.606(1) and 2.628(2) A for 3 and 6, respectively) compared with those of Ru(3.5+)(mu-OMe)(2)Ru(3.5+) species (2.5260(6) A and 2.514(2) A for 4 and 5, respectively). These structural features and magnetic and ESR data revealed the electronic configurations of sigma(2)pi(2)delta(2)delta(2)pi(2) and sigma(2)pi(2)delta(2)delta(2)pi(1) for Ru(3+)(mu-OR)(2)Ru(3+) and Ru(3.5+)(mu-OR)(2)Ru(3.5+), respectively, in which the former is diamagnetic and the latter is paramagnetic with S = (1)/(2) ground state. Compound 5 forms a one-dimensional chain with alternating arrangement of a Ru(3.5+)(mu-OMe)(2)Ru(3.5+) unit and a free benzo-15-crown-5-ether molecule by intermolecular hydrogen bonds (O(H(2)O).O(crown-ether) = 2.91-3.04 A). The cyclic voltammetry in DMF affords characteristic metal-origin voltammograms; two reversible and two quasi-reversible redox waves were observed. The feature of cyclic voltammograms for the Ru(3+)(mu-OR)(2)Ru(3+) species (2, 3, and 6) and the Ru(3.5+)(mu-OR)(2)Ru(3.5+) species (4 and 7) are similar to each other, indicating that both species are electrochemically stable. The isolation of the pyrazine-trans-coordinated species, [Ph(4)P][Ru(Cl(4)Cat)(2)(L)(2)] (L = pyrazine (8), 2,5-dimethylpyrazine (9)), revealed the selective isolation of 6 from pyrazine-containing solution. UV-vis spectral variation by ethanolysis for 9 demonstrated the selective conversion from the pyrazine-trans-coordinated species to the Ru(3+)(mu-OEt)(2)Ru(3+) species without an oxidation to the Ru(3.5+)(mu-OEt)(2)Ru(3.5+) species. This result suggests the presence of equilibrium between [Ru(Cl(4)Cat)(2)(L)(2)](-) and Ru(3+)(mu-OEt)(2)Ru(3+) species in the synthetic condition for 6.

It is well known that proinflammatory cytokines produced by host cells play an important role in periodontal tissue destruction. However, the localization of the cytokines in in vivo periodontal tissues during development of periodontal disease has not been determined. Immunohistochemical expression of proinflammatory cytokines including IL-1alpha, IL-1beta, and TNF-alpha was examined at 1 and 3 h, and 1, 2, 3, and 7 days after topical application of lipopolysaccharide (LPS; 5 mg/ml in physiological saline) from E. coli into the rat molar gingival sulcus. In the normal periodontal tissues, a small number of cytokine-positive epithelial cells were seen in the junctional epithelium (JE), oral sulcular and oral gingival epithelium, in addition to macrophages infiltrating in the subjunctional epithelial area and osteoblasts lining the alveolar bone surface. Epithelial remnants of Malassez existing throughout periodontal ligament were intensely positive for IL-1beta but negative for the other two cytokines. At 3 h after the LPS treatment, almost all cells in the JE were strongly positive for the cytokines examined. In addition, several cytokine-positive cells, including neutrophils, macrophages, and fibroblasts, were seen in the subjunctional epithelial connective tissue. At day 2, expression of the cytokines in the JE gradually decreased, while cytokine-positive cells in the connective tissue increased in number. Positive staining of the cytokines was seen in osteoclasts and preosteoclasts which appeared along the alveolar bone margin in this period. The number of cytokine-positive cells decreased by day 7. These findings indicate that, in addition to macrophages, neutrophils, and fibroblasts, the JE cells are a potent source of TNF-alpha, IL-1alpha, and IL-1beta reacting to LPS application, and suggest that JE cells may play an important role in the first line of defense against LPS challenge, and the proinflammatory cytokines transiently produced by various host cells may be involved in the initiation of inflammation and subsequent periodontal tissue destruction.

Elevation of serum anti Saccharomyces cerevisiae antibody (ASCA) has been reported in patients with Crohn's disease. We analysed the subclasses of Immunoglobulin (Ig) G reaction in ASCA in sera from patients with inflammatory bowel disease, healthy controls, and patients with intestinal Behçet's disease. Serum samples were obtained from 29 patients with Crohn's disease, 30 patients with ulcerative colitis, 7 patients with intestinal Behçet's disease, and 12 healthy controls. Serum IgG subclasses IgG1, IgG2, IgG3, and IgG4 of ASCA were analysed using ELISA. IgG4 ASCA was significantly increased in patients with inflammatory bowel disease. In patients with intestinal Behçet's disease, IgG1, IgG3, and IgG4 ASCA were increased. Differential responses, in terms of subclasses in ASCA, were found in patients with inflammatory bowel disease and patients with intestinal Behçet's disease, which may represent different pathophysiologies of these intestinal inflammatory diseases.

A series of redox isomers of [CrIII(X4SQ)(X4Cat)2]2-, [CrIII(X4SQ)2(X4Cat)]-, and [CrIII(X4SQ)3]0 (X = Cl and Br, SQ = semiquinonate, and Cat = catecholate) have been synthesized and characterized as charge-transfer (CT) compounds with metallocenium cations: (CoIIICp2)2[CrIII(Cl4SQ)(Cl4Cat)2] (1), (CoIIICp2)2[CrIII(Br4SQ)(Br4Cat)2] (2), (FeIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)].C6H6 (4), (FeIIICp2)[CrIII(Br4SQ)2(Br4Cat)].CS2 (5), and (FeIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)][CrIII(Cl4SQ)3] (6). First, the oxidation states of the chromium complexes are strongly dependent on the redox potentials of the metallocenes used. The CoIICp2, exhibiting stronger reduction power than FeIICp2, is useful for two-electron reduction of the [CrIII(X4SQ)3]0, affording [CrIII(X4SQ)(X4Cat)2]2- (1 and 2), which are first isolated and crystallographically characterized in the solid state. In contrast the reaction with FeIICp2 affords only [CrIII(X4SQ)2(X4Cat)]- (4 and 5). Second, solvents influence crystal structures of these compounds. The solvent set of C6H6/CS2 gives 1:1:C6H6 compound 4 with unique charged anions, [CrIII(Cl4SQ)2(Cl4Cat)]-, while the other set, n-C6H12/CS2, affords 1:2 compound 6 including the two redox isomers, [CrIII(Cl4SQ)2(Cl4Cat)]- and [CrIII(Cl4SQ)3]0. The [CrIII(X4SQ)(X4Cat)2]2- anions in 1 and 2 show no significant interconnection between them (discrete type), while the [CrIII(X4SQ)2(X4Cat)]- anions in 4-6 show one-dimensional column-type structures with the aid of intermolecular stacking interactions of the ligand moieties. The anions in 4 show additional stacking interaction with the [FeIIICp2]+ to form one-dimensional ...[D][A][S][D][A]... (D = [FeIIICp2]+, A = [CrIII(Cl4SQ)2(Cl4Cat)]-, and S = C6H6) type mixed-stack arrangements similar to that of previously reported (CoIIICp2)[CrIII(Cl4SQ)2(Cl4Cat)].C6H6 (3). Compound 6 forms a two-dimensional sheet structure where the two redox isomers, [CrIII(Cl4SQ)2(Cl4Cat)]- and [CrIII(Cl4SQ)3]0, are included. The sheet is regarded as a mixed-valence molecular assembly. Two types of the anions, [CrIII(X4SQ)(X4Cat)2]2- (1 and 2) and [CrIII(X4SQ)2(X4Cat)]- (4-6), exhibiting an intramolecular mixed-valence state, show intramolecular intervalence CT transition (IVCT) from the Cat to the SQ at near 5800 and 4300 cm-1, respectively, both in the solution and in the solid states. The intermolecular mixed-valence state of 6 was characterized by absorption spectroscopy, electric conductivity, and SQUID magnetometry. Interestingly, this mixed-valence state of the chromium module is dependent on the redox active nature of the coordinated ligands.

Colonic varices is a rare entity that is caused by portal hypertension in most instances. In the case reported here, barium enema and colonoscopy showed multiple tortuous polypoid lesions with intact mucosal surface. Inferior mesenteric angiography showed arteriovenous malformation in the sigmoid colon, complete obstruction of the inferior mesenteric vein, and tortuous dilated marginal veins. We assume that the colonic varices of this case was secondary to complete obstruction of the inferior mesenteric vein following AVM of the sigmoid colon. Close follow-up should is warranted in cases of colonic varices because of the risk of bleeding.

A precise understanding of immunological mechanisms is needed to prevent transplant vasculopathy.The developing process of transplant vasculopathy was investigated by retransplanting rat cardiac allografts and measuring the expressions of 21 different genes inside the retransplanted allografts under nonimmunosuppressive conditions.Significant transplant vasculopathy developed if WKY hearts were grafted to LEW and retransplanted to WKY 5 days after the initial grafting, but it did not in allografts retransplanted 3 days after the initial grafting. The disease did not progress in retransplanted isografts or if nude rats were used as the initial recipients. However, the development of transplant vasculopathy was not affected by changing the second recipients to the F1 progeny of donor x recipient or to nude animals. Among the expressions of 21 different genes observed in allografts at 1, 14, 30, or 60 days after retransplantation, those of T-cell activation-related genes, such as interferon-y and Fas ligand, showed the earliest and the most dramatic difference between 3- and 5-day-retransplanted allografts whereas macrophage/monocyte activation-related genes showed little difference. Furthermore, reverse transcription-polymerase chain reaction analyses of allografts retransplanted to nude animal indicated that T cells of the initial recipient origin survive and remain activated even 60 days after retransplantation.The T-cell response occurring between 3 and 5 days after grafting was identified as the critical parameter to the disease progression. Once alloreactive T cells enter a graft, they may be able to survive a long period and promote chronic rejection.

A rat pancreas transplantation model with insulin-dependent diabetes mellitus (IDDM) recurrence was established using a Wistar-Furth (WF; RT1u, RT6.2) rat as a donor and diabetes-prone (DP; RT1u, rt6.1 gene carrier) BioBreeding rat as a recipient. Interestingly, NKR-P1+TCRalphabeta+ (NKT) cells have recently been reported to have immunoregulatory functions in preventing autoimmune diabetes. The purpose of this study was to specifically examine the contribution of NKT cells in the prevention of IDDM recurrence.Graft survivals with or without anti-intercellular adhesion molecule-1/leukocyte function-associated antigen-1 monoclonal antibodies were examined comparing pancreaticoduodenal (PD) transplantation with islet transplantation or pancreas-alone transplantation excluding duodenum and peripancreatic lymph nodes, in an IDDM recurrent model. The cells of the spleen were analyzed by flow cytometry (including intracellular interleukin (IL)-4 analysis), and serum cytokine levels (IL-4 and interferon-gamma) were determined by enzyme-linked immunosorbent assays (ELISA).Only those DP recipients transplanted with PD grafts with monoclonal antibody treatment were free from IDDM. Flow cytometric analyses of spleen cells showed that NKT cells in them, compared with those in the recurrent DP recipients (mean7%), increased significantly (13.7+/-3.1% in the total splenic T cells), most of which (85.9+/-4.3%) were derived from the donor (RT6.2+). The absolute number of RT6+NKT cells significantly increased in the nonrecurrent DP recipients, whereas that of RT6-NKT cells was similar with those of the other recurrent DP recipients. These RT6+NKT cells were predominantly CD4+ and showed significantly more expressions of intracellular IL-4 than the other T cells. By ELISA, serum interferon-gamma was not detectable (13 pg/ml) in any of the rats. However, IL-4 was detected at 111.6+/-47.8 pg/ml only in the nonrecurrent DP recipients.Unlike islet or pancreas-alone transplants, NKT cells, especially RT6+NKT cells derived from PD grafts, may have an important immunoregulatory function of preventing IDDM recurrence, involving a Th2 deviation.

Purified CD34+ haematopoietic progenitor cells were cultivated with stem cell factor, interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) for 7 d, and thereafter non-adherent cells were divided into two groups. Cells in one group (group A) were further cultivated for 7 d with four cytokines, and cells in the other group (group B) were further cultivated for 7 d with G-CSF alone. On day 14, 220-fold and 130-fold increases in the numbers of non-adherent cells were achieved for groups A and B respectively. These cell preparations contained 65% granulocytes for group A and 95% granulocytes for group B. These cells gained the ability to respond effectively with chemotaxis, phagocytosis and superoxide (O2-) release. Cells in group B were appropriately primed by G-CSF, GM-CSF, tumour necrosis factor alpha and IL-1beta for enhanced release of O2 -. The responsiveness of these cells was identical to that of peripheral blood neutrophils, indicating that cells in group B may be in the resting state. In contrast, cells in group A were not primed by these cytokines for enhanced release of O2- and released a large amount of O2- spontaneously, indicating that cells in group A may be in the activated state. These findings indicate that mature neutrophils with normal functions were expanded ex vivo in group B and suggest that these cells could be used for possible autologous neutrophil transfusion to prevent bacterial infections during severe neutropenia after cytotoxic chemotherapy.

From 1997, basic maternal and child health services have been provided through municipalities. The ministry of Health and Welfare has requested all municipalities to publish a MCH promotion plan. We conducted a qualitative analysis of important contents of the plans using an evaluation index of original dichotomous variables. Out of 3,256 municipalities, 2,873 developed the plans for MCH promotion. Most of the plans present descriptions of the significance of MCH promotion planning, goals of the plans, problems of current MCH statistics and services, and plans of providing services. The proportion was low for plans which have needs assessment of target population, indicators of evaluation of plans, description of the relationship between objectives and services, importance of objectives, action plans, specific chapter or evaluation of the plan, monitoring of the plan, and plans for informing public of the MCH plan. Therefore, the MCH promotion plans have weaknesses in evaluation and action. The MCH promotion plans of middle sized cities were more likely to have these important contents. We will continue to analyze the processes for producing of excellent MCH promotion plans to extract universal promoting factors for producing MCH promotion plans.

The configurations of hepatic veins, particularly the complementary territorial relationships between the veins, in the right surgical lobes of 156 human livers, the segments of which were identified clearly according to the portal ramification, were studied. In order to assess the functional roles of the vessels, we compared the diameter values of the vessels in the upper region of the lobe under the assumption that this parameter corresponds very closely to the actual blood flow volume through the vessel. The right hepatic vein (RHV) sometimes (17%) developed poorly and drained neither segment V (S5) nor VI (S6); instead, the inferomedial part of the S6 was often (26%) drained by the middle hepatic vein (MHV). However, most thick short hepatic veins (SHVs) did not drain S6 specifically instead of a poorly-developed RHV, but usually drained both S6 and segment VII (S7), irrespective of the configurations of other veins. Sometimes (8%), the RHV, rather than the MHV, drained a large part of S5. Overall, in the lower region of the lobe, the RHV, SHV and MHV showed complementary venous drainage relationships. Furthermore, the RHV usually (75%) ran not between S5 and S6 but through S6, corresponding to its usual territory, and could not be regarded as the intersectorial landmark in the lower region. Although various names have been given to the thick venous tributaries in the upper region of the right lobe, we systematically classified these tributaries into 5 types of "right superior radicles" (RSR), according to their topographical relationships with the right superior portal branches (P7 and P8), RHV, MHV, SHVs and their tributaries. When just thick RSRs were considered, the 5 types (anterior, posterior, lateral, medial and intersegmental) were observed in 90%, 88%, 89%, 38% and 34%, respectively. Notably, all but the intersegmntal RSRs almost always corresponded to a specific segmental territory (S7 or segment VIII (S8) and had specific terminals (at the RHV or MHV), suggesting that these 4 RSRs were proper segmental or intrasegmental veins, whereas, the 5th type showed a different configuration, i.e., an intersegmental vein that drained both S7 and S8, ran along and above the RHV and merged with it. Our morphometric examination of the upper region revealed that the sizes of P7 and P8 increased or decreased simultaneously, and suggested that the RSRs played limited roles in venous return. Rather than the RSRs, the SHVs appeared to drain the overflow in excess of the venous return capacity of the RSRs. Despite their limitations and possible complementary relationships with some veins, however, all the superior veins tended to developed evenly well or poorly. Overall, the venous return did not seem to converge into a single particular vein, but was carried away by multiple superior veins: the RHV, MHV, SHVs, and 5 RSRs.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL) -3 induced tyrosine phosphorylation of 92-kDa protein in normal human monocytes. We identified this 92-kDa protein as STAT5, but not as STATs1, 3, and 6 nor c-fes and vav protooncogene products, and demonstrated its translocation to the nucleus, enhancement of specific DNA binding capacity, and potentiation of trancriptional activity by GM-CSF. N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA) induced tyrosine phosphorylation of 42- and 44-kDa proteins, which were identified as extracellular signal-regulated kinase (ERK), in human monocytes. In marked contrast to neutrophils and MO7e cells, GM-CSF did not induce tyrosine phosphorylation and activation of ERK in monocytes. Among upstream signaling molecules of ERK, Shc was constitutively associated with Grb2 and was not tyrosine-phosphorylated by GM-CSF and FMLP, and Sos1 and c-Raf-1 were not phosphorylated by GM-CSF, IL-3, TNF, and FMLP in monocytes, whereas all these signaling molecules were affected and/or utilized by GM-CSF in MO7e cells. In contrast to neutrophils, p38 was constitutively phosphorylated and agonist-dependent phosphorylation and activation was not detected in human monocytes. Superoxide release stimulated by FMLP was inhibited partially by PD98059 or SB203580, a specific inhibitor of ERK or p38 pathway, and was almost completely inhibited by the combination of both inhibitors, whereas PMA-induced superoxide release was resistant to these two inhibitors in monocytes. PD98059 inhibited GM-CSF-dependent proliferation of MO7e cells. Present results indicate trancriptional roles of STAT5 and functional roles of ERK and/or p38 in normal human monocytes stimulated by physiological receptor-mediated agonists GM-CSF and FMLP. Possible roles of ERK in proliferation of transformed cells were also suggested.

A 26-year-old female with hereditary neutropenia had Pustulosis Palmaris et Plantaris. Drug administration did not improve her symptoms. Following administration of granulocyte colony stimulating factor (G-CSF; filgrastim), her neutrophil count increased from 300 to 58,000/microliters, and her dermatosis improved. Pustulosis Palmaris et Plantaris has been described as a representative second lesion of focal infection. Neutropenia may be one cause of Pustulosis Palmaris et Plantaris due to refractory focal infection. In the present case, increase in neutrophils with G-CSF may have improved focal infection, resulting in improvement in refractory Pustulosis Palmaris et Plantaris.

To clarify the differences of the signaling pathways used by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor- (TNF), we investigated activation of mitogen-activated protein kinase (MAPK) subtype cascades in human neutrophils stimulated by these cytokines. G-CSF exclusively tyrosine-phosphorylated extracellular signal-regulated kinase (ERK). GM-CSF tyrosine-phosphorylated ERK strongly and p38 MAPK weakly, whereas TNF tyrosine-phosphorylated p38 MAPK strongly and ERK weakly. Consistent with these findings, MEK, an upstream kinase of ERK, was phosphorylated by G-CSF, GM-CSF, and TNF, whereas MKK3/MKK6, an upstream kinase of p38 MAPK, was phosphorylated by GM-CSF and TNF, but not by G-CSF. The potency of these cytokines to phosphorylate ERK and MEK was GM-CSFG-CSFTNF, whereas that to phosphorylate p38 MAPK and MKK3/MKK6 was TNFGM-CSF. C-Jun amino-terminal kinase (JNK) was not tyrosine-phosphorylated by any cytokine despite the existence of JNK proteins in human neutrophils, whereas it was tyrosine-phosphorylated by TNF in undifferentiated and all-trans retinoic acid-differentiated HL-60 cells. Increased phosphorylation of ERK or p38 MAPK was detected within 1 to 5 minutes after stimulation with each cytokine and was dependent on the concentrations of cytokines used. MEK inhibitor (PD98059) reduced tyrosine phosphorylation of ERK, but not p38 MAPK, induced by G-CSF, GM-CSF, or TNF. GM-CSF- or TNF-induced superoxide (O2-) release was inhibited by p38 MAPK inhibitor (SB203580) in a dose-dependent manner, suggesting the possible involvement of p38 MAPK in GM-CSF- or TNF-induced O2- release. The results indicate that G-CSF, GM-CSF, and TNF activate the overlapping but distinct MAPK subtype cascades in human neutrophils and suggest that the differential activation of ERK and p38 MAPK cascades may explain the differences of the effects of these cytokines on human neutrophil functions.

Tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) rapidly primed human neutrophils for enhanced superoxide (O2-) release, and membrane depolarization stimulated by chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine), interleukin 8, concanavalin A (Con A) and ionomycin. Combined stimulation of human neutrophils with the optimal concentrations of TNF plus GM-CSF showed no additive or synergistic effects according to the subsequent stimuli and within the parameters tested. Particularly, a high synergistic priming effect of these two cytokines was observed when Con A was used as a triggering agonist of O2- release. The priming of human neutrophils with the optimal concentrations of TNF plus G-CSF, however, always resulted in the same effect as TNF alone. TNF and GM-CSF triggered O2- release directly in human neutrophils for prolonged time periods, and combined stimulation of human neutrophils with the optimal concentrations of TNF plus GM-CSF triggered an added amount of O2- release. TNF and GM-CSF by themselves induced an increase in cytoplasmic pH (intracellular alkalinization), an important signaling event for functional activation of neutrophils, though combined stimulation of human neutrophils with the optimal concentrations of the two cytokines had no additive effects on cytoplasmic pH. The present results show cooperative interaction between TNF and GM-CSF in their stimulatory effects on particular functions in human neutrophils, and these synergistic effects are probably mediated via a mechanism distal to or independent of intracellular alkalinization.

A 61-year-old Japanese woman was hospitalized because of general malaise. The patient demonstrated hypertension, hypokalemia and chronic renal failure (CRF). Plasma aldosterone concentration and urinary excretion of aldosterone were elevated. Abdominal computed tomographic scan revealed right adrenal tumor and multiple cysts in both kidneys. Adrenal scintigram using 131I-adosterol disclosed uptake of the isotope in the area corresponding to the adrenal tumor. Plasma aldosterone concentration and renin activity (PRA) in an upright posture and daily variations in adrenocorticotropic hormone, cortisol, aldosterone levels and PRA were compatible with aldosterone-producing adrenocortical adenoma. After administration of spironolactone and manidipine hydrochloride, a calcium antagonist, general malaise disappeared, and blood pressure and serum potassium level returned to the normal range without adrenalectomy. Although adrenalectomy is known to be effective for the treatment of aldosterone-producing adrenocortical adenoma, several papers reporting cases of aldosterone-producing adrenocortical adenoma with CRF indicated that surgical therapy was not always optimal in terms of postoperative conditions. Taken together, the conservative therapy may be one of the choices considering the prognoses of hypertension and renal dysfunction in patients with aldosterone-producing adrenocortical adenoma with CRF.

Desmoid tumors develop in the muscle or aponeurosis, but rarely in the chest wall. We report a patient with desmoid tumor in the chest wall. A 30-year-old female visited our hospital due to an abnormal shadow in the chest detected at a health examination. No definite diagnosis could be made by chest CT, MRI, or Ga scintigraphy, and finally a biopsy demonstrated desmoid tumor. The left anterior chest and posterolateral chest (lung apex) were opened, and tumors were resected together with the chest wall. No radiotherapy was performed. No recurrence has been observed for 1.5 years after operation. This tumor does not yield distant metastasis, but its recurrence rate is very high. Therefore, we intend to follow this patient for a long period.

Ifosfamide, Carboplatin and Etoposide (ICE) therapy was used to treat 4 patients, 2 with refractory osteosarcoma, and one each with relapsed brain tumor and newly diagnosed brain tumor. ICE therapy was administered in doses of Ifosfamide 1,800 mg/m2 x 5, Carboplatin 400 mg/m2 x 2 and Etoposide 100 mg/m2 x 5. A total of 30 courses were administered. Two cases of osteosarcoma had a stable disease (range, 3-9 months) and 2 cases of brain tumor had a complete response by magnetic resonance imaging. Moderate or severe toxicity evaluated on a per course basis included: neutropenia 83%, thrombocytopenia 93%, fever 30%, hepatotoxicity 3%, and hemorrhagic cystitis 3%. The median time to hematologic recovery was 20 days. ICE therapy is highly effective for the treatment of refractory or recurrent solid tumors with acceptable toxicity.

The novel, modified instrumentation of a capillary zone electrophoresis (CZE) system and theory are proposed for the measurement of diffusion coefficient. The solute zone in capillary tubing is forced back and forth repeatedly by the aid of negative and positive applied high voltage, respectively, and the peak widths are recorded for the estimation of diffusion coefficient. The diffusion coefficients of Ce(III) and Cu(II) in aqueous solution were determined, and the former hydration number of Ce(III) was estimated by comparison with both diffusion coefficients.

In order to obtain information on the elderly cared for in long-term facilities, regarding their needs and the actual services received in these facilities, and to determine which facility could provide the most suitable service, elderly in two areas, urban S area and rural N area, were surveyed. The results were as follows. (1) The proportion of elderly placed in hospitals where the suitable care placements were hospitals was 84.6% in S area, and 66.6% in N area. (2) In elderly cared for in long-term facilities, the proportion of persons where the suitable care placement was in-home care was 11.7% in S area, and 14.1% in N area. (3) Therefore estimates for the elderly that would be for at home increases by 21.1% in S area and 27.2% in N area than the estimated figures used in plan for Elderly-Health Welfare in 2,000 AD.

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synergistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1 beta. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-alpha, IL-1 beta, or tumor necrosis factor alpha, while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.

The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.

The two-dimensional C 1s photoelectron intensity angular distributions (PIADs) and spectra of exfoliated graphene flakes and crystalline graphite were measured using a focused soft X-ray beam. Suitable graphene samples were selected by thickness characterization using Raman spectromicroscopy after transferring mechanically exfoliated graphene flakes onto a 90-nm-thick SiO2 film. In every PIAD, a Kagomé interference pattern was observed, particularly clearly in the monolayer graphene PIAD. Its origin is the overlap of the diffraction rings formed by an in-plane C–C bond honeycomb lattice. Thus, the crystal orientation of each sample can be determined. In the case of bilayer graphene, PIAD was threefold-symmetric, while those of monolayer graphene and crystalline graphite were sixfold-symmetric. This is due to the stacking structure of bilayer graphene. From comparisons with the multiple scattering PIAD simulation results, the way of layer stacking as well as the termination types in the edge regions of bilayer graphene flakes were determined. Furthermore, two different C 1s core levels corresponding to the top and bottom layers of bilayer graphene were identified. A chemical shift to a higher binding energy by 0.25 eV for the bottom layer was attributed to interfacial interactions.