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1.
Sci Adv ; 7(16)2021 04.
Article in English | MEDLINE | ID: mdl-33853775

ABSTRACT

Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method's ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology.

2.
Am J Transplant ; 14(6): 1290-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24731050

ABSTRACT

Blocking the CD40-CD154 interaction is reported to be effective for transplantation management and autoimmune disease models in rodents and nonhuman primates. However, clinical trials with anti-CD154 mAbs were halted because of high incidence of thromboembolic complications. Thus, we generated and characterized a fully human anti-CD40 mAb ASKP1240, as an alternative to anti-CD154 mAb. In vitro ASKP1240 concentration-dependently inhibited human peripheral blood mononuclear cell proliferation induced by soluble CD154. In addition, ASKP1240 did not destabilize platelet thrombi under physiological high shear conditions while mouse anti-human CD154 mAb (mu5C8) did. And ASKP1240 itself did not activate platelet and endothelial cells. In vivo administration of ASKP1240 (1 or 10 mg/kg, intravenously) to cynomolgus monkeys, weekly for 3 weeks, significantly attenuated both delayed-type hypersensitivity and specific antibody formation evoked by tetanus toxoid. The immunosuppressive effect was well correlated with the CD40 receptor saturation. Thus, these results suggest that ASKP1240 is immunosuppressive but not prothromboembolic, and as such appears to be a promising therapeutic candidate for the management of solid organ transplant rejection and autoimmune diseases therapy.


Subject(s)
Antibodies, Monoclonal/immunology , CD40 Antigens/immunology , Immunosuppressive Agents/pharmacology , Animals , Antibodies, Monoclonal, Humanized , Antibody-Dependent Cell Cytotoxicity/drug effects , Cross Reactions , Flow Cytometry , Humans , Hypersensitivity, Delayed/drug therapy , Hypersensitivity, Delayed/immunology , Immunosuppressive Agents/immunology , Macaca fascicularis , Mice
3.
J Anim Sci ; 91(8): 3989-96, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23736046

ABSTRACT

The aim of this study was to determine the loading capacity of a trotting Taishuh pony by gait analysis using a motion analysis system. Seven Taishuh Ponies (5 mares and 2 geldings) and their rider were fitted with a marker (70 mm in diameter placed on their chest) and recorded by 2 high-resolution digital DVD cameras (at a sampling frequency of 60 Hz) as they were trotting along a straight course. Each horse performed 7 tests: 1 test with a loaded weight of 70 kg, 5 tests with random loaded weights between 80 kg and 120 kg, and a final test with a loaded weight of 70 kg again. Three-dimensional movements of each marker were analyzed using motion capture system. The time series of the vertical displacements of the marker was subjected to spectrum analysis by the maximum entropy method, and the autocorrelation coefficient was calculated. The first 2 peaks of the autocorrelation were defined as symmetry and regularity of the gait, and the sum of symmetry and regularity was defined as stability. The cross-spectrum analysis (Blackman-Tukey method) also was performed to analyze the time lag and cross-correlation coefficient between the time series of both pony and rider. Among ponies, symmetry in the 120 kg test (0.54) was significantly lower than that in the first 70 kg test (0.75, P < 0.05) and stabilities in the 100 kg (1.17) and 120 kg (1.17) tests were significantly less than that in the first 70 kg (1.46, P < 0.05). Regarding the rider, there were no significant differences in symmetry, regularity, and stability between loaded weights. The time lag between the time series of horse and rider in the 120 kg test (47.6 ms) was significantly greater than that in the first 70 kg (14.3 ms, P < 0.05) test. These results suggests that the maximum permissible load weight of the Taishuh pony trotting at 3.0 m/s over a short distance was less than 100 kg, which is 43% of the BW.


Subject(s)
Horses/physiology , Weight-Bearing/physiology , Animals , Biomechanical Phenomena , Body Composition , Body Weight , Equine-Assisted Therapy , Female , Gait/physiology , Humans , Male
4.
Skin Pharmacol Physiol ; 22(5): 240-7, 2009.
Article in English | MEDLINE | ID: mdl-19690449

ABSTRACT

Although many mouse models of atopic dermatitis have been reported, few rat models have been studied. In this study, a rat chronic allergic dermatitis model was developed and evaluated as a pharmacological model of atopic dermatitis. Prominent ear thickening and scratching were induced after the application of 2,4-dinitrochlorobenzene to the right ear of Brown Norway rats 3 times per week for 3 weeks. Histopathologically, infiltration of T cells in the ear was observed on day 7, and eosinophils and mast cells were found in addition to T cells on day 21. The expression of interferon-gamma and interleukin-4 was increased on day 7 when compared with normal rats. However, interferon-gamma expression had disappeared by day 21. Tacrolimus ointment applied after ear tissue thickening fully developed, suppressed chronic dermatitis in a dose-dependent manner. This model has some symptomatic and histopathological similarities to atopic dermatitis and might be useful in pharmacological studies.


Subject(s)
Dermatitis, Atopic/chemically induced , Dinitrochlorobenzene/toxicity , Disease Models, Animal , Animals , Chronic Disease , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Dinitrochlorobenzene/administration & dosage , Drug Administration Schedule , Ear , Haptens/administration & dosage , Haptens/toxicity , Male , Rats , Rats, Inbred BN , Time Factors
5.
J Oral Rehabil ; 36(9): 627-35, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19602100

ABSTRACT

To examine the stiffness of the masseter muscle using sonographic elastography and to investigate its relationship with the most comfortable massage pressure in the healthy volunteers. In 16 healthy volunteers (10 men and 6 women), the Masseter Stiffness Index (MSI) was measured using EUB-7000 real-time tissue elastography. They underwent massages at three kinds of pressures using the Oral Rehabilitation Robot (WAO-1). A subjective evaluation regarding the comfort of each massage was recorded on the visual analogue scale. Elastography was also performed in two patients with temporomandibular joint dysfunction with the myofascial pain. The mean MSI of the right and left muscles in the healthy volunteers were 0.85 +/- 0.44 and 0.74 +/- 0.35 respectively. There was no significant difference between the right and left MSI in the healthy volunteers. The MSI was related to massage pressure at which the healthy men felt most comfortable. The two temporomandibular disorder patients had a large laterality in the MSI. The MSI was related to the most comfortable massage pressure in the healthy men. The MSI can be one index for determining the massage pressure.


Subject(s)
Elasticity Imaging Techniques/methods , Massage/methods , Masseter Muscle/diagnostic imaging , Temporomandibular Joint Dysfunction Syndrome/rehabilitation , Adult , Elasticity Imaging Techniques/instrumentation , Female , Humans , Male , Massage/instrumentation , Masseter Muscle/physiology , Middle Aged , Pain Measurement , Pressure , Sensory Thresholds , Temporomandibular Joint Dysfunction Syndrome/diagnostic imaging
6.
Caries Res ; 41(2): 161-4, 2007.
Article in English | MEDLINE | ID: mdl-17284919

ABSTRACT

The purposes of this study were to investigate the enamel maturation process in the occlusal pit of sound first molars by measuring electrical resistance. Ninety-nine sound first molars in 34 children (mean age of 6.47 +/- 0.51 years) were measured electrically once every 6 months and were monitored for a maximum of 66 months. Electrical resistance increased during the posteruptive period. However, the results suggest that posteruptive enamel maturation in the occlusal pits may not be completed even 66 months after tooth eruption.


Subject(s)
Dental Enamel/growth & development , Dental Enamel/physiology , Child , Child, Preschool , Dental Enamel Permeability , Dental Fissures/physiopathology , Electric Impedance , Humans , Longitudinal Studies , Molar/physiology , Porosity , Tooth Calcification/physiology , Tooth Eruption
7.
Caries Res ; 40(6): 487-93, 2006.
Article in English | MEDLINE | ID: mdl-17063019

ABSTRACT

The purpose of this study was to estimate the average daily amount of fluoride from the diet ingested by Japanese children of ages susceptible to dental fluorosis in two areas with different fluoride concentrations in the water supply. Thirty-eight children aged 2-8 years participated in a survey of fluoride intake. Twenty-one out of 38 children lived in an area in which the community water fluoride concentration was an average of 0.555 ppm (moderate fluoride area: MFA), and 17 lived in a low fluoride area (LFA), which ranged between 0.040 and 0.131 ppm. To measure the fluoride intake, diets were collected with a duplicate-diet technique. The fluoride concentrations in each sample were measured using the diffusion technique of Taves and the electrode technique. Meanwhile, after clinical examinations for dental caries and fluorosis, 228 subjects aged 13-15 years were selected for analysis from the same communities. The mean DMFT in the MFA was significantly lower than that in the LFA. The severest grade of dental fluorosis observed was 'very mild' according to Dean's fluorosis index in both areas. The total daily fluoride intakes were 0.0252-0.0254 mg F/kg/day in the MFA and 0.0126-0.0144 mg F/kg/day in the LFA. Differences in the fluoride concentration of drinking water in this study were reflected in the fluoride intake from the diet in a typical Japanese diet.


Subject(s)
Cariostatic Agents/administration & dosage , Diet , Fluoridation/adverse effects , Fluorides/administration & dosage , Fluorosis, Dental/epidemiology , Adolescent , Asian People/statistics & numerical data , Cariostatic Agents/analysis , Child , Child, Preschool , Epidemiologic Methods , Fluorides/analysis , Humans
8.
Int J STD AIDS ; 16(9): 644-5, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16176638

ABSTRACT

Streptococcus pyogenes (the Lancefield group A streptococcus) is a cause of pharyngitis and impetigo. However, it has rarely been implicated as a sexually transmitted pathogen. We herein report two cases of severe balanitis due to S. pyogenes in sexually active men. It is postulated that penile cellulitis developed following the invasion of S. pyogenes through a traumatic abrasion acquired during fellatio performed by commercial sex workers. Both patients were treated successfully with oral administration of penicillin.


Subject(s)
Balanitis/microbiology , Balanitis/pathology , Streptococcus pyogenes/pathogenicity , Adult , Humans , Male , Middle Aged , Streptococcal Infections/microbiology , Streptococcal Infections/pathology
9.
Int Dent J ; 54(3): 126-30, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15218891

ABSTRACT

AIM: To determine whether Japanese preschool-aged children swallow fluoride solution while rinsing and how much fluoride was retained in the mouth after rinsing. METHODS: The subjects were 769 children who participated in a school-based fluoride mouth rinse programme (FMR) using 0.05% sodium fluoride solution daily. The group of younger, mean age of 4 years and 10 months, experienced the FMR for two months, and the group of older children, mean age of 5 years and 4 months, did it for at least 8 months, rinsing for a minute using 7 ml of the solution. The amount of fluoride retained in the mouth was estimated as the amount present in the net rinsing solution prepared minus what returned to the solution expectorated. RESULTS: No child swallowed all the solution. The rate of fluoride retained was 12.0% (mean = 0.19 mg) in the younger group and 10.7% (mean = 0.17 mg) in the older. Only six children retained over 0.5 mg of fluoride. With the extra survey using weekly intervals, the amount retained was below 0.5 mg in all children. CONCLUSION: That Japanese preschoolaged children could perform fluoride mouth rinsing safely and efficiently.


Subject(s)
Cariostatic Agents/administration & dosage , Deglutition , Fluorides/administration & dosage , Mouthwashes/therapeutic use , Age Factors , Cariostatic Agents/pharmacokinetics , Child, Preschool , Fluorides/pharmacokinetics , Follow-Up Studies , Humans , Japan , Mouth/metabolism , Safety
10.
J Comp Pathol ; 131(1): 38-51, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15144798

ABSTRACT

A transplantable tumour (RY) and cell lines (RY-PB and clone RY-B-E3 isolated from RY-PB) were established from a naturally occurring endometrial stromal sarcoma (ESS) found in a 24-month-old female F344 rat. The primary tumour and RY tumours, which had been serially passaged in syngeneic female rats up to the 10th generation, consisted of spindle or round cells arranged in ill-defined bundles or sheets. Neoplastic cells of the primary and RY tumours, as well as cultured cells of RY-PB and RY-B-E3, showed positive reactions to vimentin, ED1/ED2 (both for rat macrophages/histiocytes), OX6 (for dendritic cells expressing rat MHC class II antigens), and lysosomal enzymes such as acid phosphatase and non-specific esterase, in varying degrees. Ultrastructurally, neoplastic cells characteristically had tubulovesicular system-like structures and variously developed lysosomes in the cytoplasm. Neoplastic cells also exhibited immunoexpression to an alpha-smooth muscle actin (alpha-SMA). The addition of transforming growth factor (TGF)-beta1 to RY-PB and RY-B-E3 cultures increased the number of alpha-SMA-positive cells, whilst the positive cell number was decreased by anti-TGF-beta antibody. The RT-PCR method revealed the expression of TGF-beta1 mRNA in the cultured cells. The present study showed that rat ESS-derived cells exhibited dendritic cell-like and myofibroblastic cell-like phenotypes. The histogenesis of ESSs in human beings and rats remains poorly understood, and these tumour lines may therefore become useful tools for further research.


Subject(s)
Cell Line, Tumor , Endometrial Neoplasms/pathology , Sarcoma, Endometrial Stromal/pathology , Sarcoma, Experimental/pathology , Animals , Apoptosis/physiology , Cell Transplantation , DNA Fragmentation , Dendritic Cells/metabolism , Dendritic Cells/pathology , Endometrial Neoplasms/metabolism , Female , Fibroblasts/metabolism , Fibroblasts/pathology , Immunohistochemistry , Microscopy, Electron, Transmission , Neoplasm Transplantation , RNA, Messenger/analysis , Rats , Rats, Inbred F344 , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Endometrial Stromal/metabolism , Sarcoma, Experimental/metabolism , Transforming Growth Factor beta/biosynthesis , Transforming Growth Factor beta1
11.
Clin Exp Allergy ; 33(11): 1555-60, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14616868

ABSTRACT

BACKGROUND: It is well-known that FK506 strongly inhibits cytokine production by T cells in vitro. However, less evidence is available from in vivo studies of ocular allergy. OBJECTIVE: To study the anti-inflammatory effect of FK506 eye drops on late and delayed-type responses in several animal models of ocular allergy. METHODS: Rats and guinea-pigs were sensitized with egg albumin (EA) in adjuvant and later challenged by topical EA application to their eyes to examine the late response. Biopsy specimens of conjunctiva were stained with haematoxylin-eosin or stained for T cells and eosinophils. In addition, rats, rabbits and guinea-pigs were sensitized with complete Freund's adjuvant and later challenged by injecting purified protein derivatives for the delayed-type response. Bulbar conjunctival oedema and hyperaemia were graded by score in rabbits, and Evans blue (EB) extravasation was measured in rats and guinea-pigs. FK506 (0.01-1%) and steroid (0.1%) eye drops were instilled in the eyes of animals several times, before and after challenge. RESULTS: FK506 eye drops inhibited T cell and eosinophil infiltration in the late response and EB extravasation in the delayed-type response in rats. Also, they inhibited conjunctival oedema, hyperaemia and ocular mucus in the delayed-type response in rabbits. These effects were similar to those of steroid eye drops (betamethasone sodium phosphate, fluorometholone). FK506 eye drops also inhibited inflammatory cell infiltration, the loss of conjunctival epithelium and decrease of goblet cells in the late response as well as EB extravasation in the delayed-type response in guineapigs, a steroid-resistant species. CONCLUSION: FK506 eye drops inhibit late and delayed-type responses in animal models of ocular allergy.


Subject(s)
Conjunctivitis, Allergic/prevention & control , Hypersensitivity, Delayed/prevention & control , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Animals , Conjunctivitis, Allergic/immunology , Conjunctivitis, Allergic/pathology , Disease Models, Animal , Dose-Response Relationship, Immunologic , Eosinophils/immunology , Glucocorticoids/therapeutic use , Guinea Pigs , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/pathology , Male , Ophthalmic Solutions , Rabbits , Rats , Rats, Inbred BN , T-Lymphocytes/immunology
12.
Acta Neuropathol ; 106(3): 221-33, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12811582

ABSTRACT

Transplantable tumor (KE) and clone cell (KE-F11) lines were established from a spontaneous malignant schwannoma found in an aged F344 rat. The primary tumor and KE tumors consisted of oval or spindle cells arranged in ill-defined bundles. Cultured KE-F11 cells exhibited polygonal or spindle configurations. Immunohistochemically, neoplastic cells in KE and KE-F11 reacted to vimentin, S-100 protein, neuron-specific enolase, myelin basic protein, and glial fibrillary acidic protein in varying degrees, indicating neurogenic features; occasional cells reacted to alpha-smooth muscle actin. Cells positive for lysosomal enzymes (acid phosphatase and non-specific esterase), and ED1 (rat macrophage specific) were observed in KE-F11, and electron microscopically, cells with many lysosomes were frequently present, indicating expression of macrophage-like phenotypes. Bioassay analysis revealed that KE-F11 cells produced high levels of nerve growth factor. DNA synthesis was inhibited by addition of transforming growth factor-beta1 (TGF-beta1), and Northern blot analysis revealed that expression of c-myc, a cell cycle-related immediate early gene, was depressed by TGF-beta1. Likely, TGF-beta1 is a factor capable of inhibiting cellular growth of Schwann cells. mRNA expression of the low-density lipoprotein receptor-related protein (LRP) was seen in KE-F11 cells by Northern blot analysis, and the level was decreased by lipopolysaccharide (LPS) treatment. LRP may be attributable to regulation of Schwann cell functions. KE-F11 cells seeded on laminin-coated dishes exhibited more extended cytoplasmic projections than on collagen type I-coated dishes. The present study provides evidence that biological properties of malignant schwannoma-derived cells might be affected by exogenous factors such as TGF-beta1, LPS and laminin. These tumor lines may be useful for studies on pathobiological characteristics of Schwann cells.


Subject(s)
Macrophages/ultrastructure , Nerve Growth Factor/metabolism , Neurilemmoma/metabolism , Transforming Growth Factor beta/metabolism , Actins/metabolism , Animals , Blotting, Northern , Cell Count , Cell Line, Transformed , Desmin/metabolism , Dose-Response Relationship, Drug , Genes, jun/physiology , Genes, myc/physiology , Glial Fibrillary Acidic Protein/metabolism , In Vitro Techniques , Keratins/metabolism , Lipopolysaccharides/pharmacology , Macrophages/pathology , Male , Microscopy, Electron , Myelin Basic Protein/metabolism , Neurilemmoma/pathology , Neurilemmoma/ultrastructure , PC12 Cells , Phenotype , Phosphopyruvate Hydratase/metabolism , RNA, Messenger/biosynthesis , Rats , Rats, Inbred F344 , Reverse Transcriptase Polymerase Chain Reaction/methods , S100 Proteins/metabolism , Staining and Labeling , Time Factors , Transforming Growth Factor beta1 , Vimentin/metabolism
13.
Br J Cancer ; 88(10): 1522-6, 2003 May 19.
Article in English | MEDLINE | ID: mdl-12771916

ABSTRACT

The heparin-binding growth factor midkine (MK) is the product of a retinoic acid-responsive gene, and is implicated in neuronal survival and differentiation, and carcinogenesis. We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas. As MK is a secretory protein, it can be detected in the blood. Here, we show a significant correlation of the plasma MK level with prognostic factors of neuroblastomas. The plasma MK level was determined in 220 patients with neuroblastomas, and compared with that in children without malignant tumors (n=17, <500 pg ml(-1)). The plasma MK level became significantly elevated with advancing stages (stage 1: 445 pg ml(-1) (median), n=73; stage 2: 589, n=39; stage 3: 864, n=40; stage 4: 1445, n=56; and stage 4S: 2439, n=12). More importantly, a higher MK level was strongly correlated with poor prognostic factors: over 1 year of age (P=0.0299), MYCN amplification (P<0.0001), low TrkA expression (P=0.0005), nonmass screening, sporadic neuroblastomas (P<0.0001), and diploidy/tetraploidy (P=0.0007). Thus, these results demonstrate that the plasma MK level is a good marker for evaluating the progression of neuroblastomas. Moreover, considering the ability of antisense MK oligodeoxyribonucleotide to suppress tumour growth of colorectal carcinoma cells in nude mice, as recently reported, the present study suggests that MK is a possible candidate molecular target for therapy for neuroblastomas.


Subject(s)
Biomarkers, Tumor/analysis , Carrier Proteins/blood , Cytokines , Gene Expression Regulation, Neoplastic , Nerve Growth Factors/blood , Neuroblastoma/pathology , Animals , Carrier Proteins/biosynthesis , Humans , Immunoenzyme Techniques , Infant , Infant, Newborn , Mice , Mice, Nude , Midkine , Nerve Growth Factors/biosynthesis , Neuroblastoma/genetics , Oligoribonucleotides, Antisense , Prognosis
14.
Vet Pathol ; 39(3): 322-33, 2002 May.
Article in English | MEDLINE | ID: mdl-12014496

ABSTRACT

To shed some light on the mechanisms behind renal fibrogenesis, the present study immunohistochemically investigated the participation of different macrophage populations and myofibroblastic cells in rat renal interstitial fibrosis developed chronically after repeated injection of cisplatin (2 mg/kg body weight, once weekly for 7 weeks). During the 19-week recovery period after the final injection, fibrotic lesions progressively developed in the corticomedullary junction, with the greatest level at post-final injection (FPI) week 5, and then the lesions were gradually repaired by PFI week 19, indicative of a healing process. In conformity with the development of fibrotic lesions, the number of myofibroblastic cells reacting with an anti-alpha-smooth muscle actin antibody was increased, with a peak at PFI week 3, and collagens (types I, III, and IV), fibronection, and laminin were excessively accumulated in these areas. Interstitial cells forming the fibrotic lesions showed mitotic activity at the early stages, whereas they disappeared by apoptosis in the healing process. A large number of cells reacting with an antibody of ED1 (for exudate macrophages), ED2 (for resident macrophages), or OX6 (for major histocompatibility complex class II-presenting macrophages and interstitial dendritic cells) had already appeared at PF1 week 1, and then their numbers increased, with a peak at PFI weeks 7, 3, and 9 in ED1-, ED2-, and OX6-positive cells, respectively. Thereafter, the number of ED1- and ED2-positive cells decreased, whereas the number of OX6-positive cells persisted at a high level until PFI week 19. In the healing process, clusters of lymphocytes were present, the development of which might have been related to OX6-positive cells. The present study demonstrated that chronically developing rat renal interstitial fibrosis might be produced by the complicated mechanisms evoked by interactions between different macrophage populations and myofibroblastic cells, because macrophages show heterogeneous functions depending on microenvironmental factors.


Subject(s)
Fibroblasts/pathology , Fibrosis/pathology , Macrophages/pathology , Nephritis, Interstitial/pathology , Animals , Apoptosis/physiology , Bromodeoxyuridine/metabolism , Cisplatin/toxicity , Extracellular Matrix Proteins/metabolism , Fibrosis/chemically induced , Immunohistochemistry , In Situ Nick-End Labeling , Kidney/drug effects , Kidney/pathology , Macrophages/metabolism , Male , Nephritis, Interstitial/chemically induced , Rats , Rats, Inbred F344 , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1
15.
J Comp Pathol ; 126(1): 66-70, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11814323

ABSTRACT

Three-dimensional angioarchitecture in a transplantable fibrosarcoma (SS) in F344 rats was investigated by scanning electron microscopy (SEM) of vascular corrosion casts. Tumours were produced in syngeneic rats by implantation of a tumour fragment from another SS tumour. Viable SS tumours, observed up to post-implantation (PI) week 5, showed a high degree of vascularization, consisting of arterioles and veins, and intertwining capillaries branching from such vessels. The capillaries showed numerous finger-like outgrowths, indicating active sprouting of endothelial cells and contributing to tumour growth. In contrast, SS tumours in rats given a single dose (4 mg/kg/bodyweight) of cisplatin at PI week 1 were reduced in volume, lacking in capillary outgrowths, and of low vascular density. Necrotic areas in SS tumours were surrounded by capillaries with sharp tips and wrinkled surfaces. Thus, the findings indicated differences in three-dimensional angioarchitecture between vigorously developing tumours and (1) tumours degenerating as the result of treatment with an anti-cancer drug, or (2) necrotic tumour tissues. SEM of vascular corrosion casts may prove useful for the evaluation of neovascularization in mesenchymal tumours.


Subject(s)
Blood Vessels/ultrastructure , Fibrosarcoma/blood supply , Salivary Gland Neoplasms/blood supply , Submandibular Gland/blood supply , Animals , Blood Vessels/drug effects , Capillaries/drug effects , Capillaries/ultrastructure , Cisplatin/therapeutic use , Corrosion Casting , Fibrosarcoma/diagnostic imaging , Fibrosarcoma/drug therapy , Male , Microscopy, Electron, Scanning , Neoplasm Transplantation , Rats , Rats, Inbred F344 , Salivary Gland Neoplasms/diagnostic imaging , Salivary Gland Neoplasms/drug therapy , Submandibular Gland/diagnostic imaging , Tumor Cells, Cultured , Ultrasonography
16.
J Org Chem ; 66(26): 8944-6, 2001 Dec 28.
Article in English | MEDLINE | ID: mdl-11749626

ABSTRACT

The conjugate addition of arylboronic acids to alpha,beta-unsaturated amides was carried out in the presence of a chiral rhodium catalyst and an aqueous base. The catalyst prepared in situ from Rh(acac)(CH(2)=CH(2))(2) and (S)-binap provided (R)-N-benzyl-3-phenylbutanamide with 93% ee in the addition of phenylboronic acid to N-benzyl crotonamide. The reaction suffered from incomplete conversion resulting in moderate yields, but addition of an aqueous base, such as K(2)CO(3) (10-50 mol%) was found to be highly effective to improve the chemical yields. The role of the base giving a RhOH species active for transmetalation with arylboronic acids was discussed.

17.
Int Arch Allergy Immunol ; 126(3): 239-47, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11752882

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammation usually observed in patients with an individual or a familial history of atopic diseases, precipitated by environmental factors including mite antigens (Ag). However, the exact etiology of AD is unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is necessary. In this study, we developed a new animal model of AD induced by mite Ag in NC/Nga mice. METHODS: We injected the extracts of mite Ag intradermally at the ventral side of the ear of SPF NC/Nga mice on days 0, 2, 4, 7, 9, 11, 14 and 16, and measured the clinical symptoms and the ear thickness. On day 18, we collected blood and submandibular lymph nodes (LN) of the immunized ear to perform a histochemical analysis, and to measure the plasma immunoglobulins and cytokines. RESULTS: The NC/Nga mice immunized with mite Ag suffered from AD-like skin lesions including erythema followed by edema, excoriation and scaling. The histological and immunohistochemical examinations of the affected skin showed epidermal hyperplasia with hyperkeratosis, severe infiltration of CD4+ T lymphocytes, eosinophils and macrophages, and degranulation of mast cells. The total plasma IgE level was markedly elevated in mite Ag-treated mice. LN cells of mice immunized with mite Ag synthesized IgE in an Ag-dependent manner and secreted interleukin-4 (IL-4) and IL-5 but not interferon-gamma. CONCLUSIONS: NC/Nga mice treated with mite Ag manifest clinical and immunological aspects similar to patients with AD, suggesting that this model is suitable for exploring the pathogenesis of human AD.


Subject(s)
Allergens/immunology , Dermatitis, Atopic/immunology , Mites/immunology , Animals , Antigens/immunology , CD4-Positive T-Lymphocytes , Dermatitis, Atopic/etiology , Disease Models, Animal , Female , Humans , Immunoglobulin E/immunology , Mice , Mice, Inbred BALB C
18.
Neurosci Lett ; 314(1-2): 37-40, 2001 Nov 13.
Article in English | MEDLINE | ID: mdl-11698141

ABSTRACT

Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.


Subject(s)
Auditory Pathways/metabolism , Auditory Perception/physiology , Brain Stem/metabolism , Gene Expression/physiology , Neurons/metabolism , Opioid Peptides/genetics , RNA, Messenger/metabolism , Animals , Auditory Pathways/cytology , Brain Stem/cytology , Cochlea/physiology , Efferent Pathways/cytology , Efferent Pathways/metabolism , In Situ Hybridization , Inferior Colliculi/cytology , Inferior Colliculi/metabolism , Male , Mice , Mice, Inbred ICR , Neural Inhibition/physiology , Neurons/cytology , Olivary Nucleus/cytology , Olivary Nucleus/metabolism , Synaptic Transmission/physiology , Nociceptin
19.
Inflamm Res ; 50(10): 509-14, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11713905

ABSTRACT

OBJECTIVE AND DESIGN: The anti-arthritic properties of FK506 were compared with methotrexate (MTX) in established adjuvant-induced arthritis (AIA) in rats. MATERIAL: Female Lewis rats. TREATMENT: Arthritic rats were orally administered with FK506 (1-5.6 mg/kg) and MTX (0.1-1 mg/kg) from days 15-24. METHODS: Arthritis was induced by injection of Mycobacterium tuberculosis into the right hind footpad on day 0. Efficacy was determined on the basis of paw inflammation measured by paw volume and histological change, hyperalgesia and grip strength. Grip strength measurement was employed as an indication of function of paws in arthritic rats. Peripheral white blood cell (WBC) counts and thymus weights were measured, mainly as indicators of toxic side effects. RESULTS: FK506 suppressed paw inflammation and hyperalgesia without toxic effects on WBC and thymus in established AIA. MTX slightly suppressed paw inflammation and hyperalgesia at the highest dose (1 mg/kg). Toxic effects were observed at lower doses than the effective treatment dose with MTX. Grip strength was found to decrease during development of AIA. FK506, but not MTX, treated rats recovered grip strength loss. CONCLUSIONS: The results show that FK506 is more effective and less toxic than MTX in treating established AIA in rats.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Experimental/drug therapy , Methotrexate/therapeutic use , Tacrolimus/therapeutic use , Animals , Arthritis, Experimental/pathology , Female , Foot/pathology , Hand Strength , Hyperalgesia/drug therapy , Hyperalgesia/pathology , Leukocyte Count , Organ Size/drug effects , Rats , Rats, Inbred Lew , Thymus Gland/drug effects , Thymus Gland/pathology
20.
J Digit Imaging ; 14(3): 111-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11720332

ABSTRACT

The authors have developed a new stereoscopic liquid crystal display that provides real-time 3-dimensional image viewing without special eyeglasses. The device consists of 3 major parts: (1) an image display composed of a 10.4-inch color liquid crystal plate with a resolution of 640 x 480, (2) an automatic head tracking system, and (3) a special backlight unit for the right and left eyes. Eight radiologists interpreted 60 cases of magnetic resonance angiography (29 cases of cerebrovascular disease and 31 normal cases) to compare film display and the liquid crystal display (ie, pseudo 3-dimensional display and true 3-dimensional display). Using a continuously distributed scale ranging from 0% to 100%, the observers ranked their confidence levels in determining the presence or absence of steno-occlusive disease, aneurysm, and arteriovenous malformation (AVM) and their locations. For statistical evaluation, receiver operating characteristic (ROC) analysis and Brier score were used. For detecting AVM, film reading showed a significantly higher value in the area under the binormal ROC curve (Az) than did pseudo-3-dimensional display (P < .05). Excluding this, however, no significant difference existed in Az values among the 3 viewing methods. Also, there was no significant difference in Brier score between not only the stereoscopic view and nonstereoscopic view groups, but also the senior and junior groups. Subjective estimation of true 3-dimensional display showed that vessels were more distinguishable with less eye fatigue compared with stereoscopic film reading. The stereoscopic liquid crystal display provided almost equal efficacy to film reading; however, the short optimum distance for observation and the low resolution should be improved.


Subject(s)
Cerebrovascular Disorders/diagnosis , Imaging, Three-Dimensional/instrumentation , Magnetic Resonance Angiography/methods , Data Display , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional/methods , Observer Variation , ROC Curve , Time Factors
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