Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 55 records · Page 3Linked to original sources

PubMed2001

Critical contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infected hu-PBL-NOD-SCID mice.

Apoptosis is a key for CD4+ T cell destruction in HIV-1-infected patients. In this study, human peripheral blood lymphocyte (PBL)-transplanted nonobese diabetic (NOD)-severe combined immunodeficient (SCID) (hu-PBL-NOD-SCID) mice were used to examine in vivo apoptosis after HIV-1 infection. As the hu-PBL-NOD-SCID mouse model allowed us to see extensive infection with HIV-1 and to analyze apoptosis in human cells in combination with immunohistological methods, we were able to quantify the number of apoptotic cells with HIV-1 infection. As demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), massive apoptosis was predominantly observed in virus-uninfected CD4+ T cells in the spleens of HIV-1-infected mice. A combination of TUNEL and immunostaining for death-inducing tumor necrosis factor (TNF) family molecules indicated that the apoptotic cells were frequently found in conjugation with TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD3+CD4+ human T cells. Administration of a neutralizing anti-TRAIL mAb in HIV-1-infected mice markedly inhibited the development of CD4+ T cell apoptosis. These results suggest that a large number of HIV-1-uninfected CD4+ T cells undergo TRAIL-mediated apoptosis in HIV-infected lymphoid organs.

Animals↗

PubMed2001

New 5-HT1A receptor agonists possessing 1,4-benzoxazepine scaffold exhibit highly potent anti-ischemic effects.

A series of new 3-substituted-4-(4-aminobutyl)-1,4-benzoxazepin-5(4H)-one derivatives (1-5) which showed a very high affinity for 5-HT1A receptor with good selectivity over dopamine D2 receptor was synthesized. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one (5: SUN N4057) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

Animals↗

PubMed2001

Topographic analysis of astigmatism induced by scleral shortening in pig eyes.

BACKGROUND: Corneal astigmatism is a severe postoperative problem in foveal translocation surgery. We evaluated the corneal astigmatism induced by scleral shortening in pig eyes in vitro. METHODS: We created three sizes of scleral shortening in pig eyes and examined the preoperative and postoperative corneal astigmatism. The three sizes of scleral shortening were; 6 mm x 12 mm, 9 mm x 12 mm, and 6 mm x 16 mm (radial x circumferential). The shortenings were created 11 mm from the limbus with 10 eyes in each group. Videokeratographic measurements were performed using the CAS System 2000, preoperatively and postoperatively, and the astigmatism caused by the scleral shortening was evaluated. RESULTS: The surgically-induced astigmatism was 2.1 +/- 1.2 diopters (D) in the 6 mm x 12 mm group, 5.2+/-1.5 D in the 9 mm x 12 mm group, and 3.7+/-1.0 D in the 6 mm x 16 mm group. Corneal astigmatism caused by scleral shortening depended on both the radial and circumferential shortening. Pre- and postoperative topographic corneal maps showed an irregular astigmatism pattern (lazy bowtie pattern). Because the central zone of the cornea showed a relatively regular astigmatism, the corneal astigmatism induced by scleral shortening did not affect the predicted corneal acuity. CONCLUSIONS: In foveal translocation surgery with scleral shortening, an excessive scleral resection in the radial direction can cause clinically intolerable regular and irregular astigmatism. Minimal scleral shortening that will satisfy the required translocated distance is recommended to reduce the risk/benefit ratio.

Animals↗

PubMed2001

Epithelial pigment slide in contact lens wearers: a possible marker for contact lens-associated stress on corneal epithelium.

PURPOSE: To compare the incidence of epithelial pigment slide among wearers of various types of contact lenses. METHODS: Prospectively, we studied 432 eyes of 432 patients. The patients were separated into 6 groups: hard contact lens (HCL) wearers (n = 166), conventional soft contact lens (CSCL) wearers (n = 30), extended disposable lens (EDCL) wearers (n = 46), frequent replacement SCL (FRCL) wearers (n = 60), daily disposable SCL (DDCL) wearers (n = 65), and normal controls (n = 65). The incidence of prominent pigment slide, defined as spike-like epithelial opacities in the corneal limbus and longer than 1 mm from the base to the apex of the wedges-shaped process detected by slit-lamp examination, was compared in these 6 groups. The relationship between the incidence of prominent pigment slide and the length of contact lens wear was examined. RESULTS: The overall incidence of prominent pigment slide in the CSCL, EDCL, HCL, FRCL, DDCL, and normal groups was 63.3, 23.9, 13.9, 8.3, 7.7, and 4.6%, respectively. The incidence of prominent pigment slide in the CSCL and EDCL groups was significantly higher than that in the control group. A higher incidence of prominent pigment slide was correlated with longer wearing period in each group. CONCLUSIONS: The presence of epithelial pigment slide may be a marker for contact lens-associated stress to the corneal epithelium.

Biomarkers↗

PubMed2001

Different recurrence patterns after phototherapeutic keratectomy in the corneal dystrophy resulting from homozygous and heterozygous R124H BIG-H3 mutation.

PURPOSE: To report the recurrence pattern of corneal deposits after phototherapeutic keratectomy in patients with corneal dystrophies resulting from homozygous and heterozygous Arg124His (R124H) mutation of the BIG-H3 gene. METHODS: Slit-lamp examination was performed on patients with corneal dystrophy resulting from a genetically confirmed BIG-H3 R124H mutation. RESULTS: The recurrence of corneal deposits after phototherapeutic keratectomy in patient with heterozygous R124H mutation was mild; the granular opacities occurred as spot lesions in the central cornea. The patient with a homozygous mutation had a more severe pattern, and the recurrent lesions were diffuse and occurred in the periphery between the corneal epithelium and laser-ablated stroma. The recurrence-free interval in homozygous patients was shorter. CONCLUSION: The mutation genotype of BIG-H3 gene determines the recurrence pattern after phototherapeutic keratectomy.

Aged↗

PubMed2001

Two patterns of opacity in corneal dystrophy caused by the homozygous BIG-H3 R124H mutation.

PURPOSE: To investigate the opacity pattern in corneas with an Arg124His (R124H) homozygous mutation of the BIG-H3 gene. METHODS: Slit-lamp examination was performed on eight patients with corneal dystrophy resulting from a genetically confirmed BIG-H3 R124H homozygous mutation. The birthplace of each patient also was determined. RESULTS: Slit-lamp examination disclosed two types of opacity patterns in corneas with the BIG-H3 R124H homozygous mutation. Type I (n = 4) is a spot-like opacity present in the anterior stroma in which the lesions are confluent. Type I is the same pattern that previous reports have shown to be caused by the BIG-H3 R124H homozygous mutation. The type II corneal opacity pattern (n = 4) is a reticular opacity in the anterior stroma with round translucent spaces. Type II opacity has not been reported previously in association with any corneal dystrophy. The patients with the type I opacity do not share a common birthplace; however, interestingly, the patients with the type II opacity traced their origin to Tottori prefecture in western Japan. CONCLUSION: The BIG-H3 homozygous R124H mutation induces the development of two distinct patterns of corneal opacity, the recognition of which can establish an accurate diagnosis of corneal dystrophy caused by the homozygous BIG-H3 R124H mutation independent of genetic analysis. In addition, genetic factors or circumstantial influences other than the gene responsible for the corneal dystrophy may influence the pattern of corneal opacity.

Adult↗

PubMed2001

Factors that influence the surgical effects of astigmatic keratotomy after cataract surgery.

OBJECTIVE: To determine the factors affecting the surgical effect of astigmatic keratotomy (AK) when against-the-rule astigmatism is present following cataract surgery. DESIGN: Prospective interventional noncomparative case series. PARTICIPANTS: Twenty eyes of 19 patients from four medical centers who had against-the-rule astigmatism following cataract surgery. INTERVENTION: AK with a 6 mm optical zone, two linear 3-mm length incisions (T-cut) and a depth of 90% of the central thickness was performed on all subjects. MAIN OUTCOME MEASURES: Vector analysis of astigmatic correction. Multiple regression analysis for seven covariates including age, spherical equivalent of the manifest refraction, preoperative astigmatism, corneal diameter, corneal thickness, mean radius of corneal curvature and axial misalignment. RESULTS: Multiple regression analysis showed that the preoperative astigmatism (p = 0.014) and the axis deviation (p = 0.005) were significantly correlated with the surgical effects. CONCLUSIONS: Even with a uniform surgical procedure, the surgical effects of AK in eyes with against-the-rule astigmatism can be affected by the amount of preoperative astigmatism and the intraoperative axis misalignment. Adding the amount of preoperative astigmatism to the nomogram and improvement of surgical procedures will be required to obtain better surgical predictability of AK following cataract surgery.

Aged↗

PubMed2001

A study on the density and distribution of uterine Natural Killer cells at mid pregnancy in mice genetically-ablated for CCR2, CCR 5 and the CCR5 receptor ligand, MIP-1 alpha.

Several chemoattractants mediate Natural Killer (NK) cell migration. The CC-chemokines, monocyte inflammatory protein (MIP)-1 alpha, regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage chemotactic protein (MCP)-1 are the most potent. Peripheral NK cells express the CC-chemokine receptor CCR2, for MCP-1 and CCR5, for MIP-1 alpha and RANTES. These chemokines are detected in the uterus during the estrous cycle and become elevated during pregnancy. To assess the roles of CCR2, CCR5 and MIP-1 alpha in NK cell migration to the uterus and localization within implantation sites, histological analysis was conducted on implantation sites from mice genetically-ablated for CCR2, CCR5, MIP-1 alpha or CCR2 and MIP-1 alpha. Uterine NK (uNK) cell densities in both the decidua basalis and mesometrial lymphoid aggregate of pregnancy (MLAp) of all mutant strains matched wildtype controls. Ratios of vascular: non-vascular uNK cell position were identical in mutants and controls. In the decidua basalis, 25-35% and in the MLAp, 15-20% of uNK cells were perivascular. Intravascular uNK cells were observed in the decidua basalis but not in the MLAp and were more numerous at gestation day 10 than 12. Two measures of uNK cell activation, cell diameter and cytoplasmic granule number, were similar in the mutants and controls. Thus, migration, distribution and activation of NK cells within the pregnant uterus are independent of CCR2, CCR5 and MIP-1 alpha.

Animals↗

PubMed2001

Crystal structure of a novel-type archaeal rubisco with pentagonal symmetry.

BACKGROUND: Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme of the Calvin-Benson cycle and catalyzes the primary reaction of CO2 fixation in plants, algae, and bacteria. Rubiscos have been so far classified into two types. Type I is composed of eight large subunits (L subunits) and eight small subunits (S subunits) with tetragonal symmetry (L8S8), but type II is usually composed only of two L subunits (L2). Recently, some genuinely active Rubiscos of unknown physiological function have been reported from archaea. RESULTS: The crystal structure of Rubisco from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 (Tk-Rubisco) was determined at 2.8 A resolution. The enzyme is composed only of L subunits and showed a novel (L2)5 decameric structure. Compared to previously known type I enzymes, each L2 dimer is inclined approximately 16 degrees to form a toroid-shaped decamer with its unique L2-L2 interfaces. Differential scanning calorimetry (DSC), circular dichroism (CD), and gel permeation chromatography (GPC) showed that Tk-Rubisco maintains its secondary structure and decameric assembly even at high temperatures. CONCLUSIONS: The present study provides the first structure of an archaeal Rubisco, an unprecedented (L2)5 decamer. Biochemical studies indicate that Tk-Rubisco maintains its decameric structure at high temperatures. The structure is distinct from type I and type II Rubiscos and strongly supports that Tk-Rubisco should be classified as a novel type III Rubisco.

Amino Acid Sequence↗

PubMed2001

Contribution of myeloperoxidase to coronary artery vasculitis associated with MPO-ANCA production.

The role of myeloperoxidase (MPO) in the pathogenesis of vasculitis associated with MPO-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) was examined in a murine animal model. Coronary artery vasculitis was induced in C57BL/6 mice with and without endogenous MPO by intraperitoneal injection of Candida albicans-derived substances (CADS). The corresponding levels of MPO-ANCA in sera of mice with and without vasculitis were measured and compared in both wild-type and MPO-deficient animals. The MPO-ANCA titers in sera were significantly higher in mice with vasculitis than in vasculitis-negative mice, indicating that MPO-ANCA correlated with vasculitis formation. However, the increase of MPO-ANCA titers observed in sera of wild C57BL/6 mice were strongly suppressed in MPO-deficient C57BL/6 mice, accompanied with prevention of vasculitis formation. These results show that MPO acted as an antigen for MPO-ANCA production by CADS and was followed by the vasculitis formation. Vasculitis did develop in a few MPO-deficient mice, though the incidence of vasculitis was much lower in MPO-deficient mice than in C57BL/6 mice.

Animals↗

PubMed2001

Distribution of the tetracycline resistance determinant tetQ gene in oral isolates of black-pigmented anaerobes in Japan.

We investigated the distribution of tetracycline resistance determinant tetQ in oral black-pigmented anaerobes using a polymerase chain reaction (PCR) METHOD: A total of 185 healthy subjects were divided into 3 groups based on subject age: young (6 to 10 years, n=58), middle (11 to 40 years, n=96), and elder (exactly 70 years, n=31). The prevalence of black-pigmented anaerobes in the gingival sulcus among these groups was 29.3%, 28.2%, and 64.5%, respectively. The prevalence of Prevotella nigrescens among these groups was 22.4%, 15.6%, and 32.3%, respectively, whereas the prevalence of Prevotella intermedia was 1.7%, 4.2%, and 35.5%, respectively. Porphyromonas gingivalis was found only in the elder group (16.1%). The prevalence of the tetQ gene in the black-pigmented anaerobes-positive subjects was almost the same among the 3 groups (approximately 30%). The tetQ gene was found in 27.5% (46 of 167) of P. nigrescens isolates, whereas it was found in only 6.4% (3 of 47) of P. intermedia isolates and in none of the 19 P. gingivalis isolates. Restriction endonuclease digestion patterns of the PCR products revealed 83.6% of 49 tetQ-positive isolates were of subtype A2H2 (AluI type 2, HpaII type 2).

Adolescent↗

PubMed2001

The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease.

OBJECTIVE: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD). RESEARCH METHODS AND PROCEDURES: The SPARC mRNA expressions both in vivo and in vitro were detected by Northern blot analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent assay. First, we investigated the plasma SPARC levels of 88 unrelated adult Japanese subjects (62 men and 26 women; average age: [+/- SD] 50 +/- 12 years; body mass index [BMI]: 16 to 46 kg/m(2)). Additionally 31 subjects with CAD diagnosed by coronary angiography (20 men and 11 women) were also investigated. RESULTS: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte differentiation. Consistent with these results, plasma SPARC levels proved a positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly, plasma SPARC concentrations were significantly elevated in age- and BMI-matched subjects with CAD (p < 0.05). DISCUSSION: SPARC was expressed in adipose tissues and its expression was enhanced in obese mice. In human, plasma SPARC levels were elevated in obesity and CAD patients. This elevated SPARC may be involved in the progression of CAD.

Adipose Tissue↗

PubMed2001

Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation.

We report a favourable outcome in 15 patients with severe aplastic anaemia (SAA) who were < 20 years of age and who underwent bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched unrelated donor. All patients were non-responders to intensive immunosuppressive therapy (IST) and were multiply transfused. The conditioning regimen consisted of cyclophosphamide (60 mg/kg/d, on d -4 and -3), anti-thymocyte globulin (2.5 mg/kg/d, on d -5 to -2) and total body irradiation (2.5 Gy x 2/d, on d -2 and -1). Patients received cyclosporine and methotrexate for prophylaxis of graft-versus-host disease (GVHD), except for the last four who received tacrolimus instead of cyclosporine. Donor/recipient pairs were identical for HLA class I and II antigens by serological typing, but four pairs were found to have a mismatch at the HLA-A, -B or -DRB1 locus by high-resolution typing. All patients achieved rapid engraftment and are alive at 2-86 months after transplantation (median follow-up, 51 months). Moderate to severe acute GVHD occurred in 5 out of 15 patients (33%); only one patient developed extensive chronic GVHD. Considering our encouraging results, unrelated donor transplantation for SAA is recommended as a salvage therapy in non-responders to IST.

Adolescent↗

PubMed2001

Intracavitary chemotherapy with 5-fluoro-2'-deoxyuridine (FdUrd) in malignant brain tumors.

BACKGROUND: After completing basic research on the anti-tumor effects and neurotoxicity of 5-fluoro-2'-deoxyuridine (FdUrd) and the balance of thymidine kinase and thymidine phosphorylase activities and confirming the safety of intrathecal FdUrd administration in a previous clinical study of meningeal carcinomatosis, intracavitary administration of FdUrd was performed as a second trial in patients with malignant glioma and metastatic brain tumors. METHODS: The study population consisted of 13 patients, six with glioblastoma, one with anaplastic astrocytoma and six with metastatic brain tumors. This treatment was applied for cystic, small-volume residual or recurrent tumors. FdUrd (1-10 microg) was administered every day at least 25 times through an Ommaya device placed in the cyst or closed postoperative cavity reconstructed with a patch of galea aponeurotica. Intracavitary chemotherapy with FdUrd was preceded by radiation therapy in two patients but no other adjuvant therapy was performed. RESULTS: No side effects such as headache, nuchal pain, convulsive attack, bone marrow suppression or liver dysfunction were observed during the course of chemotherapy. Seven of the 13 patients showed responses: complete response six, minor response one, no change two and progressive disease four after the twenty-fifth intracavitary administration of FdUrd when tumor sizes on CT scans and MRI before and after intracavitary chemotherapy were compared. CONCLUSIONS: Intracavitary FdUrd chemotherapy may be useful for the treatment of small-volume tumors.

Adult↗

PubMed2001

Gender- and age-related differences in corneal topography.

PURPOSE: To investigate gender- and age-related differences in the corneal topography of a normal population. METHODS: One hundred thirty-two topographic examinations were collected from 100 patients ranging in age from 23 to 83 years (average, 57.35+/-17.38 years). Data were segregated by gender and further divided into younger (less than 50 years) and older (50 years or more) age groups. The topographic indices of Surface Regularity Index, Surface Asymmetry Index, Irregular Astigmatism Index, Standard Deviation of Corneal Power, Corneal Eccentricity Index, Coefficient of Variation of Corneal Power, Simulated Keratometry 1 and 2, and Average Corneal Power were examined. The astigmatism pattern and corneal irregularity were determined and compared with respect to gender and age. RESULTS: The corneas of older men were flatter than those of older women (p < 0.001). The vertical corneal meridian, but not the horizontal meridian, showed statistically significant gender-related changes with aging (p < 0.001). Older men had a significantly higher potential for against-the-rule astigmatism than women (p < 0.001). Corneal irregularity (measured in terms of the Surface Regularity Index and Irregular Astigmatism Index) increased with age (p < 0.001 and p < 0.001, respectively), although there was no gender-related difference. In the younger group, no gender-related differences in corneal curvature or astigmatism pattern were found. CONCLUSION: Aging influences changes in patterns of astigmatism differently in men and women. Decreases in levels of sex hormones may play a role in gender-related changes in corneal structure with age.

Adult↗

PubMed2001

Utility of Etest in choosing appropriate agents to treat fungal keratitis.

PURPOSE: To evaluate the utility of Etest in choosing the appropriate treatment of fungal keratitis. METHODS: Etest was used to determine the drug sensitivities of isolates from the eyes of three patients with fungal keratitis, and the clinical outcomes of treatment with selected drugs were evaluated. RESULTS: In all cases, drug sensitivity demonstrated by Etest accorded with clinical efficacy of the drugs. CONCLUSION: The results in these cases suggest that evaluating drug sensitivities with Etest is an efficient means of selecting optimal pharmacotherapy for fungal keratitis.

Aged↗

PubMed2001

Wavefront technology in ophthalmology.

Wavefront sensing is an emerging technology that can measure irregular astigmatism as a higher-order wavefront aberration. The application of wavefront sensing in ophthalmology might enable the non-invasive observation of living retinal cone cells; the measurement of detailed visual function of the central nervous system by eliminating higher-order aberrations during examinations by adaptive optics; the correction of irregular astigmatism; and the prevention of iatrogenic irregular astigmatism induced by conventional refractive surgical procedures. In addition, it will be theoretically possible to obtain supernormal vision by wavefront-guided refractive surgery.

Astigmatism↗

PubMed2001

Synthesis of a mouse model of the dysfibrinogen Vlissingen/Frankfurt IV.

The dysfibrinogen Vlissingen/Frankfurt IV is characterized as a deletion of Asn319 and Asp320 from the C-terminus of the gamma-chain of fibrinogen. This dysfibrinogen, which was identified in several family members that are all heterozygous for the in-frame 6-bp deletion, is associated with both venous and arterial thrombosis. Here, we describe the generation of a murine model of the V/F IV dysfibrinogen using gene targeting of mouse gamma-chain DNA. Preliminary analysis shows that the human and mouse variant fibrinogens are similar: analogous to the human V/F IV protein, the D1 fragment of the variant mouse fibrinogen is partially protected from digestion in the presence of calcium or Gly-Pro-Arg-Pro. These heterozygous mice provide the first opportunity to examine the association of thrombophilia and dysfibrinogenemia in a controlled genetic background.

Animals↗