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Biomedical subjects

N Otsuki

Publications and source records attributed to N Otsuki.

At least 19 recordsLinked to original sources

Expression and regulation of human CD275 on endothelial cells in healthy and inflamed mucosal tissues.

The CD275-CD278 costimulatory pathway is a new pathway for CD28-B7 family molecules involved in the effector phase of T-cell-mediated immune responses. Expression of CD275 in oral mucosa at healthy and disease states has not been examined. We generated monoclonal antibodies against human CD275 and investigated its expression and regulation in cultured tissue cell lines and oral mucosal tissues. CD275 on monocytes was efficiently upregulated by interleukin-4, while interferon-gamma abrogated this effect. CD275 on cultured endothelial cells (EC) was rapidly enhanced by tumour necrosis factor-alpha. In healthy oral mucosa, CD275 was not detected on keratinocytes, Langerhans cells or intraepithelial lymphocytes within the epithelium or on interstitial dendritic cells or lymphocytes in the sub-epithelium. Constitutive expression of CD275 on EC in the connective tissues was observed in healthy mucosa, but CD275 expression on EC in oral lichen planus was either upregulated or down regulated. Approximately 20% of the T cells found within infiltrating mononuclear cells in the sub-epithelium expressed high levels of the CD278 receptor. CD275 on lymphoid and nonlymphoid cells is positively or negatively regulated by various cytokines. Our results suggest that CD275 on EC is involved in the recruitment or extravasation of receptor-positive effector T cells into inflamed tissues.

Adult↗

Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases.

BACKGROUND: Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for 15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation. OBJECTIVES: To demonstrate immunohistochemically the expression of hK6, hK8 and hK13 in normal skin tissue and to show an increased cell number expressing kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis (AD). METHODS: Samples of normal, PV and AD skin were obtained. hK6-, hK8- and hK13-specific antibodies were produced and used for immunohistochemical analysis. Multiple KLK mRNAs were synthesized and used for in situ hybridization study. RESULTS: Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically identified as new skin serine proteases in the whole SC, SG, sebaceous glands, eccrine sweat glands, hair follicles and nerves. We also demonstrated an increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK distribution was rather diffuse and expanded into the lower epidermis. CONCLUSIONS: The colocalization of various hKs seems to be essential for the regulation of serine protease activity in skin and for steady desquamation and skin barrier function. Moreover, the increased number of cells expressing multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their pathogenesis.

Adult↗

Stat6 activation and Th2 cell differentiation [correction of proliferation] driven by CD28 [correction of CD28 signals].

CD28 engagement by specific monoclonal antibody (mAb) or binding of the natural ligands, CD80 and CD86, induces tyrosine phosphorylation of CD28, which in turn recruits and activates the signal transducer and activator of transcription 6 (Stat6). The Stat6 association with CD28 is specifically induced by CD80 or CD86 ligand binding and is not dependent upon the secretion of IL-4 or IL-13. Activated Stat6 translocates to the nucleus and binds to a Stat6-responsive element on the human IL-4 promoter. CD28 ligation induces Stat6-dependent transcriptional activation of a reporter gene under the control of a multimerized Stat6-responsive element fused to an essential part of the IL-4 promoter. Primary stimulation of naive CD4(+) T cells with anti-CD28 mAb in the presence of IL-2, but in the absence of anti-CD3 mAb induces preferential production of IL-4 and expression of CCR4 mRNA after secondary stimulation with anti-CD3, indicating the preferential differentiation of Th2 cells. These findings suggest that initial IL-4 production required for commitment of naive T cells toward Th2 cells may be provided in response to signals delivered via CD28 by antigen-presenting cells.

Animals↗

Novel proteoglycan linkage tetrasaccharides of human urinary soluble thrombomodulin, SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1-4Xyl.

O-linked sugar chains with xylose as a reducing end linked to human urinary soluble thrombomodulin were studied. Sugar chains were liberated by hydrazinolysis followed by N-acetylation and tagged with 2-aminopyridine. Two fractions containing pyridylaminated Xyl as a reducing end were collected. Their structures were determined by partial acid hydrolysis, two-dimensional sugar mapping combined with exoglycosidase digestions, methylation analysis, mass spectrometry, and NMR as SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1+ ++-4Xyl. These sugar chains could bind to an HNK-1 monoclonal antibody. This is believed to be the first example of a proteoglycan linkage tetrasaccharide with glucuronic acid 3-sulfate and sialic acid.

Binding Sites, Antibody↗

Infective endocarditis-induced crescentic glomerulonephritis dramatically improved by plasmapheresis.

A 50-year-old woman was referred to our hospital because of skin purpura, anemia, high fever, and acute renal insufficiency. Five years ago, she had been diagnosed as having ventricular septal defect without any complications. A blood culture drawn during the hospitalization grew Streptococcus viridans. She was diagnosed as having infective endocarditis-induced crescentic glomerulonephritis (GN) according to echocardiography and renal biopsy results. Although antibiotic treatment alone showed no apparent efficacy, after the initiation of plasmapheresis, the high fever and acute renal insufficiency were dramatically improved. After clinical stability was achieved, closure of the ventricular septal defect was performed. This result suggests that plasmapheresis may be beneficial in the treatment of infective endocarditis-induced crescentic GN. The possible mechanisms of this therapy are discussed.

Acute Kidney Injury↗

A case of myasthenia gravis in childhood associated with chronic inflammatory demyelinating polyradiculoneuropathy.

We report a 14-year-old girl who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia gravis, which was clinically of ocular type, but with waning phenomenon of the extremities, occurred at 2 years and 4 months of age. Muscle weakness of the lower extremities gradually developed over the next 6 years. The electrophysiological and pathological findings fulfilled the criteria of "possible CIDP" with severe axonal involvement. The signs of myasthenia gravis and CIDP fluctuated synchronously. A common immunological abnormality was suggested to underlie this rare association of myasthenia gravis and CIDP in childhood.

Adolescent↗

Protective effect of dipyridamole against lethality and lipid peroxidation in liver and spleen of the ddY mouse after whole-body irradiation.

The effects of dipyridamole on radiation damage in the mouse were investigated. Dipyridamole (i.p. 2 mg/mouse) administered 1 h before exposure, protected against gamma-irradiation. Pretreatment significantly decreased the death rate at 30 days from 89 to 33% (p<0.001) after 9 Gy whole-body irradiation. LD50 at 30 days was increased from 6.67 to 7.65 Gy in the dipyridamole pretreated group. The level of thiobarbituric acid reactive substances (TBARS) in the liver and spleen, a measure of free radical initiated liver peroxidation, increased 155, 193, 195, and 236% of control (without irradiation) in liver, and 132, 146, 168, and 276% of control (without irradiation) in spleen on days 2, 4, 7, and 10 after 9 Gy of whole-body irradiation respectively. The TBARS levels in both liver and spleen 2 days after irradiation were reduced to 73 +/- 7 and 60 +/- 19% respectively after dipyridamole treatment (2 mg/mouse, i.p. injection 1 h before exposure). In electron microscopic studies, mitochondria and endoplasmic reticulum in the irradiated mouse liver were swollen, but otherwise appeared normal after dipyridamole treatment. These results suggest that dipyridamole has a protective effect on animal survival 30 days after 60Co gamma-irradiation and inhibits lipid peroxidation - which is thought to play a part in the radiation injury in mouse liver and spleen.

Animals↗

Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: imaging and pathology findings.

PURPOSE: To investigate the imaging and pathologic characteristics of acute encephalopathy with bilateral thalamotegmental involvement in infants and children. METHODS: Five Japanese children ranging in age from 11 to 29 months were studied. We performed CT imaging in all patients, 10 MR examinations in four patients, and an autopsy in one patient. RESULTS: The encephalopathy affected the thalami, brain stem tegmenta, and cerebral and cerebellar white matter. The brain of the autopsied case showed fresh necrosis and brain edema without inflammatory cell infiltration. Petechiae and congestion were demonstrated mainly in the thalamus. CT and MR images showed symmetric focal lesions in the same areas in the early phase. These lesions became more demarcated and smaller in the intermediate phase. The ventricles and cortical sulci enlarged. MR images demonstrated T1 shortening in the thalami. The prognosis was generally poor; one patient died, three patients were left with severe sequelae, and only one patient improved. CONCLUSIONS: The encephalopathy might be a postviral or postinfectious brain disorder. T1 shortening in the thalami indicated the presence of petechiae.

Acute Disease↗

[CT and MR imaging of desmoid tumors--comparison of two modalities].

As desmoid tumors invade locally and postoperative recurrence is common, accurate diagnosis of the extent of the tumor is needed prior to surgery. CT and/or MRI evaluation of tumor extension was retrospectively studied in eight patients with desmoid tumors, and the results were correlated with the histopathological findings. All tumors were completely resected even in patients who were evaluated by CT alone. However, the delineation of tumor and local invasion were not clearly demonstrated by CT. On the other hand, the delineation of tumor and local invasion were well visualized on MRI. The MRI picture of desmoid tumors was mainly composed of two different areas of signal intensity. The area of hypointensity in both T 1- and T 2-weighted images was found to have abundant collagen fibers, while the area of isointensity or slight hyperintensity in T 1-weighted images and hyperintensity in T 2-weighted images was found to have fibroblasts. In conclusion, MRI is better suited to the evaluation of patients with desmoid tumors than CT.

Adolescent↗

[CT features of chronic maxillary osteomyelitis in adults].

CT findings were reviewed in four adult patients with chronic maxillary osteomyelitis (CMO) that was histologically proved. The CT features of CMO included bone destruction and soft tissue mass, predominantly in the inferior portion of the maxillary antrum (all 4 cases), thickening of the antral wall (3 cases) and abnormal soft tissue around the antrum associated with or without bony wall destruction (3 cases). CMO could not be distinguished from cancer of the maxillary antrum on CT because of the similar findings. However, abnormal soft tissue around the antrum together with an undestructed bony antral wall may be useful for differentiating the two diseases.

Adult↗

[CT-guided percutaneous lung biopsy using a cutting needle and an automated biopsy gun. Comparison with lung biopsy using a manual aspiration needle].

Twenty-five percutaneous lung biopsies using a 20-gauge cutting needle and automated biopsy gun (ABG) were performed under CT guidance in 25 patients with thoracic lesions. This procedure was compared with that using a 21-gauge manual aspiration needle in 36 patients (40 examinations, 37 lesions) in terms of success rate, rate of correct diagnosis, mean examination time and rate of complications. Specimens obtained from lung biopsy were graded by a histopathologist according to quality and quantity from 0 to 4 (pathological score). There were no statistically significant differences between the two procedures in terms of success rate, rate of correct diagnosis and rate of complications; only the time required was significantly different. However, sufficient biopsy material and a mean pathological score of G-II 2.8 (that of G-I was 1.9, p less than 0.05) could be obtained by the biopsy procedure using the cutting needle. The above results indicated that aspiration needle biopsy was adequate for lung biopsy, but that a cutting needle and ABG should be used when a good biopsy specimen is needed for tissue diagnosis.

Adolescent↗

Two cases of Fabry's disease: a hemizygote with a point mutation in the alpha-galactosidase A gene and his relative.

A 34-year-old Japanese male had leg pain, edema of the legs, hypohidrosis, whorl-like opacities of the bilateral cornea, bilateral subcapsular cataracts, and chest discomfort on exercise. He had no characteristic angiokeratomas but did have telangiectases. The electrocardiogram revealed high voltage. The echocardiogram revealed mild mitral regurgitation. The alpha-galactosidase A activity in cultured lymphoblasts was deficient (0.5 nmol/h/mg protein). Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts. He had a G--> A transition at nucleotide 982 in the coding sequence of the alpha-galactosidase A gene which resulted in a glycine to arginine amino acid substitution at residue 328. His uncle also had leg pain, edema of the legs, hypohidrosis, and chest pain on exercise. He had no characteristic angiokeratomas but did have telangiectases. Cardiovascular examination revealed hypertrophic cardiomyopathy and stenoses of coronary arteries. Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts.

Adult↗