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Biomedical subjects

H Mizutani

Publications and source records attributed to H Mizutani.

At least 37 records · Page 2Linked to original sources

Arrangement of D-periodic collagen fibrils and association of proteoglycans with fibrils in the synovium of the mouse temporomandibular joint.

The present study was performed to examine changes in the arrangement of D-periodic collagen fibrils in the synovium of the growing temporomandibular joint in mice. At 1 week of age, the mandibular condyle was undeveloped, and only a few collagen fibrils were recognizable in the subintimal layer of the synovium. At 8 weeks, the mandibular condyle was structurally developed with an increase of collagen fibrils in the synovium; a fully mature condyle was observed at 6 months of age. The close association of proteoglycans with collagen fibrils in the synovium of the growing joint was examined by both conventional and energy-filtering transmission electron microscopy of cupromeronic blue-stained specimens. Proteoglycans were associated with D-periodic collagen fibrils in the short filamentous form in random fashion at 1 week of age, but in a regular pattern with D-periodicity at 6 months. These associations in the synovium could be correlated with the mechanical character of the temporomandibular joint.

Age Factors↗

[A case of tuberculous pericarditis developing constrictive pericarditis].

A case of constrictive pericarditis which developed after the onset of clinical manifestation of tuberculous pericarditis was reported. A 75-year-old male, complaining of anorexia, was admitted to our hospital. Adenosinedeaminase (ADA) level in pericardial effusion was found to be increased, and the culture of pericardial effusion was positive for tubercle bacilli. Diagnosed as having tuberculous pleuritis and pericarditis, he underwent chemotherapy for tuberculosis. However, massive pleural effusion developed later and pleural effusion drainage was carried out. Despite repeated drainage, pleural effusion continued to recur. Chest CT revealed apparent pericardial thickening, in addition, cardiac catheterization revealed elevation of mean right atrial pressure and marked deterioration of cardiac functions including decrease of cardiac output. These findings were compatible with constrictive pericarditis. After these investigations a diagnosis of constrictive pericarditis was established, and the patient underwent a pericardiectomy. Pathological examination of resected specimens revealed tuberculous inflammation.

Aged↗

[Bronchiolo-alveolar cell carcinoma arising after active pulmonary tuberculosis' report of two cases].

We report on two patients diagnosed as having active pulmonary tuberculosis who later developed lung cancer. In both cases, the lung cancer was detected during the treatment of pulmonary tuberculosis. Both patients were initially considered to be experiencing exacerbation of pulmonary tuberculosis. Case 1 was seen in a 74-year-old man. His chest roentgenogram revealed microscopic cavitary lesions with infiltration into both lung fields. His sputum tested positive for acid-fast bacilli. Although he was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA), his general condition deteriorated, and the infiltrative shadows in the lung fields had expanded on subsequent chest radiography. Transbronchial lung biopsy (TBLB) yielded findings compatible with a diagnosis of bronchiolo-alveolar cell carcinoma. Case 2 occurred in a 52-year-old man. His chest radiograph revealed cavitary lesions with infiltration into both lung fields. His sputum also tested positive for acidfast bacilli. Despite medication with INH, RFP, EB and PZA, the infiltrative shadow in his chest radiograph increased in size. Bronchiolo-alveolar cell carcinoma was confirmed after examination of the sputum cytology. Case 1 was diagnosed as lung cancer 10 months after being admission to the hospital, and Case 2, seven months after hospitalization. Recent discussion concerning the simultaneous occurrence of pulmonary tuberculosis and bronchogenic carcinoma suggests a high frequency of coexistence of the two diseases. However, the coexistence of active tuberculosis with bronchiolo-alveolar cell carcinoma, as in our cases, is rare.

Adenocarcinoma, Bronchiolo-Alveolar↗

[A case of tuberculous peritonitis diagnosed by a direct smear of ascitic fluid complicated with an active pulmonary tuberculosis and intestinal tuberculosis].

We sometimes encounter difficulties in differentiating tuberculous peritonitis from other inflammatory disorders or ascites due to carcinomatous peritonitis. Acid-fast bacilli are very rarely detected in ascites. In this study, we reported a case of tuberculous peritonitis accompanied with active pulmonary tuberculosis in which acid-fast bacilli were detected in ascites. The patient was a 37-year-old single man who had been admitted to our hospital on February 28, 2000, because acid-fast bacilli were detected in sputum, faces and ascites by a direct smear. He had a lower abdominal distention and pain. His serum CA 125 level was high, 121 U/ml. Abdominal ultrasonography showed marked ascites in Douglas pouch. However adenosine deaminase level was not high in his ascites. During treatment by the combination chemotherapy with INH, RFP, EB, and PZA, serum CA 125 level was decreased.

Adult↗

[A comparison between midline and paramedian approaches for combined spinal-epidural anesthesia].

We compared midline approach with paramedian approach for combined spinal-epidural anesthesia (CSEA) by needle through needle technique. Seventy patients undergoing elective gynecological surgery received CSEA with a 27 G Whitacre spinal needle, which protrudes 12 mm beyond the tip of the Tuohy needle. The successful subarachnoid puncture with first attempt was noted in 33 patients (94%) of midline group (M group), in 31 patients (89%) of paramedian group (P group). At the subarachnoid puncture, skin to epidural space distance (43.2 mm vs 53.4 mm) and protrusion length of spinal needle (5.5 mm vs 8 mm) were significantly longer in the P group than in the M group. Abdominal radiography revealed the flexion of epidural catheter in 19 patients (54%) of M group and in 2 patients (6%) of P group. The choice of midline or paramedian approach for CSEA did not affect the success rate of the subarachnoid puncture, but paramedian approach required longer protrusion length of the spinal needle than midline approach. To raise the success rate of subarachnoid puncture by paramedian approach, a long protruded spinal needle is recommended.

Adult↗

[Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism].

Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism were reported. Case 1; a 73-year-old male, complaining of edema, was admitted to our hospital. He had been treated for his multi-drug-resistant pulmonary tuberculosis during the past 1 year with an antituberculous regimen consisting of ethambutol (EB), ethionamide (ETH) and PAS. A thyroid profile performed when he was admitted to our hospital showed several marked abnormalities: serum thyroid stimulating hormone (TSH) was elevated (69.4 microIU/ml: normal, 0.4-4.2 mIU/ml), free thyroxine level (T4) (0.01 ng/dl; normal, 0.70-1.60 ng/dl) and free triiodothyronine level (Ts) (0.60 pg/ml; normal, 2.3-4.1 pg/ml) were low. PAS was discontinued after he was admitted to our hospital, since PAS was believed to be the cause of the hypothyroidism. A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (13.4 mIU/ml), the free T4 (0.93 ng/dl) were normal. During treatment with PAS, he had never received thyroid replacement therapy. Case 2; A 22-year-old female, complaining of hemosputum. She had been treated for her multi-drug-resistant pulmonary tuberculosis during the past 11 months with an antituberculous regimen consisting of EB, ETH and PAS. A thryoid profile performed when she was admitted to our hospital showed several marked abnormalities: elevated serum TSH (112.7 mIU/ml), and low T4 (2.0 micrograms/dl) and T3 (1.1 ng/ml). A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (5.1 mIU/ml). Drug-induced hypothyroidism is an infrequent side effect of therapy with PAS, and only a few cases of PAS-induced hypothyroidism have been reported so far. In this report, we describe patients with hypothyroidism who were receiving therapy for multi-drug-resistant tuberculosis, tuberculosis namely, resistant to at least isoniazid (INH) and rifampicin (RFP), with a regimen that contained PAS.

Adult↗

[A case of pulmonary eosinophilic granuloma arising rapidly 30 years after the start of smoking and remitting spontaneously without smoking cessation].

A case of pulmonary eosinophilic granuloma which arose rapidly after 30 years of smoking and remitted spontaneously without smoking cessation is reported. The patient was a 54-year-old man complaining of a dry cough who had been smoking 30 cigarettes a day for 30 years. Chest roentgenography showed multiple nodular shadows and cystic lesions in the upper and middle fields of both lungs. Chest computed tomography revealed multiple small cysts and small nodular lesions, mainly in both upper lung fields. CT findings strongly suggested pulmonary eosinophilic granuloma. A transbronchial lung biopsy (TBLB) was performed and 4 specimens were obtained, of which 3 showed granulomatous lesions with eosinophils and histiocytes. Furthermore, the granulomatous lesions were positive for S-100 protein staining. The symptoms and radiographic findings improved markedly within about 6 months after the onset of symptoms without treatment. Many cases of this disease were diagnosed in the past by open lung biopsy, but the number of cases diagnosed by TBLB is now increasing. The effectiveness of open lung biopsy has been emphasized in the diagnosis of pulmonary eosinophilic granuloma, but TBLB is also useful for diagnosis, especially in the active or early stage of the disease.

Eosinophilic Granuloma↗

Skin-specific caspase-1-transgenic mice show cutaneous apoptosis and pre-endotoxin shock condition with a high serum level of IL-18.

To study the pathophysiological roles of overexpressed caspase-1 (CASP1), originally designated as IL-1 beta-converting enzyme, we generated transgenic mice in which human CASP1 is overexpressed in their keratinocytes. The transgenic mice spontaneously developed recalcitrant dermatitis and skin ulcers, characterized by the presence of massive keratinocyte apoptosis. The skin of the mice contained the active form of human CASP1 and expressed mRNA for caspase-activated DNase, an effector endonuclease responsible for DNA fragmentation. Their skin and sera showed elevated levels of mature IL-18 and IL-1 beta, but not of IFN-gamma. The plasma from these animals induced IFN-gamma production by IL-18-responsive NK cells. Administration of heat-killed Propionibacterium acnes, a potent in vivo type 1 cell inducer, caused IFN-gamma-mediated lethal liver injury in the transgenic mice, which was completely inhibited by treatment with neutralizing anti-IL-18 Ab. These results indicated that in vivo overexpression of CASP1 caused spontaneous apoptotic tissue injury and rendered mice highly susceptible to exogenous type 1 cell-inducing condition in collaboration with endogenously accumulated proinflammatory cytokines.

Animals↗

Cyanide-bridge Fe-Fe and Fe-Co molecular squares: structures and electrochemistry of

Cyanide-bridged iron-iron and iron--cobalt molecular squares of [Fe(II/4)(mu-CN)4(bpy)8[(PF6)4 x 4H2O (1), [Fe(II/2)Co(II/2)(mu-CN)4(bpy)8](PF6)4 x 3CHCl3 x 2CH3CN (2), and [Fe(II/2)Co(III/2)(mu-CN)4(bpy)8](PF6)6 x 2CHCl3 x 4CH3NO2 (3) (bpy =2,2'-bipyridine) were prepared. X-ray structure analyses for 1-3 were performed and their electrochemistry was studied. In 1-3, four metal ions are bridged by cyanide groups to form tetranuclear macrocycles ("molecular squares"). Each metal ion in the square is six-coordinate: four of the coordination sites are occupied by the nitrogen atoms of two of bpy ligands and the remaining cis coordination sites are occupied by cyanide-carbon or cyanide-nitrogen atoms. In 1, Fe-C (cyanide) (1.899(4)-1.927(4)A) and Fe-N(cyanide) (1.929(4)-1.950(4)A) distances are typical of low-spin Fe2+ ions. In 2, Fe-C(cyanide) and Co(2+)-N(cyanide) bond lengths are in the range 1.919(5)-1.963(5)A and 1.850(5)-2.017(5) A, respectively: in contrast, shorter bond lengths are observed for the metal to cyanide-carbon and cyanide-nitrogen (1.878(7)- 1.893(7) A) in 3. As a result, the molecular squares in 1. 2, and 3 have sides of 4.947(1)4.986(1) A, 5.001(1)-5.053(1) A, and 4.910(1)-4.918(1) A, respectively. Magnetic susceptibility measurements revealed that the Fe2+ and Co3- ions in 1 and 3 are diamagnetic, while the high-spin Co2+ ions in 2 are weakly coupled through the low-spin Fe2 ions. Cyclic voltammograms of the squares are presented, and the electrochemically generated mixed-valent species [Fe(II/2)Fe(III/2)(mu-CN)4(bpy)8]6+ was discussed in terms of the intervalence transfer band.

Journal Article↗

Prevention of coronary vascular disease by transplantation of T-cell-depleted bone marrow and hematopoietic stem cell preparation in autoimmune-prone w/BF(1) mice.

This project was designed to investigate the application of bone marrow transplantation to a progressive and ultimately fatal systemic autoimmune disease. Male (NZW x BXSB)F1 (W/BF1) mice develop acute systemic autoimmune disease characterized by degenerative coronary vascular disease (CVD) with myocardial infarctions, hypertension, thrombocytopenia, glomerulonephritis, and persistently elevated levels of circulating immune complexes. After preliminary studies established the onset of disease between 10 and 12 weeks of age, 6- to 8-week-old male W/BF1 mice were targeted for transplantation with either T-cell-depleted bone marrow or purified hematopoietic stem cells from haploidentical B6C3/F1 mice. Posttransplantation flow cytometric analysis of splenocytes demonstrated donor phenotypes in W/BF1 recipient mice that had received T-cell-depleted marrow or hematopoietic stem cell preparations (lineage negative, CD71 negative) from B6C3/F1 donors. Survival of W/BF1 mice transplanted with bone marrow from normal B6C3/F1 donors was very high, and assessment at 100 days after transplantation revealed reduction in onset and severity of disease. Autoantibodies to cardiolipin and double-stranded DNA were markedly reduced to levels present in normal mice. Immunohistochemistry of heart and kidney tissue revealed significant amelioration of degenerative CVD and glomerulonephritis in the majority of W/BF1 recipients of marrow transplants from B6C3/F1 donors. All engrafted W/BF1 mice displayed normal immunologic competence 100 days posttransplantation.

Animals↗

IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6.

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.

Animals↗

Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli.

4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. The crystal structure of ADCL from Escherichia coli has been solved using MIR phases in combination with density modification. The structure has been refined to an R-factor of 20.6% at 2.2 A resolution. The enzyme is a homo dimer with a crystallographic twofold axis, and the polypeptide chain is folded into small and large domains with an interdomain loop. The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. Although the main chain folding of the active site is homologous to those of D-amino acid and L-branched-chain amino acid aminotransferases, no residues in the active site are conserved among them except for Arg59, Lys159, and Glu193, which directly interact with the coenzyme and play critical roles in the catalytic functions. ADC was modeled into the active site of the unliganded enzyme on the basis of the X-ray structures of the unliganded and liganded forms in the D-amino acid and L-branched-chain amino acid aminotransferases. According to this model, the carboxylates of ADC are recognized by Asn256, Arg107, and Lys97, and the cyclohexadiene moiety makes van der Waals contact with the side chain of Leu258. ADC forms a Schiff base with PLP to release the catalytic residue Lys159, which forms a hydrogen bond with Thr38. The neutral amino group of Lys159 eliminates the a-proton of ADC to give a quinonoid intermediate to release a pyruvate in accord with the proton transfer from Thr38 to the olefin moiety of ADC.

Amino Acid Sequence↗

Three-dimensional structure of the purple intermediate of porcine kidney D-amino acid oxidase. Optimization of the oxidative half-reaction through alignment of the product with reduced flavin.

The three-dimensional structure of the purple intermediate of porcine kidney D-amino acid oxidase (DAO) was solved by cryo-X-ray crystallography; the purple intermediate is known to comprise a complex between the dehydrogenated product, an imino acid, and the reduced form of DAO. The crystalline purple intermediate was obtained by anaerobically soaking crystals of oxidized DAO in a buffer containing excess D-proline as the substrate. The dehydrogenated product, delta(1)-pyrrolidine-2-carboxylate (DPC), is found sandwiched between the phenol ring of Tyr 224 and the planar reduced flavin ring. The cationic protonated imino nitrogen is within hydrogen-bonding distance of the backbone carbonyl oxygen of Gly 313. The carboxyl group of DPC is recognized by the Arg 283 guanidino and Tyr 228 hydroxyl groups through ion-pairing and hydrogen-bonding, respectively. The (+)HN=C double bond of DPC overlaps the N(5)-C(4a) bond of reduced flavin. The electrostatic effect of the cationic nitrogen of DPC is suggested to shift the resonance hybridization of anionic reduced flavin toward a canonical form with a negative charge at C(4a), thereby augmenting the electron density at C(4a), from which electrons are transferred to molecular oxygen during reoxidation of reduced flavin. The reactivity of reduced flavin in the purple intermediate, therefore, is enhanced through the alignment of DPC with respect to reduced flavin.

Animals↗

Cassiopeia flap: modification of Limberg flap for saving normal skin.

Local flaps have the advantages of texture matching and increased flap survival rate. The proper local flap planning for each lesion causes the dermatologist to be reluctant to employ them. We propose a modified local flap, the "Cassiopeia flap", with three simple marking points made on the ends of the diameter and on the equidistant point along the diameter; two points from equilateral triangles form a "W (Cassiopeia)". We applied this modification to ten lesions on the face, scalp, trunk and thigh with excellent results.

Dermatologic Surgical Procedures↗

A case of acute graft-versus-host disease following autologous peripheral blood stem cell transplantation.

A 42-year-old woman developed severe erythema with exfoliative scaling on the bilateral palms and soles and erosive dermatitis on the axillae and groin eight days after an autologous peripheral blood stem cell transplantation for the treatment of non-Hodgkin's lymphoma. She also developed exanthema; however she did not show intestinal, hepatic, or renal involvement. The skin biopsy revealed characteristic apoptotic cell death of the epidermis with eosinophilic necrosis, and she was diagnosed with acute graft-versus-host disease (GVHD). The cutaneous lesions responded to topical corticosteroid treatments and improved within a month without systemic immunosuppressing therapies. The cutaneous GVH reaction did not recur. However, she was treated with an intermittent thrombocyte transfusion because of persistent thrombocytopenia. On day 130, she developed intestinal pneumonia and died due to respiratory dysfunction. Unlike an allo-bone marrow graft, GVHD after an autologous stem cell transplantation is not common. Even for an autologous transplantation, GVH may develop with less characteristic clinical manifestations.

Adrenal Cortex Hormones↗

Physicochemical Properties of 2-Vinylpyridine Telomers Possessing Multihydrocarbon Chains in Aqueous Solution and at the Silica/Aqueous Solution Interface.

Physicochemical properties of multialkylated surfactants of partially quaternized 2-vinylpyridine telomers having multihydrocarbon side chains (nRm-2VPQ: n, number of chains; m, alkyl chain length) in aqueous solutions were investigated. The critical micelle concentration (cmc) and surface tension at the cmc were 13 µmol dm(-3) and 52 mNm(-1) for 2.1R(8)-2VPQ, 7.1 µmol dm(-3) and 37 mNm(-1) for 2.5R(12)-2VPQ, and 4.7 µmol dm(-3) and 40.0 mNm(-1) for 3.4R(12)-2VPQ, respectively. The aggregation numbers at the cmc determined by the light scattering method were 4 +/- 1 for 2.1R(8)-2VPQ, 45 +/- 10 for 2.5R(12)-2VPQ, and 11 +/- 1 for 3.4R(12)-2VPQ. Thus, the number of chains and the alkyl chain length of the telomers affected the micellar properties in aqueous solutions. At the interface of the silica/aqueous solution, the adsorbed amounts of the telomers increased sharply at their low concentrations and reached a plateau by forming a monolayer and a subsequent bilayer. Silica suspensions also showed a dispersion-flocculation-redispersion sequence with the telomer concentration, where the maximum sedimentation rate was influenced by the number of chains and the alkyl chain length of the telomers. Copyright 1999 Academic Press.

Journal Article↗

A mutation in the extracellular cysteine-rich repeat region of the beta3 subunit activates integrins alphaIIbbeta3 and alphaVbeta3.

Inside-out signaling regulates the ligand-binding function of integrins through changes in receptor affinity and/or avidity. For example, alphaIIbbeta3 is in a low-affinity/avidity state in resting platelets, and activation of the receptor by platelet agonists enables fibrinogen to bind. In addition, certain mutations and truncations of the integrin cytoplasmic tails are associated with a high-affinity/avidity receptor. To further evaluate the structural basis of integrin activation, stable Chinese hamster ovary (CHO) cell transfectants were screened for high-affinity/avidity variants of alphaIIbbeta3. One clone (AM-1) expressed constitutively active alphaIIbbeta3, as evidenced by (1) binding of soluble fibrinogen and PAC1, a ligand-mimetic antialphaIIbbeta3 antibody; and (2) fibrinogen-dependent cell aggregation. Sequence analysis and mutant expression in 293 cells proved that a single amino acid substitution in the cysteine-rich, extracellular portion of beta3(T562N) was responsible for receptor activation. In fact, T562N also activated alphaVbeta3, leading to spontaneous binding of soluble fibrinogen to 293 cells. In contrast, neither T562A nor T562Q activated alphaIIbbeta3, suggesting that acquisition of asparagine at residue 562 was the relevant variable. T562N also led to aberrant glycosylation of beta3, but this was not responsible for the receptor activation. The binding of soluble fibrinogen to alphaIIbbeta3(T562N) was not sufficient to trigger tyrosine phosphorylation of pp125(FAK), indicating that additional post-ligand binding events are required to activate this protein tyrosine kinase during integrin signaling. These studies have uncovered a novel gain-of-function mutation in a region of beta3 intermediate between the ligand-binding region and the cytoplasmic tail, and they suggest that this region is involved in integrin structural changes during inside-out signaling.

Amino Acid Substitution↗

Peritumoral edema in osteoid osteoma on magnetic resonance imaging.

OBJECTIVE: To determine whether there is a relationship between the peritumoral edema caused by osteoid osteoma seen on magnetic resonance (MR) imaging and the patient's age, duration of symptoms, or location of the lesion. DESIGN AND PATIENTS: All histologically proven osteoid osteomas seen in our institutions during a 5-year period in patients with known age, gender, duration of symptoms, and available radiological and MR imaging examinations were included in this study. The extent of the edema in the bone marrow and extraosseous soft tissue around the nidus of osteoid osteoma on T2-weighted MR imaging were graded from 1 (nonexistent) to 4 (extensive) by two masked observers. The relationships between the patient's age, duration of symptoms, and location of lesions were evaluated by Pearson's correlation coefficient and analysis of variance. RESULTS: Twenty-seven cases met the inclusion criteria. The observer agreement on grading was good. Patients of 15 years of age or younger had significantly higher grades than patients older than 15 years. There was a moderate negative linear correlation between the patient's age and peritumoral edema. No significant relationship was identified between edema and the duration of symptoms or the location of lesions. CONCLUSION: Osteoid osteomas in younger patients tend to be associated with more extensive peritumoral edema.

Adolescent↗