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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2002

Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury.

14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.

Animals↗
PubMed2002

Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients.

The present study was undertaken to assess the effect of hyperthyroidism on stiffness in the common carotid artery (CCA) in patients with Graves' disease (GD) and elucidate the mechanism by which arterial stiffness is increased in hyperthyroidism. The arterial stiffness index beta (stiffness beta) was evaluated in the CCA using an ultrasonic phase-locked echo-tracking system. Stiffness beta was defined as the logarithm of the ratio of systolic to diastolic blood pressure divided by the fractional diameter increase during the cardiac cycle and thus established as a measure of arterial stiffness uninfluenced by the change in blood pressure. Seventy euthyroid GD patients were measured for CCA stiffness beta to determine its relationship to retinal blood flow and plasma levels of vascular injury markers. To investigate the effect of hyperthyroidism, 27 GD patients were measured for changes during antithyroid drug (ATD) therapy in stiffness beta and in hemodynamic parameters, retinal blood flow and plasma vascular injury markers. In euthyroid GD patients, stiffness beta in the CCA showed a significant and positive correlation with systolic blood pressure and pulse pressure, but not with peripheral blood flow in the central retinal artery. ATD therapy significantly reduced stiffness beta from 5.23 +/- 2.10 to 4.36 +/- 1.48. The fractional reduction of stiffness beta during ATD therapy correlated significantly with reductions in pulse pressure and retinal blood flow, but not with the reductions in systolic and mean blood pressure, or any of the plasma injury markers. In summary, the significant increase in stiffness beta in the hyperthyroid state may reflect the harmful effect of hyperthyroidism on the arterial wall, which may in turn result from increased stroke volume.

Adolescent↗
PubMed2002

Incisal and condylar paths during habitual mouth opening movement of children with anterior reverse bite in the primary dentition.

The purpose of this study was to evaluate whether the path of habitual mouth opening was influenced by anterior reverse bite malocclusion in children. Two groups of children with the primary dentition were chosen: (i) 10 children with anterior reverse bite (reverse bite group) and (ii) 10 with normal occlusion (normal occlusion group). Their habitual mouth opening movements were measured by an opto-electronic movement-analysing system with 6 d.f. at a sampling rate of 100 Hz. These movements were projected on the sagittal plane at the incisal and condylar points. To characterize the path, we used the angles between the path and the horizontal plane. In the initial stage of opening, the incisal path of the reverse bite group was displaced more posteriorly from the intercuspal position than that of the normal occlusion group. However, as opening continued, the direction of the path of the reverse bite group was more anterior than those of the normal occlusion group. During the entire opening movement, the condylar path of the reverse bite group was flatter than those of the normal occlusion group. In conclusion, it was demonstrated that anterior reverse bite in the primary dentition clearly affects the paths of habitual opening movements.

Analysis of Variance↗
PubMed2002

Laparoscopic adrenalectomy: comparison of transperitoneal and retroperitoneal approaches.

OBJECTIVE: To compare the effectiveness and efficiency of transperitoneal anterior laparoscopic adrenalectomy with that of retroperitoneal posterior laparoscopic adrenalectomy. PATIENTS AND METHODS: A retrospective comparison was undertaken of 28 patients who underwent transperitoneal anterior laparoscopy with 22 patients who underwent retroperitoneal posterior laparoscopy between April 1994 and November 2000. There were 18 men and 32 women (mean age 51.0 years, range 23-68) with varying diagnoses. Of the 50 patients, 31 had primary aldosteronism, eight had Cushing's syndrome, three had phaeochromocytoma, one had an 18-hydroxydeoxycorticosterone-induced adenoma and seven had non-functioning adrenal adenoma. Adrenal tumours were confirmed by hormonal assays, biochemical tests and computed tomography. To determine the site of the functioning adenoma, hormones were assayed from adrenal vein sampling. Thirty adrenal tumours were located on the right and 20 on the left. RESULTS: There were no significant differences in general demographic variables between the transperitoneal and retroperitoneal groups. The mean duration of surgery for transperitoneal and retroperitoneal laparoscopy was 202 and 221 min, respectively, and the mean blood loss 113 and 192 mL, respectively. The time to first oral intake, days to full diet, time until ambulatory and duration of hospitalization did not differ significantly between the two approaches. As the body mass index increased, the duration of surgery increased for both approaches. As more procedures were performed the duration of surgery decreased for both approaches. CONCLUSIONS: There were no significant differences between the transperitoneal and retroperitoneal approaches for laparoscopic adrenalectomy.

Adrenal Gland Diseases↗
PubMed2002

Molecular identification of Trichophyton rubrum isolate from a dog by chitin synthase 1 (CHS1) gene analysis.

A nonsporulating isolate from a dog with dermatophytosis was identified as Trichophyton rubrum by molecular analysis. The nucleotide sequence analysis of the chitin synthase 1 (CHS1) gene from the isolate indicated more than 99% sequence similarity with other human and canine isolates of T rubrum. The molecular typing suggested that isolates of T. rubrum from human and canine sources were genetically identical.

Animals↗
PubMed2002

Changes of endothelin in streptozotocin-induced diabetic rats: effects of an angiotensin converting enzyme inhibitor, enalapril maleate.

Endothelin-1 (ET-1) concentrations are increased in patients with diabetes mellitus, particularly those with diabetic retinopathy, or essential hypertension. We hypothesized that ET-1 might participate in the development and progression of diabetic microangiopathy. In this study, the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril maleate, on diabetic angiopathy were examined in streptozotocin (STZ)-induced diabetic (STZ-DM) rats by monitoring variations in renal function and ET-1 concentrations in blood and organ tissues. Significant increases in kidney weight and in concentrations of urinary albumin, N-acetyl-fl-d-glucosamidase (NAG) and serum ET-1 were observed in the STZ-DM rats as compared with the non-diabetic rats, and the concentration of ET-1 in the kidneys tended to be increased. Microscopic and electron microscopic analyses showed increased mesangial cell proliferation, matrix expansion and enlarged mesangial area in the kidney of the diabetic rats. After administration of the ACE inhibitor, increased concentrations of urinary albumin and NAG in the STZ-DM rats were reduced to the control values with a slight improvement in the electron microscopic changes. These data suggest that ET-1 may be involved in the development and progression of diabetic nephropathy and may explain, in part, why diabetes is liable to complicate hypertension. ACE inhibitor may help to restore diabetic nephropathy in the STZ-induced diabetic rats.

Acetylglucosaminidase↗
PubMed2001

Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation.

Islet transplantation corrects chronic hyperglycemia by augmentation of insulin supply from the graft tissue, but the role of endogenous beta-cells after transplantation is not clear. In the present study, we examined endogenous beta-cell function after glucose homeostasis had been reestablished by islet graft in streptozotocin (STZ)-induced diabetic rats. Fed plasma glucose levels in diabetic rats transplanted with a large number of islets (2500 islets) into the left kidney capsule soon became lower (139.8 +/- 8.2 mg/dl) and close to the level in controls (129.7 +/- 11.3 mg/dl), and IPGTT exhibited a pattern of plasma glucose response almost identical to control. The insulin and DNA contents, islet area, and the distribution of beta-cells that were markedly deteriorated in islets of STZ rats were significantly restored in transplanted rats. The insulin release in response to glucose or alpha-ketoisocaproate was less in STZ rats, while in islets of transplanted rats the secretion recovered to levels similar to controls. On the other hand, arginine-induced insulin release was conversely hyperresponsive in STZ rats, but in transplanted rats, the response was decreased similar to controls. Thus, as the plasma glucose level normalizes, residual beta-cells show a recovery of function that cannot be accounted for by the increase in mass alone.

Animals↗
PubMed2001

The enantioselective immunoaffinity extraction of an optically active ibuprofen-modified peptide fragment.

Acyl glucuronides are known to produce the covalently bound protein adducts which may be the cause of hypersensitivity and toxic responses to acidic drugs. The structural analysis of the drug-protein adducts is therefore needed. From this point of view, we developed an enantioselective immunoaffinity extraction method, which employs an immobilized antibody to specifically isolate peptide fragments that have been modified with optically active ibuprofen. Rabbits were immunized with (S)-ibuprofen coupled to bovine serum albumin through a beta-alanine group. The elicited antibody strongly recognizes the asymmetric center and the isobutylphenyl moiety of (S)-ibuprofen and its conjugates but has a low affinity for their anti podes. A 0.5-mL aliquot of the immunosorbent (11.5 mg of IgG/mL gel) prepared by immobilization of the antibody was capable of retaining up to 1 microg of (S)-ibuprofen. When a mixture of substance P with (R)- and (S)-ibuprofen-modified substance P was loaded on the immunosorbent, the (S)-ibuprofen-modified substance P was selectively retained. The modified peptide was quantitatively recovered by elution with 10 mM ammonium acetate buffer (pH 5.0)/methanol (5:95, v/v). The proposed method would be useful for the structural characterization of optically active ibuprofen-modified human serum albumin.

Antibodies↗
PubMed2001

Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain.

A novel dual specificity phosphatase (DSP) designated LMW-DSP2 was cloned with a combination of reverse transcription-polymerase chain reaction and cDNA library screening strategies. The LMW-DSP2 open reading frame of 194 amino acids contained a single DSP catalytic domain but lacked the cdc25 homology domain, which is conserved in most known DSPs. Northern blot and reverse transcription-polymerase chain reaction analyses revealed that LMW-DSP2 was specifically expressed in testis. Recombinant LMW-DSP2 protein exhibited phosphatase activity toward an artificial low molecular weight substrate para-nitrophenyl phosphate, and the activity was inhibited completely by sodium orthovanadate but not sodium fluoride, pyrophosphate, and okadaic acid. The substitution of critical amino acid residues, aspartic acid and cysteine, resulted in a dramatic reduction of phosphatase activity. Transient transfection of LMW-DSP2 in COS7 cells resulted in the expression of a 21-kDa protein, and the phosphatase was shown to be distributed in both the cytosol and the nucleus. LMW-DSP2 dephosphorylated and deactivated p38, to a higher extent, and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases, in transfected COS7 cells and in vitro. Interestingly, mutation in a conserved docking motif of p38 and SAPK/JNK as well as in a cluster of aspartic acids of LMW-DSP2 did not affect the deactivation of the mitogen-activated protein kinases by LMW-DSP2. Furthermore, the binding between LMW-DSP2 and p38 and SAPK/JNK was also not disrupted by such mutations. Among the DSPs lacking the cdc25 homology domain, LMW-DSP2 is the first one that dephosphorylates and deactivates p38 and SAPK/JNK.

Amino Acid Sequence↗
PubMed2001

Effect of pre-and postoperative plasmapheresis on posttransplant recurrence of focal segmental glomerulosclerosis in children.

BACKGROUND: Posttransplant recurrence is frequent in patients who received renal transplantation for focal segmental glomerulosclerosis (FSGS). The recurrence has been ascribed to a circulating permeability factor or factors. We have used plasmapheresis (PP) to treat recurrent FSGS and also studied whether preoperative PP is effective in preventing recurrence of FSGS. METHODS: We retrospectively analyzed 21 allografts of 20 patients with nephrotic syndrome and biopsyproven FSGS. They were divided into two groups depending on whether they had prophylactic PP; a prophylactic (n=15) and a nonprophylactic group (n=6). PP was performed two to three times prophylactically and therapeutically until proteinuria was markedly reduced. In each session, 50-75 ml/kg of the patient's plasma was exchanged with 5-8% albumin. RESULTS: FSGS recurred in 9 of 21 allografts, 4 of 6 in the nonprophylactic group, and 5 of 15 in the prophylactic group. Therapeutic PP was performed in seven of nine recurrent patients without definite adverse effect, with satisfactory results except in one patient. Children lost proteinuria after 6 to > 100 sessions of PP and the number correlated with the pretreatment level of proteinuria. The mean follow-up periods were 62.7 and 41.6 months for the prophylactic and nonprophylactic groups, respectively. At the last follow-up, 66.7% of relapsing and 81.8% of nonrelapsing patients had a functioning graft. CONCLUSION: PP appears to be effective for the prevention and treatment of posttransplant recurrence of FSGS, although further consideration of cost/benefit and risks is required before a conclusive judgement can be made.

Child↗
PubMed2001

Preparation of anhydrothrombin and characterization of its interaction with natural thrombin substrates.

Thrombin is a serine proteinase that plays a key role in thrombosis and haemostasis through its interaction with several coagulation factors. Anhydrothrombin was prepared from PMSF-inactivated thrombin under alkaline conditions, and the folded anhydrothrombin was successfully recovered after dialysis in the presence of glycerol. Anhydro-derivatives of factor Xa, factor VIIa and activated protein C could also be prepared essentially by the same procedure. Anhydrothrombin retained affinity for various natural substrates of thrombin, including fibrinogen, factor VIII, factor XIII and protein C. In addition, these proteins were bound to anhydrothrombin-agarose in a reversible manner. The K(d) values for factor VIII, fibrinogen, factor XIII and protein C were 1.2x10(-8), 4.4x10(-8), 2.8x10(-7) and 8.1x10(-5) M, respectively. Thus thrombin substrates known to interact with the exosite I of thrombin demonstrated high affinity for anhydrothrombin. Furthermore, in the presence of Na+, substantial enhancement of the association rate constant (k(ass)) was observed for interactions of fibrinogen and factor VIII with anhydrothrombin. These results suggest that anhydrothrombin is useful in the purification of thrombin substrate proteins as well as in the investigation of detailed interactions between thrombin and these substrates in their activation or degradation processes.

Chromatography, Affinity↗
PubMed2001

Capabilities of liposomes for topological transformation.

Dynamic behaviors of liposomes caused by interactions between liposomal membranes and surfactant were studied by direct real-time observation by using high-intensity dark-field microscopy. Solubilization of liposomes by surfactants is thought to be a catastrophic event akin to the explosion of soap bubbles in the air; however, the actual process has not been clarified. We studied this process experimentally and found that liposomes exposed to various surfactants exhibited unusual behavior, namely continuous shrinkage accompanied by intermittent quakes, release of encapsulated liposomes, opening up, and inside-out topological inversion.

Lipids↗
PubMed2001

Circulating factor VIII immune complexes in patients with type 2 acquired hemophilia A and protection from activated protein C-mediated proteolysis.

Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII antigen despite having low levels of FVIII activity were studied. The antibodies reacted exclusively with the light chain of FVIII but not with the C2 domain, and their epitopes were therefore ascribed to the regions in the A3-C1 domains. Heavy and light chains of FVIII were detected in plasma-derived immune complexes extracted by using protein G Sepharose. Direct binding assays using anhydro-activated protein C (anhydro-APC), a catalytically inactive derivative of activated protein C (APC) in which the active-site serine is converted to dehydroalanine, were used to examine the relation between immune complexes and APC. The intact FVIII, 80-kd light chain, and 72-kd light chain bound in a dose-dependent manner to anhydro-APC, with K(d) values of 580, 540, and 310 nM, respectively, whereas no appreciable binding was detected for the heavy chain. The 3 autoantibodies blocked FVIII binding to anhydro-APC by approximately 80% and consequently inhibited APC-induced FVIII proteolytic inactivation. These antibodies also bound to a synthetic peptide, His2009-Val2018, which contains the APC binding site. The findings suggest that binding of type 2 autoantibodies, recognizing residues His2009 to Val2018, protects FVIII from APC-mediated proteolysis and might contribute to the presence of FVIII immune complexes in the circulation.

Antigen-Antibody Complex↗
PubMed2001

Bile acid acyl adenylate: a possible intermediate to produce a protein-bound bile acid.

The non-enzymatic production of a protein-bound adduct by the action of the acyl adenylate of bile acids is described. On incubation of deoxycholyl adenylate with substance P in phosphate buffer, peptides covalently bound with one or two molecules of the bile acid were detected. The modified peptides were structurally characterized by time-of-flight mass spectrometry with matrix-assisted laser desorption/ionization (MALDI-TOFMS) in the post-source decay mode, and by liquid chromatography/electrospray ionization MS/MS. The deoxycholic acid was bound on substance P through the amino group at Arg-1 and/or Lys-3. The adenylate of cholic acid also produced the protein-bound bile acid on incubation with lysozyme, and the binding sites of the cholic acid appeared to be the lysine residues at 1, 33, 97 and 116. The results clearly suggest that bile acid adenylates in vivo may act as active intermediates to produce covalently bound bile acid adducts with peptides and proteins by nucleophilic displacement of the 5'-adenylic acid through the free amino groups.

Adenosine Monophosphate↗
PubMed2001

Msx2 is a repressor of chondrogenic differentiation in migratory cranial neural crest cells.

During early mouse embryogenesis, cranial neural crest cells (CNCC) emigrate from the posterior midbrain and rhombomeres 1 and 2 of the anterior hindbrain into the first branchial arch-derived maxillary and mandibular processes and there provide cell lineages for several phenotypes, including cartilage, bone, and tooth. Here, we report that Sox9 and Msx2 were coexpressed in a subpopulation of CNCC during their migration. Because Sox9 is a transactivator of chondrogenesis, and Msx genes can act as transcriptional repressors, we hypothesized that Sox9 expression indicates the determination of CNCC-derived chondrogenic cell lineage and that Msx2 represses chondrogenic differentiation until CNCC migration is completed within the mandibular processes. To test whether Msx2 represses chondrogenesis, we designed experiments to inhibit Msx2 function in migratory CNCC in primary cultures through the expression of loss-of-function Msx2 mutants. We showed that infection of migratory CNCC with adenovirus Msx2 mutants accelerated the rate and extent of chondrogenesis, as indicated by the expression level of type II collagen and aggrecan, and the amount of alcian blue staining. Adenovirus infections did not apparently interfere with CNCC proliferation or migration. These findings suggest that an important early event in craniofacial morphogenesis is a transient expression of both Sox9 and Msx2 during emigration into the forming mandibular processes followed by restricted expression of Sox9 within CNCC- derived chondroprogenitor cells. We conclude that Msx2 serves as a repressor of chondrogenic differentiation during CNCC migration.

Adenoviridae↗
PubMed2001

Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of paediatric and geriatric patients with fatal haemolytic uraemic syndrome.

Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and renal failure. Infection with enterohaemorrhagic Escherichia coli (EHEC), mainly O157:H7, has been strongly implicated as the major cause of HUS in children. The pathogenesis of HUS caused by the infection is not well understood and the defined sites of Stx in kidney of EHEC-infected humans has not been clearly demonstrated. The aim of this study was to investigate and compare the locations of Stx deposition in kidneys of paediatric and geriatric patients who died from enterohaemorrhagic E. coli O157 (EHEC) associated HUS, using an immunoperoxidase staining of the tissues. The study revealed that binding of Stx was relatively less and limited only to the renal tubules of an adult case (81 years old), while more binding was found at both renal tubules and glomeruli of an infant case (21 months old). The Stx binding in the infant's glomeruli was at podocytes, mesangial and endothelial cells. It has been known that young children are more susceptible than adults to HUS. One possibility for this is that the more extensive binding of the Stx to the kidney tissue of the paediatric patient might be due to the higher synthesis and expression of Stx receptors, i.e. Gb(3), in infants and less so in the aged individuals. However, other alternatives are possible, for example, the difference in stage of HUS in individual patients. Thus it is too early to draw any conclusion on this enigma and further investigation is required.

Aged↗
PubMed2001

Location of lesions in multiple evanescent white dot syndrome and the cause of the hypofluorescent spots observed by indocyanine green angiography.

PURPOSE: To determine the location of the lesions in the retina of a patient with multiple evanescent white dot syndrome (MEWDS) and to resolve the conflict in the cause of the hypofluorescent spots observed in the late phase of indocyanine green angiography (ICGA). CASE REPORT: A 27-year-old woman presented with a unilateral enlarged blind spot and a central scotoma. Fundus examination of the left eye showed many round, indistinctly circumscribed white dots extending from the posterior pole toward the periphery. Fluorescein angiography demonstrated hyperfluorescence due to staining at the location of the white dots. Staining was also observed on the venous wall which was consistent with periphlebitis. The location of the scotomas corresponded with the hypofluorescent spots observed around the optic disc and in the macula in the late phase of ICGA. The scotomas disappeared with the resolution of the hypofluorescent spots, and the sites of other hypofluorescent spots were in accord with the sites of periphlebitis. Visual evoked cortical potentials disclosed no laterality, and the critical fusion frequency was reduced but normalized with the disappearance of the scotoma. CONCLUSION: The initial lesions of MEWDS occur in the retinal pigment epithelium and photoreceptor cells, but when MEWDS is complicated by periphlebitis, the inflammatory lesions extend to the inner layers of the retina. The inflammatory changes involve the choroid and all layers of the retina, which then block the weak background fluorescence in the later phase of ICGA and cause the hypofluorescent spots. The visual field defects are probably caused by retinal dysfunction due to the inflammatory changes.

Adult↗