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Biomedical subjects

M Imai

Publications and source records attributed to M Imai.

At least 19 recordsLinked to original sources

Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team.

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.

Adolescent↗

Kinetic pathway to double-gyroid structure.

We have investigated the structural development during order-order transitions to the double-gyroid (DG) phase of nonionic surfactant/water systems based on two-dimensional small-angle x-ray scattering patterns from highly oriented ordered mesophases. The lamellar (L) to DG transition proceeds through two intermediate structures, a fluctuating perforated layer structure having ABAB stacking and a hexagonal perforated lamellar structure with ABCABC stacking (HPLABC). For a hexagonally packed cylinder (H) to DG transition, we also observed the HPLABC structure as the intermediate phase, thus the HPLABC is an entrance structure for the DG phase. The hexagonal perforated lamellar (HPL) structure consists of hexagonally packed holes surrounded by the planar tripods, and the transition from HPL structure to the DG phase proceeds by rotation of the dihedral angle of connected tripods. A geometrical consideration shows that large deformations of HPL planes are necessary to form the DG structure from the HPLABC structure, whereas the transition from a HPL structure with ABAB stacking (HPLAB) to the DG structure is straightforward. In spite of the topological constraints, the HPLABC structure is observed in the kinetic pathway to the DG structure.

Journal Article↗

Static and dynamic structures of spherical nonionic surfactant micelles during the disorder-order transition.

We have investigated the static and dynamic structures of nonionic surfactant micelles, a C(12)E(8)/water binary system, during the disorder-order transition using small angle x-ray scattering, static light scattering, and dynamic light scattering techniques. In the disordered phase, the micelles have spherical shape and intermicellar interactions are governed by the hard core and weak long ranged attractive potentials. With increase of the micellar concentration, the disordered micelles transform to the three characteristic ordered micellar phases, a hexagonally close packed lattice, a body centered cubic lattice, and an A15 lattice having area-minimizing structure. The stability of these phases is well explained by balance of a close packing rule and a minimal-area rule proposed by Ziherl and Kamien [Phys. Rev. Lett. 85, 3528 (2000)]. The role of hydrodynamic interactions in surfactant micellar solutions was compared with that in hard sphere colloidal particle suspensions.

Journal Article↗

Occlusal force and condylar motion in patients with anterior open bite.

Patients with open bite often show a weak occlusal force and temporomandibular disorders (TMDs). If these are the main cause of open bite, it may be hypothesized that both pre-pubertal and adult open-bite patients would show a weak occlusal force and abnormal condylar motion. The purpose of this study was to test this hypothesis. Test group subjects consisted of 13 consecutive pre-pubertal and 13 adult patients with anterior open bite. They were compared with age-matched normal subjects. The adult open-bite group showed a weaker occlusal force and a shorter range of condylar motion compared with the control subjects. In the pre-pubertal subjects, however, there were no significant differences in the occlusal force and range of condylar motion between the open-bite and control groups. Therefore, these results suggest that a weak occlusal force or TMDs may not be the main cause of open bite.

Adolescent↗

Histopathological studies of bacterial haemorrhagic ascites of ayu, Plecoglossus altivelis (Temminck & Schlegel).

A histopathological study was carried out on ayu, Plecoglossus altivelis, with bacterial haemorrhagic ascites. The fish were obtained from culture ponds in Wakayama Prefecture in 2003. The causative agent was identified as Pseudomonas plecoglossicida by a slide agglutination test using anti-P. plecoglossicida FPC941 serum. Histopathological studies revealed lesions in spleen, kidney, liver, intestine, heart and gills. Lesions in the spleen and haematopoietic tissue were prominent and invaded by P. plecoglossicida. Necrotic lesions accompanied by haemorrhage, fibrin deposition and oedema occurred in the splenic pulp and sheathed tissue, and in the kidney. The liver also had necrotic lesions and abscess formations. However, the intestine, heart and gills were only slightly invaded by P. plecoglossicida. No lesions or bacteria were observed in the brain.

Agglutination Tests↗

Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience).

PURPOSE: This study aimed to compare the effects of computer-assisted, text-based and computer-and-text learning conditions on the performances of 3 groups of medical students in the pre-clinical years of their programme, taking into account their academic achievement to date. A fourth group of students served as a control (no-study) group. METHOD: Participants were recruited from the pre-clinical years of the training programmes in 2 medical schools in Japan, Jichi Medical School near Tokyo and Kochi Medical School near Osaka. Participants were randomly assigned to 4 learning conditions and tested before and after the study on their knowledge of and skill in performing an abdominal examination, in a multiple-choice test and an objective structured clinical examination (OSCE), respectively. Information about performance in the programme was collected from school records and students were classified as average, good or excellent. Student and faculty evaluations of their experience in the study were explored by means of a short evaluation survey. RESULTS: Compared to the control group, all 3 study groups exhibited significant gains in performance on knowledge and performance measures. For the knowledge measure, the gains of the computer-assisted and computer-assisted plus text-based learning groups were significantly greater than the gains of the text-based learning group. The performances of the 3 groups did not differ on the OSCE measure. Analyses of gains by performance level revealed that high achieving students' learning was independent of study method. Lower achieving students performed better after using computer-based learning methods. CONCLUSION: The results suggest that computer-assisted learning methods will be of greater help to students who do not find the traditional methods effective. Explorations of the factors behind this are a matter for future research.

Abdomen↗

Inter-lamellar interactions modulated by addition of guest components.

We have investigated the effects of a guest component (polymer or spherical colloidal particle) confined between flexible lamellar slits on the inter-lamellar interaction by means of a small-angle X-ray scattering technique and a neutron spin echo technique. The dominant interaction between flexible lamellar membranes without guest components is the Helfrich mechanism. The addition of a neutral polymer into the lamellar phase induces an attractive inter-lamellar interaction and finally destabilizes the lamellar phase. On the other hand, spherical colloidal particles confined between flexible lamellar membranes reduce the undulational fluctuations of lamellae and bring a repulsive inter-lamellar interaction. The behavior of the layer compression modulus of the lamellar membrane containing colloidal particles is well described by the entropical repulsive inter-lamellar interaction driven by steric hindrance.

Biophysics↗

Expression of an artificial Cl- channel in microperfused renal proximal tubules.

To better understand the process of fluid movement driven by Cl- conductance, a Cl- channel-forming peptide was delivered to the luminal membrane of microperfused rabbit renal proximal tubules. When the peptide (NK4-M2GlyR) was perfused, a significant new conductance was observed within 3 min and stabilized at 10 min. Alteration of the ion composition revealed it to be a Cl(-)-specific conductance. Reabsorption of Cl- (JCl) was increased by NK4-M2GlyR, but not by a scramble NK4-M2GlyR sequence, suggesting that the active peptide formed de novo Cl- channels in the luminal membrane of the perfused tubules. In the presence of the peptide, reabsorption of fluid (Jv) was dramatically increased and JNa and JCa were concomitantly increased. We propose that introduction of the new Cl- conductance in the luminal membrane leads to a coordinated efflux of water across the membrane and an increase in cation translocation via the paracellular pathway, resulting in an increase in Jv. This novel method could prove useful in characterizing mechanisms of fluid transport driven by Cl- gradients.

Animals↗

Influenza B virus NS2, a nuclear export protein, directly associates with the viral ribonucleoprotein complex.

In Influenza A virus and Influenza B virus, the NS2 protein (nuclear export protein) has been proposed to mediate the nucleocytoplasmic trafficking of viral ribonucleoprotein (vRNP) by forming NS2-vRNP complexes. While the binding interactions of NS2 in these complexes have been well characterized for Influenza A virus, much less is known about Influenza B virus NS2 (B/NS2). In this report, we developed a specific antiserum against B/NS2 protein and demonstrated that B/NS2 was synthesized late in infection and packaged into virions after nucleocytoplasmic transport. Fractionation of detergent-disrupted virions in several conditions showed that B/NS2 remained associated with vRNP after separation of matrix protein M1 from vRNP, whereas Influenza A virus NS2 (A/NS2) was easily separated from vRNP and remained associated with M1, in accord with previous findings that A/NS2 associates with vRNP only through its binding of encapsidated M1. The results indicated that complex formation among vRNP, M1 and NS2 of Influenza B virus was different from that of Influenza A virus, and that B/NS2 associated with vRNP in the absence and presence of M1.

Active Transport, Cell Nucleus↗

[Chondromatous hamartoma of the lung with a unique demonstration on diagnostic imaging; report of a case].

A case of pulmonary hamartoma is reported with clinical, roentgenographical and histopathologic findings. The patient was a 53-year-old woman who had undergone right hemithyroidectomy for thyroid cancer 4 years before. An abnormal shadow, which was a non-clearly demarcated tumor, 2 cm in diameter, in the left middle lung field, was noted on her routine X-ray in February 2001. Physical examination and laboratory data revealed no significant findings, but computed tomography(CT) scans of the chest showed a gathering of small-sized high-density lesions in the nodule. She underwent left S8 segmentectomy on March 21, 2001. The pathology report on the frozen section was pulmonary hamartoma. Histopathologically, the lesion was characterized by a composition of bronchial epithelium, fat tissue and cartilage, with being diagnosed as a chondromatous hamartoma of the lung. The patient's postoperative course was uneventful, and she was discharged with no supportive therapy 14 days after the operation. To date, 14 months after the operation, the patient has been in good condition, without evidence of recurrence or distant metastasis on diagnostic imaging. This case is particularly interesting because a gathering of small-sized pulmonary hamartoma was demonstrated by imaging.

Female↗

Cellular component of vascular calcification. Fibroblasts are essential for calcium deposition in cultured cells.

It has been reported that calcium deposition and calcium content in cultured human aortic smooth muscle cells (SMC) increased when the cells are incubated in a medium with a high phosphate concentration (2 mM). To determine the cellular components or soluble factors contributing to the deposition, we cultured commercially available SMC, fibroblasts (Fb) and endothelial cells (Ed). These cells and their mixtures were incubated for 10 days in normal or high-phosphate media. Calcium crystals were stained by the von-Kossa staining and counted in the defined area. Calcium content was measured by a colorimetric assay. SMC were incubated in high-phosphate media (up to 2 mM) or beta-glycerophosphate (beta-GP) media, resulting in no obvious deposition of calcium crystals, irrespective of the coating of type I collagen on the dish. Next, various combinations of cells were cultured, and a significant number of depositions were observed only when Fb were included in the combination. The calcium content was significantly higher in cultures of SMC and Fb. The calcium deposition on single or mixture of the cells did not increase compared with control when cells were incubated in a high concentration of phosphate, cultured in the existence of beta-GP or uremic serum. We therefore conclude that Fb, rather than SMC or Ed, are essential for calcium deposition and calcium accumulation in culture. Phosphate concentration in the medium and uremic serum did not influence the deposition of calcium.

Calcification, Physiologic↗

Caveolar and intercellular channels provide major transport pathways of macromolecules across vascular endothelial cells.

Serum macromolecules are transported through the vascular endothelial layer to the interstitium via the caveolae and interendothelial clefts, but the nature of the permeability of these structures is unknown, and the manner of caveola-vesicle transport is controversial. We have developed a method of detecting macromolecular channels using an in situ HRP perfusion into arteries previously perfused with aldehyde and random conventional sectioning for electron microscopy. Using unbiased morphometry, 4.75% of the abluminal caveolae and 15.13% of the intercellular clefts were the tracer-positive in rat aortic endothelium. In rat aortas treated with N-ethylmaleimide, all caveolae and most free vesicles in the cytoplasm except those around the Golgi area were HRP-positive in the endothelial cells; 1.48% of abluminal caveolae were structurally recognized as caveolar channels through the endothelial layer in a plane of single section. The length density of the abluminal caveolae was decreased to about 80% to the physiological control level whereas the larger invaginations were more frequently observed. Moreover 96.17% of the intercellular clefts were HRP-positive. We suggest that a flexible channel-system functions extensively as a macromolecular transport pathway in the arterial endothelium in vivo because the tracer-labeled abluminal caveolae and intercellular clefts should be opened to the luminal surfaces methodologically. We therefore propose that caveolar channels, rather than transcytosis, provide a mechanism of caveola-vesicle transport in the endothelial cells, because free vesicles involved in transcytosis were few in number.

Animals↗

Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine.

A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). Longitudinal analysis of samples revealed that this deletion emerged upon reinitiation DDI/D4T therapy following a toxicity-induced short discontinuation of all antiretrovirals. Analysis of the resistance phenotype showed a greater than 62-fold increase of the IC50 of NVP, but no significant change in sensitivity to other single nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mutated virus showed only a moderately reduced sensitivity to DDI (6.7-fold) and D4T (4.8 fold). In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. Our findings provide evidence that the deletion of RT residue 69 selectively confers high-level NVP resistance.

Adult↗

Estrogens do not modify MAP kinase-dependent nuclear signaling during stimulation of early G(1) progression in human breast cancer cells.

Estrogens are direct mitogens for hormone-responsive human breast cancercells, where they promote cell cycle progression and induce transcriptional activation of "immediate early" and cyclin genes. Nongenomic signaling by estrogens, including rapid changes of mitogen-activated protein(MAP) kinase and other signal-transduction-cascades activity, has been proposed to be essential for the mitogenic actions of these hormones and their nuclear receptors. Because regulation of gene transcription is considered a key step in cell cycle control by mitogenic protein kinase cascades, here we investigated the possibility that estrogen might induce the activation of extracellular signal-regulated kinase (Erk) 1/2-, c-Jun NH(2)-terminal kinase-, p38- or protein kinase A-responsive transcription factors in the cell nucleus during stimulation of early G(1) progression, a timing coincident with the maximum effects of these hormones on such enzyme activity. No significant changes in protein kinase-mediated transcription factor activity could be detected here after estrogen stimulation of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb phosphorylation, all key events in cell cycle stimulation by mitogens, even in the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase (Mek)1/2 inhibitor. Thus, estrogens do not appear to convey significant protein kinase-dependent signaling to the cell nucleus during the early phases of human breast cancer cell stimulation. Furthermore, hormonal regulation of G(1) gene transcription can occur even without additional activation of the Mek-Erk1/2 pathway by estrogen receptors.

Breast Neoplasms↗

Superconductivity of ternary silicide with the AlB(2)-type structure Sr(Ga(0.37),Si(0.63))(2).

A ternary silicide Sr(Ga(0.37),Si(0.63))(2) was synthesized by a floating zone method. Electron diffraction and powder x-ray diffraction measurements indicate that the silicide has the AlB(2)-type structure with the lattice constants of a = 4.1427(6) A and c = 4.7998(9) A, where Si and Ga atoms are arranged in a chemically disordered honeycomb lattice and Sr atoms are inercalated between them. The silicide is isostructural with the high-temperature superconductor MgB(2) reported recently. Electrical resistivity and dc magnetization measurements revealed that it is a type-II superconductor with onset temperature of 3.5 K.

Journal Article↗

A novel recombinant adeno-associated virus vaccine induces a long-term humoral immune response to human immunodeficiency virus.

Recombinant adeno-associated virus (AAV) has attracted tremendous interest as a promising vector for gene delivery. In this study we have developed an HIV-1 vaccine, using an AAV vector expressing HIV-1 env, tat, and rev genes (AAV-HIV vector). A single injection of the AAV-HIV vector induced strong production of HIV-1-specific serum IgG and fecal secretory IgA antibodies as well as MHC class I-restricted CTL activity in BALB/c mice. The titer of HIV-1-specific serum IgG remained stable for 10 months. When AAV-HIV vector was coadministered with AAV-IL2 vector, the HIV-specific cell-mediated immunity (CMI) was significantly enhanced. Boosting with AAV-HIV vector strongly enhanced the humoral response. Furthermore, the mouse antisera neutralized an HIV-1 homologous strain, and BALB/c mice immunized via the intranasal route with an AAV vector expressing the influenza virus hemagglutinin (HA) gene showed protective immunity against homologous influenza virus challenge. These results demonstrate that AAV-HIV vector immunization may provide a novel and promising HIV vaccination strategy.

AIDS Vaccines↗

Impact of HIV type 1 protease, reverse transcriptase, cleavage site, and p6 mutations on the virological response to quadruple therapy with saquinavir, ritonavir, and two nucleoside analogs.

Genotype alterations of HIV-1 protease, reverse transcriptase, cleavage sites p7/p1 and p1/p6, as well as p6(gag) and transframe protein p6* were studied in an observational cohort of 42 individuals who received antiretroviral therapy consisting of saquinavir, ritonavir, and two nucleoside analogs. In a multivariate logistic regression analysis, the prior protease inhibitor experience (odds ratio, 6.20; 95% CI, 1.22-31.38) and the presence of primary protease mutations (odds ratio, 9.99; 95% CI, 1.05-94.72) were independently associated with virological failure. Moreover, a trend was observed in that individuals with N-terminal amino acid insertions in the proline-rich motif of the p6(gag) protein were less likely to experience virological failure (OR, 0.17; 95% CI, 0.02-1.35; p = 0.09). In contrast, the presence of secondary protease, reverse transcriptase, or cleavage site mutations was not independently associated with treatment failure. However, mutations at cleavage site p7/p1 (p = 0.01) and C-terminal p6* mutations (p = 0.02) were both associated with primary protease mutations. In conclusion, the presence of primary protease mutations was the most important predictor of the subsequent virological response. Moreover, there is some evidence that insertions in the proline-rich area of the p6(gag) protein may affect the virological response. The relationship between mutations of cleavage sites or C-terminal p6* residues and protease mutations suggests that these alterations may serve a compensatory role, increasing viral fitness.

Adult↗

Identification of a new multigene four-transmembrane family (MS4A) related to CD20, HTm4 and beta subunit of the high-affinity IgE receptor.

We report here the cloning of eight new cDNAs that encode a family of proteins related to the B-cell-specific antigen CD20, a hematopoietic-cell-specific protein HTm4, and high affinity IgE receptor beta chain (FcvarepsilonRIbeta). They include four clones from human, and another four clones from mouse. They share similar structure (four transmembrane domains) with amino acid identities of 25-40%. Therefore, they represent distinct genes and comprise a gene superfamily. This superfamily is now named membrane-spanning four-domains, subfamily A (the approved symbol is MS4A) to distinguish them from tetraspanins with similar structure. The highest homologies among these proteins are found in the transmembrane domains, especially in the first and second transmembrane domains, and conserved residues are also recognized in the inter-transmembrane domains. In northern blot, they were mostly expressed in lymphoid tissues: thymus and spleen. However, some were expressed in nonlymphoid tissues including brain, heart, kidney, liver, testis, lung, GI tracts, and pancreas. They may represent proteins functioning either directly as ligand-gated ion channels or as essential components of such channels. The identification of this relatively large gene family in various tissues will allow the further elucidation of physiological significance of this gene family, that is currently unclear.

Amino Acid Sequence↗