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Biomedical subjects

M Imai

Publications and source records attributed to M Imai.

At least 109 records · Page 6Linked to original sources

Removal of digoxin and doxorubicin by multidrug resistance protein-overexpressed cell culture in hollow fiber.

BACKGROUND: Drug removal by hemoperfusion is not effective because of its lower capacity and nonspecificity. We invented a new hybrid type of hemodialysis system. METHODS: An immortalized proximal tubular cell line (PCTL) overexpressing human multidrug resistance protein-1 (MDR-1) was cultured either on polus filter membranes or on hollow fiber modules. The modules were incubated in an incubator conditioned with 95% O2/5% CO2 that was kept at 37 degrees C. At 10 days on culture, the drug-transporting capacity of these systems was examined. RESULTS: MDR was successfully expressed in the PCTL as evaluated by Western blot. Basolateral to apical transport of 3H-digoxin, a substrate of MDR, was examined by using the cells cultured on a microporous membrane. PCTL-MDR showed a 10-fold increase in MDR protein and a 12-fold increase of 3H-digoxin transport through a cell layer on a microporous membrane. The increase of the transport was abolished by the addition of 5 microM verapamil, an inhibitor of MDR, to the apical side. When digoxin or doxorubicin was infused in the capillary side of the hollow fiber modules after 10 days on culture, the largest portion of the drugs was transported to the pericapillary side (P < 0.001). This transport was also abolished by an addition of verapamil to the pericapillary side. Transport of para-aminohippurate was not different between two cells, and inulin was not transported in this system. CONCLUSION: The hybrid hollow fiber system can selectively remove a significant amount of drugs that have an affinity to MDR from the medium, and perfuse them to the capillary side in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Preliminary results of pelvic autonomic nerve-preserving surgery combined with intraoperative and postoperative radiation therapy for patients with low rectal cancer.

BACKGROUND: In Japan, lateral lymphadenectomy was widely performed for patients with stage II-III rectal tumors because it was thought to contribute to good local control, but the pelvic autonomic nerves were thus sacrificed. Although autonomic nerve-sparing surgery with lateral lymph node dissection has been tried from around 1987, the type of nerve sparing varied and the indications were not established. To examine the possibility of expanding the indications for total pelvic autonomic nerve preservation for patients with low rectal cancer, we conducted a pilot study. METHODS: Between 1993 and 1997, a total of 50 patients with low rectal cancer underwent pelvic autonomic nerve preservation with lateral lymphadenectomy of both sides and intraoperative radiation therapy followed by postoperative radiation therapy. RESULTS: The median follow-up period for surviving patients was 41 months. The 3-year local control rates for all patients, with stage I-II and stage III tumors were 88% (95% confidence interval, 78-97%), 97% (90-100%) and 73% (52-94%), respectively. The site of local recurrences was not near or within the preserved plexus. CONCLUSIONS: The preliminary results showed good local control rate for patients with stage I-II tumors. For patients with stage III tumors, the local control rate was unsatisfactory, but nerve sparing was not the cause of local recurrence. Further investigation of function-preserving surgery without decreasing curability is needed.

Adult↗

Elasticity effects on domain coarsening of the lamellar-gyroid transition observed in a nonionic surfactant system.

The coarsening process of the gyroid phase of a nonionic surfactant system is investigated by time resolved small angle neutron scattering (SANS) and small angle neutron Laue diffraction techniques. The time evolution of SANS patterns shows anomalous coarsening of the gyroid domains. The observed Laue spot from a gyroid domain becomes elongated along the radial direction with the elapse of time and at a certain time the elongated spot is split into two spots. The results can be interpreted as follows. During the coarsening process, mismatch of the lattice orientation at the domain boundary brings strong stress to the gyroid domain, resulting in the distortion of the domain. The stored stress in the domain finally brings splitting of the gyroid domain. The elastic and fragile nature of the gyroid domains composed of the "soft matter" is responsible for the anomalous coarsening.

Journal Article↗

Characterization of mouse DAF on transfectant cells using monoclonal antibodies which recognize different epitopes.

Several membrane proteins prevent host cells from homologous complement attack. In humans, one such protein, decay-accelerating factor (DAF), exists as two isoforms, a GPI anchored form and a secreted form, which are generated by alternative splicing. DAF in mouse is also expressed as two isoforms, a GPI anchored form (GPI-DAF) and a transmembrane form (TM-DAF), which are produced from two separate genes. In this study, we transfected cDNA of mouse GPI-DAF or TM-DAF into Chinese hamster ovary (CHO) cells. Both isoforms of DAF on CHO cells were shown to regulate mouse complement C3 deposition mediated by the classical and alternative pathways and the inhibitory activity of both isoforms was species restricted. The two mouse DAF isoforms were effective against rat complement but not against human and guinea pig complement. Furthermore, we produced hamster mAbs to mouse DAF using GPI-DAF transfectant cells and established seven unique mAbs (RIKO-1-7). Western blotting analysis using RIKO-3, which reacts with both GPI-DAF and TM-DAF, and RIKO-4, which is an anti-GPI-DAF specific mAb, indicated that GPI-DAF was expressed on erythrocytes, spleen and testis, and that TM-DAF was expressed only in testis.

Animals↗

[Use of a rapid detection assay for influenza virus, on nasal aspirate specimens].

We investigated the usefulness of a rapid antigen detection kit using optical immunoassay for influenza virus (FLU OIA, BioStar, USA). Nasal aspirates were taken from 92 influenza suspected outpatients between March to April of 1999. Compared with virus isolation and PCR, the sensitivity of FLU OIA was 88.5% and 81.6%, and the specificity was 65.2% and 72.2%. All isolated viruses were influenza type B virus. It was difficult to differentiate the weak-positive and negative cases, leading to the rather low specificity, although the assay procedure was easy and quick. FLU OIA may be a useful rapid diagnosis kit for influenza in pediatric outpatient clinics and wards, because it can detect both influenza type A and type B viruses.

Antigens, Viral↗

[Kinetic analysis of anti-HIV titer in early stage of HIV infection--a new testing strategy to differentiate early HIV infection individuals from false positive cases].

We analyzed the anti-HIV antibody titer by particle agglutination (PA) on 11 HIV seroconversion panels. PA titer increased very rapidly and the titer went up to 1,000 or more within 18.2 days after seroconversion. The results suggest that one to two weeks of duration will be enough to differentiate persons at the early stage of HIV infection from individuals with HIV screening test initially reactive but false positive. In Japan, HIV prevalence is very low and the majority of the HIV screening test-positive (reactive) cases turned out to be false positive. This HIV testing strategy (one to two weeks interval bleeding) will be very practical and useful to differentiate early stage of HIV infection cases from the majority of false positive cases.

False Positive Reactions↗

[Evaluation of an optical immunoassay test for rapid detection of influenza A and B viral antigen].

An optical immunoassay test, FLU OIA (BIOSTAR, USA), was evaluated for the diagnosis of influenza viral infection. The reactivity of the FLU OIA test was evaluated using 42 influenza strains (25 human influenza A, 12 human influenza B, 2 swine influenza A and 3 avian influenza A strains). The FLU OIA test showed positive results for all influenza strains. There was no evidence that cross-reactivity occurred with non-influenza viruses. The detection limit of the FLU OIA test was found to be 3.0-6.5 x 10(4) pfu/assay for human influenza A and B strains. The sensitivity and specificity of the FLU OIA test compared to isolation in cell culture was 89.7% and 76.0% for testing of 54 nasopharyngeal aspirate specimens. The FLU OIA test is rapid and easy for the detection of influenza A and B viral antigen and provide a valuable tool for the rapid diagnosis of influenza viral infection.

Antigens, Viral↗

[Evaluation of a new screening assay kit for the combined detection of HIV p24 antigen and antibody--comparison of the performance of the new kit and HIV antibody assay kits].

DUO is an automated HIV infection screening test kit based on the combined detection of p24 Ag and anti-HIV-1 and anti-HIV-2 IgG in human sera or plasma using the ELFA technique (Enzyme-Linked Fluorescent Assay). The performance of DUO was compared with that of HIV-1/HIV-2 3rd generation EIA plus and particle agglutination (PA) test. A total of 141 seropositive sera, 3 seroconversion panels, 300 seronegative sera and 387 potentially cross-reactive serum samples were tested. One hundred and forty one seropositive sera in Japan and Cameroon were all positive with DUO. Three seroconversion panels (panel Q, Z, AE) were tested to evaluate sensitivity. In Panel Q, infecution was detected seven days earlier with DUO than with the 3rd generation EIA plus and PA. In Panel AE, infection was detected four days earlier with DUO than with the single antibody assays. Three hundred seronegative sera from Kanagawa prefectural public health centers were all negative with DUO as well as PA test. Three hundred and eighty seven potentially cross-reacting samples were tested to challenge the specificity of the assay. These included samples from pregnant women and hepatitis patients. In four of the 204 samples from pregnant women, false-positive results were observed with DUO. In three of the 183 samples from hepatitis patients, false-positive results were also obtained with DUO. All samples of 7 DUO positive results were negative with western blot test. Five of them were negative with RT-PCR and 2 of them were not tested because there were not enough samples. Thirty cross-reacting (false-positive) samples by PA test from blood donors were tested by DUO, and all of these were negative by DUO.

AIDS Serodiagnosis↗

Effect of protamine on ion selectivity of superficial and juxtamedullary proximal straight tubules.

Protamine is known to inhibit cation selectivity of the paracellular shunt pathway in several leaky nephron segments. Ion permeability of the superficial (SF) proximal straight tubules (PST) is selective to Cl(-), whereas that of the juxtamedullary (JM) PST is selective to Na(+). Protamine was used to estimate the contribution of the paracellular shunt pathway to ion selectivity in these segments. PSTs were isolated from the kidneys of Japanese white rabbit and microperfused in vitro. The ratio of Na(+) to Cl(-) permeability (P(Na)/P(Cl)) was estimated from the diffusion potential (dV(T)) generated by NaCl gradients. When 300 microg/ml protamine was added to the lumen, P(Na)/P(Cl) was decreased from 0.33 to 0.26 in SF-PST and from 1.80 to 1.29 in JM-PST, respectively, as the results of inhibition of cation selectivity. Addition of 30 U/ml heparin to the lumen, which neutralizes protamine, returned the ratios toward the control levels. Protamine exhibited similar effect on P(Na)/P(Cl) in the presence or the absence of ouabain in the bath, indicating that the observed voltage deflections were independent of the transcellular active transport process. Although P(Na)/P(Cl) was different between SF- and JM-PST, protamine inhibits Na(+) permeability in both segments. Preferential Cl(-) permeability in the SF-PST may be intrinsic to the paracellular route of this segment. The mechanism of this anion selectivity remains to be established.

Algorithms↗

Immune function and psychological factors in patients with coronary heart disease (I).

As part of studies on the effects, especially the preventive effects, of exercise and psychological factors on cardiovascular diseases, the association between psychological tendencies and immune response was evaluated in patients with coronary heart disease who were receiving exercise therapy. The Pearson's product-moment correlation coefficients between natural killer (NK) cell activity and various psychological scales were obtained. For the Moudsley Personality Inventory, NK cell activity had a significant positive correlation with the extraversion scale and a significant negative correlation with the neuroticism scale. NK cell activity also had a significant positive correlation with the playful humor scale and a significantly negative correlation with the Self-rating Depression Scale. The positive correlation of NK cell activity with the extraversion scale and the humor scale and its negative correlation with the neuroticism scale suggest an association between a positive-feeling tendency and high NK cell activity. The negative correlations of NK activity with the depression scale and neuroticism scale indicate that decreased or excessive expression of feelings inhibits NK cell activity. Thus, high NK activity appears to be associated with optimal expression of feelings.

Aged↗

Peripheral arterial coil embolization for hepatic arteriovenous malformation in Osler-Weber-Rendu disease; useful for controlling high output heart failure, but harmful to the liver.

A 55-year-old Japanese housewife, who had Osler-Weber-Rendu disease, was admitted to our hospital because of frequent epistaxis and worsening exertional dyspnea. The computed tomography and hepatic arteriography revealed large hepatic arteriovenous malformation, which was considered to be the leading cause of her high output heart failure. Two series of hepatic arterial coil embolization procedures were performed to reduce hepatic shunt flow. They temporarily improved her cardiac condition, but gradually induced progressive hepatic failure due to intrahepatic cholangitis. Hepatic dysfunction restricted her quality of life and lead to a fatal clinical course one year after the second coil embolization.

Arteriovenous Malformations↗

[Childhood multiple sclerosis and allied demyelinative diseases].

We report five cases of multiple sclerosis (MS) and three cases of allied demyelinative diseases starting during childhood. Three of the MS patients presented with atypical initial symptoms, such as acute encephalitis or myelitis, making an early clinical diagnosis difficult. Ophthalmologic symptoms were noted in four of MS children, and in two with allied demyelinative diseases. Therefore, if a child shows ophthalmologic symptoms (i.e. optic neuritis, ophthalmoplegia), brain magnetic resonance imaging (MRI) should be conducted for the differential diagnosis of MS and other demyelinative diseases. Cerebrospinal fluid analysis is not useful for the initial diagnosis of MS, because pleocytosis and increase of oligoclonal IgG band in cerebrospinal fluid are seen in both MS and other demyelinative disorders. However, neuron specific enolase (NSE) is slightly higher in the latter than in the former. T2-weighted MRI of multiple sclerosis showed multiple high intensity areas in the white matter of the cerebrum and cerebellum, capsula interna, and crus cerebri etc. Most of these lesions were clinically silent, being characteristic of MS. In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.

Biomarkers↗

[Lissencephaly type I: electroencephalographic findings and neuroradiological classification].

Lissencephaly type I is a diffuse type of migration disorder that contains agyria and/or pachygyria on the brain surface. We experienced 5 cases of this disease and evaluated their electroencephalographic findings and seizure types based on the neuroradiological classification of lissencephaly. Ages at seizure onset ranged from 2 months to 4 months (mean 3.2 months). The patients with complete agyria had generalized tonic seizures, and those with pachygyria partial seizures or tonic spasms. The characteristic findings of complete agyria in electroencephalogram were high-voltage alfa activity. The amount of high-voltage slow waves increased with the ratio of pachygyria on the brain surface. The appearance of multifocal spikes and sharp waves suggested irregular arrangement of pachygyria on the brain surface.

Brain↗

Antigenic and genetic analyses of H5 influenza viruses isolated from ducks in Asia.

The hemagglutinin (HA) of six H5 influenza virus strains isolated from ducks in Japan and China in 1976 to 1996 were analyzed antigenically and genetically. Antigenic analysis using a panel of monoclonal antibodies revealed that the HA of H5 influenza viruses isolated from ducks are antigenically closely related to each other. Phylogenetic analysis indicates that the isolates from ducks in Hokkaido were derived from an ancestor common with the highly pathogenic isolates from chickens and humans in Hong Kong in 1997.

Animals↗

[Topography and number of cortical tubers in tuberous sclerosis: comparison between patients with and without West syndrome].

To reveal the role of cortical tubers in the pathophysiology of West syndrome associated with tuberous sclerosis, we studied their numbers and topography, focusing on the differences between patients with infantile spasms and without infantile spasms. We reviewed the clinical date on the seizure types, seizure evolution and developmental status of 13 patients: 8 patients with infantile spasms (the West syndrome group) and 5 patients without infantile spasms (the non-West syndrome group). The number, size and location of the cortical tubers were evaluated on 5 mm-thick T2-weighted MR images. The average number of cortical tubers of the West syndrome group was 11.4 per patient, being larger than that of the non-West syndrome group (7.8). The West syndrome group included two patients with only one tuber. The average number of the cortical tubers in the occipital lobes of the West syndrome group was 2.4, which was larger than that of the non-West syndrome group (0.8). From these results, a large number of cortical tubers, which suggest involvement of larger cerebral cortical regions, increase the possibility of the West syndrome in patients with tuberous sclerosis. On the other hand, some patients with only one or few cortical tubers developed West syndrome, which may suggest the presence of a region critical on the development of West syndrome. Our results also suggest that lesions in the occipital lobes might be more significant than those in other lobes. However, the results of this study are diverse, to some extent, which may have resulted from variable epileptogenicity of the cortical tubers. It is necessary to conduct further study, including a greater number of patients, to reveal topographic pathophysiology in West syndrome.

Cerebral Cortex↗

[The survey of HIV infection among clients of foreign female prostitutes in Tokyo Metropolitan].

OBJECTIVES: It is important to elucidate the risks to foreign female prostitutes of HIV infection from their clients. We determined the prevalence of HIV among clients of foreign female prostitutes using anonymous testing of condom semen samples. METHODS: A total of 250 client condom semen samples were collected with client age and nationality by 15 Latin American and 37 Thai female prostitutes in Tokyo from March to May 1995. We screened by ELISA (GENELAVIA MIXT, Pasteur Sanofi Diagnostics) for antibody to HIV 1 and 2, and then confirmed by Western Blot (LAV Blot 1, LAV Blot 2, Sanofi Diagnostics Pasteur) and distinguished by Immuno Blot PEPTI-LAV 1, 2, (Sanofi Diagnostics Pasteur). RESULTS: The nationality of customers was reported as Japanese (74.8%), Iranian (7.6%), Pakistan (5.6%), Indian (2.8%), Taiwanese (2.0%), and Chinese (1.2%) with other nationalities less than 1.0%. Estimated age categories of the clients were < 20 (1.2%), 20-29 (41.2%), 30-39 (36.4%), 40-49 (12.4%), > or = 50 (6.4%) and undetermined (2.4%). Of the 250 samples collected, only 219 were sufficient for testing. Two samples (0.90%, 95% CI = 0.4-2.2%) were HIV 1 positive, both from Japanese clients (1.2% of Japanese clients, 95% CI = 0.5-2.9%). These data suggested that the prevalence of HIV in clients of female prostitutes was relatively high, and can be considered a risk group in Japan. The sentinel surveillance by anonymous of client condom semen samples is a very useful method to quantify HIV prevalence in this risk group.

Acquired Immunodeficiency Syndrome↗

Modulation of nucleoside [correction of nucleotide] triphosphate diphosphohydrolase-1 (NTPDase-1)cd39 in xenograft rejection.

BACKGROUND: There is increasing evidence showing that extracellular nucleosides [corrected] may be important mediators of vascular inflammation. Nucleoside [corrected] triphosphate diphosphohydrolase-1 (NTPDase-1, identical to CD39), the major vascular endothelial ectonucleotidase, is responsible for the hydrolysis of both extracellular ATP and ADP in the blood plasma to AMP. Studies were therefore conducted to evaluate the role of vascular NTPDase-1/cd39 in modulating platelet activation and vascular injury in cardiac xenografts. MATERIALS AND METHODS: Cardiac xenografts from both wild-type and cd39 knockout mice (C57BL/6 x 129 Svj) were transplanted into Lewis rats. Alterations in cd39 mRNA transcripts and NTPDase activity expression were evaluated in wild-type grafts in untreated rats and then following complement depletion and immunosuppression. Rejection responses were studied with both mutant and wild-type grafts in the following models: presensitization with or without complement depletion, complement depletion alone, and with chronic immunosuppression to induce long-term graft survival. RESULTS: NTPDase biochemical activity in wild-type xenografts rapidly decreased after transplantation but soon rebounded with graft survival. Elevated levels of cd39 mRNA with associated increases in NTPDase activity were observed in all long-term surviving wild-type grafts. Hyperacute xenograft rejection times were comparable in wild-type and mutant grafts but cd39-deficient grafts were subject to more rapid rejection and exhibited pronounced vascular injury in complement-depleted, presensitized rats. The cd39-deficient grafts in immunosuppressed recipients were subject to increased intravascular platelet sequestration and fibrin deposition; this resulted in focal myocardial infarction in long-term surviving mutant xenografts. CONCLUSIONS: Augmentation of NTPDase-1 activity may be an important adaptive response for graft survival. Our results suggest that NTPDase-1/cd39 influences pathways of vascular injury in cardiac xenografts.

Adenosine Triphosphatases↗