Machine perfusion preservation for liver transplantation from non-heart-beating donors with agonal stage.
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Animals↗
Biomedical subjects
M Uchiyama
Publications and source records attributed to M Uchiyama.
Intercomparison of whole-body counters by using a subject who had incorporated 137Cs into the body.
During the years 1996-2000, eight whole-body counting facilities (WBC) from Finland, Germany, Japan and Russia took part in an intercomparison using a resident of the Russian town of Novozybkov who had been seriously contaminated as a result of the Chernobyl accident. The subject R (adult male, height 172 cm average body mass 64 kg; and 137Cs body burden within the range of 1-15 kBq) was investigated in the participating institutions during his business trips. The experimentally obtained data for his 137Cs body burden were compared with the predicted values, which had been deduced from the measurements of subject R using the reference WBC (St Petersburg Institute of Radiation Hygiene) and from his effective half-time of 137Cs in the body (68 days). The obtained results did not deviate more than 20% from reference activities. Four facilities were able to quantity the 40K in the subject's body. The differences between reported values of potassium did not exceed 10%. For subject R, the average annual effective dose from radiocaesium was 0.25 mSv and it was 0.18 mSv from 40K in the years 1996/97. The reliability of using a subject with naturally incorporated artificial radionuclides ('walking standard') instead of an anthropomorphous phantom for calibration and intercomparison of whole-body counters in a large-scale nuclear accident is discussed.
Accidents↗
New in-vivo calibration phantoms and their performance.
New in-vivo calibration phantoms (anthropometric phantoms) were developed to meet the needs for Japanese standard phantoms. Two important characteristics of these phantoms were that (1) they were designed using Japanese body size survey data, and (2) they were designed so that they can be adapted to various positions or geometries. The performance of these phantoms was tested with respect to body size, activity distribution along the axis, and counting efficiency. The actual dimensions of the anthropometric phantoms were compared with the survey data. Most items (31 of 47) indicated good agreement between the actual values and the survey data for the adult anthropometric phantom. The activity distribution for the anthropometric phantoms was compared with that for block phantoms that simulate a uniform activity distribution. The anthropometric phantoms have some gaps in their joints. The measurement results, however, indicated that these gaps did not significantly affect the overall accuracy of the measurements. Differences in counting efficiency between the block phantoms and the anthropometric phantoms for the same age were no more than 6%.
Adult↗
Nephron structure and immunohistochemical localization of ion pumps and aquaporins in the kidney of frogs inhabiting different environments.
Amphibians inhabit areas ranging from completely aqueous to terrestrial environments and move between water and land. The kidneys of all anurans are similar at the gross morphological level: the structure of their nephrons is related to habitat. According to the observation by light and electron microscopy, the cells that make up the nephron differ among species. Immunohistochemical studies using antibodies to various ATPases showed a significant species difference depending on habitat. The immunoreactivity for Na+,K(+)-ATPase was low in the proximal tubules but high in the basolateral membranes of early distal tubules to collecting ducts in all species. In the proximal tubule, apical membranes of the cells were slightly immunoreactive to H(+)-ATPase antibody in aquatic species. In the connecting tubule and the collecting duct, the apical membrane of intercalated cells was immunoreactive in all species. In aquatic species, H+,K(+)-ATPase immunoreactivity was observed in cell along the proximal, distal tubule to the collecting duct. However, H+,K(+)-ATPase was present along the intercalated cells of the distal segments from early distal to collecting tubules in terrestrial and semi-aquatic species. In the renal corpuscle, the neck segment and the intermediate segment, immunoreactivities to ion pumps were not observed in any of the species examined. Taking together our observations, we conclude that in the aquatic species, a large volume of plasma must be filtered in a large glomerulus and the ultrafiltrate components are reabsorbed along a large and long proximal segment of the nephron. Control of tubular transport may be poorly developed when a small short distal segment of the nephron is observed. On the contrary, terrestrial species have a long and well-developed distal segment and regulation mechanisms of tubular transport may have evolved in these segments. Thus, the development of the late distal segments of the nephron is one of the important factors for the terrestrial adaptation.
Animals↗
Regiocontrolled deprotonative-zincation of bromopyridines using aminozincates.
Regiochemistry in the deprotonation of bromopyridines was found to be greatly influenced by the choice of metal amide base, and DA-zincate and TMP-zincate turned out to be excellent complementary practical agents for regioselective metalation of bromopyridines.
Journal Article↗
Receptor-mediated delivery of all trans-retinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene.
All trans-retinoic acid (RA)-loaded poly(L-lactic acid) (PLA) nanoparticles coated with galactose-carrying polymer, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of released RA from its loaded nanoparticles on morphology and DNA synthesis of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles was checked by fluorescence and confocal laser microscopy. It was found that the shapes of most hepatocytes attached onto polystyrene dish precoated with collagen solution were flat and spreading at low concentration of RA for the RA-loaded nanoparticles, whereas their shapes were round at even low concentration of RA when RA was mixed with the nanoparticles. From the fluorescence and confocal laser microscopic studies, it was suggested that the nanoparticles coated with galactose-carrying polymers were internalized by the hepatocytes through the receptor-mediated mechanism. The RA-loaded nanoparticles were more potent stimulators of hepatocyte DNA synthesis than the free RA system in the presence of epidermal growth factor (EGF) owing to the controlled release of RA from the RA-loaded nanoparticles.
Animals↗
Regulation of asialoglycoprotein receptor expression in the proliferative state of hepatocytes.
It is necessary to proliferate hepatocytes and to increase the number of hepatocytes for development of bioartificial liver (BAL) and reconstitutive therapy. But usually the cell has a precarious balance between proliferation and differentiation: as the cell proliferation increases, functional differentiation decreases. Therefore, it is desirable for the hepatocytes to be functional by differentiation as a material for such clinical use not to be proliferative. In this study, we investigated the background of hepatocyte proliferation for the springboard of control between proliferation and differentiation of hepatocytes, and we focused attention to the asialoglycoprotein receptors (ASGP-R) of the hepatocytes. Partially hepatectomized (PH) rats were used as a model animal. When the isolated hepatocytes were plated onto the artificial extracellular matrix of poly-(N-p-vinylbenzyl-O-beta-d-galactopyranosyl-d-gluconamide) (PVLA) having galactose residues as cell-specific ligand, the rate of adhesion was decreased along with liver regeneration. Interestingly, the release of the ASGP-R from hepatocytes in serum after PH in vivo and reduction of ASGP-R of the hepatocytes in the proliferative state occurred due to cell growth in vitro. It is suggested that the ASGP-R on the hepatocyte surface during the differentiation was released in the proliferative state.
Animals↗
Immune responses and protection in different strains of aged mice immunized intranasally with an adjuvant-combined influenza vaccine.
Immune responses and protection against influenza virus infection were compared between young (2 months) and aged (18 months) BALB/c, C3H and C57BL/6 (B6) mice after intranasal vaccination. The mice were immunized with 2.5 microg protein of A/PR/8/34 (PR8) (H1N1) virus vaccine containing a cholera toxin adjuvant. In both the young and aged BALB/c mice, high levels of PR8-specific antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue (NALT) 7 days after immunization. Nasal wash IgA and serum IgG antibody (Ab) responses to the PR8 haemagglutinin (HA) 4 weeks after immunization were slightly higher in the young mice than in the aged mice. The young mice showed complete protection against challenge infection, while the aged mice showed only a partial protection. In the C3H mice, NALT-AFC, and IgA and IgG Ab responses were higher in the young mice than those in the aged mice in parallel with the more efficient protection in the young mice than in the aged mice. Both the young and aged B6 mice showed no NALT-AFC responses, scarce IgA and IgG Ab responses and no protection. In the BALB/c mice, IgG1 and IgG2a levels were significantly lower in the aged mice. On the other hand, in the C3H mice, only IgG2a level was significantly lower in the aged mice. Similar results were obtained in terms of immune responses and protection between the young and aged mice of three different strains of mice after intra-nasal immunization with 0.1 microg of PR8 vaccine containing the adjuvant, two-times at 4-week intervals. In the B6 mice, the immune response was improved by immunization with a higher dose of the adjuvant-combined vaccine. These results suggest that local Ab responses, as well as systemic Ab responses, are downregulated in aged mice, although the degree of the downregulation of immune responses differs from strain to strain.
Adjuvants, Immunologic↗
Essential role of Sna41/Cdc45 in loading of DNA polymerase alpha onto minichromosome maintenance proteins in fission yeast.
Assembly of replication complexes at the replication origins is strictly regulated. Cdc45p is known to be a part of the active replication complexes. In Xenopus egg extracts, Cdc45p was shown to be required for loading of DNA polymerase alpha onto chromatin. The fission yeast cdc45 homologue was identified as a suppressor for nda4 and named sna41. Nevertheless, it is not known how Cdc45p facilitates loading of DNA polymerase alpha onto chromatin, particularly to prereplicative complexes. To gain novel insight into the function of this protein in fission yeast, we characterized the fission yeast Cdc45 homologue, Sna41p. We have constructed C-terminally epitope-tagged Sna41p and Pol alpha p and replaced the endogenous genes with the corresponding tagged genes. Analyses of protein-protein interactions in vivo by the use of these tagged strains revealed the following: Sna41p interacts with Pol alpha p throughout the cell cycle, whereas it interacts with Mis5p/Mcm6p in the chromatin fractions at the G(1)-S boundary through S phase. In an initiation-defective sna41 mutant, sna41(goa1), interaction of Pol alpha p with Mis5p is not observed, although Pol alpha p loading onto the chromatin that occurs before G(1) START is not affected. These results show that fission yeast Sna41p facilitates the loading of Pol alpha p onto minichromosome maintenance proteins. Our results are consistent with a model in which loading of Pol alpha p onto replication origins occurs through two steps, namely, loading onto chromatin at preSTART and association with prereplicative complexes at G(1)-S through Sna41p, which interacts with minichromosome maintenance proteins in a cell cycle-dependent manner.
Carrier Proteins↗
The influence of lifestyle and health status factors on sleep loss among the Japanese general population.
STUDY OBJECTIVE: To examine the relationship between lifestyle, health status factors and sleep loss. DESIGN: A cross-sectional questionnaire survey conducted by the Ministry of Health and Welfare, Japan. SETTING: N/A. PATIENTS OR PARTICIPANTS: Approximately 30,000 subjects selected from the general population in Japan. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: This study indicated that approximately 28% of the general population sleep less than 6 hours nightly and approximately 65% sleep less than 7 hours. However, approximately 80% of the population reported getting sufficient sleep. Multiple logistic regression analysis showed that being females, being of younger age, living in an urban environment, being unemployed, and having an unhealthy lifestyle (i.e., lack of exercise, poor health status, and irregular eating habits) were associated with sleep loss. CONCLUSION: In this study, sleep loss was found to be associated with having an unhealthy lifestyle and being in poor general health. These findings suggest that health education and promotion of a healthy lifestyle should be advocated.
Adult↗
Low birth weight, developmental milestones, and behavioral problems in Chinese children and adolescents.
This study examined the association of low birth weight (LBW) and developmental milestones with behavioral and emotional problems in a general population sample of 3344 Chinese children and adolescents aged 6-16 years in 1997. Parents completed a self-administrated questionnaire including information about birth weight and developmental milestones (i.e. lifting the head up, tooth eruption, speech, walking and bedwetting cessation), and the Child Behavioral Checklist (CBCL). Teachers completed the Teacher's Report Form (TRF) to assess classroom behavior problems. Results indicated that LBW and delayed developmental milestones were significantly associated with an increased risk for almost all parent- and teacher-reported behavioral problems after controlling for the potential effects of child's gender, age and birth order, parental ages at birth, education, occupation, complications at birth and number of children in the family. LBW was significantly associated with delay in achieving all developmental milestones including lifting of the head, tooth eruption, sitting without support, walking without help, speech as saying words with meaning, and bedwetting cessation. It is concluded that LBW and delayed early childhood development may predict the occurrence of a wide range of behavioral and emotional problems in later childhood and adolescence.
Adolescent↗
Mesityllithium as a reagent for chemoselective halogen-lithium exchange reaction.
[figure: see text] Mesityllithium was found to be an excellent selective lithiating agent to prepare aryllithium compounds having alkoxycarbonyl groups. To extend our studies on chemoselective lithiation, an important precursor for the synthesis of camptothecin was prepared using a halogen-lithium exchange reaction followed by an intramolecular 1,2-addition.
Camptothecin↗
Use of digirad 2020tc Imager, a multi-crystal scintillation camera with solid-state detectors in one case for the imaging of autografts of parathyroid glands.
99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy with Digirad 2020tc ImagerTM (2020tc), which was a multi-crystal scintillation camera with solid-state detectors was performed for patients with secondary hyperparathyroidism having autografts of parathyroid glands in the right arm. With the 2020tc camera, three abnormal accumulations were found in the right arm. The images obtained with this camera were superior in resolution to those obtained with a conventional NaI crystal gamma camera (ZLC7500, Siemens, Germany). The next day, resection of autografts of parathyroid glands was done. Four hyperplastic parathyroid glands were resected and all were hyperplastic in pathological findings.
Cesium↗
Redistribution in I-123 N-isopropyl-p iodoamphetamine single-photon emission computed tomography in cerebrovascular disease and the effects of rehabilitation.
We performed N-isopropyl-p (I-123) iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) on 28 patients with severe cerebrovascular disease before rehabilitation, and compared the degree of redistribution and the assessment of activities of daily living (ADL). We calculated a redistribution (RD) ratio in the central and peripheral parts of the lesions: RD ratio (c) and RD ratio (p). We classified the patients into four groups based on the degree of redistribution: complete: both RD ratio (c) and (p) > or = 75; peripheral: RD ratio (c) < 75, RD ratio (p) > or = 75; incomplete: both RD ratio (c) and (p) < 75 and at least one of RD ratio (c) or (p) > or = 25; no redistribution: both RD ratio (c) and (p) < 25. We assessed the ADL using the modified Barthel index (BI). deltaBI was defined as BI after rehabilitation-BI before rehabilitation (BIpost-BIpre). The deltaBI of the four groups were as follows: complete-redistribution group (40.8 +/- 22.8), peripheral-redistribution group (40.0 +/- 15.8), incomplete-redistribution group (27.2 +/- 22.6), no-redistribution group (8.8 +/- 12.3). The deltaBI of the complete and peripheral redistribution groups were significantly higher than that of the no-redistribution group. However, deltaBI was almost the same in the complete- and peripheral-redistribution groups. This suggests that the effect of rehabilitation might be closely related to the viability of the peripheral part of the lesion.
Activities of Daily Living↗
Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in a CDC45 homolog and interacts genetically with polalpha.
Proteins involved in the initiation of DNA replication play critical roles in the assembly and loading of replication complexes at replication origins. To gain further insight into the regulation of initiation, we screened in fission yeast for temperature-sensitive mutants which arrested at the G1/S boundary, and isolated nine mutants which arrested with a 1C DNA content at 36 degrees C. By linkage analysis, two complementation groups were identified which were not allelic to known G1 arrest mutations. One of the mutants isolated, sna41goul, arrested with a G1 DNA content and expressed a pleiomorphic phenotype, i.e., a mixture of cut and cdc phenotypes, at 36 degrees C. The point of arrest was identified as after START but before the hydroxyurea-induced block, by taking advantage of the mutant rad26.a14, which has a defect in an early S phase-specific checkpoint, and by performing reciprocal shift experiments. sna41 goal is allelic to sna41+, which is homologous to the CDC45 gene of budding yeast, and the mutation lies in a motif that is highly conserved in Cdc45-related proteins. The temperature sensitivity of the sna41goal mutant can be suppressed to some extent by ts mutations in polalpha. Our genetic results are consistent with a model in which Cdc45 plays crucial roles in the assembly of the replication apparatus at replication origins.
Carrier Proteins↗
Treatment of ruptured undifferentiated sarcoma of the liver in children: a report of two cases and review of the literature.
Undifferentiated (embryonal) sarcoma of the liver (USL) is a highly malignant tumor of early life. Treatment choices for USL, especially with intraperitoneal rupture, are uncertain. Outcomes have been almost uniformly poor until recently. We describe two 7-year-old girls treated for ruptured USL. In the more recent patient, operative biopsy was followed by three cycles of cisplatin (CDDP), adriamycin (ADR), and cyclophosphamide (CPM). A fluid-filled cavity in the tumor showed enlargement and was drained. Two cycles of CDDP, ADR, vincristine (VCR), and ifosfamide were accompanied by reduction in tumor size, and trisegmentectomy was performed. She has no evidence of disease 3.5 years after surgery. In the other patient, left lobectomy was followed by a less intensive regimen, including CPM, VCR, and fluorouracil. This patient died of dissemination within 5 months. In 170 reported pediatric patients with USL, the 2-year disease-free survival was 17%. For the 96 such patients reported since 1980, 2-year disease-free survival had improved to 27%. More aggressive chemotherapy has been associated with this change. Of 8 patients with tumor rupture whose details have been reported (including the 2 present patients) after resection of the tumor, 4 died, 1 was alive with disease, and 3 were free of disease at 8, 49, and 58 months, respectively, after diagnosis. Ruptured USL should be treated with combination chemotherapy including CDDP and ADR, as well as with curative resection.
Antineoplastic Combined Chemotherapy Protocols↗
Postoperative fecoflowmetric analysis in patients with anorectal malformation.
Because conventional methods of evaluating anorectal function do not necessarily provide good correlations between investigative results and symptoms in patients who have undergone surgery for an anorectal malformation (ARM), we recently introduced feco-flowmetry (FFM) to simulate natural anorectal evacuation. The purpose of this study was to embody significant parameters to elucidate the dynamics of anorectal activity on FFM. The parameters of FFM were compared with those of manometry and Kelly's clinical score (KCS) in 24 patients who underwent surgery for an ARM. There were three fecoflow patterns, namely, block (B) type, segmental (S) type, and flat (F) type. The B-type or S-type patterns were seen in patients classified as "clinically good." There were close relationships between the fecoflow pattern and both the operative procedure and the KCS (P = 0.01 and 0.001, respectively). Maximum fecal stream flow rate (Fmax) precisely reflected the tolerance rate of intended normal saline solution in the colorectum (TR), the evacuative rate (ER), and KCS. Fmax > 45 ml/s or TR > 70% or ER > 50% was statistically regarded as the borderline of fecal continence. Thus, the fecoflow pattern might reflect the motor activity of the pelvic floor muscle. FFM provided quantiative and qualitative evaluations concerning anorectal motor activity in patients who had undergone surgery for an ARM.
Adolescent↗
Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions.
PURPOSE: To evaluate an interaction between simvastatin and itraconazole in in vitro studies and to attempt a quantitative prediction of in vivo interaction in humans. METHODS: The inhibitory effect of itraconazole on simvastatin metabolism was evaluated using human liver microsomes and the Ki values were calculated for the unbound drug in the reaction mixture. A physiologically-based pharmacokinetic model was used to predict the maximum in vivo drug-drug interaction. RESULTS: Itraconazole competitively inhibited the metabolism of simvastatin to M-1 and M-2 with Ki values in the nM range. The area under the curve (AUC) of simvastatin after concomitant dosing with itraconazole was predicted to increase ca. 84-101-fold compared with that without administration of itraconazole. Taking into consideration the fact that this method predicts the maximum interaction, this agrees well with the clinical observation of a 19-fold increase. A similar prediction, based on the Ki value without taking into account the drug adsorption to microsomes, led to an underevaluation of the interaction. CONCLUSIONS: It was demonstrated that the competitive inhibition of CYP3A4-mediated simvastatin metabolism by itraconazole is the main cause of the drug interaction and that a Ki value corrected for drug adsorption to microsomes is the key factor in quantitatively predicting the maximum in vivo drug interactions.
Anticholesteremic Agents↗