Immunohistochemical analysis of tubulointerstitial changes of chronic allograft nephropathy.
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Chronic Disease↗
Biomedical subjects
Y Yamaguchi
Publications and source records attributed to Y Yamaguchi.
C4d deposition in the glomeruli and peritubular capillaries associated with transplant glomerulopathy.
Transplant glomerulopathy (TGP) is a unique disease entity with characteristic pathological findings. Although ultrastructural studies for TGP have been performed, histogenesis of TGP is not fully understood. The present study was designed to investigate the relation of complement fragment C4d to the histogenesis of TGP. Nine cases of isolated TGP were randomly selected. A commercially available monoclonal antibody against complement fragment C4d was used in allograft biopsies. To evaluate the extent and severity of deposition of the C4d complement in the glomerular and peritubular capillaries, indirect immunofluoresce method was performed on frozen sections. Intense deposition of C4d in the glomerular basement membrane and peritubular capillaries was found in association with morphological appearance of TGP. Peritubular capillaries were affected in all the patients, showing splitting and multilayering of peritubular capillary basement membrane. These changes, which diffusely affect most capillaries, and their severity pattern were quite similar in each patient. In early stages of all patients with cellular rejection, C4d was not detected in the glomerular and peritubular capillaries. In addition, no C4d deposition was detected in all zero-hour biopsies without diagnostic abnormality. These findings suggest that C4d deposition in the glomerular and peritubular capillaries might be associated with the pathogenesis of TGP in renal transplantation.
Adult↗
Acute effects of ethanol on feeding behavior and leptin-induced STAT3 phosphorylation in rat hypothalamus.
OBJECTIVE: Drinking ethanol stimulates the appetite, producing a positive energy balance. The mechanism by which ethanol regulates the appetite in the central nervous system, however, has not been fully understood. The aim of this study is to investigate the interaction of ethanol with the satiety effect of leptin, a hormone which suppresses the appetite in the hypothalamic region. DESIGN: : Leptin (7.5 micro g) or the same dose of phosphate buffer saline (PBS) was administered into the third ventricle (i.c.v.), 30 min after an intraperitoneal injection (i.p.) of ethanol (0.5 g/kg body weight) or the same dose of PBS. MATERIALS: Adult male Sprague-Dawley rats weighing 290-320 g were used. MEASUREMENTS: Food intake was measured 2, 12 and 24 h after leptin i.c.v. infusion. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was analyzed by Western blotting. RESULTS: The cumulative food intakes in the saline/leptin group (saline i.p.+leptin i.c.v.) were markedly reduced to about 45% of the saline/PBS group (saline i.p.+PBS i.c.v.) at 2, 12 and 24 h time points (P<0.05, 0.001, and 0.005, respectively). As compared with the saline/leptin group, those of the ethanol/leptin group (ethanol i.p.+leptin i.c.v.) were significantly increased to the level seen in the saline/PBS group at 12 and 24 h time points (P<0.05, and P<0.005 vs the saline/leptin group, respectively). Ethanol administration resulted in about a 50% reduction of the leptin-induced STAT3 tyrosine phosphorylation seen in the hypothalamic protein as compared to that of the saline/leptin group. CONCLUSION: These findings suggest that ethanol-induced enhancement of the appetite may, in part, result from leptin resistance transiently caused by ethanol to attenuate the leptin signal transduction.
Animals↗
Analyses of absorbed dose to tooth enamel against external photon exposure.
Absorbed dose to tooth enamel was examined against external photon exposure by measurements with thermoluminescence dosemeters (TLDs) and Monte Carlo calculations. TLDs were placed in a realistic physical phantom to measure dose to the teeth region in a head. A voxel-type phantom was constructed from computed tomography (CT) images of the physical phantom. Monte Carlo calculations with this voxel-type phantom were performed to analyse the results of the experiments. The data obtained were compared to the enamel doses, which were calculated with a modified MIRD-type phantom and already given in a previous paper. It was confirmed that the data derived with the MIRD-type phantom are applicable for retrospective individual dose assessments by electron spin resonance (ESR) dosimetry using teeth for the photon energy region above 300 keV. The analysis, however, indicated that the configuration of the head can affect the enamel dose relative to external exposure to photons with energy below 100 keV.
Calibration↗
Development and assessment of a new radioactive decay database used for dosimetry calculation.
The present paper discusses the technical issues and a scheme for their resolution before undertaking the development of a new radioactive decay database to succeed ICRP38. The scheme consists of the following procedures. (1) The consistency of nuclear structure data files used as input to the computer code EDISTR is established by referring to the latest nuclear parameters and by comparing the computed energies of emitted radiations with total decay energy. (2) A method for calculating detailed spectra of X rays and Auger electrons is incorported into EDISTR to enhance the treatment of atomic relaxation processes initiated by electron vacancies from internal conversion and electron capture. (3) Quality assurance of the compiled data is undertaken by comparisons with experimental data and other decay databases prepared from different computer codes and libraries. JAERI and ORNL are cooperating to implement the scheme in order to assemble a comprehensive radioactive decay database including over 1000 nuclides.
Database Management Systems↗
Conversion coefficients from fluence to effective dose for heavy ions with energies up to 3 GeV/A.
Radiological protection against high-energy heavy ions has been an essential issue in the planning of long-term space missions. The fluence to effective dose conversion coefficients have been calculated for heavy ions using the particle and heavy ion transport code system PHITS coupled with an anthropomorphic phantom of the MIRD5 type. The calculations were performed for incidences of protons and typical space heavy ions--deuterons, tritons, 3He, alpha particles, 12C, 20Ne, 40Ar, 40Ca and 56Fe--with energies up to 3 GeV/A in the isotropic and anterior-posterior irradiation geometries. A simple fitting formula that can predict the effective dose from almost all kinds of space heavy ions below 3 GeV/A within an accuracy of 30% is deduced from the results.
Algorithms↗
Analysis of dose-LET distribution in the human body irradiated by high energy hadrons.
For the purposes of radiological protection, it is important to analyse profiles of the particle field inside a human body irradiated by high energy hadrons, since they can produce a variety of secondary particles which play an important role in the energy deposition process, and characterise their radiation qualities. Therefore Monte Carlo calculations were performed to evaluate dose distributions in terms of the linear energy transfer of ionising particles (dose-LET distribution) using a newly developed particle transport code (Particle and Heavy Ion Transport code System, PHITS) for incidences of neutrons, protons and pions with energies from 100 MeV to 200 GeV. Based on these calculations, it was found that more than 80% and 90% of the total deposition energies are attributed to ionisation by particles with LET below 10 keV microm(-1) for the irradiations of neutrons and the charged particles, respectively.
Body Burden↗
Dose assessment from activated sodium within a body in criticality accidents.
Some data were derived using recent sophisticated methods to rapidly convert specific activity of induced 24Na to average dose over a whole body in criticality accidents. Monte Carlo calculations using the MCNP-4B code were performed to study energy spectra of neutrons and gamma rays for some criticality systems with fissile uranium. Absorbed dose to the human body and the activation of sodium were also analysed against external radiation by simulations using a MIRD-5 type phantom and the calculated energy spectra. It was found that the neutron dose assessment from induced 24Na would be important to give medical staff initial guidance for treatment of a victim. However, the energy distribution of incident neutrons to the human body did not significantly influence the conversion from the specific activity of 24Na to dose from gamma rays induced within a body. Analyses were made to clarify the dependence of conversion from 24Na specific activity to neutron dose on the orientation toward the source and the size of the human body. The total dose estimated based upon the obtained data ranged from 33 mGy to 514 mGy for a given specific activity of 1.4 kBq 24Na per g 23Na for some criticality assemblies. This study suggested that the size of uranium solution and material around the fuel should be defined to properly estimate the total dose, including the dose from external photons.
Dose-Response Relationship, Radiation↗
The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application.
The overexpression of estrogen receptor alpha (ERalpha) is frequently observed in the early stage of breast cancer. We previously reported that the specific promoter of the ERalpha gene is responsible for this enhanced transcription of the gene, and identified the cis-acting elements which play an important role in its transcription. Furthermore, methylation of the ERalpha gene promoters also contribute to the regulation of gene transcription. Elucidation of these mechanisms of ERalpha gene expression may provide useful information for the early detection and chemoprevention of breast cancer. On the other hand, the expression of ERbeta has been reported in breast cancer. We have also assessed the significance and function of ERbeta and its variant types in breast cancer, and suggest that ERbeta and ERbetacx specifically suppress the function of ERalpha through different mechanisms. ERbeta isoforms may be important functional modulators of the estrogen-signaling pathway in breast cancer cells, and might affect the clinical outcome of patients. Moreover, to address the role of these ERs on the estrogen-dependent growth of breast cancer cells and to develop a diagnostic tool, we have analyzed the gene expression profiles of estrogen-responsive genes using cDNA microarray. Based on these results, the expression of several candidate genes in breast cancer tissues were analyzed by real-time RT-PCR and by immunohistochemical techniques, in order to discover new predictive factors for the endocrine therapy of patients with breast cancer. These studies could provide new clues for the elucidation of the estrogen-dependent mechanisms of cancer and the clinical benefits for patients.
Breast Neoplasms↗
Enhanced insulin gene expression by reduced intracellular glutathione level in insulin secreting cells MIN6.
Glutathione (GSH) participates in deoxidization and elimination of hydrogen peroxide and other reactive oxygen species, and plays an important part in the antioxidant system. To investigate the effect of GSH content on insulin gene expression, we utilized a stable transfectant, designated as ribo-MIN6 cells, which were stably transfected with the ribozyme of gamma-glutamylcysteine synthetase (gamma-GCS), exhibiting approximately 50% reduction of intracellular GSH content. We transiently transfected a luciferase expression vector driven by human preproinsulin gene promoter spanning from -1998 to +237 (pINS-1998/luc) and several deletion constructs into ribo-MIN6. Furthermore, transient transfection with ribozyme vector and pINS-1998/luc into wild-type MIN6 cells was also carried out. Luciferase activity was about 9-fold higher in ribo-MIN6 cells as compared to wild-type MIN6 cells. In the transient transfection of pINS-1998/luc with gamma-GCS ribozyme vector into wild-type MIN6 cells, the luciferase activity was increased in proportion to the added amounts of ribozyme vector. In transfection with deletion constructs, two major sites were found to be critical for insulin promoter activity. For the wild-type MIN6 cells, regions important for the promoter activity were also located at regions similar to those of ribo-MIN6 cells. Our results suggest that the suppression of intracellular GSH level might, in part, regulate the insulin gene expression.
Animals↗
Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives.
We investigated the controlled release of human insulin at an initial stage from poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA microcapsules were prepared by the novel solvent evaporation multiple emulsion process. When the crystalline insulin was dispersed in dichloromethane as solid-in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA microcapsules exhibited marked rapid release of insulin within several hours in both in vivo and in vitro experiments. On the other hand, the addition of glycerol or water in the primary dichloromethane dispersion results in drastically suppressed initial release. It was found by SEM observation that water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean diameter of 300-500 nm were formed in this primary solution. This phenomenon can be theoretically presumed to occur because insulin and PLGA molecules, having amphiphilic properties, converge on the interface between the hydrophilic additive and dichloromethane. Hence, insulin molecules heterogeneously located in the inside of PLGA microcapsules, not on the surface, would be gradually released with PLGA hydrolytic decomposition. As an additional effect of glycerol, the initial burst was further suppressed due to the decrease of the glass transition temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA molecules took place at around 37 degrees C, the porous structure of microspheres immediately disappeared after immersion in PBS or subcutaneous administration. The insulin diffusion through the water-filled pores would be effectively prevented. The strict controlled initial release of insulin from the PLGA microsphere suggested the possibility of utilization in insulin therapy for type I diabetic patients who need construction of a basal insulin profile.
Animals↗
Momentum distribution of 15B fragments from the breakup of 17B.
The two-neutron removal cross section (sigma(-2n)) and the longitudinal momentum distribution of 15B fragments from the breakup of 17B on 9Be were measured at 70A MeV. The distribution in the projectile rest frame is characterized by a FWHM of 80+/-10 MeV/c for 15B. The sigma(-2n) is found to be 0.22+/-0.05 b. A Glauber-type analysis of the data provides clear evidence of a two-neutron halo structure in 17B.
Journal Article↗
Identification of early-responsive genes associated with the hypersensitive response to tobacco mosaic virus and characterization of a WRKY-type transcription factor in tobacco plants.
In order to identify genes that are involved in the defense reaction against pathogen attack, we screened for examples that are regulated during the hypersensitive response (HR) to infection by tobacco mosaic virus (TMV) of tobacco ( Nicotiana tabacum cv. Xanthi nc) carrying the N gene, which confers resistance to TMV. Among seven genes initially identified by fluorescent differential display, one clone was further characterized because its transcripts accumulated rapidly and transiently after the onset of HR. Its full-length cDNA of 1346 bp encoded a polypeptide consisting of 258 amino acids. The deduced protein contained a single WRKY domain, a Cys(2)His(2) zinc-finger motif and a leucine-zipper motif, showing high similarity to WIZZ, a member of the family of WRKY transcription factors in tobacco. The gene was thus designated TIZZ. A GFP-TIZZ fusion protein was found to localize to the nucleus upon introduction into epidermal cells of onion. Bacterially expressed TIZZ was able to bind to the W-box (TTGAC) element that is recognized by other WRKY proteins, but transactivation assays showed it to be unable to activate reporter gene expression by itself. TIZZ transcripts were induced in TMV-infected nahG transgenic tobacco plants, in which salicylic acid fails to accumulate. Neither exogenously applied salicylic acid nor mechanical wounding induced TIZZ transcript accumulation. These results indicate the presence of salicylic acid-independent pathways for HR signal transduction, in which a novel type of WRKY protein(s) may play a critical role for the activation of defense.
Amino Acid Sequence↗
Decrease in the insulin receptor protein level by anti-insulin receptor antibodies: roles of tyrosine kinase activity and receptor internalization.
To investigate the mechanism of severe impairment of insulin action in type B insulin resistance, we extracted IgG from the serum of a patient with type B insulin resistance (B-IgG) and analyzed the inhibiting effect of B-IgG not only on insulin signaling but also on IGF-I signaling in Chinese hamster ovary (CHO) cells expressing human insulin receptor or human IGF-I receptor. Preincubation with 1 mg/ml B-IgG prevented insulin-induced phosphorylation of insulin receptor and insulin receptor substrate-1 (IRS-1) but did not alter the IGF-I-induced phosphorylation of the IGF-I receptor and IRS-1. (125)I-insulin binding was inhibited by 93% after preincubation with B-IgG at 37 degrees C and was recovered up to 50% of the control value by acid washing. However, when cells were preincubated with B-IgG at 4 degrees C, the insulin binding completely recovered the control value by acid washing. (125)I-IGF-I binding was not altered by B-IgG preincubation. Immunoblot study revealed that the protein level of the insulin receptor was strongly decreased by preincubation with 1 mg/ml B-IgG at 37 degrees C, but never at 4 degrees C. The IRS-1 protein level did not change by B-IgG preincubation. In order to know the role of the insulin receptor internalization in the inhibiting effect of B-IgG, we employed CHO cells expressing mutant insulin receptors which do not undergo internalization (CHO-K1018R). B-IgG incubation of CHO-K1018R at 37 degrees C failed to decrease the protein level of the insulin receptor. The present data indicate that IgG from the diabetic patient with type B insulin resistance decreased insulin receptor protein level, probably due to the enhanced degradation rate of the insulin receptor, in which insulin receptor tyrosine kinase activity and internalization are required for this process. This effect of B-IgG was specific for the insulin receptor with no effect on either IGF-I receptor or IRS-1, as reflected by the IGF-I effectiveness on glycemic control in this patient.
Animals↗
A novel A97P amino acid substitution in alpha-galactosidase A leads to a classical Fabry disease with cardiac manifestations.
BACKGROUND: Fabry disease results from a genetic deficiency of alpha-galactosidase A (GLA) activity. Phenotype-genotype correlations in this condition have not as yet been fully elucidated. OBJECTIVE: To report a case of a male patient with classical Fabry disease and his mother, a heterozygous female with Fabry disease, showing cardiac involvement, and to identify the underlying GLA gene mutation in this particular phenotype. PATIENTS/METHODS: Genomic DNA was extracted from the patient, his mother and the unaffected family members. Biopsy specimens of skin, heart and kidney were examined using light and electron microscopy. The mutation was identified by polymerase chain reaction and direct sequencing and was confirmed by restriction enzyme fragment length polymorphism. RESULTS: The G-->C transversion was identified in codon 97 of the GLA gene and resulted in an A97P amino acid substitution that was a novel pathogenic GLA gene mutation. The male patient who had classical Fabry disease was hemizygous and his mother was heterozygous for this mutation. CONCLUSIONS: These results indicate that the A97P amino acid substitution in GLA might tend to induce classical Fabry disease.
Adult↗
Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients.
We analysed the genomic and conformational variability of the hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) to evaluate the importance of its biological role. A total of 865 genotype 1b HVR1 subclones were collected from serially sampled sera in 11 patients with chronic hepatitis C, four of whom received interferon therapy. Consequently, 169 distinct sequences were examined for amino acid substitutions as well as hydrophilic or hydrophobic profile at each amino acid position within HVR1. Secondary structure of HVR1 was also predicted by the method of Robson in 90 distinct sequences from eight patients, including three interferon-treated patients. Some positions within the HVR1 were invariable or nearly so as to amino acid substitution. Hydrophilic or hydrophobic residues exclusively predominated at several positions. These constrained amino acid replacement and hydrophilic or hydrophobic profiles were conserved irrespective of interferon therapy, though the frequency of amino acid replacement was greater at almost all amino acid positions within the HVR1 in interferon-treated patients. The quasispecies of HCV showed various secondary structures of HVR1, but many sequences seemed to have common characteristics. beta sheet conformations around both the N-terminus and position 20 (numbered from the NH2 terminus of E2 envelope glycoprotein), and/or coil structures around the C-terminus of HVR1 could be identified. These results suggest that HVR1 amino acid replacements are strongly constrained by a well-ordered structure, in spite of being tolerant to amino acid substitutions, and imply an important biological role of the HVR1 protein in HCV replication.
Adult↗
Interferon retreatment reduces or delays the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.
Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic hepatitis C patients, especially those who do not respond completely to interferon therapy. Interferon has been reported to reduce the incidence of hepatocellular carcinoma (HCC) not only in sustained virological responders but also in transient biochemical responders. However, the incidence of HCC increases in 5 years or more after interferon therapy in transient biochemical responders. The aim of this study is to assess whether interferon retreatment reduces the incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was not eradicated during initial interferon therapy. We enrolled 309 patients who were not sustained virological responders after initial interferon treatment consisting of a total dose of more than 250 megaunits of interferon and were followed for more than 2 years after treatment. Ninety-nine patients received interferon retreatment and 210 did not. Two courses of interferon therapy were administered in 84, three courses in 14 and five courses in one. The incidence of HCC was compared between patients with retreatment and those without. In the clinical characteristics, retreated patients were younger and followed up for a longer time period. The cumulative incidence of HCC was significantly lower in retreated patients. In multivariate analysis, patients' age (P=0.018) and the number of courses of interferon therapy (P=0.022) were independently associated with HCC incidence. These results suggest that interferon retreatment reduces or delays the incidence of HCC in chronic hepatitis C patients who did not completely respond to initial therapy.
Adult↗
Adult case of squamous cell carcinoma arising on congenital esophageal stenosis due to fibromuscular hypertrophy.
This study relates to an adult case of squamous cell carcinoma arising on congenital esophageal stenosis. The patient was a 65-year-old man who had suffered from dysphagia and vomiting since birth and was diagnosed as having congenital esophageal stenosis. The patient had not received any treatment because his symptoms were mild. The patients suffered from severe dysphagia since he was 20 years old and had received balloon therapies several times; however, the effects were transient. After admission to our hospital, he underwent a transhiatal esophagectomy without thoracotomy. Histopathological examination of the resected specimen revealed a thick muscular mucosae associated with hypertrophic fibromuscular components and poorly to moderately differentiated squamous cell carcinoma in the region of stenosis. This case report is the first of a patient with squamous cell carcinoma arising on congenital esophageal stenosis.
Aged↗