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M Terada

Publications and source records attributed to M Terada.

At least 145 records · Page 8Linked to original sources

Relationship between in vivo FK506 clearance and in vitro 13-demethylation activity in living-related liver transplantation.

BACKGROUND: Although it is important to maintain an appropriate blood concentration of FK506 after liver transplantation, significant interindividual variability in the actual FK506 dosage has been observed, presumably due to the wide variability of cytochrome P450 3A4 activity in liver microsomes. METHODS: A study was conducted in patients undergoing living-related liver transplantation and their donors to investigate the relationship between the in vitro FK506 demethylation activity in graft liver microsomes and the in vivo blood clearance of FK506. Liver biopsy tissue was obtained from 17 living donors to measure the in vitro formation rate of 13-demethyl derivative (M-I: the major metabolite of FK506). Erythromycin N-demethylation activity in vitro was also assessed in 11 cases. The FK506 blood clearance (CLss) was calculated from its constant infusion rate and steady-state blood concentration on day 4 after transplantation in 17 recipients. RESULTS: The FK506 infusion rate varied 4.6-fold from 8.3 to 38.4 ng/min/kg. The mean CLss of FK506 was 22.1+/-10.8 ml/min (10.1-45.2 ml/min). The M-I formation rate showed a wide variability, ranging from 0.098 to 0.571 nmol/min/mg protein. A significant correlation was observed between the in vitro estimated total metabolic ability of the graft for FK506 (M-I formation rate x graft weight) and the in vivo CLss of FK506 (r=0.770, P<0.001). Erythromycin N-demethylation (0.066-0.443 nmol/min/mg protein) showed a strong correlation with the M-I formation rate (r=0.891, P<0.01). CONCLUSIONS: The in vivo FK506 clearance can mainly reflect in vitro FK506 demethylation activity.

Adolescent↗

Cloning the cDNA for a new human zinc finger protein defines a group of closely related Krüppel-like transcription factors.

We have identified a novel zinc finger protein that has been named ubiquitous Krüppel-like factor (UKLF) based on structural considerations and the pattern of gene expression. UKLF was isolated by the polymerase chain reaction approach using degenerate oligonucleotides corresponding to the DNA-binding domain of erythroid Krüppel-like factor (EKLF) and cDNA prepared from human vascular endothelial cells. The carboxyl-terminal portion of UKLF contains three zinc fingers of the Cys2-His2 type and binds in vitro to the CACCC motif of the beta-globin promoter and to the Sp1 recognition sequence. The amino-terminal portion of UKLF consists of a hydrophobic region rich in serines and a negatively charged segment with several glutamic acid residues. The first 47 amino acids of the acidic region are nearly identical to the amino-terminal portion of another Krüppel-like factor, the so-called core promoter-binding protein (CPBP) or Zf9. Like CPBP/Zf9, UKLF can function as a transcription activator in co-transfection assays. However, this activity is lost when the highly conserved amino-terminal segment is deleted. These findings indicate that UKLF and CPBP/Zf9 represent a distinct subgroup of closely related Krüppel-like activators of transcription. Mapping of the UKLF gene to chromosome 2 suggested that UKLF and CPBP/Zf9 translocated to different chromosomes following duplication from an ancestral gene.

Amino Acid Sequence↗

Vasculitis-susceptible genes in mice with a deficit in Fas-mediated apoptosis.

Autoimmune diseases show complex pathological manifestations, which frequently involve systemic vasculitis. This complication is understood to be a manifestation of advanced disease, or to represent distinct entities, restricted by genetic and/or environmental factors. An MRL/Mp strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop systemic vasculitis coincidentally with glomerulonephritis, arthritis and sialoadenitis, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. Thus, this is a suitable model for analyzing the genetic basis of vasculitis in autoimmune diseases. To genetically dissect these complex pathological manifestations, a linkage analysis of each lesion with polymorphic microsatellite markers was performed by using MRL/lpr x (MRL/lpr x C3H/lpr)F1 backcross mice. Vasculitis-susceptible gene loci were mapped on chromosomes 3 and 4, which were not associated with glomerulonephritis, arthritis and sialoadenitis. These results indicate that systemic vasculitis in MRL/lpr mice may be under the control of host genes which are different from those for other autoimmune diseases.

Animals↗

Concomitant caudate lobe resection as an option for donor hepatectomy in adult living related liver transplantation.

In this article, we describe a successful adult living related partial liver transplantation (LRLT) using the left lobe with the left-side caudate lobe (the Spiegel lobe and the left side of the paracaval portion). The size of the donor's left lobe was 29% of the recipient's standard liver volume and did not seem to meet our criteria for adult-to-adult LRLT. However, the donor had a thick left-side caudate lobe. The estimated volume of the left lobe with the left-side caudate lobe was 32%, which met our criteria for the adult recipient. The recipient's CT scan on day 87 after transplantation showed the preserved blood flow and no biliary congestion in the left-side caudate lobe, which suggests maintenance of lobe function. This procedure may be an option for adult-to-adult LRLT in which the donor has a thick left-side caudate lobe.

Adult↗

Presence of Streptococcus anginosus DNA in esophageal cancer, dysplasia of esophagus, and gastric cancer.

We recently reported cloning of Streptococcus anginosus (S. anginosus) DNA fragments containing the 16S ribosomal gene from DNA samples of surgical specimens of gastric cancers. To investigate the specificity of S. anginosus infection, Southern blot analysis with S. anginosus 16S ribosomal DNA probe and PCR analysis with S. anginosus-specific primers were performed in DNA samples prepared from 15 esophageal cancers, 43 gastric cancers, 16 lung cancers, 10 cervical cancers, 14 renal cell carcinomas, 10 colorectal cancers, and 19 bladder cancers. We frequently found S. anginosus DNA sequences in DNA samples from esophageal cancer and gastric cancer tissues, as well as in those from dysplasia of the esophagus of esophageal cancer patients. No S. anginosus DNA bands were detected by Southern blot analysis on DNAs from the noncancerous portions of the esophagus or the stomach. By PCR analysis with 35 cycles, only 7% of the noncancerous portion of the esophagus was shown to contain S. anginosus sequences. No S. anginosus sequences were found in DNAs from cancers in lung, cervix, and kidney, but they were found in 1 of 10 colon cancers.

Base Sequence↗

Molecular cloning and functional analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo. Maintenance of the stem-cell phenotype of ES cells in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) such as leukemia inhibitory factor (LIF). Here we report the cloning of complete rat LIF cDNA and its nucleotide sequence so as to facilitate studies of rat ES cell technologies on tumor biology. The nucleotide sequence of the rat LIF cDNA indicated that the rat LIF has 91% amino acid sequence identity with murine LIF. The cloned rat LIF cDNA has a putative biological activity as a differentiation-inducing factor on the murine myeloid leukemia cell line M1 cells. Culture supernatant of the rat LIF cDNA-transduced rat fibroblast cell line could maintain the stem-cell phenotype of rat ES cells which showed alkaline phosphatase activity, and this effect was much stronger than that by murine LIF. The availability of rat LIF which shows DIA will assist the in vitro analysis of rat ES cells, and culture of these cells is a route for the generation of gene targeting in rat.

Amino Acid Sequence↗

Photic stimulation-induced alteration of brain energy metabolism measured by 31P-MR spectroscopy in patients with MELAS.

We examined brain energy metabolism by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the occipital cortex in a mother and a daughter with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) during photic stimulation. The peak area ratio of phosphocreatine markedly decreased during photic stimulation, and subsequently increased after the stimulation. This method, photic stimulation-31P-MRS, may be useful in assessing brain energy metabolism in neurological diseases.

Adult↗

Delayed Wallerian degeneration and increased neurofilament phosphorylation in sciatic nerves of rats with streptozocin-induced diabetes.

It is known that Wallerian degeneration (WD) is prerequisite for nerve regeneration, which is impaired in experimental diabetic rats. To elucidate the effect of hyperglycemia on WD, we studied the time course of WD after axotomy in streptozocin-diabetic (DM) and control rats. Sciatic nerves were removed at several time points after axotomy (days 0-24). Morphometric analysis indicated that WD was delayed in DM throughout experimental period. Quantitative immunohistochemical analysis showed that the early recruitment of macrophage did not differ between the two groups, although its late recruitment was significantly decreased in DM at 15 and 24 days post-axotomy, which suggested that the macrophage-associated process did not contribute to delayed WD in diabetes. Immunoblot analysis showed a delay in the degradation of neurofilaments (NFs) in DM during WD. Phosphorylated NFs detected by SMI31 were more recognized in DM, while the opposite was true for unphosphorylated NFs detected by SMI32. Since it is known that the sensitivity of NF to calpain-mediated proteolysis is modulated by its carboxyl-terminal phosphorylation state and phosphorylated NFs are resistant to calpains, we concluded that abnormal NF phosphorylation state in diabetes could be one of the mechanisms by which axonal degeneration was delayed.

Animals↗

Molecular cloning of human Frizzled-6.

The Frizzled genes encode receptors for WNTs, secreted glycoproteins implicated in development as well as in carcinogenesis. In this paper, we report molecular cloning of Hfz6, the human homologue of Mfz6. Nucleotide sequence analysis showed that the Hfz6 gene encodes the 706 amino-acid protein with seven transmembrane domains, a cystein-rich domain in the N-terminal extracellular region, two N-linked glycosylation sites, and two cystein residues in the second and third extracellular loops. Hfz6 mRNA 4.4-kb in size was detected in various normal adult and fetal tissues, and a larger amount of Hfz6 mRNA was detected in both fetal lung and fetal kidney. The Hfz6 gene has been mapped to human chromosome 8q22.3-q23.1. In conclusion, we have cloned Hfz6, which encodes a seven-transmembrane receptor with the cystein-rich domain in the N-terminal extracellular region, but without the Ser/Thr-X-Val motif in the C-terminus.

Amino Acid Sequence↗

Targeting strategy for gene delivery to carcinoembryonic antigen-producing cancer cells by retrovirus displaying a single-chain variable fragment antibody.

Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy. Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach. Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies. Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells. These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.

3T3 Cells↗

A novel monoclonal antibody permitting recognition of NKT cells in various mouse strains.

By immunizing mouse lymphoma cell line tMK-2U derived from intermediate TCR cells of BALB/c nude mouse, U5A2-13 monoclonal antibody (mAb, a rat IgG2a) was established. U5A2-13 antigen (Ag) was expressed on around 65% of TCRint cells in the liver of the various mouse strains including both NK1.1- and NK1.1+ mouse strains, while NK1.1 Ag was expressed only in NK1.1+ C57BL/6 mouse strain. Among CD3+ cells, 26.3% cells co-expressed U5A2-13 Ag and NK1.1+ Ag, while small proportions of the CD3+ cells were U5A2-13+NK1.1- (9.2%) or U5A2-13-NK1.1+ (4.4%). Among NK1.1+ cells, 54.9% cells co-expressed CD3 and U5A2-13 Ag, while some proportions of the cells were U5A2-13+CD3- (19.4%) or U5A2-13-CD3+ (9.8%). It was found that approximately 85% of NK1.1+CD3+ cells coexpressed U5A2-13 Ag. U5A2-13 Ag with low fluorescence intensity was also expressed on 55% of NK1.1+CD3-NK cells. U5A2-13 Ag immunoprecipitated from tMK-2U cells consisted of three proteins, which were 65 kDa, 33 kDa and 32 kDa under both reducing and non-reducing conditions and these were apparently different from NK 1.1 Ag. These results indicated that U5A2-13 mAb was able to define a similar population to NK1.1+CD3+T cells and to 55% of NK1.1+CD3-NK cells in various strains, through recognizing a different molecule from NK1.1 Ag.

Animals↗

[Surgical management of patent ductus arteriosus in low body weight infants].

Between January 1980 and December 1994, seventeen premature infants weighing less than 2500 g underwent surgical management for the isolated patent ductus arteriosus (PDA). Indometacine therapy for closure of PDA was not effective for all these patients. In terms of the body weight at birth, they were divided into two groups; Group I (G-I) consisted of ten patients with birth weight less than 1000 g and Group II (G-II) of seven patients weighing more than 1000 g. The age at operation was 22.1 +/- 15.4 days in the G-I and 14.3 +/- 11.4 days in the G-II. The ductus was ligated in all patients but one of the G-II, in whom it was divided. There were five (50%) hospital deaths in the G-I and none in the G-II. The causes of death in the G-I were related to necrotizing enterocolitis (NEC) in two and infant respiratory distress syndrome (IRDS), acute renal failure, and broncho-esophagial fistula in each. The age at operation tended to be older in nonsurvivors rather than in survivors in the G-I (28.0 +/- 16.8 days vs. 16.2 +/- 14.0 days, respectively, but the difference did not reach significance). Before surgery, all patients in the G-I required mechanical ventilator support and nine of them were associated with IRDS. In contrast, only two patients in the G-II needed mechanical ventilation preoperatively. The postoperative period of intubation was also significantly longer in the G-I than in the G-II (51.6 +/- 35.2 days vs. 2.2 +/- 1.5 days, respectively, p < 0.05). In conclusions, the surgery for PDA can be safely performed even in small premature babies weighing less than 1000 g. When medical therapy for PDA is not effective in the premature patients, the surgical management should be considered as early as possible before their conditions become worse due to such critical complications as NEC, IRDS, and renal failure.

Cardiac Surgical Procedures↗

Hemodynamic effects of human atrial natriuretic peptide after modified Fontan procedure.

BACKGROUND: Reduction of pulmonary vascular resistance and maintenance of urine output are important after the modified Fontan procedure. Atrial natriuretic peptide (ANP) has the effects of a vasodilator (including the pulmonary arteries) and a physiologic diuretic, and newly synthesized human ANP is available. We measured plasma ANP levels before and after the Fontan procedure and examined the effects of human ANP on hemodynamic parameters after the Fontan procedure. METHODS: Eight patients, aged 2 to 15 years, underwent the Fontan procedure (atriopulmonary connection). Blood samples were taken before and 3 hours after operation, and plasma ANP levels were measured by radioimmunoassay. The correlation between central venous pressure and ANP was examined. Human ANP was infused intravenously at a dosage of 0.1 microg x kg(-1) x min(-1) for 1 hour after the Fontan procedure under controlled ventilation and another blood sample was obtained. Urine volume and central venous pressure were measured, and pulmonary vascular resistance and the cardiac index were calculated by the thermodilution catheter method before and after human ANP infusion. One hour after human ANP infusion was discontinued, the evaluation was repeated. No other diuretics were given and the infusion rates of catecholamine were kept constant during these measurements. RESULTS: Plasma ANP levels before and after the Fontan procedure were 29.1 and 54.9 pg/mL, respectively, and a positive correlation was obtained between central venous pressure and plasma ANP levels (r = 0.661, p < 0.05). Human ANP infusion significantly decreased central venous pressure and pulmonary vascular resistance, and increased urine volume and the cardiac index, whereas the plasma ANP level was elevated to 617.5 pg/mL. Systemic blood pressure did not change significantly. CONCLUSIONS: Atrial natriuretic peptide is secreted in response to elevated central venous pressure after the Fontan procedure, but its concentration might not be sufficient. Human ANP can be a therapeutic choice after the Fontan procedure as a physiologic diuretic and a pulmonary vasodilator.

Adolescent↗

Atrial septal displacement for repair of anomalous pulmonary venous return into the right atrium.

BACKGROUND: In the repair of anomalous connection of the pulmonary veins to the right atrium, the use of a baffle of pericardium to divert the pulmonary venous blood into the left atrium could cause pulmonary venous obstruction as a result of thickening of the pericardial patch. Anomalous pulmonary venous drainage to the right atrium caused by malposition of the atrial septum primum can be repaired by displacing the shifted septum primum to the normal position. METHODS: In 5 patients with total (n=2) or partial (n=3) anomalous pulmonary venous drainage into the right atrium, the septum primum was shifted toward the left atrium and the pulmonary veins drained into the anatomic right atrium despite their normal connection with the posterior wall of the left atrium. This method consisted of incision of the posterior edge of the atrial septum primum and displacement of the incised atrial septum between the anomalous pulmonary veins and both venae cavae. No patch was used. RESULTS: Postoperative echocardiography showed a wide pathway from the pulmonary veins to the left atrium with no stenotic portions. No atrial arrhythmias occurred after the operation. CONCLUSIONS: This technique may be advantageous because it allows for future growth of the route of the pulmonary venous pathway and avoids postoperative supraventricular arrhythmias.

Arrhythmias, Cardiac↗

A new spontaneous animal model of NIDDM without obesity in the musk shrew.

The EDS (early-onset diabetes in suncus) colony has been developed as a new closed breeding colony of the musk shrew (Suncus murinus, Insectivora) exhibiting a high incidence of spontaneous diabetes mellitus. We investigated the characteristic features of diabetic shrews in this colony. All diabetic shrews are characterized by glycosuria (Tes-tape value > or = 3+), hyperglycemia (23.3 +/- 0.8 mmol/l) and polyuria, and they were affected by the age of 3 months. Cumulative incidence (64.1% in males and 27.8% in females) was kept intact after the age of 3 months. The growth pattern of diabetic shrews was similar to that of non-diabetic shrews, and obesity was not consistent in diabetic shrews. The intraperioneal glucose tolerance test revealed both impaired glucose tolerance and impaired insulin secretion in diabetic shrews. Insulin sensitivity of diabetic shrews decreased in the intraperioneal insulin tolerance test. Neither severe hypertrophy nor lymphocytic infiltration was observed in pancreatic islets of diabetic shrews. These facts suggested that diabetic shrews in the EDS colony should be classified as early-onset non-insulin dependent diabetes mellitus (NIDDM) without obesity. Early-onset of severe hyperglycemia with impaired glucose tolerance is a distinctive character compared with other non-obese NIDDM models in rodents. We concluded that the diabetic shrews in the EDS colony are a new animal model of human NIDDM without obesity.

Age of Onset↗

Toxin-induced IDDM (insulin dependent diabetes mellitus) in the musk shrew.

We administered streptozotocin (STZ) and alloxan (AL) to the musk shrew (Suncus murinus, Insectivora) to determine the effective diabetogenic dose of the two toxins for this species. A single intraperitoneal (i.p.) injection of 75 mg/kgBW or the consecutive 5-day s injection of 25 mg/kgBW of STZ to non-fasted shrews, effectively (100%) induced hyperglycemia (> or = 300 mg/dl) with hypoinsulinaemia (< 30% of control level) in male shrews at 10 days after administration. Morphological studies showed cytological changes of B cells in the pancreatic islets of diabetic shrews. Hyperglycemic shrews induced by STZ were thus in IDDM (insulin dependent diabetes mellitus), and showed high susceptibility to the diabetogenic effect of STZ as compared with rodents. Shrews showed a sex difference in the diabetogenic susceptibility to STZ as do mice (male > female). They also showed a species specific resistance to the diabetogenic effect of AL. Of the eight shrews (with 8-hr fasting) that has been treated with a single injection of 200 mg/kgBW of AL, seven (88%) survived at least 10 days, showing no signs of hyperglycemia. All shrews died within 3 day s after injection of 250 or 300 mg/kgBW. These results indicated that the STZ-induced diabetic shrew is a unique animal model and may be useful for IDDM research. On the other hand, the musk shrew was highly resistant to the diabetogenic effects of AL.

Alloxan↗