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Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 37 records · Page 2Linked to original sources
PubMed2004

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats.

It is well known that progesterone and estrogen are essential hormones for maintaining pregnancy in most mammals. Some specific roles of progesterone for the maintenance of pregnancy have been clarified, but the role of estrogen is not well known. This study examines the effects of the aromatase inhibitor, fadrozole hydrochloride (Fad), on fetuses, uterine physical properties and the mRNA expression of the uterine enzymes that are related to collagen metabolism during late pregnancy in rats. Continuous s.c. infusion with 300 micro g/day Fad from day 14 of pregnancy (day 1=the day of sperm detection) reduced the concentration of plasma estradiol-17beta (E(2)), and did not change that of plasma progesterone, compared with controls. The treatment increased the intrauterine pressure and reduced the size and compliance of the uterine tissue framework. It also caused injuries (hematomata on the extremities) in about one-quarter of fetuses by day 20. The collagen content of the uterine ampullae was not changed by the treatment. Uterine mRNA expressions of matrix metalloproteinase-1 (MMP-1), which degrades collagens, and of lysyl oxidase (LO), which is necessary for the formation of intra- and inter-molecular cross-links of collagen, were examined by quantitative RT-PCR. The treatment with Fad had no effect on the expression of MMP-1 mRNA and increased that of LO mRNA. Daily s.c. injection with 0.2 micro g E(2) restored the changes in uterine physical properties and the mRNA expression of LO caused by the Fad treatment, and prevented fetal injury, indicating that the influences of Fad treatment are due to estrogen deficiency but not to toxicological effects of Fad. These results imply that estrogen deficiency during late pregnancy in rats obstructs development of the uterine tissue framework so as to cause fetal injury. It is possible that an increase in the uterine expression of LO gene may be involved in this obstruction.

Animals↗
PubMed2003

Delayed implantation induced by fadrozole hydrochloride in rats.

The effect of aromatase inhibitors on the implantation process is not well known. This study examined the anti-implantation action in rats of a nonsteroidal aromatase inhibitor of high specific activity, fadrozole hydrochloride (Fad). Continuous subcutaneous infusion of Fad at 300 microg/day from Day 1 (the day of sperm detection) through Day 7 of pregnancy using a mini-osmotic pump was found to delay the initiation of implantation by 1 or 2 days with no negative effects on embryonic viability. The Fad treatment delayed preimplantation embryo development and zona shedding by embryos. The treatment also delayed the period of maximum sensitivity to a decidualizing stimulus (intraluminal infusion of sesame oil) by 2 days. The results show that continuous treatment with Fad has multiple anti-implantation effects in rats.

Animals↗
PubMed2003

Mechanical analyses of morphological and topological transformation of liposomes.

Liposomes are micro-compartments made of lipid bilayer membranes possessing the characteristics quite similar to those of biological membranes. To form artificial cell-like structures, we made liposomes that contained subunit proteins of cytoskeletons: tubulin or actin. Spherical liposomes were transformed into bipolar or cell-like shapes by mechanical forces generated by the polymerization of encapsulated subunits of microtubules. On the other hand, disk- or dumbbell-shaped liposomes were developed by the polymerization of encapsulated actin. Dynamic processes of morphological transformations of liposomes were visualized by high intensity dark-field light microscopy. Topological changes, such as fusion and division of membrane vesicles, play an essential role in cellular activities. To investigate the mechanism of these processes, we visualized the liposomes undergoing topological transformation in real time. A variety of novel topological transformations were found, including the opening-up of liposomes and the direct expulsion of inner vesicles.

Biomechanical Phenomena↗
PubMed2003

Monoclonal IgA antibody-mediated expulsion of Trichinella from the intestine of mice.

To assess the potential role of IgA antibody in expulsion of the nematode of the genus Trichinella from the intestine, a panel of IgA monoclonal antibodies (mAbs) were produced from the mesenteric lymph node cells from BALB/c mice orally vaccinated with irradiated muscle larvae of Trichinella britovi. One IgA mAb, HUSM-Tb1, formed immunoprecipitates on the surface of live muscle larvae, and by immunohistochemistry reacted with their stichocytes and cuticular surface, but not with those tissues of the adult stage or newborn larvae. Intraperitoneal injection of BALB/c mice with this mAb 5 h before challenge conferred a high level of protection (more than 95%) against T. britovi infection, when 2.0 mg of specific IgA/20 g body weight was given to a mouse. The same treatment produced a similar effect in SCID mice lacking functional T- and B-cells, indicating no requirement of synergistc T-cell factors for the effect. Passive transfer of the mAb at the time of challenge or later showed less or no effect upon worm expulsion. It is concluded that the mucosal IgA response, when adequately induced, can impede the establishment of infective Trichinella parasites in the mouse intestine.

Animals↗
PubMed2003

Persistent infection of Mongolian jirds with a non-pathogenic trypanosome, Trypanosoma (Herpetosoma) grosi.

Non-pathogenic trypanosomes of the subgenus Herpetosoma are normally host specific, and laboratory models include Trypanosoma lewisi in rats and Trypanosoma musculi in mice. Two isolates of Trypanosoma grosi, originating from Apodemus agrarius and Apodemus peninsulae, grew well in Mongolian jirds, Meriones unguiculatus, after intraperitoneal inoculation of 2 x 10(5) or a minimum 500 bloodstream forms. The course of T. grosi infection in jirds resembled T. musculi infection in mice, rather than T. lewisi infection in rats. At week 2 to 3 p.i. trypanosomes disappeared from the bloodstream, and neither prednisolone treatment nor splenectomy prevented parasite elimination from the bloodstream. However, these treatments induced a marked increase in peak parasite counts. Regardless of prednisolone treatment or splenectomy, all jirds after day 21 p.i. became resistant to the reinfection. Although no trypanosomes were detected in the bloodstream of recovered jirds, dividing parasites persisted in the medullary capillaries of the kidney, like T. musculi infection in mice. We propose the T. grosi infection in jirds as an additional laboratory model for the study of non-pathogenic trypanosomes.

Animals↗
PubMed2003

Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator.

Herpes simplex virus thymidine kinase (HSV-tk)/gancyclovir (GCV) therapy has the ability to inhibit tumor formation in animal models but the results of clinical trials have been disappointing. To improve the performance of tk/GCV therapy, we tried combination therapy designed to enhance its cytotoxic effects by introducing genes that induce apoptosis of the tumor cells through different pathways. We concentrated our efforts on the use of Bim, a BH3-only member of death activators in the Bcl-2 superfamily, because Bim is not involved in the pathways through which HSV-tk/GCV therapy induces apoptosis in malignant glioma cells. Among three alternative splicing variants, BimEL, BimL, and BimS, BimS lacks the binding domain for the dynein light chain LC8, which negatively regulates the proapoptotic function of BimEL and BimL. All four malignant glioma cell lines, U251, A172, T-430, and U373 underwent cell death after transfer of BimS using an adenovirus vector (AVC2). Intriguingly, combination of AVC2-BimS with AVC2-tk markedly increased the sensitivity of U251 cells to GCV both in vitro and in vivo. In contrast, AVC2-BimL did not induce significant cell death. These results indicated that BimS had the ability to improve the efficiency of HSV-tk/GCV therapy in the treatment of malignant glioma and suggested that the targeting of different proapoptotic pathways may be a useful strategy for the development of an effective gene therapy approach to treatment.

Adenoviridae↗
PubMed2002

Successful non-T cell-depleted HLA haplo-identical three-loci mismatched hematopoietic stem cell transplantation from mother to son based on the feto-maternal microchimerism in chronic myelogenous leukemia.

A 17-year-old male with chronic myelogenous leukemia in blast crisis received a non-T cell-depleted (TCD) HLA haplo-identical three-loci mismatched hematopoietic stem cell transplant (HSCT) from his mother. Long-term feto-maternal microchimerism was detected by nested polymerase chain reaction with sequence-specific primer typing. The post-transplantation prophylaxis against graft-versus-host disease (GVHD) was tacrolimus with minidose methotrexate. Sustained engraftment was obtained. Acute GVHD (grade 2) developed, but improved rapidly. Bone marrow aspiration on day 120 showed complete remission. Non-TCD HLA haplo-identical HSCT based on feto-maternal microchimerism might be feasible and has important implications in the selection of alternative family donors in HSCT.

Adolescent↗
PubMed2002

A novel infant acute lymphoblastic leukemia cell line with MLL-AF5q31 fusion transcript.

Infant acute lymphoblastic leukemia (ALL) is characterized by the presence of the proB phenotype (CD10(-)/CD19(+)), poor prognosis and frequent rearrangement of the mixed lineage leukemia (MLL) gene. The most frequent rearrangement is t(4;11)(q21;q23), the role of whose product, the MLL-AF4 fusion transcript, has been extensively studied in leukemogenesis. In a cell line of infant leukemia with MLL rearrangement denoted KP-L-RY, panhandle PCR amplification of cDNA revealed the presence of a fusion transcript, MLL-AF5q31, indicating that AF5q31 is also a partner gene of MLL. In this fusion transcript the MLL exon 6 is fused in frame to the 5' side of the putative transactivation domain of AF5q31. The AF5q31 protein is a member of the AF4/LAF4/FMR2-related family of proteins, which have been suggested to play a role in hematopoietic cell growth and differentiation. The MLL-AF5q31 fusion transcript, although probably rare, appears to be associated with the pathogenesis of infant ALL like MLL-AF4. Co-expression of HoxA9 and Meis1 genes in the KP-L-RY cell line indicated possible functional similarity between MLL-AF4 and MLL-AF5q31. Further understanding of the function of AF5q31 as well as the specific leukemogenic mechanism of MLL-AF5q31 awaits future studies.

Acute Disease↗
PubMed2002

Schistosoma mansoni: kinetics of glomerulonephritis in Mongolian gerbils and its correlation with intensity and duration of infection.

The frequent occurrence of glomerular lesions in schistosomiasis patients has been reported, although appropriate animal models for the study of schistosomal glomerulonephritis have not been developed. To analyze the relationship between glomerulonephritis and Schistosoma mansoni infection, gerbils, Meriones unguiculatus, were infected with different number of cercariae and sacrificed at different weeks of post infection. Fifty cercariae were the optimum dose to produce the disease, glomerulonephritis, without early death of the animal. Infected gerbils showed heterogeneous types of glomerular lesions with increased serum creatinine level. Immune complex deposition was not detected at glomeruli of infected gerbils even by means of immunuofluorescence and also by transmission electron microscopy. However, infiltration of mononuclear cells in and around some of the altered glomeruli was observed. Immunohistochemical staining, using monoclonal antibody (HUSM-M.g. 15) specific to gerbil's T-cells, revealed significant infiltration of T-cells. These findings suggest that T-cells might be involved in the development of glomerulonephritis. Gerbil could be a useful model to clarify the role of T-cells in the development of glomerulonephritis of schistosomiasis.

Animals↗
PubMed2002

Evaluation of bedmaking-related airborne and surface methicillin-resistant Staphylococcus aureus contamination.

The number of airborne methicillin-resistant Staphylococcus aureus (MRSA) before, during and after bedmaking was investigated. Air was sampled with an Andersen air sampler in the rooms of 13 inpatients with MRSA infection or colonization. Sampling of surfaces, including floors and bedsheets, was performed by stamp methods. MRSA-containing particles were isolated on all the sampler stages-stage 1 (>7 microm diameter) to stage 6 (0.65-1.1 microm). The MRSA-containing particles were mostly 2-3 microm diameter before bedmaking and >5 microm during bedmaking. The number was significantly higher 15 min after bedmaking than during the resting period, but the differences in counts after 30 and 60 min were not significant. MRSA was detected on many surfaces. The results suggest that MRSA was recirculated in the air, especially after movement. To prevent airborne transmission, healthcare staff should exercise great care to disinfect inanimate environments. Further studies will be needed to confirm the level of MRSA contamination of air during bedmaking and establish measures for prevention of airborne transmission.

Air Microbiology↗
PubMed2001

Change in concentrations of luteinizing hormone subunit messenger ribonucleic acids in the estrous cycle of beef cattle.

Changes in the concentrations of LH subunit messenger ribonucleic acids (mRNAs) and in the LH content of the anterior pituitary of beef cattle were studied during the estrous cycle. Japanese beef cows were classified according to the expected day of the estrous cycle: stage I (early-luteal phase, days 1-4; day 1=day of ovulation), stage II (early-mid-luteal phase, days 5-10), stage III (late-mid-luteal phase, days 11-17) and stage IV (follicular phase, days 18-20), according to the morphology of the ovaries. The anterior pituitaries of the cows were collected and the levels of alpha and LHbeta subunit mRNAs were determined by slot-blot analyses. The LH content of the anterior pituitary was measured by radioimmunoassay. The level of alpha subunit mRNA in the pituitary of cows was highest in stage I and decreased significantly by stage II (P<0.05); thereafter it tended to increase. The level of LHbeta subunit mRNA did not change significantly during the estrous cycle. The LH content of the pituitary of cows was low in stage I and tended to increase by stage II, then to decrease from stage II to III, and to increase significantly from stage III to IV (P<0.05). These results suggest that the highest levels of gene expressions of alpha subunit in the anterior pituitary occur in the early-luteal phase of beef cows, while the LH content is increased most in the follicular phase. The enhanced gene expressions of common alpha subunit in the early-luteal phase could be important in replenishing the bovine anterior pituitary with LH, which is depleted of hormone by the LH surge or the enhanced pulsatile release.

Animals↗
PubMed2001

A novel class of plant-specific zinc-dependent DNA-binding protein that binds to A/T-rich DNA sequences.

Complementary DNA encoding a DNA-binding protein, designated PLATZ1 (plant AT-rich sequence- and zinc-binding protein 1), was isolated from peas. The amino acid sequence of the protein is similar to those of other uncharacterized proteins predicted from the genome sequences of higher plants. However, no paralogous sequences have been found outside the plant kingdom. Multiple alignments among these paralogous proteins show that several cysteine and histidine residues are invariant, suggesting that these proteins are a novel class of zinc-dependent DNA-binding proteins with two distantly located regions, C-x(2)-H-x(11)-C-x(2)-C-x((4-5))-C-x(2)-C-x((3-7))-H-x(2)-H and C-x(2)-C-x((10-11))-C-x(3)-C. In an electrophoretic mobility shift assay, the zinc chelator 1,10-o-phenanthroline inhibited DNA binding, and two distant zinc-binding regions were required for DNA binding. A protein blot with (65)ZnCl(2) showed that both regions are required for zinc-binding activity. The PLATZ1 protein non-specifically binds to A/T-rich sequences, including the upstream region of the pea GTPase pra2 and plastocyanin petE genes. Expression of the PLATZ1 repressed those of the reporter constructs containing the coding sequence of luciferase gene driven by the cauliflower mosaic virus (CaMV) 35S90 promoter fused to the tandem repeat of the A/T-rich sequences. These results indicate that PLATZ1 is a novel class of plant-specific zinc-dependent DNA-binding protein responsible for A/T-rich sequence-mediated transcriptional repression.

AT Rich Sequence↗
PubMed2001

The effect of transforming growth factor-alpha on the progression of decidualization in rats.

Although transforming growth factor-alpha (TGF-alpha), one of the epidermal growth factor (EGF) family of growth factors, is expressed in the rat decidual cells, its roles in decidualization remain to be elucidated. This study examined the effect of TGF-alpha on the progression of decidualization and a possibility for involvement of prostaglandins (PGs) in its action. Pseudopregnant rats were ovariectomized and given endometrial trauma on Day 5 (vaginal plug = Day 1) and were daily treated with 2 mg progesterone thereafter. Immunocytochemical localization of EGF receptor was distinctly evident in the decidual, stromal and epithelial cells on Day 7. Continuous infusion of TGF-alpha (500 pg/h) into the uterine lumen from Day 7 significantly increased weights of the uterine horns with deciduomata on Day 9. Although injection on Day 7 of indomethacin, an inhibitor of PGs synthesis, decreased the uterine weight, this effect was overridden by the continuous infusion of this growth factor. These results demonstrated the stimulatory action of TGF-alpha on the progression of decidualization. Further, TGF-alpha increased the secretion of prostaglandin E in cultured decidual and/or stromal cells dose-dependently, suggesting the possibility that PGs mediate the action of this growth factor.

Animals↗
PubMed2001

Trihelix DNA-binding protein with specificities for two distinct cis-elements: both important for light down-regulated and dark-inducible gene expression in higher plants.

The DE1 sequence is a cis-regulatory element necessary and sufficient for light down-regulated and dark-inducible expression of the pea GTPase pra2 gene. This sequence does not show any sequence similarity to the previously reported ones involved in light-regulated gene expression. A one-hybrid screen isolated a cDNA encoding a DNA-binding protein, named DF1, with specificity for the DE1 sequence 5'-TACAGT. DF1 has domains similar to the trihelix DNA-binding domain found in the GT-1 and GT-2 proteins, which are plant transcription factors. The DE1-binding domain of DF1 is most similar to the carboxyl-terminal trihelix domain of the rice GT-2 protein with specificity for the GT2 sequence 5'-GGTAATT, which is also necessary for dark-inducible expression of the rice phyA gene. An electrophoretic mobility shift assay showed that this DNA-binding domain specifically binds to two types of DNA sequences, DE1 and GT2. Additionally, using DF1/GT-1 chimeras, we show that the second and third helices of the trihelix DNA-binding domain of DF1 are responsible for this dual DNA binding specificity. Our results show that DF1 has specificity for the two distinct cis-regulatory elements, both important for light down-regulated and dark-inducible gene expression in higher plants.

Amino Acid Sequence↗
PubMed2001

Interaction of plasma proteins with cytochromes P450 mediated metabolic reactions: inhibition by human serum albumin and alpha-globulins of the debrisoquine 4-hydroxylation (CYP2D) in liver microsomes of human, hamster and rat.

The effect of human serum albumin (HSA), alpha1-acid glycoprotein (alpha1-AGP), and alpha- and gamma-globulins on the in vitro metabolism of debrisoquine in human, hamster and rat liver microsomes was studied. Interaction of albumin with cytochrome P450 mediated phenytoin metabolism has been reported. Since plasma protein binding of phenytoin is high, in the present study a weakly protein bound drug, debrisoquine, was studied. Debrisoquine is a substrate of CYP2D6. The debrisoquine 4-hydroxylation was measured using a radio-TLC method. Among the four plasma proteins, alpha-globulins had the strongest inhibitory effect on the debrisoquine 4-hydroxylase activity. The inhibition with 2% alpha-globulins was 42+/-18% for human and higher for hamster and rat liver microsomes (65-71%). HSA had less effect than alpha-globulins. In the presence of HSA, the decrease in activity was between 18 and 35% for all liver microsomes studied. The debrisoquine 4-hydroxylase activity was not significantly changed by alpha1-AGP or gamma-globulins. Using an ultra-filtration method, the protein binding of debrisoquine to 4% HSA, 0.5% alpha1-AGP, 2% alpha-globulins and 2% gamma-globulins was found to be 22, 20, 22 and 5%, respectively. Since the observed inhibition is inconsistent with level of protein binding, it appears, particularly in the case of alpha-globulins, that the plasma proteins interact with CYP2D directly.

Adrenergic Agents↗
PubMed2001

Capabilities of liposomes for topological transformation.

Dynamic behaviors of liposomes caused by interactions between liposomal membranes and surfactant were studied by direct real-time observation by using high-intensity dark-field microscopy. Solubilization of liposomes by surfactants is thought to be a catastrophic event akin to the explosion of soap bubbles in the air; however, the actual process has not been clarified. We studied this process experimentally and found that liposomes exposed to various surfactants exhibited unusual behavior, namely continuous shrinkage accompanied by intermittent quakes, release of encapsulated liposomes, opening up, and inside-out topological inversion.

Lipids↗