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Biomedical subjects

T Moriguchi

Publications and source records attributed to T Moriguchi.

At least 19 recordsLinked to original sources

Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean.

Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.

Animals↗

Olfactory discrimination deficits in n-3 fatty acid-deficient rats.

Docosahexaenoic acid (DHA), a long chain n-3 fatty acid, is present in high concentrations in the central nervous system. Although the role that DHA may play in neural function is not well understood, infants fed formulas containing low levels of n-3 fatty acids have decreased visual acuity and neurodevelopmental test scores. The present experiment assessed whether dietary manipulations that decrease the concentration of DHA in the brain interfered with olfactory-based learning. We fed rats a diet that provided adequate n-3 fatty acids or a diet that was deficient in n-3 fatty acids for two generations. The second generation n-3-deficient group had 81% less brain DHA (82% less in olfactory bulb) compared to the n-3-adequate group and made significantly more errors in a series of olfactory-cued, 2-odor discrimination tasks compared to the adequate group. These results suggest that lower levels of central nervous system DHA lead to poorer performance in a series of simple odor discrimination tasks.

Animals↗

The effects of aged garlic extract on lipid peroxidation and the deformability of erythrocytes.

The effects of aged garlic extract (AGE) on lipid peroxidative damage and the deformability of erythrocytes were evaluated in rats. The deformability of erythrocytes was measured using the micropore filtration method. AGE significantly prevented the decrease of erythrocyte deformability induced by lipid peroxidation in a dose-dependent manner. The addition of AGE significantly inhibited an increase in thiobarbituric acid-reactive substances (TBARS) and hemolysis rate and prevented the loss of intraerythrocytic ATP and 2,3-diphosphoglycerate (2,3-DPG) in oxidized erythrocytes. Moreover, AGE significantly suppressed not only the hemolysis rate induced by peroxidation but also hemolysis due to nonperoxidation. These results suggest the possibility that AGE improves microcirculation and rheological blood properties and preserves the structure and function of erythrocytes not only through an antioxidant process, but also via the glycolysis pathway and membrane stabilization of erythrocytes.

2,3-Diphosphoglycerate↗

Ameliorative effect of S-allylcysteine, a major thioallyl constituent in aged garlic extract, on learning deficits in senescence-accelerated mice.

This study examined the effect of S:-allylcysteine (SAC), a major thioallyl compound found in aged garlic extract, on the memory deficit and age-related changes of senescence-accelerated mice. Senescence-accelerated prone P8 mice fed a diet supplemented with 40 mg SAC/kg diet for 8 mo had a significantly attenuated decrease in the conditioned avoidance response compared with those not given SAC. In the elevated plus-maze test using senescence-accelerated prone P10 mice, the percentage of time spent on the open arm was greater compared with the senescence-resistant control mice. Chronic dietary treatment with 40 mg SAC/kg diet decreased the time in the open arm in senescence-accelerated prone P10 mice. These studies suggest that diet supplementation with SAC may reduce age-related learning disabilities and cognitive disorders in senescence-accelerated mice.

Aging↗

Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.

Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J.-P., and Kawasaki, T. (1997) J. Biol. Chem. 272, 28622-28629]. Several MLK family proteins have been proposed to function as MAP kinase kinase kinases in the c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway. In the present study, we demonstrated that, like other MLKs, LZK activated the JNK/SAPK pathway but not the ERK pathway. LZK directly phosphorylated and activated MKK7, one of the two MAPKKs in the JNK/SAPK pathway, to a comparable extent to a constitutive active form of MEKK1 (MEKK1DeltaN), suggesting a biological role of LZK as a MAPKKK in the JNK/SAPK pathway. Recent studies have revealed the essential roles of scaffold proteins in intracellular signaling pathways including MAP kinase pathways. JIP-1, one of the scaffold proteins, has been shown to be associated with MLKs, MKK7, and JNK [Whitmarsh, A.J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R.J. (1998) Science 281, 1671-1674], suggesting the presence of a selective signaling pathway including LZK, MKK7, and JNK. Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain. In addition, LZK-induced JNK activation was markedly enhanced when LZK and JNK were co-expressed with JIP-1. These results constituted important clues for understanding the molecular mechanisms regulating the signaling specificities of various JNK activators under different cellular conditions.

Adaptor Proteins, Signal Transducing↗

One-stage facial augmentation with an intraoral groin adipose flap transfer.

A free groin adipose flap using an intraoral approach was used to correct facial contour deformities instead of a groin dermis-fat flap. The major disadvantages of the latter flap are that multistage debulking procedures are required and there are wide postoperative donor scars because of the wide skin portion included in the flap. To overcome these weaknesses the authors developed a free groin, customized ("berry picked") adipose flap, which was transferred by an intraoral approach for reconstruction of congenital hemifacial (orbitozygomatic) hypoplasia. The advantages of this method include one-stage augmentation without secondary defatting, no skin grafting of the donor defect, a donor scar in a concealed area, and possible transfer through an intraoral approach that results in minimal invasive surgery with no scar at the graft site.

Adipose Tissue↗

Free medial plantar perforator flaps for the resurfacing of finger and foot defects.

In this article, three cases in which free medial plantar perforator flaps were successfully transferred for coverage of soft-tissue defects in the fingers and foot are described. This perforator flap has no fascial component and is nourished only by perforators of the medial plantar vessel and a cutaneous vein or with a small segment of the medial plantar vessel. The advantages of this flap are minimal donor-site morbidity, minimal damage to both the posterior tibial and medial plantar systems, no need for deep dissection, the ability to thin the flap by primary removal of excess fatty tissue, the use of a large cutaneous vein as a venous drainage system, a good color and texture match for finger pulp repair, short time for flap elevation, possible application as a flow-through flap, and a concealed donor scar.

Adolescent↗

Free tensor fasciae latae perforator flap for the reconstruction of defects in the extremities.

In the three cases presented in this study, free tensor fasciae latae perforator flaps were used successfully for the coverage of defects in the extremities. This flap has no muscle component and is nourished by muscle perforators of the transverse branch of the lateral circumflex femoral system. The area of skin that can by nourished by these perforators is larger than 15 x 12 cm. The advantages of this flap include minimal donor-site morbidity, the preservation of motor function of the tensor fasciae latae muscle and fascia lata, the ability to thin the flap by removing excess fatty tissue, and a donor scar that can be concealed. In cases that involve transection of the perforator above the deep fascia, the operation can be completed in a very short period of time. This flap is especially suitable as a free flap for young women and children who have scars in the proximal region of the lateral thigh or groin region that were caused by split-thickness skin grafting or full-thickness skin grafting during previous operations.

Adult↗

Cloning and expression of CitPDS1, a gene encoding phytoene desaturase in citrus.

A cDNA clone encoding phytoene desaturase (PDS) was isolated from citrus (Citrus unshiu Marc.). The transcript of the isolated PDS (CitPDS1) was not detected by conventional RNA gel-blot analysis; instead, it was detected by a sensitive reverse transcription-PCR (RT-PCR). The CitPDS1 transcript in the juice sacs/segment epidermis (edible part) was at a low level in the young fruit, and it increased toward maturation like citrus phytoene synthase (CitPSY1). In the peel, in contrast to CitPSY1, the transcript of which was induced toward maturation, the level of the CitPDS1 transcript remained constant after an increase in July, indicating non-coordinate regulation of CitPDS1 and CitPSY1 in the peel.

Amino Acid Sequence↗

Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the pancreas.

In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.

Carcinoma, Pancreatic Ductal↗

Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum.

The loss of docosahexaenoic acid (DHA) from the retina or brain has been associated with a loss in nervous-system function in experimental animals, as well as in human infants fed vegetable oil-based formulas. The reversibility of the loss of DHA and the compensation by an increase in the n-6 docosapentaenoic acid (DPAn-6) was studied in young adult rats. Long-Evans rats were subjected to a very low level of n-3 fatty acids through two generations. The F2 generation, n-3-deficient animals at 7 weeks of age were provided a repletion diet containing both alpha-linolenate and DHA. A separate group of F2 generation rats had been maintained on an n-3-adequate diet of the same composition. Tissues from the brain, retina, liver, and serum were collected on weeks 0, 1, 2, 4, and 8 from both groups of animals. The concentrations of DHA, DPAn-6, and other fatty acids were determined and the rate of recovery and length of time needed to complete DHA recovery were determined for each tissue. The DHA level in the brain at 1 and 2 weeks after diet reversal was only partially recovered, rising to approximately 20% and 35%, respectively, of the n-3-adequate group level. Full recovery was not obtained until 8 weeks after initiation of the repletion diet. Although the initial rate of retinal DHA accretion was greater than that of brain DHA, the half-time for DHA recovery was only marginally greater. On the other hand, the levels of DHA in the serum and liver were approximately 90% and 100% replaced, respectively, within 2 weeks of diet reversal. A consideration of the total amounts and time courses of DHA repleted in the nervous system compared with the liver and circulation suggests that transport-related processes may limit the rate of DHA repletion in the retina and brain.-- Moriguchi, T., J. Loewke, M. Garrison, J. N. Catalan, N. Salem, Jr. Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum. J. Lipid Res. 2001. 42: 419--427.

Animals↗

[High-dose therapy and peripheral blood stem cell transplantation for patients with aggressive non-Hodgkin's lymphoma remaining in initial remission: results of a feasibility study].

High-dose therapy with peripheral blood stem cell transplantation (HDT/PBSCT) was performed as one aspect of front-line therapy in patients with poor-risk aggressive non-Hodgkin's lymphoma (high-intermediate/high risk) according to the age-adjusted international prognostic index (aaIPI). Twenty-nine patients were enrolled in this study between November 1994 and March 1999. CHOP + etoposide (CHOP-E) was used as an initial chemotherapy and as a chemotherapy agent for the purpose of cell harvesting. Peripheral blood stem cells were harvested from 17 patients, and HDT with CEC (carboplatin, etoposide, cyclophosphamide)/PBSCT was performed in 11 patients. Eighteen patients dropped out, including five for whom CHOP-E therapy was ineffective and 5 who did not give consent for cell harvesting or HDT/PBSCT. CHOP-E therapy produced complete remission (CR) in 15 out of 26 patients (58%) after discounting the 3 who were ineligible among the 29 who were initially enrolled. The median observation period after PBSCT in the 11 patients who underwent HDT/PBSCT was 25 months (3 to 50 months), and the 3-year disease-free survival rate was 73%. No serious complications associated with the transplantation were observed. We were able to confirm the feasibility and safety of HDT/PBSCT as one form of front-line therapy for aggressive non-Hodgkin's lymphoma in patients under 60 years of age.

Adolescent↗

Direct measurement of human lung cancerous and noncancerous tissues by fourier transform infrared microscopy: can an infrared microscope be used as a clinical tool?

We have analyzed very small amounts of human lung cancerous tissues directly by a Fourier transform infrared microscopy (FT-IR-MC). The corrected peak heights (H1045 and H1467) obtained from the bands at 1045 and 1467 cm(-1) due to glycogen and cholesterol were chosen for a quantitative evaluation of the malignancy. We found that the H1045/H1467 ratio is an exceptionally useful factor for discrimination of the cancerous tissues from the noncancerous tissues. If the H1045/H1467 ratio from the measured spectrum is larger than 1.4, we can say with confidence that the tissue contains squamous cell carcinoma or adenocarcinoma at least partially. Furthermore, we carried out the microscopic mapping of the tissues containing both cancerous and noncancerous sections, demonstrating that the color map reflects small changes in the spatial distribution of cancer cells in the tissues. The present method may also be applicable to analysis of other cancers, such as colorectal cancerous tissues in which glycogen level has a critical factor for their malignancy. In addition, since FT-IR-MC costs relatively little and does not require a special operator training for collecting and analyzing the spectra, it seems to be perhaps the apparatus best suited to clinical usage, especially in rather small hospitals.

Adenocarcinoma↗

Synthesis and properties of aminoacylamido-AMP: chemical optimization for the construction of an N-acyl phosphoramidate linkage.

This paper describes the design and synthesis of a new type of aminoacyl-adenylate analogue (aa-AMPN) having an N-acyl phosphoramidate linkage where the oxygen atom of the mixed anhydride bond of aminoacyl-adenylate (aa-AMP) is replaced by an amino group. This new type of aa-AMP analogue is expected to be useful as material for studies on the recognition mechanism of the aminoacylation of tRNA and other biochemical reactions. The condensation of phosphoramidite derivatives of carboxamides with nucleoside derivatives failed, because the activated phosphoramidite derivatives reacted with not only the hydroxyl groups but also another reactive species. An alternative approach was examined by the reaction of 5'-O-phosphoramidite adenosine derivatives with carboxamide derivatives. The TBTr and TSE groups were chosen for protection of the amino group of amino acid amides and the phosphate group, respectively. Detailed studies revealed that the use of 5-(3,5-dinitrophenyl)-1H-tetrazole as an activating catalyst of phosphoramidites resulted in rapid condensation within 10 min to give fully protected aa-AMPN derivatives. No side reaction occurred. Deprotection of these products via a two-step procedure gave aa-AMPN derivatives in good yields. It also turned out that aa-AMPNs thus obtained are stable under both acidic and basic conditions, such as 0.1 M HCl (pH 1.0) and 0.1 M NaOH (pH 13.0).

Adenosine Monophosphate↗

The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death.

Evi-1 encodes a nuclear protein involved in leukemic transformation of hematopoietic cells. Evi-1 possesses two sets of zinc finger motifs separated into two domains, and its characteristics as a transcriptional regulator have been described. Here we show that Evi-1 acts as an inhibitor of c-Jun N-terminal kinase (JNK), a class of mitogen-activated protein kinases implicated in stress responses of cells. Evi-1 physically interacts with JNK, although it does not affect its phosphorylation. This interaction is required for inhibition of JNK. Evi-1 protects cells from stress-induced cell death with dependence on the ability to inhibit JNK. These results reveal a novel function of Evi-1, which provides evidence for inhibition of JNK by a nuclear oncogene product. Evi-1 blocks cell death by selectively inhibiting JNK, thereby contributing to oncogenic transformation of cells.

Adaptation, Biological↗