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M Maeda

Publications and source records attributed to M Maeda.

At least 649 records · Page 36Linked to original sources

Cerebrovasodilatation of metabolic and non-metabolic origin elicited by chemical stimulation of the lateral periaqueductal gray matter in anaesthetized rats.

We attempted to elucidate the mechanisms operating in the mediation of the cerebrovasodilator action of the defence area within the periaqueductal gray matter, employing radiolabelled microsphere flowmetry in 50 anaesthetized rats. The caudal two-thirds of this brain region were chemically stimulated with N-methyl-D-aspartate (1 nmol as 100 nl in a 10-mM solution). Besides eliciting a distinctive pattern of haemodynamic defence responses, the stimulation consistently provoked a cerebrovasodilator action, preferentially in the supratentorial brain regions. In particular, 56% of the overall flow increase in the parasagittal cerebral cortex was solely attributable to the unique cerebrocortical vasodilator action of the periaqueductal gray matter, independent of unspecific effects of concomitantly occurring hypertension itself. This flow change was not associated with a specific change in the metabolic rate for O2 of this cortical region. We conclude that the major part of the unique cerebrocortical vasodilator action provoked from the defence area within the periaqueductal gray matter was mediated by non-metabolic mechanisms. The involvement of the metabolic mechanism could be of only minor importance, if any. Cerebral vasodilatation may be involved in the natural defence reactions for coping with the emergency that threatens the animal.

Anesthesia↗

Metabolic pathway of 2-deoxy-2-[18F]fluoro-D-talose in mice: trapping in tissue after phosphorylation by galactokinase.

To make clear the metabolic fate of 2-deoxy-2-[18F]fluoro-D-talose ([18F]FDT) in animals, the in vivo and in vitro metabolism of non-radioactive 2-deoxy-2-fluoro-D-talose (FDT) was investigated by 19F-NMR spectroscopy. Based on the 19F-NMR spectral analyses, 2-deoxy-2-fluoro-alpha-D-talose-1-phosphate (FDT-1-P) was identified as a single metabolite in the organs of tumor-bearing mice after FDT administration (60 mg/kg). In the liver, almost all FDT was converted to FDT-1-P within 10 min after FDT injection and the phosphate form remained unchanged for at least 3 h. FDT was well converted to FDT-1-P by galactokinase in vitro. The FDT-1-P formed, however, failed to convert to a uridylate derivative by treatment with galactose-1-phosphate uridyltransferase. The observed low affinity of galactose-1-phosphate uridyltransferase for the FDT-1-P could account for the accumulation mechanism of FDT-1-P in vivo. Similar metabolic studies of [18F]FDT with radio-TLC demonstrated the [18F]FDT-1-P as a single metabolite of [18F]FDT in the mouse liver. These results indicate that [18F]FDT enters a D-galactose metabolic pathway and undergoes a metabolic trapping in the [18F]FDT-1-P form by galactokinase in the tissues such as liver and tumor. Consequently, [18F]FDT is expected to be a new radiopharmaceutical for the measurement of galactokinase activity by positron emission tomography.

Animals↗

8-[18F]fluorooctanoic acid and its beta-substituted derivatives as potential agents for cerebral fatty acid studies: synthesis and biodistribution.

Fluorine-18 labeled analogs of 8-fluorooctanoic acid and its structurally modified derivatives with methyl or gem-dimethyl branching or with oxygen substitution at the C3 position were prepared using nucleophilic substitution of the tosylate precursors by [18F]fluoride ion, for evaluation as tracers for cerebral fatty acid metabolism. Tissue distribution studies in rats showed low brain uptakes of these 18F-labeled fatty acid analogs with poor brain-to-blood ratios of activity. The oxygen-substituted analog did not show any significant accumulation of radioactivity in most tissues. The initial brain uptake of activity after injection of ethyl 8-[18F]fluorooctanoate and its free acid remained virtually unchanged over an extended time period, beta-Monomethyl and beta-gem-dimethyl branched analogs had similar brain uptake at the early time period, but they showed rapid clearance of activity from the brain. TLC analysis showed no incorporation of 8-[18F]fluorooctanoic acid and its beta-dimethyl analogs into brain lipids. It was also shown in the metabolite analysis that the labeled metabolites produced from 8-[18F]fluorooctanoic acid are found in blood, and that they could enter the brain to a significant degree. On the contrary, such radioactive metabolites could not be found in the brain in the experiment with the beta-gem-dimethyl branched analog. Thus, the present studies showed that retention of radioactivity in the brain with 8-[18F]fluorooctanoic acid derivatives is mainly attributable to their radioactive metabolites, and that the rapid clearance of beta-branched analogs from the brain is due to the lack of availability as substrates in the cerebral fatty acid metabolism.

Animals↗

Expression and localization of aminopeptidase N, neutral endopeptidase, and dipeptidyl peptidase IV in the human placenta and fetal membranes.

OBJECTIVE: Our purpose was to determine the distribution of membrane-bound cell surface peptidases, namely aminopeptidase N, neutral endopeptidase, and dipeptidyl peptidase IV in the human placenta and fetal membranes. STUDY DESIGN: Frozen tissue sections of the first-trimester chorionic villi, term placentas, and term fetal membranes were stained by indirect immunofluorescence with specific monoclonal antibodies. RESULTS: In the first trimester chorionic villi cytotrophoblasts expressed both neutral endopeptidase and dipeptidyl peptidase IV, but syncytiotrophoblasts expressed only neutral endopeptidase. Stromal cells in the chorionic villi expressed the three peptidases at various intensities. In the term placentas villous syncytiotrophoblasts expressed neutral endopeptidase weakly, and the villous stromal cells expressed large amounts of both aminopeptidase N and dipeptidyl peptidase IV but neutral endopeptidase weakly or faintly. In the term fetal membranes amniotic epithelial cells and chorion laeve expressed both neutral endopeptidase and dipeptidyl peptidase IV. Decidual cells in the decidua parietalis moderately or highly expressed aminopeptidase N. CONCLUSION: Three peptidases, aminopeptidase N, neutral endopeptidase, and dipeptidyl peptidase IV, are expressed by different cell populations in the human placenta and fetal membranes, suggesting their respective and important roles at the maternofetal interface.

Aminopeptidases↗

Role of caeca in the nitrogen nutrition of the chicken fed on a moderate protein diet or a low protein diet plus urea.

1. A study was carried out to investigate whether the back-flow of urine into the caeca benefits the nitrogen economy of adult cockerels fed on a diet containing 100 g protein/kg and when dietary urea is absorbed, excreted into urine and utilised. 2. No significant effects of colostomy on nitrogen utilisation were observed in chickens fed on 100 g/kg protein diet, whereas colostomy was highly effective in decreasing it in chickens on a diet containing 50 g protein/kg plus urea (P < 0.05). 3. Nitrogen utilisation in conventional birds was significantly less when a diet of moderate protein content was fed than when a low protein diet plus urea was fed, but the opposite effect was seen with colostomised birds (P < 0.05). 4. Colostomy increased urea excretion (nitrogen/kg body weight/day) from 4 to 9 mg in chickens fed on the moderate protein diet, but greatly, from 45 to 182 mg, in those fed on the low protein diet plus urea (P < 0.05). 5. Blood urea concentration increased by about 20 mg per 100 ml in 3 h, a value which was maintained up to 6 h but which returned to the prefeeding concentration at 24 h; both control and colostomised chickens on the low protein diet plus urea responded similarly. 6. After feeding urea, half the daily excretion of urea was observed to occur within 6 and 9 h, respectively, in control and colostomised chickens.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗

Gastric proton pump (H+/K(+)-ATPase): structure and gene regulation through GATA DNA-binding protein(s).

Progress in molecular biological studies on the gastric proton pump (H+/K(+)-ATPase) now enable us to discuss not only its subunit protein structures and catalysis but also the organizations of its subunit genes and their cell-specific transcription. The primary structures of the catalytic alpha and glycosylated beta subunits are similar to those of the corresponding subunits of Na+/K(+)-ATPase. The residues located in the catalytic and cation binding sites have been proposed from the combined results of protein chemical studies and sequence comparisons of P-type cation transporting ATPases. Most of the positions of exon/intron boundaries of the genes for the H+/K(+)- and Na+/K(+)-ATPase alpha and beta subunits are conserved, suggesting that the alpha and beta subunit genes, respectively, of the two ATPases were derived from common ancestors. In contrast to the Na+/K(+)-ATPase subunits, the H+/K(+)-ATPase alpha and beta subunits are expressed specifically in gastric parietal cells. Consistent with their cell-specific transcription, a gastric mucosal nuclear protein(s) was shown to recognize a sequence motif in the 5'-upstream regions of the H+/K(+)-ATPase alpha and beta subunit genes. Furthermore, novel zinc finger proteins (GATA-GT1 and GATA-GT2) that bind to this motif were found in the gastric parietal cells. These proteins are likely to play important roles in transcriptional regulation of the gastric proton pump genes.

Amino Acid Sequence↗

Conserved Glu-181 and Arg-182 residues of Escherichia coli H(+)-ATPase (ATP synthase) beta subunit are essential for catalysis: properties of 33 mutants between beta Glu-161 and beta Lys-201 residues.

Twenty-two mutants between beta Glu-161 and beta Lys-201 of Escherichia coli H(+)-ATPase beta subunit could grow by oxidative phosphorylation, but 11 other such mutants, beta Glu-181-->Gln, Asp, Asn, Thr, Ser, Ala, or Lys and beta Arg-182-->Lys, Ala, Glu, or Gln, could not. The beta Asp-181, beta Lys-182, and other defective mutants had 1.4, 1, and < 0.1%, respectively, of the wild-type membrane ATPase activity. Partially purified F1-ATPases from all mutants at positions 181 and 182, except for the beta Asp-181 and beta Lys-182 mutants, showed very low unisite catalysis. Purified F1-ATPases of the beta Gln-181 and beta Ala-181 mutants showed no multisite (or steady state) catalysis and slow unisite catalysis (< or = 1% of that of the wild type): their defects could be attributed to decreased catalytic rates (low k+2 and k-2). Changes of the k+2 and k-2 values in the beta Asp-181 enzyme, which showed detectable multi- and unisite catalysis, were less marked (27 and 21%, respectively, of wild-type rates). The beta Gln-182 enzyme showed defective catalysis (< or = 0.1% of the multi- and approximately 1% of the unisite catalyses of the wild type), whereas the beta Lys-182 enzyme showed 1 and 85% of the wild-type multisite and unisite catalytic rates, respectively. beta Lys-182 had wild-type values of k+2 and k-2, but beta Gln-182 had k+2 about 10-fold lower than that of wild type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Augmentation of 5-fluoro-2'-deoxyuridine cytotoxicity by 5-phenethyl-2'-deoxyuridine in human gastric cancer cells in culture.

5-Phenethyl-2'-deoxyuridine (PEUdR) augmented 5-fluoro-2'-deoxyuridine (FUdR) cytotoxicity up to 100-fold in several human gastric cancer cell lines. PEUdR also potentiated 5-fluorouracil (5-FU) cytotoxicity about 5-fold. In contrast, PEUdR reversed 5-fluorouridine (FUR) cytotoxicity in all cell lines studied. PEUdR was not cytotoxic up to 200 microM. PEUdR inhibited the incorporation of [3H]thymidine and [14C]uridine into acid-insoluble fractions, and also inhibited uptake of [3H]thymidine into KATO III cells. Thus, PEUdR inhibits pyrimidine nucleoside transport and salvage enzymes, which potentiates the cytotoxicity of FUdR and reverses the effect of FUR in human gastric cancer cells. These results may contribute to more effective cancer chemotherapy with FUdR and 5-FU.

Carbon Radioisotopes↗

Antimetastatic effects of synthetic peptides containing the core sequence of the type III connecting segment domain (IIICS) of fibronectin.

The antimetastatic activities of synthetic peptides corresponding to fragments of the adhesion-related molecules, such as fibronectin and laminin, were examined. We prepared three peptides derived from the type III connecting segment domain (IIICS) of fibronectin: Glu-Ile-Leu-Asp-Val (EILDV), Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST), Arg-Glu-Asp-Val (REDV), and a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg (YIGSR). Each peptide inhibited the experimental tumor metastasis of B16-BL6 melanoma, while EILDV had the strongest effect. The peptides conjugated with poly(ethylene glycol) (PEG) were more effective than the unmodified peptides in molar ratio terms. A mixture composed of PEG hybrids with EILDV, REDV and YIGSR significantly inhibited tumor metastasis.

Amino Acid Sequence↗

A case of generalized lichen nitidus with Koebner's phenomenon.

A 12-year-old boy was seen in our department with a three year history of eruptions on his back consisting of normal colored or slightly reddish, pinhead-sized papules, which had gradually spread to his trunk within the previous year. Four days before the first visit, May 13, 1992, the eruption involved his entire extremities. On the back side of his lumbar region, Koebner's phenomenon was observed. He had received several medications for more than two years to treat this eruption in several hospitals, but none were effective. He was in good general health. Mantoux reaction was negative two months after BCG injection. Histopathologic features of the papules included focal epidermal hyperplasia and elongation of the rete ridges in a narrow area and a well demarcated dense lymphohistiocytic infiltrate on the papillar layer. Biscoclaurine alkaloids (20 mg/day) and Jumi-haidoku-to (TJ-6; 7.5 g/day) were administered to the patient after the biopsy. No topical ointments were applied. Two weeks after of these treatments, he reported moderate pruritus on the back. The eruption diminished rapidly within 2 weeks after the therapy began. Almost all the eruptions were cured within one year. Mantoux reaction developed 8 x 8 mm erythema two and half months after the treatment began, and it was significantly positive (23 x 30 mm) 6 months later.

Alkaloids↗

Cloning, sequencing, and expression of thermophilic Bacillus sp. strain TB-90 urease gene complex in Escherichia coli.

The urease of thermophilic Bacillus sp. strain TB-90 is composed of three subunits with molecular masses of 61, 12, and 11 kDa. By using synthetic oligonucleotide probes based on N-terminal amino acid sequences of each subunit, we cloned a 3.2-kb EcoRI fragment of TB-90 genomic DNA. Moreover, we cloned two other DNA fragments by gene walking starting from this fragment. Finally, we reconstructed in vitro a 6.2-kb DNA fragment which expressed catalytically active urease in Escherichia coli by combining these three DNA fragments. Nucleotide sequencing analysis revealed that the urease gene complex consists of nine genes, which were designed ureA, ureB, ureC, ureE, ureF, ureG, ureD, ureH, and ureI in order of arrangement. The structural genes ureA, ureB, and ureC encode the 11-, 12-, and 61-kDa subunits, respectively. The deduced amino acid sequences of UreD, UreE, UreF, and UreG, the gene products of four accessory genes, are homologous to those of the corresponding Ure proteins of Klebsiella aerogenes. UreD, UreF, and UreG were essential for expression of urease activity in E. coli and are suggested to play important roles in the maturation step of the urease in a co- and/or posttranslational manner. On the other hand, UreH and UreI exhibited no significant similarity to the known accessory proteins of other bacteria. However, UreH showed 23% amino acid identity to the Alcaligenes eutrophus HoxN protein, a high-affinity nickel transporter.

Alcaligenes↗

Identification and functional analysis of a developmentally regulated extracellular signal-regulated kinase gene in Dictyostelium discoideum.

We have cloned a developmentally regulated mitogen-activated protein kinase (extracellular signal-regulated kinase) from Dictyostelium discoideum designated ERK1. Using anti-pTyr antibodies, we show that ERK1 is phosphorylated on tyrosine in vivo and that it will phosphorylate myelin basic protein. The gene expresses two transcripts, one that is preferentially expressed during vegetative growth and early development and one that is induced during the multicellular stages. Developmental Western blots (immunoblots) using anti-ERK1 antibodies indicate that ERK1 is present throughout development. ERK1/lacZ reporter constructs suggest that, in the multicellular stages, the gene is preferentially expressed in a subpopulation of cells scattered throughout the organism, similar to the pattern seen with anterior-like cell markers. Antisense mutagenesis from a derepressible promoter indicates that ERK1 is essential for vegetative growth. Overexpression of ERK1 from either the Actin 15 promoter or the ERK1 promoter results in abnormal morphogenesis starting at the slug stage. Overexpression of ERK1 in null mutants of the phosphotyrosine phosphatase PTP2 results in the production of large aggregation streams and subsequent abnormal morphogenesis that indicate a genetic interaction between ERK1 and PTP2. These cells produce very large aggregation streams that break up into very small mounds that undergo abnormal morphogenesis. The genetic interaction between ERK1 and PTP2 appears to be specific since overexpression of ERK1 in a ptp1- null mutant does not produce the same phenotype. Our results indicate that ERK1 plays an essential role during the growth and differentiation of D. discoideum.

Amino Acid Sequence↗

Clinical evaluation of plasma exchange and high dose intravenous immunoglobulin in a patient with Isaacs' syndrome.

The clinical effects of plasma exchange and high dose intravenous immunoglobulin (IVIg) were evaluated in a 41 year old woman with Isaacs' syndrome. After double filtration plasma exchange, symptoms almost disappeared for two to three weeks and the recorded continuous muscle action potentials were considerably decreased. Symptoms recurred within a few months. On the other hand, IVIg worsened the symptoms of the disorder: during and after IVIg at a dose of 0.2 g/kg/day (total 50 g), widespread myokymia, pseudomyotonia, and muscle cramps gradually increased. Symptoms improved after another course of plasma exchange.

Action Potentials↗

CT-guided biopsy of the chest: usefulness of fine-needle core biopsy combined with frozen-section pathologic diagnosis.

PURPOSE: To improve the diagnostic accuracy of computed tomography (CT)-guided biopsy of the chest. MATERIALS AND METHODS: The usefulness of fine-needle core biopsy combined with immediate frozen-section diagnosis by pathologists was prospectively studied. Fifty-five biopsies of the chest were performed under CT guidance in 55 patients with 36 malignant and 19 benign processes. Initial biopsy was always attempted with a 21-gauge modified Menghini needle; tissue samples were sent to the pathology department immediately after biopsy for pathologic diagnosis of the frozen sections. RESULTS: In 47 of 55 lesions (85%) sufficient materials for diagnosis were obtained and enabled correct final diagnosis. Specific histologic diagnosis was possible in 25 (74%) of 34 malignant and 10 (77%) of 13 benign lesions. In all of the eight other lesions, cytologic diagnosis of aspirated material was correct. No false-positive or false-negative results have occurred. CONCLUSION: Histologic diagnosis with frozen sections improves diagnostic accuracy of chest biopsy; immediate pathologic diagnosis is an encouraged adjunct.

Adolescent↗

A new monoclonal antibody (POG-1) detects a differentiation antigen of porcine granulosa and thecal cells and indicates heterogeneity of thecal-stromal cells.

To identify the differentiation antigen of ovarian cells, we raised a murine monoclonal antibody (POG-1 antibody) reactive to porcine granulosa and thecal cells in the ovary. Immunofluorescence staining showed that expression of the POG-1 antigen on granulosa and theca interna cells increased gradually in accordance with follicular development. The thecal cells just outside the basal lamina surrounding the follicles did not express the antigen, whereas some stromal cells around the theca externa layer in the large follicles did express it. These expression profiles indicated the heterogeneity of thecal-stromal cells and that the POG-1 antigen was a differentiation-related antigen of granulosa and thecal cells. Luteal cells also expressed the antigen. In organs other than the ovary, some endocrine and exocrine cells, such as Leydig cells and secretory cells of the breast, expressed the antigen. The POG-1 antigen was purified from granulosa cells by immunoaffinity chromatography. Polyacrylamide gel electrophoresis profiles showed that the antigen consisted of two specific proteins; the major one had a molecular mass of 77, and the other had a molecular mass of 81 kilodaltons. Analysis of the purified POG-1 antigen may contribute to understanding the differentiation mechanism of granulosa and thecal cells.

Animals↗

Bestatin, a potent aminopeptidase-N inhibitor, inhibits in vitro decidualization of human endometrial stromal cells.

We have reported that human endometrial stromal cells (ESC) express a cluster of differentiation-13 antigen/aminopeptidase-N, and the expression of this peptidase antigen was shown to increase with the decidualization of ESC. To clarify the role of this peptidase in human endometrium, the effect of bestatin ([(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-(S)-leucine), an inhibitor of aminopeptidase-N, on the decidualization of ESC in vitro was examined. Purified human ESC were cultured for 12 days in the presence of 10(-6) mol/L progesterone with or without bestatin. Decidualization was assessed by PRL production and morphological transformation. The effects of a stereoisomer of bestatin and of pepstatin were similarly examined using the same culture system. Bestatin inhibited progesterone-induced PRL production in a dose-dependent manner, with no effect on cell number or viability, whereas neither its stereoisomer nor pepstatin inhibited aminopeptidase activity or PRL production. The morphological transformation of ESC was also inhibited by bestatin, but not by its stereoisomer or pepstatin. These findings demonstrate that the inhibition of aminopeptidase-N activity blocks the in vitro decidualization of ESC and suggest an important role for this peptidase in the functional differentiation of human ESC.

Adult↗

Cytokines stimulate dipeptidyl peptidase-IV expression on human luteinizing granulosa cells.

We have previously reported that dipeptidyl peptidase-IV (DPPIV) is a differentiation antigen for human granulosa cells that is initially expressed during corpus luteum formation. To investigate the involvement of cytokines in luteal cell differentiation, we examined the expression and activity of DPPIV in human luteinizing granulosa cells cultured in vitro. Human granulosa cells obtained from patients who had undergone in vitro fertilization were cultured for 7 days in the absence (controls) or presence of hCG (1 U/mL), tumor necrosis factor-alpha (TNF alpha; 10 ng/mL), or interleukin 1-alpha (IL-1 alpha; 10 ng/mL). Flow cytometry showed that the percentage of cultured granulosa cells treated with TNF alpha and IL-1 alpha that was positive for DPPIV expression was significantly higher than that in controls (43.7 +/- 5.4% and 43.4 +/- 5.6%, respectively, vs. 21.7 +/- 3.5%; P < 0.01), whereas hCG treatment produced no remarkable difference in DPPIV expression (24.0 +/- 5.2%). The DPPIV activity of cells treated with TNF alpha and IL-1 alpha was also significantly higher than that of controls, whereas hCG treatment produced no significant difference from control values. These findings indicate that TNF alpha and IL-1 alpha stimulate DPPIV expression and activity in human luteinizing granulosa cells in vitro and suggest the involvement of cytokines in the differentiation of granulosa cells during corpus luteum formation.

Adult↗