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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 109 records · Page 6Linked to original sources

Differential responses of circulating and tissue adrenomedullin and gene expression to volume overload.

BACKGROUND: Adrenomedullin (AM), which is produced by various tissues and organs, also circulates in the blood. Circulating AM levels increase during disease states such as essential hypertension, heart failure, and renal failure. However, little is known about how circulating AM or AM production responds to volume overload (VOL). METHODS AND RESULTS: Progressive VOL was induced in rats by an aortocaval shunt (AC) or by an aortocaval shunt with banding of the abdominal aorta distal to the shunt (AC + B), which created a larger shunt volume. Plasma and tissue AM concentrations, as well as AM gene expression levels, were measured at 1, 5, and 14 days after operation. Plasma concentrations of atrial natriuretic peptide (ANP), aldosterone, and renin activity (PRA) were also examined. Pulmonary congestion, pleural effusion, and ascites rapidly progressed in the AC + B group, suggesting that VOL caused more rapid heart failure under these conditions. Plasma AM concentrations in the AC + B and AC groups at day 1 compared with those in sham-operated rats were increased by 300% and 140%, respectively, and then gradually declined. The time course of plasma AM over 14 days was similar to that of plasma aldosterone and PRA, but not of plasma ANP or intracardiac filling pressure. The increase in plasma AM was accompanied by upregulated AM gene expression in the lung and aorta and by decreased AM concentrations in the atrium, ventricle, and adrenal gland. Cardiac AM gene expression levels were increased in the hypertrophied ventricles of AC and AC + B rats. CONCLUSIONS: The major findings of the present study were 1) a rapid increase in plasma AM after the imposition of VOL in association with increased plasma aldosterone and PRA, 2) the contribution of several organs to this increase, and 3) a late increase in the AM messenger RNA (mRNA) level in the ventricles as VOL-induced ventricular hypertrophy developed.

Adrenomedullin↗

Assignment of Eubacterium sp. VPI 12708 and related strains with high bile acid 7alpha-dehydroxylating activity to Clostridium scindens and proposal of Clostridium hylemonae sp. nov., isolated from human faeces.

Unknown Eubacterium-like organisms VPI 12708 and five strains (Y-1113, I-10, M-18, TH-82 and 36S) had high bile acid 7alpha-dehydroxylating activity; the unknown Clostridium-like organisms TN-271T and TN-272 also had the same activity. Analysis of their 16S rDNA sequences demonstrated that all strains belong to cluster XIVa of the genus Clostridium (Collins et al., 1994). Strain VPI 12708 and five other strains (Y-1113, I-10, M-18, TH-82 and 36S) formed a single cluster and strains TN-271T and TN-272 formed another single cluster. Clostridium scindens JCM 6567T was the most closely related species for two clusters in the phylogenetic tree. Values for DNA-DNA similarities among C. scindens JCM 6567T, strain VPI 12708 and the other five strains were greater than 70%, showing that these micro-organisms were a single species. Therefore, we identified strain VPI 12708 and the five other strains as C. scindens. In addition, DNA-DNA similarities among C. scindens JCM 6567T, strain TN-271T and strain N-272 revealed that strains TN-271T and TN-272 were distinct from C. scindens JCM 6567T. On the basis of phylogenetic analysis and DNA-DNA similarity data, it was concluded that strains TN-271T and TN-272 are members of a new species of the genus Clostridium, for which the name Clostridium hylemonae is proposed. The type strain is strain TN-271T (= JCM 10539T).

Base Composition↗

Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload.

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

Adrenomedullin↗

Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse.

Prostaglandins (PGs) have proven important during parturition, but inhibition of PG production treating preterm labor (PTL) results in significant maternal and fetal side effects. We hypothesize that specific inhibition of either cyclooxygenase (COX)-1 or -2 may result in separation of therapeutic and toxic effects. We demonstrate that COX-2, but not COX-1, is induced during inflammation-mediated PTL caused by lipopolysaccharide (LPS) administration. A two- to threefold increase in uterine and ovarian PG concentrations coincides with this induction of COX-2. The COX-2-selective inhibitor SC-236 proved effective in stopping preterm delivery and the increases in PGs. The COX-1-selective inhibitor SC-560 also attenuated uterine and ovarian PG production after LPS but did not inhibit PTL as efficiently as SC-236. COX-1-deficient mice, which show delay in the onset of term labor, exhibited no delay in onset of PTL after LPS. These findings suggest that the mechanisms for initiation of inflammation-mediated PTL and term labor differ and that selective COX-2 inhibition may provide a means of stopping inflammation-induced PTL in humans.

Animals↗

Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects.

Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has shown that OT exerts significant effects on both the ovarian corpus luteum and the uterine myometrium during pregnancy. To better define the roles of OT during pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT-deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses. The infusion rates of OT necessary for these effects were reduced in OT KO mice. The dose of OT that delayed labor also delayed the normal decrease in plasma progesterone late in gestation, implicating a primary effect on the corpus luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred. We propose that the downregulation of OT receptors in the corpus luteum and induction of OT receptors in the myometrium serve to shift the predominant consequence of OT action during murine pregnancy from labor inhibition to labor promotion.

Animals↗

RT-PCR suggests human skeletal muscle origin of alveolar soft-part sarcoma.

In 1952, Christopherson et al. proposed that alveolar soft-part sarcoma (ASPS) was a distinct entity with unique clinical and pathological features. Since their report, its histogenesis has not been determined. In order to clarify the histogenesis of ASPS, a study using reverse transcription polymerase chain reaction using cDNAs from MyoD1 and myogenin, and the actin filament from human-skeletal-muscle-related mRNAs has been performed in 5 cases of ASPS. The expression of MyoD1 and myogenin was determined in 5 and 2 cases of the 5 cases, respectively. Moreover, expression of the many mRNAs from the actin filament of skeletal muscle was also found in ASPS. According to these findings, it is now postulated that ASPS is of skeletal muscle origin.

Actins↗

Enhanced adrenomedullin production by mechanical stretching in cultured rat cardiomyocytes.

Adrenomedullin (AM) is secreted from cultured cardiac myocytes. In this study, we examined whether mechanical stretching stimulates AM production in cardiac myocytes, and if so, whether angiotensin II (Ang II) is involved in that mechanism. Neonatal rat cardiac myocytes cultured in serum-free medium were stretched 10% or 20% on flexible silicone rubber culture dishes, and AM mRNA expression was examined by quantitative polymerase chain reaction. The AM mRNA levels in the myocytes stretched 10% and 20% for 24 hours significantly increased by 56% (P<0.05) and 88% (P<0.01), respectively, when compared with the levels in nonstretched cells. AM secretion into the medium after the myocytes were stretched 10% and 20% increased by 22% (P<0.05) and 45% (P<0.01), respectively. In nonstretched myocytes incubated with 10(-6) mol/L Ang II for 24 hours, AM mRNA and secretion increased by 86% (P<0.05) and 36% (P<0. 01), respectively. These effects of Ang II were abolished by 10(-6) mol/L CV-11974, an Ang II type I (AT(1)) receptor antagonist, but not by 10(-6) mol/L PD-123319, an Ang II type II antagonist. Stretch-induced increases of AM gene expression and secretion were significantly inhibited (P<0.05) in the presence of 10(-6) mol/L CV-11974 by 46% and 52%, respectively; however, they were not affected by 10(-6) mol/L PD-123319. These findings indicate that AM production from cardiac myocytes is augmented by mechanical stretching, partially through the AT(1) receptors, which suggests a local interaction between AM and the renin-angiotensin system in stretched cardiac myocytes.

Adrenomedullin↗

Impact of emotion on memory. Controlled study of the influence of emotionally charged material on declarative memory in Alzheimer's disease.

BACKGROUND: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake. AIMS: To test our previous findings in a controlled experimental study. METHOD: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not. RESULTS: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls. CONCLUSIONS: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia.

Aged↗

The acute and chronic stimulatory effects of endothelin-1 on glucose transport are mediated by distinct pathways in 3T3-L1 adipocytes.

We have recently shown that pretreatment with endothelin-1 (ET-1) for 20 min stimulates GLUT4 translocation in a PI3-kinase-dependent manner in 3T3-L1 adipocytes (Imamura, T. et al., J Biol Chem 274:33691-33695). This study presents another pathway by which ET-1 potentiates glucose transport in 3T3-L1 adipocytes. ET-1 treatment (10 nM) leads to approximately 2.5-fold stimulation of 2-deoxyglucose (2-DOG) uptake within 20 min, reaching a maximal effect of approximately 4-fold at approximately 6 h, and recovering almost to basal levels after 24 h. Insulin treatment (3 ng/ml) results in an approximately 5-fold increase in 2-DOG uptake at 1 h, and recovering to basal levels after 24 h. The ETA receptor antagonist, BQ 610, inhibited ET-1 induced glucose uptake both at 20 min and 6 h, whereas the ETB receptor antagonist, BQ 788, was without effect. Interestingly, ET-1 stimulated 2-DOG uptake at 6 h, not at 20 min, was almost completely blocked by the protein-synthesis inhibitor, cycloheximide and the RNA-synthesis inhibitor, actinomycin D, suggesting that the short-term (20 min) and long-term (6 h) effects of ET-1 involve distinct mechanisms. GLUT4 translocation assay showed that 20 min, but not 6 h, exposure to ET-1 led to GLUT4 translocation to the plasma membrane. In contrast, 6 h, but not 20 min, exposure to ET-1 increased expression of the GLUT1 protein, without affecting expression of GLUT4 protein. ET-1 induced 2-DOG uptake and GLUT1 expression at 6 h were completely inhibited by the MEK inhibitor, PD 98059, and partially inhibited by the PI3-kinase inhibitor, LY 294002, and the G alpha i inhibitor, pertussis toxin. The PLC inhibitor, U 73122, was without effect. These findings suggest that ET-1 induced GLUT1 protein expression is primarily mediated via MAPK, and partially via PI3K in 3T3-L1 adipocytes.

3T3 Cells↗

Identification of alpha-D-glucosylglycerol in sake.

alpha-D-Glucosylglycerol (GG) was found for the first time in sake (Japanese rice wine) in an amount of about 0.5%. GG was also found in miso and mirin which had been brewed by using koji. GG was hydrolyzed into glucose and glycerol in an equimolar ratio with maltase (EC 3.2.1.20, alpha-glucosidase from yeast), but not with emulsin (EC 3.2.1.21, beta-glucosidase from almond). The retention times and mass spectra of trimethylsilyl derivatives by a GC-MS analysis of GG in sake were comparable to those of various GG samples synthesized by glycol cleavage. It was proven that GG in sake consisted of three components, viz., 2-O-alpha-D-glucosyl-glycerol (GG-II), (2R)-1-O-alpha-D-glucosylglycerol (R-GG-I) and (2S)-1-O-alpha-D-glucosylglycerol (S-GG-I). The ratio of the three components in GG was 6:66:28 for sake. It is considered that GG was formed by transglucosylation of the glucosyl groups to glycerol by alpha-glucosidase from koji in the sake mash.

Chromatography, High Pressure Liquid↗

Cloning of full length cDNA, high-level expression and biological characterization of feline IL-12.

A full length cDNA of feline interleukin(IL)-12 p35 and p40 subunits was cloned. By transferring the plasmids containing both the subunit genes to mammalian cells, we expressed biologically active feline IL-12. The expressed feline IL-12 has interferon-gamma-inducing activity against both human and feline peripheral blood mononuclear cells (PBMC) and stimulates cytotoxic T lymphocyte activity against herpes simplex virus-infected human PBMCs. There were two kinds of molecules (p75, p80) in the purified recombinant feline IL-12, and both molecules exhibited biological activity. The difference between p75 and p80 was the degree of the glycosylation of the p35 chain. Moreover, when we modified the cDNA of p35 by changing some codons and deleted the 5' and 3' non-coding regions, the expression level of IL-12 increased about 100 fold.

Amino Acid Sequence↗

Developing a new model for non-insulin dependent diabetes mellitus (NIDDM) by using the Philippine wild mouse, Mus musculus castaneus.

The Philippine wild-caught castaneus mouse (Mus musculus castaneus) and laboratory mouse (C57BL/6J: B6) were used to develop a new non-insulin dependent diabetes mellitus (NIDDM) model. Offspring from the cross between a wild male and B6 female were backcrossed to the sire. One male which exhibited highest fasting hyperglycemia (190 mg/dl) among eighty-seven backcross offspring was selected at 10 weeks of age, and crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed to develop a new inbred strain named CBD (Castaneus-B6 diabetic) mouse. Mice with relatively higher fasting hyperglycemia among F0 and F1 generations were selected for breeding. From the F2 generation, mice were defined as diabetic when blood glucose levels exceeded 200 mg/dl at 120 min in intraperitoneal glucose tolerance test (IPGTT) at 10 weeks of age, and have been selectively bred. The incidence of diabetic males from the F3-F6 generation fluctuated 45-75% at 10 weeks of age and 59-72% at 20 weeks of age. Diabetic males had about two-fold higher fasting glucose and insulin levels than B6 males. Glucose-stimulated insulin secretion was impaired in diabetic CBD mice compared to B6 males at 20 weeks. Moreover, diabetic mice had slight obesity compared to B6 mice. These facts indicated that diabetic features of CBD mice resemble NIDDM in humans. The CBD strain, characterized by high incidence and early onset of diabetes with mild obesity would be of value as a new NIDDM model. The method, utilizing wild castaneus mouse of different origin from laboratory mice, maybe useful in the development of other animal models.

Animals↗

Molecular cloning of mouse alpha-1,6-fucosyltransferase and expression of its mRNA in the developing cerebrum.

Complementary DNA encoding mouse alpha-1,6-fucosyltransferase (FUT) was cloned. The deduced primary structure consisted of 575 amino acids and had 96.0% and 93.0% identity with alpha-1,6-FUT of human and porcine origin, respectively. Quantitative analysis of alpha-1,6-FUT mRNA expression during selected developmental stages of the cerebrum showed that the expression increased during later embryonic stages and was highest in the early postnatal stages (P1 to P7), after which it declined somewhat but still remained relatively high in the mature adult. The expression profile suggests important roles of FUT in the developing central nervous system.

Amino Acid Sequence↗

[Dementia and disability after initial cerebral thrombosis evaluated by MRI and their clinical course].

This study was conducted to clarify the relationship between long-term prognosis of functional status after stroke and the magnetic resonance imaging (MRI) findings as well as complications in the course. A total of 98 patients with initial cerebral thrombosis were enrolled, and 65 patients surviving 5 years after the event, were studied in terms of cognitive function and activity of daily living (ADL). Mean age at registration (3 months after the event) was 72.0 years-old and 44 were male. MRI findings were divided into eight categories including the size and laterality of infarction, in addition to six categories as previously described. The presence of dementia was identified according to the HDS-R and the DSM-III-R scales, and the extent of dementia, assessed with the CDR scale, was divided into 3 grades: none, mild, and severe. The extent of ADL status was also graded into 3 classes: independent, partially dependent, and completely dependent. Recurrence of stroke, pneumonia, and motor disorders (hip joint fracture) were counted as complications during the course. At baseline, dementia was identified in 44, consisting of 30 mild and 14 severe dementias. During 5 years, 11 cases with mild dementia showed deterioration, and 1 case without dementia developed mild dementia. At registration, there were 46 cases with partially dependent ADL status and 22 cases completely dependent, while deterioration of ADL was seen in 17 during 5 years. Multiple regression analyses showed that diffuse PVH and pneumonia were contributory factors to the development of dementia, while dementia, pneumonia and motor disorders were risk factors for deterioration of ADL. These findings suggested that in patients with cerebral thrombosis, especially in patients with diffuse PVH, pneumonia and motor disorders should be taken care of in order to prevent functional decline.

Activities of Daily Living↗

[Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy].

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Adult↗