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Biomedical subjects

A Imai

Publications and source records attributed to A Imai.

At least 199 records · Page 11Linked to original sources

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine on cerebral circulation and metabolism in cats.

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) on cerebral circulation and metabolism were examined measuring cerebral oxygen and carbon dioxide tension (BrPO2, BrPCO2) and mean arterial blood pressure (MABP) in cats. KC-404 (100 micrograms/kg) infused into the carotid artery produced no significant changes in BrPO2, BrPCO2 and MABP. 300 micrograms/kg of KC-404 infused into the femoral vein produced significant decrease in MABP, whereas BrPO2 remained constant. It is suggested that a large dose of KC-404 causes preferential cerebral vasodilation and maintenance of constant blood flow despite marked reduction in MABP.

Animals↗

Possible mechanism for preterm labor associated with bacterial infection. I: Stimulation of phosphoinositide metabolism by endotoxin in endometrial fibroblasts.

Growing evidence suggests an association between intra-amniotic infection and premature initiation of parturition. We recently demonstrated that some factor(s) including endotoxin produced by the organism stimulates endogenous phospholipase A2 resulting in liberation of arachidonic acid and prostaglandin formation (Arch. Gynecol. Obstet. 244: 1-6 (1988). The studies presented in this report were designated to evaluate the mechanism for endotoxin to stimulate phospholipase A2 using human endometrial fibroblasts. Exposure of the fibroblasts to endotoxin from Escherichia coli in the presence of [32P] phosphate increased 32P-labeling of phosphatidic acid (PA) and phosphatidyl-inositol (PI) in a dose-dependent and a time-dependent manners. The PA labeling occurred without a measurable lag time. These findings demonstrate that the endotoxin stimulates phosphoinositide metabolism in human endometrial fibroblasts by a receptor-mediated mechanism. Membrane phosphoinositide turnover stimulated by endotoxin results in cytosolic Ca2+ increment, liberation of arachidonic acid, which may be involved in the initiation of parturition.

Bacterial Infections↗

Possible mechanism for preterm labor associated with bacterial infection. II: Enhancement of endotoxin-stimulated phosphoinositide metabolism by sex steroids in human endometrial fibroblasts.

We have previously reported that bacterial endotoxin stimulated membrane phosphoinositide metabolism, which resulted in liberation of arachidonic acid and preterm initiation of parturition. The aim of this study was to explore whether ovarian steroids alter the stimulation of phosphoinositide turnover by endotoxin. The phosphoinositide turnover was evaluated by [32P] phosphate incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI) in human endometrial fibroblasts. When the cells were exposed to endotoxin from Escherichia colli, 32P-labeling of PA and PI was increased in a dose-dependent manner; EC50 was 10 ng/ml. Preincubation with estradiol-17 beta (1 microM) and progesterone (1 microM) for 24 hours, but not for a few hours, enhanced the rate of the endotoxin-stimulated phosphorylation of the lipids in the fibroblasts by decreasing EC50 value of endotoxin to 1 ng/ml. Estradiol or progesterone alone failed to show any effects. These findings demonstrated that the sex steroids may increase the sensitivity of host cells to endotoxin, suggesting the mechanism(s) by which the preterm labor associated with intra-amniotic infection is initiated.

Bacterial Infections↗

Phospholipase C activity in human placental membrane.

Receptor-stimulated hydrolysis of polyphosphoinositides by action of phospholipase C appears to be an important mediator of cell activation through the generation of the second messengers, in particular inositol triphosphate (IP3). In order to understand placental function better, activity of IP3 production from membrane in cell-free system was examined. Incubation of membrane preparation from [3H]inositol-labelled human placenta with Ca2+ in the presence of 1 mM ATP and 1 mM GTP resulted in the rapid production of IP3 in a dose dependent manner; half-maximal effect occurred at 10 microM. On the other hand, little effect was observed in the case of membrane prepared from [3H]arachidonic acid-labelled placenta, suggesting higher requirement of Ca2+ for phospholipase A2 activation. These data suggest that placenta contains phospholipase C hydrolyzing polyphosphoinositide at physiological concentration of Ca2. This is the first report to provide direct evidence of transmembrane signalling mechanisms in the human placenta, and may provide a clue to the etiology of placental disorders.

Female↗

Successful pregnancy in a patient with paroxysmal nocturnal hemoglobinuria: case report.

In this report, the maternal and fetal risks in a patient with paroxysmal nocturnal hemoglobinuria (PNH) were evaluated. A patient with PNH carried a pregnancy to successful delivery, with a healthy male infant, and suffered from postpartum cerebral subcortical thrombosis followed by recovery. An elevated level of serum lactate dehydrogenase isoenzyme (alpha-hydroxybutyrate dehydrogenase) was observed during pregnancy; the level returned to normal by delivery. However, the hemoglobin concentration during pregnancy and post-partum was kept at 8 g/dl. This is the first report of a relation between the onset of hemolysis and pregnancy. The management of pregnancy in such patients is discussed.

Adult↗

Accumulation of diacylgylcerol in platelet phosphoinositide turnover in schizophrenia: a biological marker of good prognosis?

Phosphoinositide (PI) turnover was examined by measuring phosphatidic acid (PA) and diacylglycerol (DG) production following thrombin stimulation in platelet membranes from 20 schizophrenic patients, 10 patients with other mental disorders, and 9 normal controls. In 6 of 13 acute schizophrenic patients, DG was not transformed into phosphatidic acid (PA), but accumulated in the platelets instead. The abnormal findings persisted for at least 2 months, but then reversed over a long period. Three years later, the patients with abnormal PI turnover had a significantly better outcome than other acute schizophrenic patients.

Adolescent↗

Hyperperfusion of cerebral cortex, thalamus and basal ganglia during spontaneously occurring migraine headaches.

Color-coded, cross-sectional imaging of local cerebral blood flow (LCBF) was made in a prospective manner among 22 patients with well-established common or classic migraine utilizing the stable xenon-enhanced computed tomographic (Xe CT-CBF) method. LCBF in patients during spontaneously occurring headaches (N = 12) were significantly higher compared to patients without headache (N = 10) by 25-35%. The hyperperfusion involved not only cerebral cortex but also subcortical structures including thalamus, basal ganglia, and subcortical white matter. LCBF increases were not bilateral and sometimes asymmetrical, but LCBF increases were not consistently related to the preponderant side of headache. No significant differences were observed in the degree or pattern of cerebral hyperperfusion during headaches compared among common (N = 6) and classic (N = 6) migraineurs. Results suggest a common etiology for both common and classic migraine. Results are not consistent with spreading oligemia or spreading cortical depression as a cause of migraine. The cerebral hyperperfusion appears to be mediated by various neurogenic and chemical changes accompanying migraine. The unilateral nature of migraine head pain is more likely due to dilation of extracranial vessels.

Adult↗

Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts.

Stimulated inositolphospholipid turnover has been proposed to constitute a signal-transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [32P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen.

Endometrium↗

A putative growth factor in extract from uterine cancers.

Extracts from uterine cervical and corpus cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labil, and not inacticated by removal lipid-soluble fraction, suggesting that the activity is associated with a protein. However, the cancer extract failed to stimulate phosphoinositide turnover. The substance(s) present in the uterine cancer extracts may activate endometrial fibroblasts proliferation through the transmembrane signaling mechanisms other than phosphoinositide turnover. The bindings of previously identified growth factors including somatomedine C, thrombin, insulin, fibroblast growth factor were not inhibited by the extracts. This is the first report to provide direct evidence that malignant uterine tumor may produce and secrete a putative growth factor-like peptide.

Adenocarcinoma↗

Antenatal evaluation of upper gastrointestinal dilatation complicated by non-immune hydrops fetalis and polyhydramnios.

A case of upper gastrointestinal dilatation associated with fluid collection in the peritoneal cavity is reported where the prenatal diagnosis was made sonographically in a non-immunologic hydrops fetalis. Neither generalized edema nor pleural effusion were detected. Polyhydramnios was complicated. Almost complete drainage of the abdominal fluid was accomplished with rapid re-accumulation of fetal ascites and no resolution of intestinal dilatation. After delivery by Cesarean section, the male infant died the next day due to respiratory distress syndrome. Postmortem histologic examination failed to confirm the ultrasonographic findings including ileal obstruction and subsequent hypoplasia in the colon. Despite the discrepancy between clinical and pathologic findings, the findings of this case would improve the etiology of hydrops where no possible cause is found.

Adult↗

A good outcome pregnancy in a patient with paroxysmal nocturnal hemoglobinuria.

In this report, the maternal and fetal risks in a patient with paroxysmal nocturnal hemoglobinuria (PNH) were evaluated. A patient with PNH carried a pregnancy to successful delivery, with a healthy male infant, and suffered from postpartum cerebral subcortical, but not hepatic, thrombosis followed by recovery. An elevation of serum levels of lactate dehydrogenase isoenzyme, alpha-hydroxybutyrate dehydrogenase, was observed during pregnancy. The level was ameliorated to the non-pregnant level by delivery. However, hemoglobin concentrations during pregnancy and post-partum were at least 8 g/dl. This is a first report that shows tight coupling between an onset of intravenous hemolysis and pregnancy. The management of pregnancies in such patients is also discussed.

Adult↗

Direct human T helper cell-induced B cell activation is not mediated by inositol lipid hydrolysis.

The Ag-specific interaction between cloned allospecific human Th cells and class II MHC determinants on the surface of allogeneic B cells induces a significant fraction of resting B cells to express a B cell specific activation Ag BLAST-2 (CD23). On the other hand, cross-linking of B cell surface Ig R by Ag analogues does not lead to BLAST-2 expression. By utilizing the BLAST-2 induction assay as a positive control for efficient Th-B cell interaction, we have investigated the biochemical basis of human B cell activation mediated by Ag and Th cells. Our data demonstrate that ligands for sIg R, including F(ab')2 goat anti-human IgM and Staphylococcus aureus protein A, stimulate the metabolism of B cell membrane inositol lipids as assessed by: 1) increased [3H]inositol phosphates formation in myo-[3H]inositol-labeled B cells; 2) selective incorporation of [32P]orthophosphate into phosphatidic acid and phosphatidylinositol, but not into phosphatidylethanolamine or phosphatidylcholine; and 3) rapid increase in B cell cytoplasmic ionized Ca2+ concentration ([Ca2+]i). In contrast, direct Th-B cell interaction leads to high intensity BLAST-2 expression on the B cell surface but this response is not mediated by changes in inositol lipid metabolism or [Ca2+]i. Further, Th-B cell interaction does not affect the changes in B cell inositol lipid metabolism or [Ca2+]i triggered by sIg cross-linking. Taken together, our results suggest that Ag and Th cells induce different functional B cell responses by activating distinct second messenger systems within the B cell.

Antigens↗

Imaging local cerebral blood flow by Xenon-enhanced computed tomography--technical optimization procedures.

Methods are described for non-invasive, computer-assisted serial scanning throughout the human brain during eight minutes of inhalation of 27%-30% Xenon gas in order to measure local cerebral blood flow (LCBF). Optimized Xenon-enhanced computed tomography (XeCT) was achieved by 5-second scanning at one-minute intervals utilizing a state-of-the-art CT scanner and rapid delivery of Xenon gas via a face mask. Values for local brain-blood partition coefficients (L lambda) measured in vivo were utilized to calculate LCBF values. Previous methods assumed L lambda values to be normal, introducing the risk of systematic errors, because L lambda values differ throughout normal brain and may be altered by disease. Color-coded maps of L lambda and LCBF values were formatted directly onto CT images for exact correlation of function with anatomic and pathologic observations (spatial resolution: 26.5 cubic mm). Results were compared among eight normal volunteers, aged between 50 and 88 years. Mean cortical gray matter blood flow was 46.3 +/- 7.7, for subcortical gray matter was 50.3 +/- 13.2 and for white matter was 18.8 +/- 3.2. Modern CT scanners provide stability, improved signal to noise ratio and minimal radiation scatter. Combining these advantages with rapid Xenon saturation of the blood provides correlations of L lambda and LCBF with images of normal and abnormal brain in a safe, useful and non-invasive manner.

Aged↗

LCBF values decline while L lambda values increase during normal human aging measured by stable xenon-enhanced computed tomography.

Results of measurements of LCBF and L lambda values utilizing optimal CT-CBF methods under resting conditions are reported among thirty-two neurologically normal volunteers aged between 20 and 88 years. Measurements were made during inhalation of 26-30% stable xenon gas for 8 min and serial scanning utilizing a state-of the-art CT scanner with both eyes closed and ears unplugged. LCBF values for cortical gray matter were lowest in occipital cortex and highest in frontal cortex. Gray matter flow values were also high in subcortical structures with highest values measured in the thalamus. For white matter, highest flow values were measured in the internal capsule. Changes in LCBF and L lambda values were analyzed with respect to advancing age. Significant age-related declines in LCBF values were observed in occipital cortex and frontal white matter. Significant age-related increases in L lambda values were measured in frontal and temporal cortex, caudate nucleus and thalamus. Possible explanations are offered for these age-related increases in L lambda values for gray matter, such as accumulation of lipofuscin in neurons and relative compacting of gray matter with advancing age. The latter increases the numbers of nerve cells sampled per volume of gray matter measured.

Administration, Inhalation↗

Preterm labor and bacterial intra-amniotic infection: arachidonic acid liberation by the action of phospholipase A2.

There is a strong association between preterm labor and infection, presumably through an increase in prostaglandin (PG) formation. The studies presented in this report were undertaken to evaluate whether bacterial products stimulate endogenous phospholipid hydrolysis and arachidonic acid liberation by the action of phospholipase A2, a rate-limiting step for PG synthesis. When human endometrial cells prelabelled with [3H]arachidonic acid to an isotopically steady state were exposed to a medium conditioned with Bacteroides fragilis, arachidonic acid liberation was stimulated, accompanied with lysophospholipid formation. Similar stimulatory effect on phospholipid degradation was also observed in the experiments with the bacterial extract. These results demonstrate that the organism produces phospholipase A2 acting on endogenous phospholipids and/or factor(s) activating phospholipase A2. Phospholipase A2 is suggested as a mechanism for the onset of labor associated with intra-amniotic infection and arachidonic acid liberation.

Amniotic Fluid↗

[Effects of stimulus modality and task instruction upon the orienting response].

The purpose of this study is to confirm that habituated orienting response (OR) is evoked when the visual and auditory stimuli are bimodally presented. In Exp. I, either visual or auditory stimulus was exposed to 20 subjects in both habituation- and test-periods. In Exp. II, the visual and auditory stimuli were exposed conversely over the habituation- (either stimulus) and the test-periods (both stimuli). A half of the 20 subjects was instructed to pedal only when the test-stimulus was presented (Experimental Group; E-G), while the other half did not receive the instruction (Control Group; C-G). Results are as follows; the amplitude of skin conductance response (SCR) to the test-stimulus was significantly larger in the E-G than the C-G in the two experiments. However, a significant increase of the SCR amplitude of the E-G to the habituation-stimulus was obtained only in the Exp. II. These tendencies indicated the occurrence of "selective" OR. In addition, the above OR to the habituation-stimulus suggested that "alertive" OR was evoked here by the presentation of stimuli in different modality.

Acoustic Stimulation↗