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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 451 records · Page 25Linked to original sources

Ornithine-containing lipids stimulate CD14-dependent TNF-alpha production from murine macrophage-like J774.1 and RAW 264.7 cells.

The ornithine-containing lipids (OL)-induced cytokine production pattern in macrophage-like J774.1 and RAW 264.7 cells was different from that in the peritoneal macrophages previously reported. OLs, as well as lipopolysaccharide (LPS) of Escherichia coli, strongly induced tumor necrosis factor (TNF) alpha but not interleukin (IL)-1beta in J774.1 cells. In the RAW cells, IL-1beta, TNF-alpha and prostaglandin E(2) were strongly induced by the OLs and LPS. OL- and serine-glycine-containing lipid (SGL)-induced TNF-alpha production in J774.1 and RAW 264.7 cells required serum. However, in CD14-deficient LR-9 cells, TNF-alpha was not induced by the OLs in the presence or absence of serum. OLs and a SGL almost completely inhibited the binding of (125)I-LPS to J774.1 cells. These results suggested that OLs and SGL activate macrophages via the CD14-dependent pathway.

Animals↗

Modulation of transforming growth factor beta function in hepatocytes and hepatic stellate cells in rat liver injury.

BACKGROUND: Transforming growth factor beta (TGF-beta) regulates hepatocyte proliferation and biosynthesis of the extracellular matrix. AIMS: This study investigated alternations in sensitivity to TGF-beta1 and binding properties for ligand in hepatocytes and hepatic stellate cells (HSC) after CCl(4) administration. METHODS: Plasma TGF-beta1 levels in rats after CCl(4) administration were determined using ELISA. Effects of TGF-beta1 were examined by DNA synthesis in hepatocytes and by measurement of fibronectin production in HSC after CCl(4) administration. Binding of (125)I TGF-beta1 was tested in these cells. RESULTS: Plasma TGF-beta1 levels were increased as early as 24 hours and were maximal by 48 hours. The antiproliferative response to TGF-beta1 decreased in hepatocytes at 48 hours and normalised at 72 hours. Fibronectin production of both normal and injured HSC was affected by TGF-beta1 treatment. Cross linked ligand/receptor complexes were detected in normal hepatocytes and HSC. However, these levels decreased specifically in hepatocytes at 48 hours and normalised by 72 hours. CONCLUSIONS: Downregulation of TGF-beta receptor occurred in hepatocytes after chemical insult and TGF-beta1 could not transduce its antiproliferative signal. Recovery of TGF-beta receptor expression causes the signal to transduce to the nucleus at 72 hours. In HSC, whenever TGF-beta1 is increased, TGF-beta1 can transduce its signal for fibronectin production via its receptor because signalling receptors are expressed constantly.

Animals↗

New optical method for analyzing cortical blood flow heterogeneity in small animals: validation of the method.

In pentobarbital-anesthetized male Sprague-Dawley rats, a small cranial window was trephined, and the cortex was transilluminated with a fine glass fiber inserted into the brain parenchyma. The light intensity at the surface area of 2 x 2 mm was recorded during intracarotid injection of 25 microl of carbon black (CB) solution. The region of interest (ROI) was divided into a 50 x 50 matrix, and the mean transit time of CB transport was calculated in each matrix element. We found rapid transits of CB along the microvasculature, with considerable heterogeneity in the avascular area, and heterogeneous efficiency in autoregulatory capacity in the ROI during hypotension. The method was validated by comparison with laser-Doppler flowmetry. The average mean difference was 0.03 +/- 0. 05%. Five percent CO(2) inhalation increased the flow by 85%, but heterogeneously. We concluded that the technique is exclusively sensitive to indicator transits in a very small area on the brain surface with potential usefulness in detecting regional heterogeneity in blood flow.

Administration, Inhalation↗

Human cerebellum plays an important role in memory-timed finger movement: an fMRI study.

The purpose of this study was to determine, by using functional magnetic resonance imaging, the areas of the brain activated during a memory-timed finger movement task and compare these with those activated during a visually cued movement task. Because it is likely that subjects engage in subvocalization associated with chronometric counting to achieve accurate timing during memory-timed movements, the authors sought to determine the areas of the brain activated during a silent articulation task in which the subjects were instructed to reproduce the same timing as for the memory-timed movement task without any lip movements or vocalization. The memory-timed finger movement task induced activation of the anterior lobe of the cerebellum (lobules IV and V) bilaterally, the contralateral primary motor area, the supplementary motor area (SMA), the premotor area (PMA), the prefrontal cortex, and the posterior parietal cortex bilaterally, compared with the resting condition. The same areas in the SMA and left prefrontal cortex were activated during the silent articulation task compared with the resting condition. The anterior lobe of the cerebellum on both sides was also activated during the silent articulation task compared with the resting condition, but these activations did not reach statistical significance (P < 0.05 corrected). In addition, the anterior cerebellum on both sides showed significant activation during the memory-timed movement task when compared with the visually cued finger movement task. The visually cued finger movement task specifically activated the ipsilateral PMA and the intraparietal cortex bilaterally. The results indicate that the anterior lobe of the cerebellum of both sides, the SMA, and the left prefrontal cortex were probably involved in the generation of accurate timing, functioning as a clock within the CNS, and that the dorsal visual pathway may be involved in the generation of visually cued movements.

Adult↗

Functional mapping of human brain in olfactory processing: a PET study.

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.

Adolescent↗

Prognosis of bronchial artery embolization in the management of hemoptysis.

BACKGROUND: Bronchial artery embolization (BAE) is a well-accepted and widely used treatment modality for the management of massive and recurrent hemoptysis. However, few reports have previously investigated the long-term results. OBJECTIVES: To investigate the prognosis of patients with hemoptysis who had undergone BAE. METHODS: Twenty-two patients with hemoptysis underwent BAE. The underlying diseases included bronchiectasis in 9, aspergillosis in 3, chronic bronchitis in 2, idiopathic bronchial bleeding in 4, and other diseases in 4. The follow-up period ranged from 25 to 88 months (median 47 months). RESULTS: After the initial BAE, 11 of 22 (50%) patients had re-bleeding (5 patients with hemoptysis and 6 patients with minor hemosputa). Among them, 1 patient suffered from recurrent massive hemoptysis and died from airway obstruction within 1 month after BAE. In addition, 10 of these 11 (90.9%) patients experienced recurrent airway bleeding within 3 years after BAE. Recurrent cases of hemoptysis were seen in 6 of 22 patients (27.3%) within 3 years and no case recurred later than 3 years after BAE. A recurrence of hemoptysis was frequently seen in patients with either bronchiectasis or pulmonary-bronchial artery (P-B) shunt. Although BAE is an effective treatment for the immediate control of hemoptysis, 5 of the patients experienced recurrent bleeding in the long-term follow-up. CONCLUSIONS: It is important to follow-up such patients until 3 years after initial BAE, especially when either ectatic changes of the bronchi on a CT scan or a P-B shunt on angiographic findings are detected.

Adult↗

Herniation of the small bowel through the port site following removal of drains during laparoscopic surgery.

BACKGROUND/AIMS: Generally, the port site is used as the delivery route for drainage after laparoscopic abdominal surgery. We report this case because of the rarity of the complication related to laparoscopic procedures. METHODS: A 75-year-old woman underwent a laparoscopic-assisted sigmoid colectomy for early stage cancer. RESULTS: After the operation, her postoperative course was uneventful. However, just after removing the drains, the small bowel was found to have herniated through the port site used as the insertion route for the drains. An emergency relaparotomy was done and a segment of the necrotic small bowel had to be resected. CONCLUSION: To prevent this complication, we suggest that, first of all, in elderly and thin patients smaller trocar insertion sites (<10 mm) should be utilized as insertion routes for the drains and, secondly, the fascial defect should be closed just after removing the drains whenever the defect measures 10 mm or more in size.

Aged↗

Polycyclic aromatic hydrocarbon carcinogens increase ubiquitination of p21 protein after the stabilization of p53 and the expression of p21.

Polycyclic aromatic hydrocarbon carcinogens (PAHs) and their metabolites have been found to result in a rapid accumulation of p53 gene product in human and mouse cells. However, the induced p53 protein was reported to be transcriptionally inactive. In the present study, the induction of p53 target gene expression after the treatment with either benzo(a)pyrene (B[a]P) or 1-nitropyrene (1-NP) was investigated. A marked induction of messenger RNA (mRNA) expressions of Mdm2, Bax, and p21 was detected in wild-type p53-expressing cells after the treatment with either B[a]P or 1-NP, whereas no significant change in mRNA expression of these genes was observed in p53-negative and mutant cells. 1-NP activated the p21 promoter in a p53-dependent manner. Binding activity of p53 to a p53 consensus sequence increased after the treatment in wild-type p53-expressing cells. Nevertheless, the induced mRNA levels of the p21 did not result in a proportional p21 protein increase, indicating the possibility of post-transcriptional regulation of the protein. With the addition of MG-132, a proteasome inhibitor, to B[a]P or 1-NP treatments, both p21 and p53 protein levels were increased; however, the increase in p21 protein levels was significantly larger than the increase in p53 protein levels. PAHs treatment increased the level of ubiquitinated p21. These results suggest that the p21 product is degraded by the ubiquitin-proteasome system. We conclude that PAHs-induced p53 protein is transcriptionally active.

Benzo(a)pyrene↗

15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.

Animals↗

Intravenous leiomyomatosis extending into the right ventricular cavity: one-stage radical operation using cardiopulmonary bypass--a case report.

The authors describe a 47-year-old woman with intravenous leiomyomatosis (IVL) extending into the right ventricular cavity. This rare entity is a neoplasm originating from smooth muscle of the uterus, with vermiform extensions into the inferior vena cava. The patient underwent a one-stage operation under simultaneous sternotomy and laparotomy, and radical excision of the tumor was successfully achieved with use of normothermic cardiopulmonary bypass. Although this tumor is histologically benign, it sometimes extends into the cardiac cavity and causes sudden death due to incarceration into the atrioventricular orifice. Moreover, recurrence or lung metastasis of IVL has been reported. The authors recommend a one stage-radical resection of the tumor or a two-staged operation within a short interval. In the literature, 24 surgical cases of the intravenous leiomyomatosis with intracardiac extension have been reported. The diagnosis and surgical treatment of this tumor are reviewed and discussed.

Cardiac Surgical Procedures↗

Perioperative temporal profile of cognitive function in elderly patients undergoing hip surgery.

To test the hypothesis that elderly patients who have surgery for femoral neck fractures may have delirium not only after surgery but before surgery, we prospectively investigated the perioperative temporal profile of cognitive function in such patients. We performed the Abbreviated Mental Test (AMT) six times in each patient (on the day of admission, 3 days after admission, on the day before surgery, 2 days after surgery, 7 days after surgery, and on the day of discharge). Patients were given no premedication and were anesthetized with spinal anesthesia using 0.2% hypobaric tetracaine. Of the 68 patients who were admitted because of a diagnosis of fractured neck of the femur and were scheduled to have surgery, 27 patients were subjected to analysis. Four and three patients showed a significant decrease (3 or more points) in AMT score 2 and 7 days after surgery, respectively. We conclude that surgery may have a stronger impact on cognitive function than environmental change shortly after admission in elderly patients with femoral neck fractures.

Aged↗

A comparative study of rural clinics in remote islands and inland areas.

The social and professional isolation of physicians remains an important issue in rural areas. However, few studies have investigated the involvement of geographic factors in the isolation. This study investigates rural public clinics in inland and remote island locations and attempts to objectively compare the isolation of these physicians. A mailed questionnaire was sent to rural clinics where graduate physicians from Jichi Medical School were working in 1994 and 1995. Among the 198 clinics with one or more full-time physicians, 185 (93 percent) responded to the inquiry. Geographic and demographic factors of the communities were compared between 43 clinics located in remote islands and the other 142 rural inland clinics. Rural clinics in remote islands have smaller subject populations, fewer part-time physicians, a longer journey to the nearest city, and a longer distance and travel time to the base hospital than rural inland clinics. Physicians in remote island clinics had less medical training and are more isolated than other physicians. More than half of the clinic physicians in remote islands have no regular training schedule, in contrast to less than a quarter of the inland clinic physicians. Almost all clinics (97.7%) in remote islands do not have a part-time physician, whereas about 20 percent of the rural inland clinics do. Physicians in remote island clinics are more socially and professionally isolated than those in inland clinics. Strategies to reduce these problems should be given priority in rural health policy and measures tailored to rural clinics in remote islands.

Education, Medical, Continuing↗

Cytological characterization of a pituitary folliculo-stellate-like cell line, Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal nitric oxide synthase expression and nitric oxide secretion.

An immortal nonhormone-producing cell line with a characteristic star-shaped morphology, named Tpit/F1, was derived from an anterior pituitary gland of a temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1 cells, we performed cytological studies, which revealed that Tpit/F1 cells express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein, basic fibroblast growth factor, and pituitary-restricted transcription factor. The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids stimulate glutamine synthase production by Tpit/F1 cells. Considering these cytological characteristics together with their morphology, we deduced that Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+ increased dose dependently on ATP administration (0-100 microM), and that this effect did not require the presence of extracellular Ca2+ and was not abolished by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+-adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2-purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA and NO secretion were increased by ATP administration (10 and 100 microM). These results suggest the biological significance of the topological colocalization of FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from endocrine cells and stimulates NO production by FS cells, and the released NO may regulate neighboring endocrine cell and blood vessels.

Adenosine Triphosphate↗

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of follicle-stimulating hormone receptors during cell differentiation in cultured granulosa cells.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) is a common environmental pollutant causing public concern. Using a cell culture system derived from rat granulosa cells that provides unique advantages for studying the molecular mechanisms underlying the action of TCDD, the influences of TCDD on FSH receptor (FSH-R) induction were examined. The treatment with FSH produced, as expected, a substantial increase in specific FSH-R expression, whereas concurrent treatment with the environmental amount of TCDD (10 pM) resulted in a significant decrease in FSH-R after being cultured from 24-72 h. Cotreatment with FSH (30 ng/ml) and increasing doses of TCDD inhibited the levels of FSH-induced FSH-R messenger RNA (mRNA) in a dose-dependent manner. Treatment with 8-Br-cAMP (1 mM) produced a significant increase in FSH-R mRNA; concurrent treatment with TCDD (10 pM) produced a significant attenuation of 8-Br-cAMP action. These findings suggest that the ability of TCDD to interfere with FSH action, as regards the induction of FSH-Rs, is exerted at sites distal to those involved in cAMP generation. Because a single transcript of 5.2 kb was seen for the Ah receptor in this granulosa cell system, the effects of TCDD may be mediated by this specific receptor. The rates of FSH-R mRNA gene transcription, assessed by nuclear run-on transcription assay, were decreased by the addition of TCDD. The effect of TCDD on FSH-R mRNA stability was determined by measuring the decay of FSH-R mRNA under conditions known to inhibit transcription. The decay curve for the 2.4-kb FSH-R mRNA transcript was not significantly changed after the addition of TCDD. These findings showed that the effect of TCDD on FSH-R mRNA was, at least in part, the result of decreased transcription.

8-Bromo Cyclic Adenosine Monophosphate↗

Phylogenetic relationship of six Glycyrrhiza species based on rbcL sequences and chemical constituents.

The nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, G. macedonica and G. pallidiflora have been determined to construct their phylogenetic tree. Based on these sequences, the six Glycyrrhiza species were divided into two groups: three, G. glabra, G. uralensis, and G. inflata, which produce glycyrrhizin as a major saponin, and the others, G. echinata, G. macedonica and G. pallidiflora, which produce macedonoside C as a major saponin. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequences of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that G. uralensis and G. inflata are closely related. Among the three macedonoside C-producing species, only one nucleotide substitution was observed between those of G. echinata and G. macedonica, indicating that these two species are also closely related.

DNA, Plant↗