Search PubMed⌕ Search

Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 505 records · Page 28Linked to original sources

Differences in body temperature changes during dressing change in surviving and non-surviving burned patients.

Change in body temperature (delta BT) while dressings were being changed was measured in 52 extensively burned adults. The patients were divided into four groups based on outcome and the prognostic burn index (PBI; age + burn index): group I (15 survivors, PBI less than or equal to 80), group II (15 survivors, PBI between 80 and 120), group III (14 non-survivors, PBI between 80 and 120), and group IV (eight non-survivors, PBI greater than 120). The body temperature before the change of dressings was the same in the four groups. The mean(s.d.) delta BT in all patients was -0.5(0.8) degrees C. The magnitude of delta BT was not related to the time required for changing dressings (r = 0.04) or to the non-epithelialized area present at each change of dressings (r = -0.05). All groups showed a similar increase in delta BT during the early period after the burn, but in group I it began to decrease progressively after the 16th day after the burn (P < 0.05). A reduction in delta BT was noted in group II from day 25, whereas it was unchanged in groups III and IV (P < 0.05). It also significantly increased 2 days before the diagnosis of sepsis (P < 0.05). These results emphasize that delta BT may provide useful information about prognosis and the development of sepsis.

Adult↗

Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity.

Although the action of bone morphogenetic protein (BMP) on osteoblast differentiation has been extensively investigated, its effect on osteoclast differentiation remains unknown. In the present study, in vitro effects of BMP-2 on osteoclast-like cell formation and bone resorption were examined. BMP-2 (1-100 ng/ml) significantly stimulated bone resorption by preexistent osteoclast-like cells in mouse bone cell cultures containing stromal cells, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclast-like cells. When BMP-2 was added to unfractionated bone cells after degeneration of preexistent osteoclast-like cells, BMP-2 dose-dependently stimulated osteoclast-like formation at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Moreover, osteoclast-like cells newly formed by BMP-2 from unfractionated bone cells possessed the ability to form pits on dentine slices. Because these results indicated that BMP-2 directly or indirectly stimulated osteoclast differentiation and activity, we next examined the direct effect of BMP-2 on osteoclast precursors in the absence of stromal cells using hemopoietic blast cells derived from spleen cells. The mRNA for BMP-2/4 receptor was detected in hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as osteoblastic MC3T3-E1 cells and MC3T3-G2/PA6 stromal cells by RNase protection assay. BMP-2 dose-dependently stimulated osteoclast-like cell formation from hemopoietic blast cells supported by GM-CSF at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced 1,25(OH)2D3-induced osteoclast-like formation from hemopoietic blast cells. The present data are the first to indicate that BMP-2 stimulates bone resorption through both direct stimulation of osteoclast formation and activation of mature osteoclasts, possibly via stomal cells, in vitro.

3T3 Cells↗

Adaptive cytoprotection in cultured rat gastric mucus-producing cells. Role of mucus and prostaglandin synthesis.

In cultured gastric mucosal cells, we investigated whether: (1) adaptive cytoprotection was associated with stimulation of endogenous prostaglandin synthesis; (2) prostaglandins given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage; and (3) a relationship existed between cytoprotection and mucus release. Cytolysis was quantified by measuring 51Cr release from prelabeled cells. Mucus release was determined by measurement of [3H]glucosamine release. Concentrations of ethanol > 12% caused cell damage and increased 51Cr release dose dependently. Pretreatment with low concentrations of ethanol (0.5-1.5%) decreased ethanol-induced 51Cr release, but also decreased prostaglandin E2 synthesis. Prostaglandin E2 and 16,16-dimethyl prostaglandin E2 given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage. Treatment with low concentrations of ethanol (1.5%) increased mucus release from cultured gastric mucosal cells. However, prostaglandin E2 and 16,16-dimethyl prostaglandin E2 did not affect mucus release. We conclude that in cultured gastric mucus-producing cells: (1) adaptive cytoprotection occurs without stimulation of endogenous prostaglandin synthesis but with increase in mucus release; and (2) exogenous prostaglandins are cytoprotective against ethanol-induced gastric mucosal cell damage without stimulating mucus release in vitro. We postulate that adaptive cytoprotection in cultured gastric mucus-producing cells is not mediated by prostaglandin, but by mucus released in response to a mild irritant.

16,16-Dimethylprostaglandin E2↗

Relationships between metal ions and oxygen free radicals in ethanol-induced damage to cultured rat gastric mucosal cells.

The current study investigated whether metal ions were cytoprotective against ethanol-induced injury to cultured rat gastric mucosal cells in vitro. Secondly, the relationships between oxygen free radicals and cytoprotection by metal ions were examined. Cultured cells exposed to ethanol produced superoxide anion, as assessed by reduction of cytochrome c, in a time-related fashion, and the production of superoxide anion increased dose-dependently as the concentration of ethanol increased. Cellular damage increased proportionately to the production of superoxide anion. ZnCl2, AlCl3, CoCl2, CuCl2, and CdCl2 significantly diminished ethanol-induced injury dose-dependently. All of the agents studied decreased the reduction of cytochrome c in ethanol-induced damage dose-dependently. These results led to the conclusions that: (1) cultured rat gastric mucosal cells exposed to ethanol generate oxygen free radicals; (2) the production of oxygen free radicals is closely linked with ethanol-induced damage to the cells; and (3) metal ions decrease ethanol-induced gastric mucosal cell damage in vitro. Metal ions protect cultured rat gastric mucosal cells from ethanol-induced damage in which oxygen free radicals participate.

Aluminum Chloride↗

Retinoic acid induces osteoclast-like cell formation by directly acting on hemopoietic blast cells and stimulates osteopontin mRNA expression in isolated osteoclasts.

Although retinoic acid (RA) has been considered to be a bone-resorbing agent both in vivo and in vitro, its mechanism remains still unclear. The present study was performed to examine the effect of RA on osteoclast-like cell formation in the presence or absence of osteoblasts and to study whether RA would affect osteopontin mRNA expression in isolated rabbit osteoclasts. RA (10(-8) and 10(-6) M) significantly stimulated the formation of osteoclast-like cell in osteoblast-containing mouse bone cell cultures. Also, RA caused a stimulation of osteoclast-like cell formation from hemopoietic blast cells supported by granulocyte macrophage-colony stimulating factor (GM-CSF) in mouse spleen cell cultures. However, RA did not affect blast cell number in these cultures and significantly inhibited GM-CSF-stimulated proliferation of hemopoietic blast cells. On the other hand, RA stimulated the bone-resorbing activity of mature osteoclasts in mouse bone cell cultures. Moreover, RA caused a stimulation of osteopontin mRNA expression in isolated rabbit osteoclasts. The present study demonstrated for the first time that RA stimulated osteoclast-like cell formation, presumably through directly acting on the hemopoietic blast cells, and that RA stimulated osteopontin mRNA expression in isolated rabbit osteoclasts.

Animals↗

A subpopulation of large ganglion neurons express IsK protein mRNA: an in situ hybridization analysis in the rat eye.

Rat IsK protein is a 130-amino acid membrane protein and subserves generation of K+ outward current. The expression of this putative K+ ion channel mRNA was explored in the eye with in situ hybridization. The ganglion cell layer of the retina expressed IsK mRNA in a subpopulation of ganglion cells composed of large cell bodies. The hybridization-positive cells were scattered throughout the retina. The hybridization signal was also localized to the epithelial cells throughout the cornea. The results provided evidence for IsK message in neuronal cells. Expression of IsK message in the eye was thus shown to be restricted to particular cell types.

Animals↗

Successful treatment of hyperphosphatemic tumoral calcinosis with long-term acetazolamide.

We describe a patient with tumoral calcinosis, in which acetazolamide (ACZ) was, for the first time, tested for its therapeutic efficacy. The 19-year-old Japanese man had been suffering from multiple recurrent calcific masses with tenderness around the finger, knee, and toe joints since 10 months of age. Radiographs revealed several calcific subcutaneous masses around the finger joints, and calcific myelitis around the right knee joint and in the calvarium. The patient had hyperphosphatemia with elevated maximal threshold of renal phosphate excretion in the presence of normal kidney function and normocalcemia, suggesting a reduced ability to excrete phosphorus in the urine. A delay of disappearance of orally administered phosphate from the blood stream was found. A serum parathyroid hormone (PTH) level was normal, and responses to PTH and ACZ were also normal regarding the induction of phosphaturia. Since the masses tended to recur easily despite repeated surgical resections, we started medical treatment with phosphorus deprivation by oral aluminum hydroxide. However, the drug alone had no effect on hyperphosphatemia or calcific lesions, and ACZ was added in expectation of making the patient's phosphorus balance negative by its phosphaturic effect. Fourteen years of administration of the two drugs apparently improved the patient's symptoms, the biochemical findings, and the calcific lesions on radiographs. Thus, ACZ appeared to be useful for tumoral calcinosis resistant to phosphorus deprivation by aluminum hydroxide alone.

Acetazolamide↗

Low oxygen extraction despite high oxygen delivery causes low oxygen consumption in patients with burns recovering slowly from operative hypothermia.

BACKGROUND: Patients with burns who eventually succumbed to their injuries tended to recover more slowly from operative hypothermia than those who survived. Slower recovery was associated with a lower postoperative oxygen consumption (VO2). We have now investigated whether this was due to impairment of oxygen delivery or extraction. METHODS: This study was performed in 13 adult patients with severely burns. One hundred four measurements of VO2 by indirect calorimetry were made during recovery from 23 episodes of operative hypothermia in 11 patients. Sixty-six measurements of oxygen transport variables by balloon-tipped pulmonary artery catheter were made after 17 episodes of operative hypothermia in six patients. Body temperature was monitored in the urinary bladder. RESULTS: The rate of temperature rise (T) showed a strong positive correlation with VO2 measured both by indirect calorimetry (r = 0.91, p < 0.001) and by balloon-tipped pulmonary artery catheter (r = 0.83, p < 0.001). Oxygen delivery (DO2) was above normal in nearly all patients. Oxygen extraction was low in patients recovering slowly (T < 1.0 degree C/hr) and high in those recovering quickly (T > or = 1.0 degree C/hr). During fast recovery VO2 (373 +/- 77 ml.min-1.m-2; mean +/- SD) was approximately three times normal and was independent of DO2. In contrast, a strong linear relationship existed between VO2 and DO2 during slow recovery (r = 0.76, p < 0.001). CONCLUSIONS: Patients with burns with slow recovery from operative hypothermia exhibited impaired oxygen extraction and dependence of VO2 on DO2 over a wide range. This picture resembles that in patients with critical illness.

Adult↗

Effect of retinoic acid on the proliferation and alkaline phosphatase activity of osteoblastic MC3T3-E1 cells by modulating the release of local regulators from monocytes.

There has been some evidence suggesting an important role of mononuclear cells at bone remodeling sites in the coupling of bone formation to bone resorption. Since cells of the monocyte-macrophage lineage produce important local regulators of bone remodeling, we examined effects of human monocytes-conditioned medium (CM) treated with retinoic acid on [3H] thymidine incorporation (TdR) and alkaline phosphatase (ALP) activity of osteoblastic MC3T3-E1 cells. Treatment of MC3T3-E1 cells with retinoic acid (10(-8) to 10(-6) M) caused an inhibition of TdR in a dose-dependent manner and an inhibition of ALP activity at 10(-6) M. Conditioned medium from monocytes untreated with retinoic acid caused a stimulation of TdR and an inhibition of ALP activity in these cells. In contrast, treatment of monocytes with retinoic acid (10(-8) or 10(-6) M) abolished both stimulation of DNA synthesis and inhibition of ALP activity induced by CM. The present study suggested that retinoic acid modulated osteoblast proliferation and ALP activity not only directly but also indirectly, presumably through modulating the release of local regulators as to bone remodeling from monocytes.

Alkaline Phosphatase↗

Hydrolysis of a carboxy-terminal fragment of parathyroid hormone-related protein by rat kidney: evidence for a crucial role of meprin.

Although parathyroid hormone-related protein (PTHrP) is known to be secreted into the circulation as heterogeneous forms, with its N-terminal and C-terminal fragments as well as the intact form, the fate of these molecules in the plasma has not been fully understood. As for a C-terminal fragment, the kidney seems to be physiologically important in its metabolism, because it is elevated in circulating plasma in patients with chronic renal failure. In this study, we examined the mechanism by which a C-terminal fragment of PTHrP was metabolized by rat kidney and by other rat organs in vitro. When human (h) PTHrP-(109-141) was incubated for 2 h with an extract of rat kidney, it was almost completely hydrolyzed. This hydrolysis was readily blocked by the additions of o-phenanthrolline and dithiothreitol, indicating the participation in this process of a metallo-protease possessing disulfide bonds. This hydrolytic activity showed a meprin-like character, with being sensitive to actinonin but not to phosphoramidon. Furthermore, the participation of meprin itself in this process was directly confirmed by the experiment comparing degradation products of the peptide by the microvillar membranes of rat kidney with those by a purified rat meprin, in which a large part of the metabolites by rat kidney membranes corresponded to those by rat meprin. Among other rat organs examined, the extracts of the small intestine pancreas, spleen and urinary bladder exerted remarkable hydrolytic activities for hPTHrP-(109-141).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Prolongation of intraventricular conduction time associated with fatal [correction of fetal] impairment of defibrillation efficiency during treatment with class I antiarrhythmic agents.

To test whether fatal deterioration of defibrillation efficiency during antiarrhythmic therapy can be prevented by avoiding extreme decrease in ventricular prevented by avoiding extreme decrease in ventricular conduction or toxic plasma drug levels, we determined the defibrillation threshold (DFT) before and during infusion of incremental doses of disopyramide (n = 8), mexiletine (n = 9), or flecainide (n = 9) in anesthetized dogs. Disopyramide did not alter DFT [from 4.4 +/- 1.5 to 4.4 +/- 1.6 J (3.1 +/- 1.2 micrograms/ml)]. Mexiletine tended to increase DFT [from 4.6 +/- 1.2 to 6.1 +/- 2.0 J (1.8 +/- 0.6 micrograms/ml); p < 0.05], and defibrillation eventually was unsuccessful in 3 of the 9 dogs. Although the plasma mexiletine level before refractory fibrillation was far beyond the human therapeutic range, prolongation of intraventricular conduction time (CT) was moderate (16 +/- 3%). Flecainide increased DFT from 4.2 +/- 1.3 to 6.1 +/- 1.5 J at a plasma level of 1.04 +/- 0.37 micrograms/ml (p < 0.0005). In 3 of 5 dogs that developed refractory fibrillation, plasma flecainide level before terminal ventricular fibrillation (VF) was not toxic, but prolongation of CT in the 5 dogs was remarkable (30 +/- 9%). Thus, VF resistant to defibrillation is not necessarily associated with both toxic plasma drug level and remarkably decreased conduction. Reliability of these valuables as indicators of fatally deteriorated defibrillation efficiency may vary among antiarrhythmic agents.

Analysis of Variance↗

Relative contribution of alpha 1-adrenoceptor blocking activity to the hypotensive effect of the novel calcium antagonist monatepil.

Monatepil, a novel calcium antagonist, has alpha 1-adrenoceptor blocking activity; in the present study, we examined the relative contribution of this alpha 1-blocking activity to its hypotensive effect. Monatepil and diltiazem produced dose-dependent hypotensive effects in anesthetized rats with the same potency. Prazosin and monatepil inhibited the L-phenylephrine (L-PE)-induced pressor response, whereas diltiazem scarcely did. The injection of prazosin produced a decrease in blood pressure (BP) in anesthetized rats. The decrease was recovered with angiotensin II (AII) infusion in a dose-dependent manner. We developed a new rat model by first intravenously injecting prazosin and then infusing AII in anesthetized rats. In this model, diltiazem produced the same hypotensive effect as it did in pretreated conditions, although the hypotensive effect of monatepil was attenuated by 20-35% as compared with pretreated conditions. These results suggest that monatepil exerts alpha 1-adrenoceptor blocking action in vivo and 20-35% of the hypotensive effect of monatepil is attributed to its alpha 1-adrenoceptor blocking activity.

Adrenergic alpha-Antagonists↗

Age-related profile of neuroblastoma: a comparison of tumors detected by mass-screening with those detected clinically.

Infants with neuroblastoma are known to have a favorable prognosis compared to those over 1 year of age. However, there is little biological information about the age-related heterogeneity of neuroblastoma. We evaluated the biological profile comparing cases detected by mass screening with those detected clinically. A total of 238 patients with neuroblastoma were classified into four groups according to their age at diagnosis. Patients in group A were 0-5 months of age (n = 31). Patients in group B were detected clinically and were 6-11 months of age (n = 25). Patients in group C were 6-11 months of age and were detected by mass-screening (n = 97). Patients in group D were more than 12 months of age (n = 85). The age-related heterogeneity was evaluated by Kaplan-Meier survival analysis, several clinical markers (neuron specific enolase, ferritin, vanillylmandelic acid and homovanillic acid) at diagnosis, tumor Ha-ras p21 expression and tumor N-myc amplification. Infant neuroblastoma had unique features in comparison to neuroblastoma diagnosed over 12 months of age. Clinical outcome of the patients in groups A and C was quite favorable. Even patients with stage III or IV disease in group A had a favorable prognosis. However, stage IVs disease in group A was not necessarily associated with a good prognosis and the early death after diagnosis was also characteristic. The biological profile of tumors in group C was similar to that in group A but different from the profile in groups B and D. Tumors in group B had a biological profile intermediate between groups A and D.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

When do brain abnormalities in cerebral palsy occur? An MRI study.

The authors used MRI to analyse retrospectively the brain images of patients with cerebral palsy (CP) to evaluate its the role in the assessment of brain abnormalities and injury, and the relationship of pre-, peri- and postnatal events to CP. 70 patients with CP aged two to 16 years who underwent MRI were divided into four groups: group 1 (26 patients) comprised subjects whose CP was considered to have been caused by neuronal migration disorders in the embryonal stage; group 2 (30 patients) contained subjects whose cause was vascular disorders; in group 3 patients (five) the cause was intra-uterine infection; and CP clearly attributable to birth asphyxia (group 4) was noted in only nine patients. The results indicate that CP of term infants is often the result of prenatal factors, and their MRI findings indicated migration and cerebral infarction. Brain MRI is an essential examination in identifying the factors causing brain damage in CP.

Adolescent↗

Permeability of NS-3, a thyrotropin-releasing hormone analogue, into the brain after its systemic administration in rats: a microdialysis study.

The concentration of NS-3 (montirelin hydrate, CG 3703), a thyrotropin-releasing hormone (TRH) analogue, in the cerebral cortex of urethane-anaesthetized rats was measured after its systemic administration (1 mg kg-1, i.v.), using in-vivo microdialysis coupled with a radioimmunoassay. The concentration in microdialysates was highest (24 nM) during the first 20 min after injection, and it fell below the detection limit (3.5 nM) 100 min after treatment. The maximal interstitial concentration was estimated to be 0.51 microM. From these results, it is suggested that NS-3 can readily penetrate into the brain.

Animals↗

Carboxyl-terminal peptides from parathyroid hormone-related protein stimulate osteoclast-like cell formation.

The role of the carboxyl (C)-terminal portion of PTH-related protein (PTHrP) in bone resorption continues to be controversial. The present study was performed to examine the effect of C-terminal PTHrP peptides on osteoclast-like cell formation as well as bone resorption in mice. C-Terminal PTHrP peptides [human (h) PTHrP-(107-139) and hPTHrP-(107-111); 10(-10)-10(-8) M] stimulated osteoclast-like cell formation in a concentration-dependent manner in osteoblast-containing mouse bone cell cultures. Moreover, osteoclast-like cells newly formed by these peptides possessed the ability to form pits on the dentine slices. The conditioned medium from UMR-106 cells and MC3T3-E1 cells pretreated with the C-terminal peptides did not affect osteoclast-like cell formation from mouse hemopoietic blast cells derived from spleen cells. The C-terminal peptides as well as hPTHrP-(1-34) stimulated osteoclast-like cell formation from mouse hemopoietic blast cells in the absence of osteoblasts, although both amino- and C-terminal peptides were unable to support hemopoietic blast cells. Protein kinase-C inhibitors (H-7 and staurosporine) almost completely inhibited the stimulation of osteoclast-like cell formation by the C-terminal peptides in both the presence and absence of osteoblasts. The C-terminal peptides did not affect bone resorption by mature osteoclasts in osteoblast-containing mouse bone cell cultures. The present study indicates that C-terminal PTHrP peptides possess the ability to stimulate osteoclast-like cell formation in both the presence and absence of osteoblasts, possibly through the pathway involving protein kinase-C activation.

Animals↗

Mitral valve repair using an annuloplasty ring made of artificial woven Dacron graft.

A woven Dacron ring made of artificial graft was successfully used in combination with a modified Kay's annuloplasty for mitral valve repair. In this procedure, after excision and repair of the redundant prolapsed leaflets, Kay's annuloplasty was performed at both commissures to reduce the posterior annulus and to coapt the leaflets. A woven Dacron ring was then seated and tied to the annulus to provide long-term stabilization and prevent its further dilatation. The mitral orifice of the patient was reduced from 33 mm to 21 mm in diameter, and neither mitral regurgitation nor stenosis was found in the postoperative evaluation.

Female↗