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Biomedical subjects

M Nagase

Publications and source records attributed to M Nagase.

At least 73 records · Page 4Linked to original sources
PubMed1997

[A case of anti-basement membrane (BM) mediated disease presenting renal and pulmonary symptoms by divergent timing].

A case of 49-year-old man with anti-GBM antibody and who manifested pulmonary and renal symptoms at divergent times. Thirty-six years previously, renal disease with unneglectable degree of proteinuria was noticed. One month before admission, he was found by chance to have elevated serum creatine (Scr); 3.4 mg/dl. At admission, his Scr was 13.7 mg/dl and Hb 12.7 g/dl, TP 5.2 g/dl with 3+ proteinuria and no glucosuria. He was a heavy smoker and remained so while admitted. Renal biopsy presented fibrocellular crescents in 100% of glomeruli with striking tubulointerstitial involvement. Immunofluorescence showed linear IgG deposition along the glomerular capillary wall. Hemodialysis was instituted, and after 13 hospital days, anti-GBM antibody at admission was high at 128 U, with negative PANCA. Plasmapheresis was also performed, but on the next day pulmonary hemorrhage occurred with a concomitant rise of anti-GBM to 250 U. Thus, steroid pulse therapy was conducted in combination with plasmapheresis. Pulmonary hemorrhage subsided along with lowering of anti-GBM (48 U), but renal failure persisted. The patient died of septicemia. Based on the clinical course of the case, the term "anti-BM mediated disease" may more properly delineate the entity of the disease rather than the classical eponym "Goodpasture's disease" which requires coexistence of pulmo- and renal manifestations for definition.

Anti-Glomerular Basement Membrane Disease↗
PubMed1997

[Do angiotensin converting enzyme and calcium channel blocker intervene in the progression of renal disease besides by lowering systemic hypertension?].

Systemic hypertension is accompanied by various renal diseases. Lowering of blood pressure is widely recognized effective for slowing further decline of renal function. Angiotensin converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) have recently emerged as antihypertensive drugs endowed with renoprotective action directed specifically to the kidney. Improvement of glomerular hypertension which is more remarkably observed in ACEI than in CCB, is thought to be a factor responsible for renoprotection. Although this effect is widely shown in experimental models, consensus has not yet been reached as to whether this effect as well as the therapeutic efficacy are really exerted in various clinical settings other than diabetic nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

In vivo effect of OPC15161, a superoxide scavenger, on anti-Thy1 nephritis.

The in vivo effect of 6-(1 H-indol-3-ylmethyl)-5-methoxy-3-(2-methylpropyl)-2(1 H)-pyrazinone, 4-oxide (OPC15161), a superoxide scavenger, was studied in rats with anti-Thy1 nephritis. Rats were divided into 4 groups: G-1, normal control; G-2, anti-Thy1 nephritis; G-3 anti-Thy1 nephritis and treated with OPC15161 (50 mg/kg/day) starting at day 0; and G-4, anti-Thy1 nephritis and treated with OPC15161 starting 3 days before antibody injection. At weeks 2 and 8, rats were killed for morphological study and at week 8 for renal clearance. Results were compared among the 4 groups. OPC15161 suppressed urinary albumin/day. Total glomerular cells, mesangial cells, ED-1-positive cells/glomerulus and glomerular volume all increased and the increases were suppressed by OPC15161. Tubulointerstitial index, assessed by point counting, was improved by OPC15161 (P < 0.05 G-3, 4, vs. G-2, not significant vs. G-1). Glomerular filtration rate decreased in all nephritic animals, but the decrease in renal blood flow was less in the treated groups. These findings indicate a favorable effect of OPC15161 on the glomerular and interstitial lesions of anti-Thy1 nephritis.

Albuminuria↗
PubMed1996

Differential effects of different forms of hydroxyapatite and hydroxyapatite/tricalcium phosphate particulates on human monocyte/macrophages in vitro.

A possible complication associated with the use of hydroxyapatite (HA) or HA/tricalcium phosphate (HA/TCP) coating on the surfaces of prosthetic devices used for dental and orthopedic implants is their potential to fragment and thus exist as wear debris. In contrast to the so-called osteoconductive properties of HA or HA/TCP coatings, in particulate form these materials may lead to an adverse pattern of cellular and tissue responses at the bone-implant interface. We have established an in vitro cell culture system to characterize the biologic and biochemical effects of various particulate materials. The present study demonstrates that the HA/TCP particles derived from different sintering temperatures exhibit differential effects on cultured human monocyte/macrophages (M/M). The HA/TCP particles dried at 110 degrees C were the most biologically active, stimulating significant release of interleukin 1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and prostaglandin E2 (PGE2), products implicated as important mediators of inflammation in diverse pathologic conditions. Other particles, sintered at either 900 or 1200 degrees C, did not stimulate production of cytokines or PGE2. HA/TCP particles from plasma-spray coatings also failed to release proinflammatory products. These results suggest that the biochemical and crystalline structural properties of particles markedly affects their capacity to modulate M/M function. This in vitro culture system should be useful in characterizing the specific physical and chemical properties of HA or HA/TCP particulates that are responsible for stimulating proinflammatory cell responses.

Biocompatible Materials↗
PubMed1996

Effects of repeated treatment with methamphetamine plus scopolamine and methamphetamine on behavioral sensitization and conditioning.

This study compared repeated treatment with methamphetamine (4.0 mg/kg, i.p.) plus scopolamine (0.5 mg/kg, i.p.) and methamphetamine alone in behavioral sensitization and drug conditioning with respect to a reciprocal balance between the dopaminergic and cholinergic systems. Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of stereotyped behavior than repeated methamphetamine treatment. Methamphetamine plus scopolamine-induced stereotyped behavior was reproduced by challenge injections of not only methamphetamine plus scopolamine and methamphetamine, but also, to a lesser extent, by scopolamine challenges. The methamphetamine plus scopolamine-sensitized rats were conditioned to a low-frequency tone (300 Hz, 100 dB) as conditioned stimulus associated with the drug state. They responded to pairings of the tone and placebo injections, but not to the tone alone or the placebo alone. The methamphetamine-sensitized rats failed to exhibit conditioning. These results suggest that methamphetamine plus scopolamine-induced pronounced behavioral sensitization may produce an enhanced conditioning. Exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for drug conditioning. We concluded that behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems, in favor of a dopaminergic dominance. Conditioning to the drug-associated tone may operate via a reciprocal balance between the dopaminergic and cholinergic systems.

Animals↗
PubMed1996

Local renin-angiotensin system in sympathetic overactivity of spontaneously hypertensive rats.

The present study was designed to clarify whether modulation of norepinephrine (NE) release by vascular angiotensin (Ang) II is involved in the increased peripheral sympathetic activity of spontaneously hypertensive rats (SHR). In the perfusion system of isolated mesenteric vascular beds, periarterial nerve stimulation (PNS)-evoked NE overflow was significantly greater in SHR than Wistar-Kyoto rats (WKY). Administration of Ang II increased PNS-induced NE overflow, which could be reversed by pretreatment with the AT1 receptor antagonist CV-11974 in both types of rats; the facilitation by Ang II was more potent in SHR. Moreover, CV-11974 by itself could attenuate PNS-evoked NE overflow, the extent of which was also significantly greater in SHR, suggesting an augmented sympatho-facilitatory effect of endogenous Ang II in SHR. Consistently, sympatho-facilitation by Ang I, which could be abolished by the angiotensin converting enzyme (ACE) inhibitor imidaprilat, was apparently greater than that of Ang II in SHR, despite no difference in WKY. These findings suggest that the increased peripheral sympathetic activity in SHR is attributed not only to the elevated sensitivity of nerve endings to Ang II but also to the increased local generation of Ang II, an effect possibly mediated by augmented vascular ACE activity.

Angiotensin II↗
PubMed1995

Methamphetamine plus scopolamine potentiates behavioral sensitization and conditioning.

The effects of repeated methamphetamine (4.0 mg/kg) plus scopolamine (0.5 mg/kg) treatment on behavioral sensitization and drug conditioning in rats were compared with the effects of repeated methamphetamine treatment. Behavioral sensitization induced by repeated methamphetamine plus scopolamine treatment was more vigorous than that induced by repeated methamphetamine treatment. Repeated methamphetamine plus scopolamine treatment produced sensitized responses, not only to methamphetamine plus scopolamine and methamphetamine but also, to a lesser extent, to scopolamine. Methamphetamine plus scopolamine-sensitized rats but not methamphetamine-sensitized rats exhibited conditioned responses to a low-frequency tone (300 Hz, 100 dB) associated with the drug state, suggesting that robust methamphetamine plus scopolamine-induced behavioral sensitization may lead to enhanced conditioning. It is plausible that robust behavioral sensitization might operate via a reciprocal balance between the dopaminergic and cholinergic systems in favor of dopaminergic dominance. Conditioning to the drug-associated tone may be mediated via a reciprocal balance between the two transmitter systems.

Acoustic Stimulation↗
PubMed1995

Strychnine poisoning: natural course of a nonfatal case.

A rare case of suicidal strychnine poisoning that resolved naturally without treatment is presented. The patient first complained of chest pain, which was originally thought to be caused by a dissecting aneurysm; however, nystagmus, dysesthesia, spastic paraplesia, and hyperreactivity to stimuli shortly developed. Diagnosis was difficult because the patient did not disclose the drinking of strychnine or the suicidal intent, and no abnormal signs were seen in the various central nervous system examinations. The natural course was observed without treatment because the patient's circulatory and respiratory condition was good. Movement disturbances in the upper extremities disappeared after 2 days, nystagmus in 3 days, and dysesthesia and spastic paraplesia in 4 days. The patient was able to stand on the fourth day and walk on the seventh. He was discharged on day 10 without any detectable ill effects.

Central Nervous System Diseases↗
PubMed1995

Determination of tributyltin and triphenyltin compounds in hair and fish using a hydrolysis technique and gas chromatography with flame photometric detection.

A hydrolysis technique and a GC method are described for the determination of tributyltin and triphenyltin compounds in human hair and fish tissue. A sample was hydrolysed with a potassium hydroxide-ethanol-water solution. Tributyltin and triphenyltin compounds in the hydrolysate were extracted with toluene, and then impurities in the extract were eliminated with anion- and cation-exchange resins. After propylation of the organotin compounds, a yellow impurity was removed with a Sep-Pak florisil cartridge, and the two propylated organotin compounds were separated using a silicone OV-1 GC column and determined by flame photometric detection. The limits of determination of tributyltin and triphenyltin compounds in the sample were 5 and 10 ng g-1, respectively, in their chloride forms. The recoveries of tributyltin chloride from hair samples were 78.8 and 90.8%, respectively, when the spiked amounts were 20 and 200 ng. The recoveries of triphenyltin chloride from hair samples were 71.7 and 72.7%, respectively, when the spiked amounts were 40 and 400 ng. The recoveries of the organotin compounds from fish were similar to the recoveries from hair.

Animals↗
PubMed1995

Intravenous midazolam suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.

The effects of intravenously (i.v.) administered midazolam on noxiously evoked activity of spinal wide dynamic range (WDR) neurons were investigated in decerebrate, spinal-cord-transected cats. Extracellular, single-unit recordings were measured during stimulation by pinching the receptive field on the hind paw and the effect of midazolam at doses of 0.25, 0.5, 1, 2, and 4 mg/kg were measured. Two series of experiments were performed to characterize the analgesic effects of midazolam. In the first, dose-response experiments (n = 59) demonstrated a dose-dependent suppression of the noxiously evoked activity of spinal WDR neurons after midazolam administration. This effect of midazolam was maximal at a dose of 1 mg/kg i.v.. The second series of experiments (n = 14) demonstrated that a benzodiazepine antagonist, flumazenil (n = 8), promptly reversed the effect of midazolam, while an opioid antagonist, naloxone (n = 6), had no effect on the effect of midazolam. The present study demonstrates that i.v. administered midazolam suppresses noxiously evoked activity of spinal WDR neurons that is reversible by a benzodiazepine antagonist. This is consistent with an analgesic action of midazolam.

Animals↗
PubMed1995

Strain variation in susceptibility to the development of monoclonal antibody 5-1-6-induced proteinuria in rats.

Susceptibility to the development of MoAb 5-1-6-induced proteinuria was investigated in four different rat strains, i.e. Brown-Norway (BN), Lewis (LEW), Sprague-Dawley (SD) and Wistar. An intravenous injection of 5 mg of MoAb 5-1-6 to female 7-week-old rats of a given strain induced massive proteinuria in BN, LEW and Wistar rats. However, SD rats developed almost no proteinuria. A similar tendency was observed in the second experiment, in which the injected dose of MoAb was adjusted according to the body weight of each rat (3 mg/100 g body weight). Immunofluorescence (IF) and immunoelectron microscopy (IEM) revealed no differences between the binding patterns of the MoAbs to normal rat kidneys derived from each strain. Quantitative study using 125I-labelled MoAb showed that there was no significant difference in the amount of antibody bound to the kidney 1 h and 5 days after injection between two rat strains, LEW and SD. Localization of 5-1-6 in vivo and its kinetics were investigated. In IF a linear-like pattern along capillary walls was observed 2 h after injection in both LEW and SD strains. This linear-like pattern was shifted to a granular pattern in proteinuric LEW rats 6 days after injection, whereas it remained linear-like in non-proteinuric SD rats. IEM confirmed this difference in the localization of injected MoAb 6 days after injection to LEW and SD rats also at the ultrastructural level. We conclude that there is a clear-cut strain difference in the development of proteinuria induced by MoAb 5-1-6. SD rats were less susceptible to MoAb-induced glomerular injury than BN, LEW and Wistar rats. Although the exact reason for strain variation in susceptibility to MoAb-induced proteinuria remains to be clarified, the movement of bound MoAb, presumably together with corresponding antigenic molecule along the glomerular epithelial cell surface followed by endocytosis into the epithelial cell, seems to be closely related to the induction of proteinuria.

Animals↗