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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 667 records · Page 37Linked to original sources

Platelet-activating factor (PAF) in male reproductive organs of guinea pigs and rats: effect of androgen on PAF in seminal vesicles.

Studies were conducted on platelet-activating factor (PAF) in male reproductive organs. Total lipids were extracted from the seminal vesicles, and PAF was purified by silicic column chromatography, thin-layer chromatography, and HPLC. PAF activities in the seminal vesicles of guinea pigs and rats as measured by assay of platelet aggregation were 0.26 and 0.25 ng PAF/mumol original phospholipids. These activities were inhibited by the specific PAF antagonists CV6209 and L652,731. In guinea pigs, PAF activity decreased to 50% and 31% of the normal level 2 wk and 4 wk, respectively, after castration. The activity increased to 136% of the normal level on administration of 1 mg of testosterone propionate every day for 1 wk beginning 2 wk after castration, but decreased to 74% of the control level on administration of vehicle. Furthermore, administration of 100 IU of hCG every other day to guinea pigs resulted in increased activity, to 132% (p < 0.05) and 154% (p < 0.01) of the activity in vehicle-treated animals on Days 1 and 3, respectively. Electron microscopic studies showed changes in the rough endoplasmic reticulum of the epithelial cells of the seminal vesicles in castrated guinea pigs. (The rough endoplasmic reticulum is involved in PAF biosynthesis.) PAF activity was also demonstrated in tissues of the testis, epididymis, and vas deferens of guinea pigs and rats, and in the prostate of rats. Thus PAF may play important physiological roles in male reproductive organs.

Animals↗

Antifibrillatory effects of class III antiarrhythmic drugs: comparative study with flecainide.

The antifibrillatory effects of flecainide 1 mg/kg + 0.05 mg/kg/min intravenously (i.v.), bretylium 6 mg/kg i.v., D-sotalol 2 mg/kg + 0.1 mg/kg/min i.v., and E-4031, a new class III drug, 50 micrograms/kg + 5 micrograms/kg/min i.v. were compared with three different methods of determining ventricular fibrillation threshold (VFT) in anesthetized open-chest dogs. In protocol 1, VFT was determined with 2-S, 50-Hz continuous pulses. Flecainide (n = 7) prolonged intraventricular conduction time (CT) and ventricular effective refractory period (ERP) and increased VFT significantly. Bretylium (n = 6) prolonged ERP slightly, but did not increase VFT significantly. Both D-sotalol (n = 6) and E-4031 (n = 6) prolonged ERP and increased VFT. In protocol 2, VFT was determined with the extrastimulus technique in dogs, with localized ventricular necrosis produced with protease. Flecainide (n = 10), D-sotalol (n = 8), and E-4031 (n = 8) restored VFT, which had been decreased by protease injection, to the baseline level, whereas bretylium (n = 8) did not. In protocol 3, the train pulse method with 100-Hz train pulses covering the vulnerable period was used in the same dogs used for protocol 2. Flecainide, bretylium, and D-sotalol increased VFT, but E-4031 did not. The antifibrillatory effects of class III drugs differ depending on the method of VFT determination. The present data suggest that the antifibrillatory effects of antiarrhythmic drugs should be assessed by different methods of VFT determination.

Analysis of Variance↗

Laterality of air volume in the lungs long after blunt chest trauma.

To clarify a cause of the persistent decrease in lung capacity seen several years after blunt chest trauma, 17 patients with blunt chest trauma (10 with unilateral lung contusion, 7 with bilateral lung contusions; 11 of these with unilateral flail chest) inflicted 1 to 6 years previously and 10 normal volunteers (control) were studied. Lung air volumes (AV) were measured by spirometry (AVsp) and by computed tomographic (CT) scan (AVCT = AVCT.Rt+AVCT.Lt) under the same conditions. Hemithoracic spaces were also calculated by CT scan. The average AVsp in patients (76% +/- 8%) was lower than in the controls (98% +/- 5%). AVCT was consistent with AVsp in all the measurements. %AVCT.Rt and %AVCT.Lt, which were adjusted by the ratio of AVCT.Rt to AVCT.Lt in the controls, decreased significantly in unilateral contused lungs (71% +/- 8%). Fifty-eight percent of contused lungs showed small fibrous changes on the CT scans. The ratio of the hemithoracic space on the flail chest side to the opposite side was 0.95 +/- 0.05. These results suggest that the persistent decrease in AV long after blunt chest trauma might be caused by a constriction of contused lung resulting from fibrous changes.

Adolescent↗

Reduction of vasoreactivity and thrombogenicity with laser-thermal angioplasty: comparison with balloon angioplasty.

UNLABELLED: The vasoreactivity and thrombogenicity of laser-thermal angioplasty were examined and compared with those of balloon angioplasty in an atherosclerotic rabbit iliac artery. Eight rabbits underwent laser-thermal angioplasty with a 1.7-mm hot-tip probe activated at 7 W with a probe temperature of 126 +/- 19 degrees C in one iliac artery. The other iliac artery was treated with balloon angioplasty using a 2.0-mm balloon. Angiographic luminal diameter increased from 0.19 +/- 0.15 to 1.54 +/- 0.35 mm by laser and from 0.29 +/- 0.22 to 1.84 +/- 0.20 mm by balloon (P less than 0.0001, respectively). However, it decreased to 1.34 +/- 0.42 for laser and 0.45 +/- 0.39 for balloon 60 minutes later (P less than 0.0001 vs immediately post). Both iliac arteries were visualized using angioscopy, which revealed thrombotic obstruction of 91% stenosis in the ballooned artery and 8% stenosis in the lased artery. Vasoreactivity of treated vessels was also investigated. Segments 3-mm long were obtained from either treated artery or control artery and examined for noradrenaline (10 -7 M) contraction. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Developed tension was 0.13 +/- 0.21 g for laser thermal and 2.33 +/- 0.4 g for its control (P less than 0.0001), and 0.15 +/- 0.16 g for balloon dilatation and 2.12 +/- 0.43 g for its control (P less than 0.0001). Neither acetylcholine at 10 -6 M or papaverine at 10 -4 M induced relaxation of treated segments. Histology showed slight thermal injury at thermally-treated sites without thrombus, and intimal and medial dissection with thrombus formation at balloon dilated site. IN CONCLUSION: (1) neither a laser-thermal recanalized or a balloon dilated obstructed artery is vasoreactive to constrictive or relaxant agents; and (2) laser-thermal angioplasty results in less thrombogenicity than balloon angioplasty under moderate probe temperature.

Angioplasty, Balloon, Coronary↗

Second messenger signaling of PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells.

The second messenger signaling mechanisms of parathyroid hormone (PTH)- and PTH-related peptide (PTHRP)-stimulated osteoclast-like cell formation were investigated in mouse hemopoietic blast cells that possessed PTH binding sites. Human (h) PTH-(1-34) or hPTHRP-(1-34) resulted in a dose-dependent stimulation of tartrate-resistant acid phosphatase-positive multinucleated cells (MNC) formation. Pretreatment with [Nle8,18Tyr34]hPTH-(3-34) significantly blocked hPTH-(1-34)- and hPTHRP-(1-34)-stimulated MNC formation. Dibutyryladenosine 3',5'-cyclic monophosphate (10(-4) M) and forskolin (10(-5) M) as well as the stimulatory diastereoisomer of adenosine 3',5'-cyclic phosphorothioate (Sp-cAMPS), a direct activator of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) (10(-4) M), stimulated MNC formation, and Rp-cAMPS, an inhibitor of PKA activation (10(-4) M), almost completely inhibited MNC formation stimulated by the aforementioned agents but not by 1,25-dihydroxyvitamin D3. Moreover, Rp-cAMPS significantly blocked PTH- and PTHRP-stimulated MNC formation. Treatment with calcium ionophores (10(-8) and 10(-7) M) and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator (10(-8) to 10(-6) M), but not 4 alpha-phorbol 12,13-didecanoate, a phorbol incapable of activating PKC, stimulated MNC formation. Two PKC inhibitors [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride and staurosporine] equally blocked PTH- and PTHRP-stimulated MNC formation. The combined pretreatment with Rp-cAMPS and PKC inhibitors completely blocked PTH- and PTHRP-stimulated MNC formation. Present findings indicate that the activation of PKA and PKC is directly linked to PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells.

Animals↗

Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats.

To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.

Acetylcholine↗

Fate of circulating oxalate in rats.

The pharmacokinetics of oxalate were studied in normal and nephrectomized rats with the use of radioisotope-labelled oxalate. The disappearance of [14C]oxalate from the plasma was analyzed with a two-compartment open model. The pharmacokinetic parameters of oxalate were compared with those for inulin. In normal rats, the plasma half-life of the elimination of oxalate was 0.33 +/- 0.06 h and that for inulin was 0.26 +/- 0.05 h (n = 10, mean +/- SD). The volume of distribution for oxalate was 56.7 +/- 6.80 and that for inulin 34.0 +/- 4.79 ml/100 g body weight, indicating that oxalate has access to additional compartments besides the extracellular volume. The total clearance of oxalate was 1.2 times higher than that for inulin. In nephrectomized rats, however, the plasma half-life of the elimination of oxalate was 1.85 +/- 0.34 h (n = 7, mean +/- SD) and that for inulin was 4.26 +/- 0.78 h. The total clearance of oxalate was 177 +/- 29 and that for inulin was 30 +/- 5 microliters/min/100 g body weight. In order to identify the extrarenal elimination route of oxalate, the bile of nephrectomized rats was collected. The hepatic clearance of oxalate was 31.2 +/- 2.7 microliters/min/100 g body weight. The biliary excretion of oxalate accounts for 17.6% of the total clearance in nephrectomized rats. Thus, other elimination processes of oxalate besides renal and hepatic clearance take place.

Animals↗

Role of endogenous atrial natriuretic peptide in DOCA-salt hypertensive rats. Effects of a novel nonpeptide antagonist for atrial natriuretic peptide receptor.

BACKGROUND: To explore roles of endogenous atrial natriuretic peptide (ANP) in blood pressure and volume regulation, we examined the effects of a newly developed ANP antagonist, HS-142-1 (HS) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS AND RESULTS: We examined 1) the effects of HS on ANP- or brain natriuretic peptide (BNP)-induced reductions in renal vascular resistance (RVR) of rat isolated perfused kidneys, 2) the effects of HS on cyclic GMP (cGMP) production in rat cultured vascular smooth muscle cells pretreated with ANP or BNP, and 3) the renal and systemic effects of HS in DOCA-salt-treated rats and control rats. We found that 1) HS dose-dependently reversed ANP- or BNP-induced decreases in RVR; 2) ANP or BNP at 100 nM caused an eightfold increase in cGMP production. These increases in cGMP were inhibited by HS in a dose-dependent fashion, and 300 micrograms/ml HS decreased cGMP to the control level. HS alone did not influence RVR or cGMP production; and 3) DOCA-salt rats showed higher plasma concentrations of ANP (198 versus 75 pg/ml) and BNP (23.7 versus 2.7 pg/ml, each p < 0.01) than the control rats. Bolus administration of 8 mg/kg HS elevated blood pressure by 8% (p < 0.01). This rise in blood pressure was attributed to an increase in systemic vascular resistance (+14%, p < 0.05). Conversely, urinary excretion of sodium (-41%), glomerular filtration rate (-27%), and plasma (-77%) and urinary cGMP (-69%, each p < 0.01) were decreased by administration of 8 mg/kg HS. These effects were dose dependent in DOCA-salt rats but slight or negligible in the control rats. CONCLUSIONS: These results suggest that endogenous ANP and BNP may be involved in the regulation of blood pressure and body fluid volume in DOCA-salt rats in which ANP and BNP secretion is augmented.

Animals↗

Loss of vasoreactivity by laser thermal energy or argon laser irradiation.

Vasoreactivity of laser-treated vessels was investigated in two different experimental conditions. The canine left circumflex coronary artery (LCx) was lased under perfusion with Krebs-bicarbonate buffer by means of a thermal laser (hot-tip probe, HT) at 7 W for 6 seconds and an argon laser beam through a 300 microns optical fiber at 3 W (tip power) for 1 second at 12 spots. A nontreated segment of the LCx served as a control. Two 3-mm long segments were obtained from the treated segment: one to measure the results of potassium (K) induced contraction, and another 3, 4 diaminopyridine (DAP; K channel inhibitor) induced contraction. In 11 instances, coronary angiography of the perfused artery showed less than 50% stenosis after laser treatment. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Contraction was induced either with 30 mM KCI or 10(-2) M DAP and expressed as developed tension (gram; g). KCI induced vasocontraction of 4.15 +/- 0.93 g in the control, 0.33 +/- 0.71 g in laser irradiated segments (P < 0.0001 vs control), and 0.02 +/- 0.06 g in thermally-treated segments (P < 0.0001 vs control). DAP induced vasocontraction of 5.21 +/- 1.32 g in the control, 0.39 +/- 0.83 g in laser irradiated segments (P < 0.0001 vs control), and 0.07 +/- 0.13 g in thermally treated segments (P < 0.001 vs control). In 4 instances, more than 50% stenosis remained and additional balloon dilatation reduced the stenosis to less than 50%. The lesions also showed reduced vasoreactivity. In vivo thermal angioplasty resulted in reduced vasoreactivity compared to control in 4 anesthetized dogs. Thus, laser and thermal angioplasty reduced vasoreactivity induced by either KCI or 3, 4 DAP. Neither acetylcholine at 10(-6) M nor papaverine at 10(-4) M was able to induce relaxation of treated segments. In conclusion, 1) the lased coronary artery loses its vasoreactivity to either a constrictive or relaxing agent, 2) although stenosis may be produced by laser energy, additional balloon dilatation can reduce residual stenosis, and 3) laser thermal or argon laser angioplasty may prevent severe coronary spasm.

4-Aminopyridine↗

Reduction of thrombogenicity with argon laser angioplasty. Comparison with balloon angioplasty.

Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser-thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally-treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA.

Angioplasty, Balloon↗

Silent lupus nephritis with fingerprint deposits.

A 26-year old woman with diffuse active lupus nephritis showed no proteinuria. Electron microscopy revealed a typical fingerprint pattern in glomerular subendothelial electron dense deposits. Out of 21 renal biopsy cases of lupus nephritis, we found fingerprint deposits in 4 cases (19%) including the present case. All of the cases showed diffuse proliferative glomerulonephritis with overt proteinuria, except the present case. To our knowledge, the present case is the first reported case of active lupus nephritis, where fingerprint deposits were found, with normal urinalysis.

Adult↗

Role of 830 nm low reactive level laser on the growth of an implanted glioma in mice.

The effect of low reactive level laser therapy (LLLT:830 nm, 60 mW, continuous wave) was studied using the model of a glioma implanted in mice. Two different models were used. In the first model, therapies were applied post the first day of glioma implantation; in the second model, post the fourteenth day of glioma implantation. Using the first model, therapies were designed as follows. 1) control group (no therapy), 2) direct LLLT (15 seconds twice per day; on the skin covering the implanted glioma), 3) indirect LLLT (15 seconds twice per day; on abdominal skin area rather than the site of the implanted glioma), 4) indirect LLLT (30 seconds twice per day), 5) anti-cancer drug (ACNU) group, 6) mouse beta-interferon (Mu-beta-IFN) group, 7) direct LLLT plus Mu-beta-IFN group, 8) ACNU plus Mu-beta-IFN group, 9) indirect LLLT (15 seconds twice per day) plus ACNU plus Mu-beta-IFN group. Using the second model, therapies were designed as follows. 1) control group (no therapy), 2) indirect LLLT (15 seconds twice per day), 3) indirect LLLT (15 seconds twice per day) plus Mu-beta-IFN group, 4) Mu-beta-IFN plus ACNU group. Our results indicated that, applied on the first day after glioma implantation, both direct and indirect LLLT were effective in inhibiting the tumor growth. In addition, it appeared that the effect of LLLT might be dose-dependent. Finally, the group of direct LLLT plus Mu-beta-IFN was most effective in limiting the tumor growth and the incidence of growth as compared with the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunogenetic and clinical characterization of slowly progressive IDDM.

OBJECTIVE: To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS: We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (< 3 mo, acute clinical-onset group, n = 134), group B (3-12 mo, intermediate group, n = 31), and group C (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS: The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C than in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects. CONCLUSIONS: These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved beta-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe beta-cell destruction in group A patients.

Adolescent↗

Identification of rat brainstem sites with neuronal Fos protein induced by acoustic stimulation with pure tones.

Induction of Fos, a proto-oncogene c-fos protein product, was immunohistochemically examined in the rat brainstem by using pure tone stimuli (0.25 kHz, 4kHz and 8 kHz) at 60 and 80 dB sound pressure levels for 30 min. In comparison with non-stimulated control rats, the brainstem of sound-stimulated rats exhibited distinct Fos-labeled neuronal cell nuclei in i) the ascending auditory nuclei, ii) the brainstem sites which receive afferents from the auditory nuclei, i.e. the pretectum and rostroventrolateral reticular nucleus, iii) the parvocellular part of the ventral lateral geniculate nucleus, lateral reticular nucleus, ventral border region of the spinal trigeminal nucleus, and the medial vestibular and spinal vestibular nuclei, all of which lack established auditory projections, and iv) the brainstem sites where some Fos-labeled neurons were present in controls. Sound stimulation at 80 dB led to widespread Fos-labeling in all these sites. Sound stimulation at 60 dB caused a decrease in number of positive cells in the brainstem sites and yielded a tone-dependent subregional distribution pattern in the dorsal cochlear nucleus and central nucleus of the inferior colliculus.

Animals↗

Transient and repetitive rises in blood pressure synchronized with plasma catecholamine increases after head injury. Report of two cases.

The authors report two patients with repetitive episodes of acute transient rise in blood pressure synchronized with increases in plasma catecholamine after severe head injury. In both cases, the paroxysmal hypertension occurred suddenly on the 2nd day posttrauma, and its frequency declined gradually, disappearing with time. The pathophysiological basis of this peculiar clinical manifestation is discussed.

Brain Injuries↗