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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 37 records · Page 2Linked to original sources

Cardiac accumulation of 125I-labeled monoclonal antibody to atrial natriuretic peptide in a rat model of myocardial infarction.

Atrial natriuretic peptide (ANP) may be an important factor in myocardial infarction and subsequent congestive heart failure. In the failing heart, ANP is expressed in both the atrium and the ventricle. ANP has now been localized with 125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial infarction. Myocardial infarction was produced in 3-month-old Wistar rats by ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated in the infarcted left ventricles of treated rats to a significantly greater extent (p < 0.01) than in the noninfarcted left ventricles of control rats. However, an irrelevant MAb also accumulated to a significantly greater extent in infarcted myocardium than in control myocardium. Thus, the accumulation of the two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to increased permeability of the injured myocardium.

Animals

Effect of combination therapy with OK432 and recombinant human interferon-alpha A/D on atrial natriuretic peptide gene expression in mice with viral myocarditis.

The effects of combination therapy with the immunomodulators OK432 (derived from the Su strain of Streptococcus pyogenes A3; 1 unit corresponds to 0.1 mg of dried streptococci dissolved in 0.1 ml of saline) and human recombinant interferon-alpha A/D (IFN) on cardiac atrial natriuretic peptide (ANP) gene expression and myocardial hypertrophy were examined in a murine model of viral myocarditis with congestive heart failure. Therapy was started 24 h after inoculation with encephalomyocarditis virus and was continued for 14 days. The plasma ANP concentration in untreated infected mice was significantly (P < .01) increased on day 10 (115 +/- 48 pg/ml) and day 30 (43 +/- 22 pg/ml) after inoculation relative to that in uninfected controls (5 +/- 4 pg/ml), whereas plasma ANP levels in treated mice were significantly (P < .01) reduced on day 10 (14 +/- 13 pg/ml) and day 30 (11 +/- 9 pg/ml) in comparison with untreated infected mice. The atrial and ventricular ANP messenger RNA (mRNA) concentrations in untreated mice showed increases of approximately 1.4- and 29.3-fold, respectively, on day 10 and increases of 1.8- and 34-fold, respectively, on day 30 compared with the concentration in uninfected controls. Combined OK432 and IFN significantly (P < .01) reduced the increase in ANP mRNA concentration in ventricles to 6.0- and 6.7-fold on days 10 and 30, respectively. Neither OK432 nor IFN monotherapy reduced the ANP mRNA concentrations in atria and ventricles compared with those in untreated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of losartan, an AT1 selective angiotensin II receptor antagonist, on isoproterenol-induced cardiac ornithine decarboxylase activity.

Ornithine decarboxylase (ODC,EC 4.1.1.7), a rate-limiting enzyme in polyamine biosynthesis, is known to be induced by a beta-adrenoceptor agonist, isoproterenol (ISO). ODC activity and cardiac polyamine content are considered to be correlated with ISO-induced cardiac hypertrophy in rat hearts. To determine whether ISO-induced cardiac ODC activity is mediated through the renin-angiotensin system, especially at the AT1-receptor, we used a nonpeptide AT1 receptor antagonist, losartan, in this study. Losartan (10 mg/kg) suppressed both heart ODC and polyamine contents in ISO-treated rats. Although metoprolol (a selective beta-adrenoceptor antagonist) totally suppressed ODC activity, these results suggest that ISO-stimulated cardiac ODC activity may be regulated through beta 2-adrenoceptors coupled with AT1 receptors in rats.

Angiotensin II

[A case of myokymia with abnormal F responses].

We reported a case of myokymia with abnormal F response. A 60-year-old male with chronic alcoholism was admitted to our hospital with complaint of muscle cramp in both legs just after drinking. Neurological examination revealed muscle pain and weakness of the legs, absence of bilateral Achilles tendon reflexes and prominent myokymia in his right quadriceps femoris and left calf muscles. The electrophysiological examination showed reduced conduction velocity, high amplitude, increased number of phases and long duration of F responses suggesting increased excitability of motoneuron pool. The epidural nerve block brought about a disappearance of the myokymia and an improvement of the abnormal features of F response. The myokymia gradually tended to be milder in the clinical course. The relationship between the myokymia and the abnormal F responses indicated that the increased excitability of spinal motoneurons might play an important role on the generation of myokymia of this patient.

Electromyography

[Usefulness of 123I-MIBG and 123I-BMIPP myocardial scintigraphy for detecting coronary artery disease and for evaluating left ventricular function].

We evaluated the diagnostic value of 123I-metaiodobenzylguanidine (MIBG) and 123I-labeled beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECTs for evaluating coronary artery disease and left ventricular function, in comparison with the diagnostic value of 201Tl (Tl) SPECT. For forty-nine patients with coronary artery disease, resting MIBG and BMIPP SPECTs were performed to detect coronary artery stenosis, compared with the diagnostic value of exercise Tl. Left ventricular ejection fraction and regional wall motion were compared with the total US (TUS) and regional US (RUS) of resting MIBG and BMIPP SPECTs, and in turn, compared with resting Tl SPECT. The sensitivity of resting BMIPP SPECT for detecting coronary artery stenosis was lower, and the specificity of resting MIBG SPECT was lower than the other two methods. The accuracy of resting MIBG SPECT for evaluating coronary lesions was nearly the same as the accuracy of exercise Tl, but higher than that of BMIPP SPECT. Left ventricular ejection fraction was well correlated with TUS of resting MIBG SPECT (r = 0.80), resting BMIPP SPECT (r = 0.77), and resting Tl SPECT (r = 0.68). Regional wall motion was most correlated with RUS of resting BMIPP SPECT, compared with that of resting Tl and MIBG SPECTs. These data suggest that resting MIBG SPECT is useful for detecting coronary artery disease and that resting BMIPP SPECT is valuable in evaluating regional left ventricular function.

3-Iodobenzylguanidine

Chronic effect of losartan in a murine model of dilated cardiomyopathy: comparison with captopril.

The long-term effects of losartan, an angiotensin II subtype-I receptor antagonist, were compared with those of captopril in a murine model of dilated cardiomyopathy caused by encephalomyocarditis virus. Four weeks after viral inoculation, 42 DBA/2 mice were given oral losartan 1.2 mg/kg/day (n = 8), 12 mg/kg/day (n = 8) or 60 mg/kg/day (n = 8) or captopril 7.5 mg/kg/day (n = 8) in drinking water or distilled water (n = 10). Mice were killed at the end of the 12-wk treatment period. Heart weight, left ventricular thickness, left ventricular cavity dimension and myocardial fiber diameter were significantly lower in mice given losartan 60 mg/kg as compared with the infected untreated group. Captopril had a similar effect on all parameters. The pathologic score of cardiac fibrosis was significantly lower in the mice treated with captopril but was not reduced in the mice treated with losartan. Moreover, as compared with the age- and sex-matched normal mice, cardiac mass and myocardial fiber diameter were significantly lower in normal mice treated with losartan 60 mg/kg. This study suggests that long-term treatment with losartan may prevent thickening of left ventricular wall and cavity dimension in dilated cardiomyopathy caused by encephalomyocarditis virus. The potency, and perhaps the efficacy, of losartan appear to be less than those of captopril.

Angiotensin Receptor Antagonists

[Determination of 1H- or 13C NMR spectra of oleandomycin (OL), the esterolitic cleavage compound of OL and OL 2'-phosphate using two-dimensional methods in D2O solution].

All signals of 1H- and 13C NMR spectra of oleandomycin and the esterolitic cleavage compound of oleandomycin, and all signals of 1H-NMR spectra of oleandomycin 2'-phosphate were determined using two-dimensional methods as 1H-1H and 13C-1H COSY NMR, and DEPT NMR in D2O solution. The two modified products of oleandomycin were prepared by two strains of Escherichia coli highly resistant to erythromycin. These results are basically useful in determination of the structure of novel metabolites of oleandomycin inactivated by bacterial action.

Deuterium

Synthesis of polymer-coated mixed-functional packing materials for direct analysis of drug-containing serum and plasma by high-performance liquid chromatography.

Silicone polymer-coated mixed-functional (PCMF) silica packing materials were developed for the direct determination of drugs contained in serum or plasma. The new stationary phases were prepared by the following three-step procedure: (1) coating porous silica with a silicone polymer; (2) partial introduction of hydrophobic groups; and (3) introduction of hydrophilic groups. Two PCMFs were synthesized, one having polyoxyethylene groups as hydrophilic groups (PCMF-POE) and the other having oligoglyceryl groups (PCMF-OG). PCMF-POE showed higher recoveries for injected proteins and a greater overall retention for drug molecules than PCMF-OG. PCMF-POE did not show any column deterioration in 500 serum sample injections (10 ml in total).

Carbamazepine

A cardiac myxoma with interleukin-6 production and cerebral metastasis.

The occurrence of cerebral metastasis from cardiac myxoma is extremely rare. We present a 70-year-old man who had atrial myxoma with two metastatic myxomas in his brain. Histopathologic examination revealed a benign myxoma. An elevated interleukin-6 (IL-6) concentration in the serum, and immunohistochemical staining of the primary myxoma by an anti-IL-6 monoclonal antibody confirmed interleukin production by the myxoma. The IL-6-positive myxoma cells were closely attached to the cerebral endothelial cells. This suggests that IL-6 production by the atrial myxoma may have been an important factor for intravascular metastasis or embolization.

Aged

KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.

KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.

Adenosine

Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice.

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

Acoustic Stimulation

Ubiquitin and ubiquitin-protein conjugates in PC12h cells: changes during neuronal differentiation.

Ubiquitin and ubiquitin-protein conjugates in PC12h cells were detected with in vitro [125I]ubiquitination, and quantified by immunoblotting. These levels were altered by nerve growth factor (NGF), which promotes neuronal differentiation. (i) Levels of high molecular weight (HMW) ubiquitin-protein conjugates ranging from 40 to 1,000 kDa were increased by 2 days of NGF treatment, and remained high up to 10 days of NGF treatment. (ii) Ubiquitin and a 23-kDa conjugate tended to be decreased from days 2 to 10 of NGF treatment. 10-Day culture with 10 nM staurosporine, n protein kinase inhibitor, that blocks NGF-induced neurite outgrowth suppressed the NGF-induced increases in levels of HMW conjugates. Cyclic AMP and forskolin, both of which promote neurite outgrowth, mimicked the NGF-induced changes in ubiquitin and HMW conjugates, but phorbol ester and epidermal growth factor had little effect. These findings suggest that changes in ubiquitin-protein conjugates are closely coupled with neuronal differentiation.

Alkaloids

The diagnostic value and limitation of magnetic resonance imaging on chondral lesions in the knee joint.

Chondral lesions of the knee joint, which have been detected via arthrotomy or arthroscopy, were examined prospectively and retrospectively through a review of previously obtained magnetic resonance images (MRIs). The study group was composed of 34 men and 29 women whose average age was 24.6 years. Of these 63 patients, there were 72 articular cartilage lesions in 65 knees. On retrospective analysis, the sensitivity of MRI, which was defined as a true positive reading for softening, fragmentation, erosion, and/or a full-thickness loss of cartilage, was 14.3%, 57.3%, 75.0%, and 100%, respectively. Although the sensitivity to early changes of chondral lesions was low, indicating the limitation of MRI at the present stage, it has been demonstrated that MRI can delineate intracartilaginous changes associated with softening and thickening of cartilage that cannot be detected even with arthroscopy. Therefore, it may be worthwhile to perform an MRI as well as arthroscopy to clarify the pathogenesis of internal derangement of the knee.

Adult

Glycosphingolipid antigens in cultured bovine brain microvascular endothelial cells: sulfoglucuronosyl paragloboside as a target of monoclonal IgM in demyelinative neuropathy [corrected].

Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GD1a, GD1b, GT1b, as well as sialyl paragloboside and sialyl lactosaminylparagloboside as the minor species. Sulfoglucuronosyl paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentration was lower in older cultures. On the other hand, the amounts of neutral GSLs were extremely low, consisting primarily of glucosylceramide. In addition, we analyzed the effect of anti-SGPG IgM antibody obtained from a patient of demyelinative polyneuropathy with macroglobulinemia against cultured BMECs. Permeability studies utilizing cocultured BMEC monolayers and rat astrocytes revealed that the antibody facilitated the leakage of [carboxy-14C]-inulin and 125I-labeled human IgM through BMEC monolayers. A direct cytotoxicity of this antibody against BMECs was also shown by a leakage study using [51Cr]-incorporated BMECs. This cytotoxicity depended on the concentration of the IgM antibody, and was almost completely blocked by preincubation with the pure antigen, sulfoglucuronosyl paragloboside. Our present study strongly supports the concept that immunological insults against BMECs induce the destruction or malfunction of the blood-nerve barrier, resulting in the penetration of the immunoglobulin molecule to attach peripheral nerve parenchyma.

Animals

Trombiculid fauna and seasonal abundance of Leptotrombidium scutellare (Acari: Trombiculidae) in an endemic area of scrub typhus (Tsutsugamushi disease) in Yamakita Town, Kanagawa Prefecture, Japan.

Using the Tullgren funnel method, we surveyed for trombiculid larvae around dwellings and in mandarin orange groves on the slopes of Sengenyama and Maruyama, Yamakita Town, Kanagawa Prefecture, Japan, during the period between 8 October 1992 and 8 January 1993. In total, 6,690 trombiculid larvae, consisting of 6,669 Leptotrombidium scutellare (Nagayo, Mitamura, Tamiya & Tenjin), 13 L. fuji Kuwata, Berge & Philip, two L. himizu (Sasa, Kumada, Hayashi, Enomoto, Fukuzumi & Obata), two Neotrombicula japonica (Tanaka, Kaiwa, Teramura & Kagaya), one Gahrliepia saduski Womersley, and three Walchia ogatai Sasa & Teramura, were taken from 240 soil samples (40 samples, six times at intervals of 2-4 wk). From the above species composition, L. scutellare is suspected to be the sole vector of scrub typhus in the survey area, where the disease is known to be caused by two serotypic strains of Rickettsia tsutsugamushi Ogata, Kawasaki and Kuroki. L. scutellare larvae rapidly increased in number in late October to form an acuminate peak of abundance in early November, followed by a gradual wane.

Agriculture