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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 793 records · Page 44Linked to original sources

Cerebral glioma: evaluation with methionine PET.

The authors examined 50 patients with cerebral glioma with use of positron emission tomography (PET) and L-[methyl]-[11C]methionine to assess the grade of malignancy and the extent of cerebral glioma. Carbon-11 methionine was highly accumulated in the lesion in 31 of 32 patients with high-grade glioma and 11 of 18 patients with low-grade glioma. The rate of uptake of C-11 methionine in high-grade glioma was significantly higher than in low-grade glioma (P < .001). However, in individual cases it was difficult to evaluate the grade of malignancy only from the degree of C-11 methionine accumulation. In most cases, the area of increased accumulation of C-11 methionine did not correspond to the abnormalities seen at computed tomography (CT). Surgical intervention confirmed that methionine PET delineated the extent of cerebral glioma more clearly than did CT. The authors concluded that methionine PET has greater utility in assessing the extent rather than the grade of malignancy of cerebral glioma.

Adolescent↗

Age-related changes in gallbladder contractility and cytoplasmic Ca2+ concentration in the guinea pig.

Gallbladder (GB) motility diminishes with aging. This study was performed to characterize mechanisms that are involved in changes in GB contractility that occur during aging. Cytoplasmic Ca2+ concentrations ([Ca2+]i) and the contractile force of guinea pig GB muscle strips were simultaneously measured using fura-2 and force-displacement transducers. The binding ability of the Ca2+ channel antagonist and GB muscle compliance were also examined. The COOH-terminal octapeptide of cholecystokinin (CCK-8) evoked a dose-dependent increase in force and [Ca2+]i. Changes of [Ca2+]i and contractile force of muscle strips in response to CCK-8 were significantly greater in young (2 mo old) compared with mature and aged (12 and 24 mo old) guinea pigs (changes in [Ca2+]i, ED50: 46.1 nM at 2 mo, 6.1 microM at 12 mo, and 2.8 mM at 24 mo; changes of contractile force, ED50: 24.8 microM at 2 mo, 2.1 mM at 12 mo, and 357 mM at 24 mo). However, the magnitude of the contraction at each percent change in [Ca2+]i was actually similar in young and aged guinea pigs. In a Ca(2+)-free buffer, the responses of [Ca2+]i and force to CCK-8 in both young and aged GB muscles decreased, but those were still dose and age dependent. Binding ability of the Ca2+ channel antagonist did not differ in the young and aged groups, but the compliance of the GB muscle strip decreased with aging. These results suggest that both a reduced mobilization of intracellular Ca2+ and a decreased muscle compliance are responsible, at least in part, for age-related reduced contraction of guinea pig GB in response to CCK.

Aging↗

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Histochemical study of alkaline phosphatase in primary human brain tumors: diagnostic implications for meningiomas and neurinomas.

Histochemical analysis of frozen, thin sections revealed the distribution of alkaline phosphatase (ALPase) in 47 primary intracranial neoplasms in humans. The cytoplasm of meningioma cells exhibited the strongest ALPase reactivity. Pretreatment of these materials by levamisol indicated that the isozymes of ALPase had the characteristic liver-bone-kidney form. In meningiomas and astrocytomas, there was no particular relationship between ALPase activity and malignancy. In neurinomas, there was weak ALPase reactivity in a few neoplastic cells. These findings are suggestive of diagnostic implications for fibroblastic meningiomas and neurinomas at the light microscopic level.

Alkaline Phosphatase↗

Chemistry and anti-tumor activity of sperabillin polymers.

Sperabillin A, 3-[[(3R,5R)-3-amino-6-[(2E,4Z)-2,4-hexadienoylamino]- 5-hydroxyhexanoyl]amino]propanamidine dihydrochloride, was polymerized on standing for several days under a highly humid atmosphere or in the presence of radical initiators. The average molecular weight of the polymers obtained could be regulated by changing the reaction conditions in the latter case. Spectral analyses of the polymers revealed that the 2,4-hexadienoyl moiety of sperabillins was polymerized in a free radical-initiated reaction. The polymers selectively inhibited the proliferation of human umbilical vein endothelial (HUVE) cells. Polymers having higher molecular weight showed stronger inhibition of HUVE cell proliferation. In addition, the polymers showed anti-tumor activity against B16 melanoma in vivo.

Amidines↗

[Inhibitory action of E3810 on H+,K(+)-ATPase and gastric acid secretion in vitro].

The inhibitory action of (+-)-sodium 2-[(4-(3-methoxypropoxy)-3-methylpyridine-2-yl) methylsulfinyl]-1H- benzimidazole (E3810) on H+,K(+)-ATPase and gastric acid secretion in vitro was investigated, and it was compared with those of omeprazole (OPZ). E3810 concentration-dependently inhibited the H+,K(+)-ATPase activity of hog gastric vesicles. Its IC50 was 0.26 microM at pH 6.1. The inhibition was irreversible in nature and reversed by dithiothreitol. The potency of E3810 was 10-times that of omeprazole. Acidification of the intravesicular (luminal) space increased 1000-fold the potency of E3810, indicating that E3810 is a specific inhibitor which binds to the luminal cysteine residue of H+,K(+)-ATPase. Prolonged incubation of up to 180 min in the absence of thiol reagents of rabbit gastric glands which had been inhibited by a low concentration of E3810 (0.3 and 0.5 microM) time-dependently and completely reversed the inhibition, as determined by aminopyrine uptake, whereas it did not recover the acid secretion in omeprazole-treated glands. These results suggest that the acid-activated E3810 is a potent specific inhibitor of H+,K(+)-ATPase, and that the duration of the inhibitory action of E3810 is much shorter than that of omeprazole in isolated gastric glands.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Statistical test of the shortening of latent periods in experimental radiation carcinogenesis under competing risks.

The mean life span of animals killed by a specific type of tumor is influenced by competing risks. The parametric inference method of Noda et al. was applied to a set of mouse experimental data in order to correct for the appearance of observed life span distribution under competing risks and to test statistical significances of difference between corrected mean life spans. Data were from an experiment on tumors induced in mice by X-rays: whole body irradiated with 600 R; head with 800 R; trunk or lower body with 800 R. The statistically significant changes were found: Whole body irradiation shortened the mean latent period of malignant lymphomas whereas the head irradiation shortened the latent periods of none of tumors. Trunk irradiation shortened mean latent periods of lung tumors. Lower body irradiation showed a tendency to shorten the mean latent periods of mammary tumors. Results that differed from the above were obtained when there was no correction for competing risks.

Animals↗

Visualisation of symptomatic nerve roots. Prospective study of contrast-enhanced MRI in patients with lumbar disc herniation.

We studied the use of gadolinium diethylenetriaminepentaacetic acid-enhanced MRI in the detection of pathological changes in the nerve roots of 25 patients with unilateral sciatica due to lumbar disc herniation. Enhancement was observed in the affected nerve roots within the root sleeve at the caudal edge of the herniation and was classified into three categories: grade 0, none; grade 1, enhancement restricted to a focal region within the sleeve; and grade 2, diffuse and homogeneous. The grade of enhancement correlated well with the severity of the sciatica, and was considered to be due to a disruption of the blood-nerve barrier, leading to oedema.

Adolescent↗

Effects of procymidone on reproductive organs and serum gonadotropins in male rats.

To investigate the mechanism and toxicological significance of testicular interstitial cell tumors (ICT) observed in a long-term rat study with procymidone, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximi de, male Sprague-Dawley rats were fed procymidone in diets for up to 6 months with a positive control group receiving a single subcutaneous injection of cadmium chloride. Examinations mainly for gonadal functions such as serum testosterone and luteinizing hormone (LH), reproductive organ weight and histopathology presented evidence of the indirect involvement of gonadotropins in the production of ICT in rats. A significant increase in both serum testosterone and LH was observed in the early stage at high dietary concentrations of procymidone without any lesion in gonadal systems in histopathology, whereas administration of cadmium chloride produced the expected substantial increase in serum LH and a concomitant decrease in serum testosterone with a marked damaging effect on gonadal systems. Increases in serum testosterone and LH levels in animals receiving procymidone were reversible. The no-effect level for procymidone on serum testosterone and LH was 300 ppm over six months of treatment. The possible mechanism of ICT production in rats by non-genotoxic procymidone, structurally similar to flutamide, a synthetic non-steroidal antiandrogen, is likely to be derived from its induction of a hypergonadotropism due to the competitive binding to the androgen receptor, preventing the normal effect of testosterone to control the circulating level of LH.

Animals↗

Hormonal disregulation mechanism in the rat thyroid tumor induced by diniconazole.

To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)- 4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1,000 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of 125I and organification of 125I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased 125I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.

Animals↗

The affinity of procymidone to androgen receptor in rats and mice.

To clarify the mechanism of gonadotropin imbalances and the differential response of rat and mouse testicular interstitial cells (Leydig cells) to procymidone, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximi de, male Sprague-Dawley rats and ICR mice were fed procymidone in diet for 2 weeks at 0, 700, 2,000 and 6,000 ppm for rats, or 0, 1,000, 5,000 and 10,000 ppm for mice. Testosterone and luteinizing hormone (LH) levels in serum, testis or pituitary and the in vitro binding affinities of procymidone, flutamide and related compounds to the androgen receptor in prostate cytosol of rats and mice were examined. Hypergonadotropism in rats and mice was clearly observed in the same order two weeks after the initiation of treatment with procymidone. Increased levels of testosterone and LH in serum at 6,000 ppm and LH in pituitary at and above 700 ppm in rats were observed. In mice, testosterone levels in serum and testis elevated at 10,000 ppm. LH levels in serum and pituitary elevated significantly as well at around 5,000 to 10,000 ppm. In the competitive binding assay, procymidone showed a significant but lower binding affinity comparing to that of cyproterone acetate, the steroidal androgen receptor antagonist, for the androgen receptor in both rats and mice under the condition that unlabeled dihydrotestosterone (DHT) effectively inhibited the binding of [3H]-DHT to the androgen receptor in both species. The relative binding affinity (RBA) of procymidone was of the same order as that of flutamide, a synthetic non-steroidal antiandrogen structurally similar to procymidone. These results indicate that procymidone is an active antiandrogen and the androgen receptor antagonism is the likely mechanism of action.

Animals↗

Alteration by prolonged oral administration of a thyrotropin-releasing hormone analog, TA-0910, of the pituitary-thyroid axis in subjects with brain stroke.

We evaluated whether prolonged oral administration of a novel analog of thyrotropin-releasing hormone (TRH), TA-0910, may change the pituitary-thyroid axis in human subjects with brain stroke. The subjects were given one oral dose of 2.5-20 mg of TA-0910 daily for 8 weeks, and then blood levels of TA-0910, thyroid hormones and thyrotropin (TSH) were measured. Plasma levels of TA-0910 were elevated with increasing doses. After administration of TA-0910, the basal levels of thyroid hormones and TSH had a tendency to increase and decrease, respectively, but those changes remained in the normal range. The secretion of TSH in response to TRH was not significantly affected by TA-0910 administration. No significant changes in other pituitary hormones were observed after TA-0910 administration. The present data indicate that prolonged oral administration of TA-0910 did not significantly alter the pituitary-thyroid axis in subjects with brain stroke.

Administration, Oral↗

[Immunohistological investigation of the histological origin and differentiation of pleomorphic adenoma of the parotid gland].

Immunohistological expressions of the cytokeratin (CK) subclass, vimentin, glial fibral antigen protein (GFAP), alpha-smooth muscle actin, and S-100 protein were investigated in pleomorphic adenoma of the parotid gland. In addition, the correlation between immunohistological findings in the normal parotid gland and those in pleomorphic adenoma was examined. Vimentin, S-100 protein, and GFAP, which were not detected in the normal parotid gland, were observed in pleomorphic adenoma. Only CK-1, which was not detected in the normal parotid gland, was expressed intensely in squamous metaplastic lesions of pleomorphic adenoma. All other CK detected in pleomorphic adenoma were also expressed in the normal parotid gland. Therefore, the expression of vimentin, S-100 protein, GFAP, and CK-1 in pleomorphic adenoma is related to oncogenesis. Since most types of CK expression were observed in solid pleomorphic adenoma lesions and all types of CK expression detected in other lesions were included, cellular differentiation between solid and nonsolid lesions was elucidated. According to the pattern of CK subclass expression, the following sequence of differentiation was suggested; solid lesion-->myxoid lesion-->chondroid lesion, solid lesion-->tubular lesion, solid lesion-->myoepithelioid lesion, and solid lesion-->squamous metaplastic lesion. In normal parotid glands, satellite cells around the ductal cells showed all types of CK subclass expression detected in myoepithelial cells, acinus cells, and ductal cells. Since the types and patterns of CK expression in solid lesions of pleomorphic adenoma are the same as those in satellite cells in the normal parotid gland, pleomorphic adenoma seems to originate from satellite cells. If satellite cells in the normal parotid gland are considered to be so-called reserve cells in the bicellular theory, the origin and cellular differentiation of pleomorphic adenoma can be explained in relation to CK subclass expression.

Actins↗

[Topics on immunogenic regions in TSH receptors for thyroid disease].

Immunogenic regions in human TSH receptors responsible for autoimmune thyroid disease were studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G(IgG) of patients with Graves' disease bound to two of eight peptides, peptide # 1 (32-56) and peptide # 5(309-337). IgG of patients with Hashimoto's thyroiditis bound to a different region of TSH receptors, peptide #8 (333-359). One of three rabbit antisera against peptide #1 showed significant thyroid stimulating activity, although rabbit antisera against peptide #5 lacked the stimulating activity. An antiserum against peptide #1, but none of those one against peptide #5, recognized TSH receptor-like immunoreactivity in human peripheral blood. The molecular weight of the immunoreactivity was approximately 60kDa, on both high performance gel filtration chromatography and Western blot analysis. The amount of peptide #1 immunoreactivity was significantly higher in Graves' plasma than that in plasma of either normal or hypothyroid patients with Hashimoto's thyroiditis. These results indicate that the main immunogenic region for Graves' IgG exists near the N-terminal of human TSH receptors and TSH receptor-like immunoreactivity is present in human peripheral blood, which may contribute to the pathophysiology of Graves' disease.

Amino Acid Sequence↗

Autoradiographic analysis of (14C-methyl)-L-methionine uptake in transplanted rat brain tumors.

To elucidate metabolic pathways of methionine in brain tumors, we studied autoradiographic images of (14C-methyl)-L-methionine (14C-Met) in transplanted rat brain tumors. 14C-Met accumulated in the tumor almost twice as much as in the gray matter 90 min after injection. The acid-insoluble fraction, which was bound to macromolecules, comprised 84% the total count of the accumulated tracers in the tumor. Analysis of 14C-Met tracer accumulation is informative for understanding amino acid metabolism in brain tumors.

Animals↗

Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo?

The significance of L-[methyl-11C]methionine (11C-Met), L-[1-11C]leucine (11C-Leu) and L-2-[18F]fluorotyrosine (18F-Tyr) for measuring protein synthesis rates in the brain and in tumors by PET was re-evaluated. Tissue uptake and protein incorporation of 3H-Met, 14C-Leu and 18F-Tyr were investigated in mice bearing the FM3A mammary carcinoma. In the control group, the uptake of all three tracers in the brain and FM3A and their incorporation into the acid-precipitable fraction (APF) increased over 60 min. When the protein synthesis in vivo was inhibited by cycloheximide, the incorporation of all three tracers into the APF was significantly reduced to 6%-32% and 3%-11% of the control in the brain and FM3A, respectively. Under these conditions, total uptake of 14C-Leu in the brain and FM3A decreased rapidly, and most of the 14C in the APF was detected as proteins. On the other hand, 3H-Met and 18F-Tyr uptake continued to increase, and significant amounts of radioactivity were incorporated into nonprotein materials. In mice given ouabain to inhibit amino acid transport, total uptake of all three amino acids by FM3A was reduced to 67%-74% of the control 5 min postinjection. These results demonstrate that uptake of the three amino acids is affected by alterations in the amino acid transport system in the brain and tumor tissues, but that only 14C-Leu uptake reflects protein synthesis rates.

Amino Acids↗

[Rupture of renal arterial aneurysm in a pregnant patient].

The author experienced a case of ruptured renal arterial aneurysm diagnosed at 32 weeks of gestation. The patient was a 32-year-old healthy woman. On admission she and her fetus were in pre-shock state. Emergency caesarean section was performed under spinal anesthesia. Postoperative CT scanning revealed the ruptured right renal artery aneurysm and hematoma around the right renal hilus. About 7 hours after caesarean section, laparotomy was performed for right nephrectomy and subtotal hysterectomy. Blood loss during operation was about 8000 ml, but postoperative course was good and she and her baby had no complications. It is suggested that arterial wall of pregnant woman has weakness due to morphological and biochemical alterations following hormonal change. Pregnant uterine compresses and dislodges abdominal aorta and inferior vena cava, and these vessel moves in a curve in a leftword and dorsal direction. Plasma volume increases in late pregnancy, therefore intra-arterial pressure is elevated. It is proposed that alterations of vessel wall, increases of circulatory blood volume and vessel displacement are implicated to the etiology of renal arterial aneurysm of pregnant woman. Pregnancy-related renal arterial aneurysm has a high risk of rupture and it is advisable to think of ruptured renal arterial aneurysm as one of the causes of hemorrhagic shock during pregnancy.

Adult↗

[The relationship between P300 latencies, and WISC-R and Wechsler memory scale results in epileptic children].

Auditory event-related potentials (ERPs) were recorded in 35 epileptic children of 9 to 13 years of age, and compared with conventional test batteries of cognitive functions. ERPs were elicited with the auditory oddball paradigm. Corrected P300 latencies showed an inverse correlation with the total score (IQ) of WISC-R and that of the Wechsler memory scale (WMS). A strong inverse correlation was also observed with specific items of these test batteries, as follows; "comprehension", "picture completion" and "coding" in WISC-R, and "associated learning", "digit span", "visual reproduction", "mental control", "orientation" and "information" in WMS. These findings suggested that the prolongation of P300 latencies in epileptic children are related with the impairment of cognitive functions. The P300 latency is correlated with a characteristic kind of cognitive function; "simple recognition", "short term memory" and "easy judgement".

Adolescent↗