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Biomedical subjects

T Minami

Publications and source records attributed to T Minami.

At least 127 records · Page 7Linked to original sources

[Preventive effect of prostaglandin E1 on cisplatin-induced nephrotoxicity].

In order to prevent the nephrotoxicity induced by cisplatin (CDDP), prostaglandin E1 (PGE1) was administered intravenously after anticancer chemotherapy to six patients with lung cancer. All patients underwent two courses of multi-drug chemotherapy with the same regimen including a single administration of 80 mg/m2 CDDP. From the 7th day of the 2nd course of chemotherapy, 120 micrograms PGE1 had been administered for five days. During the two courses of chemotherapy, serum creatinine, blood urea nitrogen, creatinine clearance (Ccr), 24-h excretions of beta 2-microglobulin (beta 2-MG) and N-acetylglucosaminidase (NAG) in urine were measured every week in all patients. The mean value of Ccr was higher in the 2nd course than in the control course (65 ml/min vs. 74 ml/min). The 24-h excretions of beta 2-MG and NAG were also reduced in the 2nd course. Out of six patients, only one was complicated by mild phlebitis at the PGE1 infusion site. From these results it was suggested that PGE1 was effective for prevention of CDDP nephrotoxicity.

Aged↗

[Horner's syndrome in a patient with diffuse malignant pleural mesothelioma].

A 63-year-old man was admitted to our hospital because of left back pain and dysesthesia in his left arm. On physical examination, the patient had ptosis, myosis, and anhydrosis on the left side, suggesting Horner's syndrome. A chest computed tomographic scan disclosed a mass lesion adjoining to the left posterior mediastinum. Although the mass lesion showed a slight decrease in size after the systemic administration of corticosteroids, no further improvement was obtained. Open chest examination revealed extended thickening of the parietal pleura with massive involvement of the upper thoracic sympathetic trunk. The diagnosis was malignant mesothelioma of sarcomatous type. Horner's syndrome is a rare but possible complication in the clinical course of malignant pleural mesothelioma.

Horner Syndrome↗

[Management after hepatectomy of colorectal cancer metastases to the liver--intrahepatic arterial infusion chemotherapy and repeated hepatectomy].

Before Dec. 1993, we resected 17 patients with hepatic metastases from colorectal cancer. Hepatic recurrences developed in 82% patients who had been given mitomycin C or doxorubicin by hepatic-artery. The one-, 3- and 5-year survival rate after surgery was, 88%, 18% and 12%, respectively. Therefore, some new types of adjuvant therapy were needed to improve survival after surgery. This is a retrospective study to determine whether preventive intrahepatic artery infusion chemotherapy (HAI) and repeated hepatectomy are of benefit for patients with hepatic metastases from colorectal cancer who underwent hepatectomy. Thirty-five patients with hepatic metastases from colorectal cancer underwent hepatectomy and were administered 1,500 mg of 5-FU 10 times via the hepatic artery for 5 hrs every 1-2 weeks to prevent hepatic recurrence after Jan. 1994. Nine patients underwent repeated hepatectomy, then HAL following the operation. Non-resectable recurrence were treated by HAI. The amounts of the infused 5-FU dose were 8.5-46.5 g (mean 23 g) and 17-31 times HAI (mean 22 times). Survival rates were 81, 67, 67% and 24%, respectively, after 1, 2, 3 and 4 years. Hepatic disease-free interval rates were 49.3% and 32.5%, respectively, after 1 and 2 years. Preventive HAI could not control hepatic recurrence but prognosis after hepatectomy was improved by these modalities compared with treatment before Dec. 1993. Survival rates of 9 patients who underwent repeated hepatectomy were 89, 89% and 37%, respectively, after 1, 3 and 4 years. The prognosis of patients with hepatic metastases from colorectal cancer was improved by HAI and repeated hepatectomy, but further studies should be undertaken to improve preventive HAI.

Adult↗

Both Ets-1 and GATA-1 are essential for positive regulation of platelet factor 4 gene expression.

In the rat platelet factor 4 (PF4) promoter, Ets motifs and GATA motifs are located at positions -880, -75 and -135, -30, respectively, and their motifs are found in the promoter region of most megakaryocyte protein genes. In order to investigate how the Ets and GATA motifs affect PF4 promoter activity, we constructed Ets and/or GATA motif mutant genes. A single disruption of either -75Ets, -135GATA, or -30GATA significantly reduced PF4 promoter activity, and double disruptions involving these motifs completely abolished it. Furthermore, gel-retardation assays revealed that Ets-1 and GATA-1 proteins from HEL and MEG-01 cells bound to the Ets motifs and GATA motifs, respectively. Co-transfection experiments showed that the overexpression of Ets-1 and/or GATA-1 enhanced the expression of the PF4 promoter reporter gene. These effects of Ets-1 and GATA-1 on PF4 promoter activity are additive. When HEL cells were treated with dimethylsulfoxide in order to induce differentiation into megakaryocytes, the mRNA level of ets-1 increased 10-fold, which might be directly correlated with the significant increase in PF4 mRNA level induced by dimethylsulfoxide. All these results strongly suggest that both Ets-1 and GATA-1 play key roles in the positive regulation of PF4 gene expression.

Base Sequence↗

In- and out-flows of elements in bones embedded in reference soils.

Possible exchanges of elements between bone and the surrounding soil after being embedded underground for 2 years were estimated. Bone pieces were samples from human vertebrae without any treatments after resection. Sixteen elements were determined by atomic emission mass spectrometry. These were divided into three types; Type I, an in-flow in which elements increased, as in Fe, Al and Ba; type II, a balanced decrease in which changes were found in S, Mg and Zn; and type III, an out-flow in which elements, such as Ca and P, entered into bones from embedded soils. These exchanges depended on the varying nature of soils and also on the time underground. The exchanges were progressed in duration of the time after burial. Data obtained are possible references to judge the time-lapse after burial of bones in relating to characters of soils embedded, and to identify proper bone elements from containment elements.

Adult↗

Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region.

A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70beta), which has a highly conserved amino acid sequence compared with that of p70/p85 S6 kinase (p70alpha) within the catalytic, kinase extension, and autoinhibitory pseudosubstrate domains, was identified. However, the amino acid sequence of p70beta differs from that of p70alpha in the noncatalytic amino-terminal region and in the carboxyl-terminal tail, which contains a proline-rich region. The majority of the regulatory phosphorylation sites identified in p70alpha are conserved in p70beta. Two isoforms of p70beta, referred to as beta1 (495 amino acids) and beta2 (482 amino acids), could be expressed from the single gene either by alternative mRNA splicing or by the use of alternative start codons. Here we report the characterization of p70beta2. Similarly to p70alpha, the catalytic activity of p70beta toward ribosomal protein S6 could be rapidly activated by serum, insulin, and phorbol ester in transiently transfected cells. The p70beta kinase was found to be significantly less sensitive to wortmannin and rapamycin than p70alpha. These results indicate that p70beta has the potential to participate in the regulation of protein synthesis and the cell cycle.

Amino Acid Sequence↗

Penetration of cisplatin into mouse brain by lipopolysaccharide.

We investigated the penetration of cisplatin into the mouse cerebral cortex-rich region (CCR) induced by lipopolysaccharide (LPS). With the injection of cisplatin into mice 3 h after the LPS treatment, platinum was detected in the CCR during the 7 days after the injection, while platinum was not detected in the CCR of cisplatin-injected mice without LPS pretreatment and of mice simultaneous treated with cisplatin and LPS. The N(G)-nitro-L-arginine methyl ester dose-dependently lowered the platinum level. A dose of 5 mg/kg of aminoguanidine reduced the increase in the platinum level of the LPS-treated mouse, and platinum was no longer detected at doses of 20 mg/kg in the aminoguanidine-injected group. At doses of 500 mg/kg aminoguanidine, however, no effect was seen on the platinum level of the CCR induced by LPS. Regarding indomethacin, the injection of 5 mg/kg resulted in a decrease in the platinum content of the CCR, but not undetectable level. These results suggest that LPS increases the penetration of cisplatin into the mouse brain, and platinum may be accumulated in the CCR. Nitric oxide and prostaglandins contribute to the penetration of platinum into the cerebral cortex.

Animals↗

Nocistatin, a peptide that blocks nociceptin action in pain transmission.

Prolonged tissue damage or injury often leads to chronic pain states such that noxious stimuli evoke hyperalgesia and innocuous tactile stimuli evoke pain (allodynia). The neuropeptide nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid-like receptor which induces both hyperalgesia and allodynia when administered by injection through the theca of the spinal cord into the subarachnoid space (that is, intrathecally). Here we show that the nociceptin precursor contains another biologically active peptide which we call nocistatin. Nocistatin blocks nociceptin-induced allodynia and hyperalgesia, and attenuates pain evoked by prostaglandin E2. It is the carboxy-terminal hexapeptide of nocistatin (Glu-Gln-Lys-Gln-Leu-Gln), which is conserved in bovine, human and murine species, that possesses allodynia-blocking activity. We have also isolated endogenous nocistatin from bovine brain. Furthermore, intrathecal pretreatment with anti-nocistatin antibody decreases the threshold for nociceptin-induced allodynia. Although nocistatin does not bind to the nociceptin receptor, it binds to the membrane of mouse brain and of spinal cord with high affinity. Our results show that nocistatin is a new biologically active peptide produced from the same precursor as nociceptin and indicate that these two peptides may play opposite roles in pain transmission.

Amino Acid Sequence↗

A possible balance of calcium accumulations among bone, cartilage, artery, and vein in single human individuals.

To elucidate the relationships between the decrease of mineral contents in human bones and the accumulation of minerals in the other human tissues, the relative contents (RCs) of calcium were analyzed by inductively coupled plasma atomic emission spectrometry among human bones, arteries, veins, and cartilages in 27 subjects (17 men and 10 women). These were resected from subjects who died in the age range from 40 to 98 yr old. Calcanei were chosen for analysis of mineral contents in contrast with femoral, popliteal and common carotid arteries, internal jugular veins, and pubic symphysis. It was found that the RCs of calcium in calcanei were agreeable to association with those in both the pubic symphysis and the femoral artery, but they were not agreeable to association with those in the popliteal and common carotid arteries, and the internal jugular veins. This suggests that calcium released from bones is accompanied by accumulations of calcium in the artery and cartilage.

Adult↗

High accumulation of minerals in the human arteries of lower limb.

To elucidate accumulation of minerals in the human arteries, the relative contents (RCs) of minerals in the arteries of the upper and lower limbs were analyzed by inductively coupled plasma atomic emission spectrometry. It was found that the RCs of calcium and phosphorus in the femoral and popliteal arteries of the lower limb increased with aging, whereas those in the axillary and radial arteries of the upper limb did not increase with aging. This result indicates that higher accumulation of calcium and phosphorus occurs in the arteries of the lower limb with aging as compared with that in the arteries of the upper limb, and the prevalence of arteriosclerosis increases in the arteries of the lower limb with aging but not in the arteries of the upper limb.

Adult↗

Effect of the lipid peroxide reaction caused by repeated cold stress on cisplatin-induced nephrotoxicity.

The peroxide reaction in mouse kidney was examined in order to determine the relationship between the lipid peroxide reaction caused by SART (specific alternation of rhythm in temperature) stress and that caused by drug administration. After exerting SART stress for one wk on 6-wk-old male ddY mice (stress group), the peroxide reaction generated by the administration of a single dose of cis-diamminedichloroplatinum (cisplatin: CDDP, 10 mg/kg, i.p.) into SART-stressed mice (stress + CDDP group) was compared with the reaction of CDDP-administered nonstressed mice (CDDP group), saline-administered nonstressed mice (saline group), and saline-administered SART-stressed mice (stress + saline group). Lipid peroxidation in the kidneys was significantly higher in the stress group upon cessation of stress exertion than in the normal group. However, no significant difference in the lipid peroxide level after administration of CDDP was observed between the CDDP groups. The renal glutathione levels were significantly different between the CDDP groups and the saline administered groups. These results indicate that the peroxide reaction is generated in the kidneys by stress, but stress has no effect on the peroxide damage caused by CDDP administration. However, the contribution of stress to renal function impairment requires further evaluation.

Animals↗

Age-related changes of element contents in the human meniscus.

The relative contents (RCs) of elements in the human menisci from 23 subjects in the age range between 65 and 93 yr were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of sulfur, calcium, and phosphorus in menisci increased progressively until the 80s, being the highest in the 80s, and thereafter decreased. The RCs of magnesium in menisci increased progressively until the 90s. Regarding the medial and lateral menisci, higher RCs of magnesium and iron, and a lower RC of phosphorus were found in lateral menisci in comparison with those in medial menisci. There were sexual differences in the RCs of calcium and phosphorus of medial and lateral menisci. The RCs of calcium and phosphorus were about 50% higher in women's menisci than in men's. Histological examinations showed that structureless mucoid masses were observed in the menisci, with very high RCs of calcium and phosphorus being detected.

Aged↗

Age-related changes of mineral contents in the human aorta and internal thoracic artery.

To elucidate accumulations of minerals in the human aorta and internal thoracic artery, their relative contents (RCs) of minerals were analyzed by inductively coupled plasma atomic emission spectrometry. Aortas from 47 men and 24 women subjects were examined. The ages of these subjects ranged from newborn to 99 yr. After the age of 40 yr, RCs of calcium and phosphorus began to increase, and thereafter increased stepwise in the 50s and 70s. In the 70s, their accumulations were markedly increased. Internal thoracic arteries from 16 men and 7 women subjects were examined. These subjects ranged in age from 65-93 yr. It was found that all the RCs of calcium were low, <5.0 mg/g dry wt, and there was no age-dependent increase of calcium contents in internal thoracic arteries.

Adolescent↗

Trace elements found to be variable in two coral reef species, Heliofungia actiniformis and Galaxea fascicularis, collected from the Ryukyu Islands.

Biominerals and metals of intertidal corals of two species (Heliofungia actiniformis, Quoy and Gaimard; Galaxea fascicularis, Linnaeus), collected from the Iriomote Island of Ryukyu, were examined with an inductively coupled plasma atomic emission spectrometer (ICP-AES). Twelve elements were detectable in the coralline skeletons dissected radially along the growth axis. The relative content (RC) of Hg periodically fluctuated and was minimum at the hollow sites of the coralline slab of Heliofungia sp., corresponding to the cyclic growth. There were two types of elements: constant elements and variable elements along the growth axis. RCs of Ca, Mg, Al, Si, and P were nearly constant. RCs of Fe, Mn, Cu, and Ba were variable, but not as regularly changed as Hg. There were positive mass correlations of Hg to Mn, Cu and Zn, but not to Ba and Fe. In contrast, these relationships were not prominent and were likely degraded by aging in the skeleton of Galaxea sp., suggesting a different mode from that of the Heliofungia sp.

Animals↗

Non-carcinogenicity of capsaicinoids in B6C3F1 mice.

The carcinogenicity of a mixture of capsaicinoids (64.5% capsaicin and 32.6% dihydrocapsaicin) was examined in B6C3F1 mice. In a 13-week toxicity study, renal toxicity was observed in 1% capsaicinoid-treated males. Next, groups of 50 mice of each sex were given 0, 0.025, 0.083 or 0.25% capsaicinoids in powdered diet for 79 weeks and killed in week 83. Food intake was reduced in mice of all capsaicinoid-treated groups, especially females, because of the pungency of capsaicinoids, and inhibition of body weight gain was apparent in females. The numbers of tumour-bearing females in the high-dose groups were significantly lower than that in the controls, and the incidences of hepatocellular neoplasms in both sexes were negatively correlated with the dose of capsaicinoids (Cochran-Armitage trend test). Renal cell adenomas developed in one mouse each of 0.025 and 0.25% capsaicinoid-treated males. The incidences of other tumours were similar in the treated and control groups. Thus, the present study indicated that a mixture of capsaicinoids is not carcinogenic in B6C3F1 mice.

Animals↗

Stimulation of nitric oxide release from rat spinal cord by prostaglandin E2.

1. We recently demonstrated that intrathecal administration of prostaglandin E2 (PGE2) and PGF2alpha induced allodynia through a pathway that includes the glutamate receptor and nitric oxide (NO)-generating systems from pharmacological studies. In order to clarify the involvement of NO in prostaglandin-induced allodynia, we measured NO released from rat spinal cord slices by a chemiluminescence method. 2. PGE2 stimulated NO release from both dorsal and ventral regions all along the spinal cord. PGE2 stimulated the release within 10 min and increased it in a time-dependent manner. 3. The PGE2-induced NO release was observed at 100 nM-10 microM. PGF2alpha stimulated the release at concentrations higher than 1 microM, but PGD2 (up to 10 microM) did not enhance it. 4. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and sulprostone (EP1 < EP3) were as potent as PGE2, but PGE1 was less potent, in stimulating NO release. While M&B 28767 (EP3) did not enhance the release, butaprost (EP2) stimulated it at 1 microM. The PGE2-evoked release was blocked by ONO-NT-012, a bifunctional EP1 antagonist/EP3 agonist. 5. The PGE2-evoked release was Ca2+-dependent and blocked by MK-801 (NMDA receptor antagonist) and L-NAME (NO synthase inhibitor). The release was also inhibited by PGD2 and dibutyryl-cyclic AMP. 6. The present study demonstrated that PGE2 stimulates NO release in the rat spinal cord by activation of NMDA receptors through the EP1 receptor, and supports our previous findings that the NO-generating system is involved in the PGE2-induced allodynia.

Animals↗

Anti-nociceptive responses produced by human putative counterpart of nocistatin.

b-nocistatin is a heptadecapeptide produced from bovine prepronociceptin and blocks the induction of hyperalgesia and touch-evoked pain (allodynia) by intrathecal administration of nociceptin or prostaglandin E2 (PGE2). Human prepronociceptin may generate a 30-amino acid peptide different in length from b-nocistatin. Here, we examine whether the human putative counterpart of nocistatin (h-nocistatin) possessed the same biological activities as b-nocistatin. Simultaneous intrathecal injection of h-nocistatin in mice blocked the induction of allodynia by nociceptin and PGE2 in a dose-dependent manner with ID50 values of 329 pg kg(-1) and 16.6 ng kg(-1), respectively. h-nocistatin was about 10 times less potent than b-nocistatin. h-nocistatin also attenuated the nociceptin- and PGE2-induced hyperalgesia. These results demonstrate that h-nocistatin is biologically active and may be involved in the processing of pain at the spinal level in humans.

Amino Acid Sequence↗

Increased vascular permeability by a specific agonist of protease-activated receptor-2 in rat hindpaw.

The present study examined the effect of intraplantar (i.pl.) administration of a selective agonist of protease-activated receptor (PAR)-2, SLIGRL-NH2(PP6-NH2), on vascular permeability in rat hindpaw. PP6-NH2, administered i.pl. at 10-100 nmol per paw, enhanced vascular permeability and caused oedema formation in rat hindpaw. SLIGRL (PP6-OH) and trypsin, by i.pl. administration, also elicited an increase in vascular permeability, although i.pl. administration of the mixture of constituent amino acids of PP6-OH at an equivalent dose did not. The PP6-NH2-induced increase in vascular permeability was abolished by repeated pretreatment with compound 48/80 to deplete bioactive amines in mast cells. These findings suggest that the activation of PAR-2 induces acute inflammation, at least partially, via mast cell degranulation in rat hindpaw.

Administration, Topical↗