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T Minami

Publications and source records attributed to T Minami.

At least 73 records · Page 4Linked to original sources

Endogenous endothelin in a rat model of acute colonic mucosal injury.

BACKGROUND: Endothelin (ET) is involved in various biologic activities in non-vascular and vascular tissues. While ET has some significant effects on gastrointestinal functions, the possible role of endogenous ET in the host response to mucosal injury has not been well clarified. METHODS: The present study describes an investigation of the effects of an endothelin A receptor antagonist, BQ-123, on lactate dehydrogenase (LDH), mucus and albumin flux into the perfusate in a rat model of acute colonic injury, induced by acetic acid perfusion. The present study also examined localization of ET in damaged rat colons by using immunohistochemistry. RESULTS: A 4% acetic acid treatment induced mild mucosal damage of perfused rat colon and increased LDH as well as albumin and protein-bound hexose release into the perfusate. Pretreatment with BQ-123 significantly reduced LDH activity and protein-bound hexose concentration in the perfusate and delayed the reduction of albumin leakage from damaged mucosa. Vascular endothelial, neural and surface epithelial cells of the colon showed strong ET-like immunoreactivity. Mucosal damage markedly influenced ET expression by epithelial cells. Mild mucosal damage decreased the ET expression by surface epithelial cells while moderate mucosal damage induced a mosaic location of ET-positive epithelial cells in the crypt. Severe mucosal damage abolished the ET expression by epithelial cells. CONCLUSIONS: Endothelin may play a role in the host response to acute mucosal damage. Mucosal ET production is significantly affected by mucosal injury.

Acetates↗

Surgical management of intractable epilepsy associated with cerebral neurocytoma.

Neuronal neoplasms of the CNS constitute a rarely encountered group of tumors. This report concerns the surgical management of seizures encountered in four cases (ranging from 2 to 10 years-of-age at onset; consisting of two males and two females) of a recently recognized morphologically unique tumor, called 'cerebral neurocytoma'. All patients were associated solely with intractable complex partial seizures. The tumor involved the temporal lobe in two cases, and the frontal in two. Magnetoencephalography (MEG) clearly demonstrated an accumulation of equivalent current dipoles originating from the interictal spikes on the cortex around the tumor. On intra-operative electrocorticography (ECoG), the epileptogenic zone was topographically distinct from the region of the tumor. No definite ECoG activities were observed at the tumor site, although this tumor did consist of small mature neuronal cells. Either a complete or a subtotal resection of the tumor and the epileptogenic cortex was performed and, post-operatively, universal freedom from seizures was demonstrated in all patients. A histological examination of the epileptogenic cortex revealed the presence of minute cortical dysplasia or tumor involvement in the hippocampus. A resection of the epileptogenic cortex along with the tumor was thus found to improve the seizure outcome in patients with neurocytoma-associated epilepsy without inducing any identifiable neurological deficits attributable to the incremental resection.

Adult↗

Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper.

We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC), F344 and Long-Evans Agouti (LEA) rats. Male rats (n=21) were given 0.1% BBN in their drinking water from week 6, 8 and 10 for one week, and killed in week 56. The incidences of transitional cell tumors (papillomas plus carcinomas) in BBN-treated LEC and F344 rats were 12% and 76%, respectively (P<0.001, experiment 1), and those in LEC and LEA rats were 11% and 95%, respectively (P<0.001, experiment 2). When male LEC and F344 rats were given 0.1% BBN in their drinking water for 7 days, the intake of BBN and the urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), were higher in the LEC rats (P<0.01). The urinary pHs of untreated LEC and F344 rats were similar between week 6 and 30. The urinary copper concentration was lower in LEC rats before jaundice than in F344 rats, but its concentrations in 28- and 50-week-old LEC rats were 1.7 and 2.3 times those in F344 rats. In a two-stage carcinogenesis study using F344 rats, i.p. injections of cupric nitrilotriacetate increased urinary copper excretion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carcinogenesis study using LEC rats, oral administration of D-penicillamine decreased urinary copper excretion, and increased BBN-induced bladder cancer, although the difference was not significant. These data show that LEC rats are resistant to bladder carcinogenesis and suggest that urinary copper has a significant role in their resistance.

Age Factors↗

Polycyclic aromatic hydrocarbon carcinogens increase ubiquitination of p21 protein after the stabilization of p53 and the expression of p21.

Polycyclic aromatic hydrocarbon carcinogens (PAHs) and their metabolites have been found to result in a rapid accumulation of p53 gene product in human and mouse cells. However, the induced p53 protein was reported to be transcriptionally inactive. In the present study, the induction of p53 target gene expression after the treatment with either benzo(a)pyrene (B[a]P) or 1-nitropyrene (1-NP) was investigated. A marked induction of messenger RNA (mRNA) expressions of Mdm2, Bax, and p21 was detected in wild-type p53-expressing cells after the treatment with either B[a]P or 1-NP, whereas no significant change in mRNA expression of these genes was observed in p53-negative and mutant cells. 1-NP activated the p21 promoter in a p53-dependent manner. Binding activity of p53 to a p53 consensus sequence increased after the treatment in wild-type p53-expressing cells. Nevertheless, the induced mRNA levels of the p21 did not result in a proportional p21 protein increase, indicating the possibility of post-transcriptional regulation of the protein. With the addition of MG-132, a proteasome inhibitor, to B[a]P or 1-NP treatments, both p21 and p53 protein levels were increased; however, the increase in p21 protein levels was significantly larger than the increase in p53 protein levels. PAHs treatment increased the level of ubiquitinated p21. These results suggest that the p21 product is degraded by the ubiquitin-proteasome system. We conclude that PAHs-induced p53 protein is transcriptionally active.

Benzo(a)pyrene↗

[Studies of metals and metallothionein in tissue].

This paper is a review of three topics related to bio-trace metals. First, the transfer of metals into tissues of patients with chronic diseases treated with hemodialysis is examined. Such diseases include chronic hepatitis, diabetes, and chronic renal failure. In these diseases, metal contents from fingernails were flexible but non-specific. Toxicity may appear as the amount of heavy metals in tissues of patients with chronic renal failure treated with hemodialysis. For example, cadmium and lead were not excreted from the blood of patients during the hemodialysis treatment, and, therefore, their amounts gradually increased in the blood of patients. The level of zinc increased and was excreted in the urine of diabetic patients and experimental animals. Calcium accumulated in the kidney of streptozotocin (STZ)-induced diabetic rats that were fed low zinc diets; and, as a result, severe renal failure occurred. From these results, complication syndromes of either metal deficiency or excesses may occur in tissues of patients with chronic diseases. Second, the role of metallothionein (MT), an inducible protein, and the properties of MT isoforms have been studied on experimental animals. In the exocrine cells of the pancreas, MT was induced by various stresses such as zinc, STZ, alloxan and 4-aminopyrazolo-(3,4-d) pyrimidine, but the effects of those stresses were not clear in the endocrine cells. Therefore, MT may have a role in the exocrine cells of the pancreas. In addition, we were able to separate completely MT-1 and MT-2 isoforms in cytosol fractions of tissues using a capillary zone electrophoresis system at neutral pH without any detergents. Each role of the MT isoforms in the tissues soon started to become clear. Third, cisplatin, a platinum-containing anti-tumor drug, did not penetrate into the brain tissue under physiological conditions, as there is a blood-brain barrier to cerebral tissues; however, it did penetrate with either short-term hypoxia or in the case of lipopolysaccharide-treated experimental animals. Nitric oxide, prostaglandin, and free radicals are related to the penetration. Older rats had a higher sensitivity to cisplatin than younger rats.

Animals↗

Age-dependent decreases of phosphorus and magnesium in human Achilles' tendons.

To elucidate changes of human tendons with aging, the authors studied age-related changes of elements in human Achilles' tendons by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. It was found that the content of calcium increased progressively with aging in the Achilles' tendons, whereas the contents of phosphorus and magnesium decreased gradually with aging. The previous investigations demonstrated that the content of calcium and phosphorus increased progressively with aging in most, but not all, human tissues, except for the bones. In ligaments, such as the anterior cruciate ligament and the ligament of the head of the femur, which are histologically similar to the Achilles' tendon, it was previously found that both the contents of calcium and phosphorus increased with aging in the ligaments. It should be noted that the content of phosphorus in the Achilles' tendons decreased during the aging process. In addition, it was found that there was a very high direct correlation between phosphorus and magnesium contents in the tendons, but not between calcium and phosphorus contents.

Achilles Tendon↗

Age-related changes of elements in human ureter.

To elucidate changes of the ureter with aging, the authors investigated age-related changes of element contents in human ureters. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The contents of calcium, sulfur, and iron in the ureters increased progressively with aging, whereas the contents of phosphorus and magnesium did not increase with aging. Significant relationships were found both between calcium and sulfur contents and between calcium and iron contents in the ureters, but not between calcium and either phosphorus or magnesium contents. It was noteworthy that a significant relationship was also found between sulfur and iron contents in the ureters. It remains uncertain whether calcium forms a compound with sulfur or iron in aged human ureters or not.

Aged↗

Toxicity of cisplatin to the central nervous system of male rabbits.

The cytotoxic effects of platinum (Pt) were studied by intraparenchymal injection of 1 mg of cisplatin (CDDP) in male rabbits. Time-serial plasma Pt levels were used as CDDP clearance indices in brain and kidney tissues. The tissue samples were also examined histologically. Changes in the blood-brain barrier (BBB) were evaluated by horseradish peroxidase (HRP) extravasation. In the brain infusion group, Pt was detected in the plasma 30 min after the start of infusion. In the kidney, Pt was detected after 10 min of CDDP injection. The maximum plasma concentration of Pt in the brain group showed diffuse edema, neuronal necrosis, karyolysis, and HRP extravasation around the injection site. In contrast, the histological damage to kidneys was minimal. The results presented here show that direct infusion of CDDP caused the most extensive cytotoxicity in the brain. The low clearance rate of CDDP from the brain and BBB disruption may explain this behavior.

Animals↗

Accumulation of calcium and phosphorus in the mitral valve in comparison with the abdominal aorta and the scaphoid bone.

To clarify why calcification of the mitral valve occurred, the authors chose the abdominal aorta and the scaphoid bone among many arteries and bones, and they studied both relationships in element contents between the mitral valve and the abdominal aorta and between the mitral valve and the scaphoid bone. The subjects consisted of 11 men and 8 women, ranging in age from 52 to 96 yr. The accumulation of calcium and phosphorus occurred progressively with aging in the mitral valve, whereas it became the highest in the sixties in the abdominal aorta and did not increase thereafter. The accumulation of calcium and phosphorus occurred in the abdominal aorta earlier than the thoracic aorta, in which it became remarkable in the seventies. It should be noted that in regard to the accumulation of calcium and phosphorus, no significant correlations were found between the mitral valve and the abdominal aorta. It is suggested that calcification of the abdominal aorta is not essentially accompanied by calcification of the mitral valve. The scaphoid bone was chosen among many bones consisting mainly of spongy bone and the relationship was examined between the calcium content in the mitral valve and the bone mineral density of the scaphoid bone. It was found that there was a low relationship between them. Therefore, it is suggested that a part of the surplus calcium released from bones is deposited in the mitral valve.

Aged↗

Differences in accumulation of elements in human cardiac valves.

To elucidate changes of human cardiac valves with aging, the authors determined age-related changes of element contents in the four human cardiac valves by inductively coupled plasma-atomic emission spectrometry and attempted to examine the relationships in the element contents among the four cardiac valves. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The accumulation of calcium and phosphorus was the highest in the aortic valve, and decreased in the order mitral, pulmonary, and tricuspid valves. The contents of calcium and phosphorus in the aortic valves corresponded to about 12 and 19 times the amounts of those in the tricuspid valves, in which the contents were very low. The contents of calcium and phosphorus in the aortic valves were about 2.5-fold the amounts of those in the mitral valves. An examination was attempted to determine whether or not there were relationships in element contents among the four cardiac valves. As for the aortic and mitral valves, there were no relationships in the contents of calcium and phosphorus between them, but there were relationships in the contents of sulfur and magnesium between them. Three out of 24 cases contained high contents of calcium and phosphorus in both the mitral and aortic valves, whereas 16 out of 24 cases contained high contents of calcium and phosphorus in the aortic valves alone, without the high contents in the mitral valves. Likewise, there were no relationships in the element contents, such as calcium, phosphorus, sulfur, and magnesium, between the mitral and pulmonary valves or between the mitral and tricuspid valves. It is suggested that the accumulation of calcium and phosphorus in the cardiac valve occurs independent of the other cardiac valves.

Aged↗

Age-related variations of elements as compared among optic, radial, and sciatic nerves.

To elucidate changes of peripheral nerves with aging, the authors studied age-related changes of element contents in the optic, radial, and sciatic nerves by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The contents of phosphorus and sulfur remained constant through ages 61 to 97 yr in three nerves, the optic, radial, and sciatic nerves. It was found that there were age-related differences in calcium content among the optic, radial, and sciatic nerves: The calcium content of the optic nerve increased progressively with aging; in the radial nerve, it was hardly changed with aging; in contrast, the calcium content of the sciatic nerve decreased gradually with aging. In addition, it was found that in the radial nerve there were moderate correlations between age and zinc or sodium content, whereas significant correlations between age and the content of silicon or iron were found in the sciatic nerve. Furthermore, there was a correlation between the silicon and iron contents in the sciatic nerves.

Aged↗

Age-dependent changes of elements in human trachea.

To elucidate compositional changes of human trachea by aging, element contents in tracheae were determined by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The sulfur content of the tracheae decreased gradually with aging. In regard to calcium and phosphorus, both the contents increased to about threefold amounts in their seventies compared with those in their sixties, and decreased thereafter. The contents of calcium and phosphorus were the highest in their seventies. Therefore, it is likely that surplus calcium released from bones is deposited temporally in the trachea, and the deposits are released from the trachea at older age. Based on our results of human cartilages, there are two types in regard to calcium accumulation: The first type is that calcium accumulation occurs progressively with aging; the second one is that calcium accumulation becomes the highest in the seventies or eighties, and decreases thereafter. Therefore, the trachea belongs to the second type. Furthermore, the magnesium content remained constant through the age range.

Aged↗

Possible contaminant origins of the red cosmetics decorating ancient burial sites in Japan.

Marker elements were estimated from the red cosmetics collected from different ancient burials and mine ruins in three separate districts of Japan. Element levels were displayed in reference to the relative amount to sulfur (RA/S), by which the cosmetics were divided into five types: I--a low Hg/S with a low Fe/S; II--both moderate Hg/S and Fe/S; III--a moderate Hg/S with a high Fe/S; III 2--a high Hg/S with a moderate Fe/S; IV--a high Hg/S with a high Fe/S. The cosmetics can be further characterized by referring to other contaminants such as Zn, Cu, and Mn. These combined analyses with contaminant metals were capable of characterizing the origins of the cosmetics; it is useful to compare them to each other. The cosmetics were identified as being due to several groups of contaminants from ancient mines in Japan, and also with this system analysis of the markers it is possible to identify them from neighboring countries.

Archaeology↗

Differences in the mineral contents between falx cerebri and tentorium cerebelli.

To elucidate age-related changes of the dura mater, the authors investigated age-related changes of mineral contents in the falx cerebri and the tentorium cerebelli by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The contents of calcium, phosphorus, and magnesium increased progressively with aging in the falx cerebri, whereas the contents of sulfur, iron, and zinc remained constant, being independent of age. In regard to the tentorium cerebelli, the contents of calcium, phosphorus, and magnesium seemed to increase progressively with aging, but the contents of sulfur, iron, and zinc hardly changed with aging. It was noteworthy that there were no significant relationships between the falx cerebri and the tentorium cerebelli in such element contents as calcium, phosphorus, magnesium, sulfur, iron, and zinc.

Aged↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 13). Effects of a single oral dose of cyclophosphamide.

As part of a collaborative effort to evaluate whether effects on male reproductive organs of chemicals can be detected within two-week in toxicity studies, eight-week-old male Sprague-Dawley rats were given a single oral administration of 100 mg/kg of Cyclophosphamide (Cp), and sacrificed at 1, 3, 7 and 14 days thereafter. The numbers of seminiferous epithelial cells were counted in the seminiferous tubules of stages II-III, V, VII and XII of the spermatogenic cycle. Animals showed decreased spermatogonia at Day 3, decreased spermatogonia and preleptotene spermatocytes at Day 7, and decreased spermatogonia and zygotene spermatocytes at Day 14. We also detected decrease of zygotene spermatocytes on careful routine/traditional histopathological examination at Day 14. These results suggest that the testicular toxicity of Cp can be detected within two weeks after treatment with a sufficient dose in rats.

Administration, Oral↗

Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ.

The effect of intrathecal nocistatin on formalin-induced pain in mice was investigated and compared with that of nociceptin/orphanin FQ (Noc/OFQ) to get information on the functional relationship between nocistatin and Noc/OFQ in the spinal cord. Subcutaneous injection of formalin into the hindpaw induced biphasic pain behaviors. Nocistatin, 1 pg, given intrathecally 1 min before 2% formalin injection, significantly attenuated the first phase of the formalin-induced pain. Also, 10 to 1000 pg of nocistatin, given 10 min after formalin injection, significantly inhibited the second phase of the formalin test. Naloxone, 5 mg/kg i.p., failed to antagonize inhibitory effects of nocistatin on either phase of the formalin-induced pain, indicating that analgesic effects of nocistatin were unrelated to the classic opioid system. At 1 to 100 pg, Noc/OFQ exerted no influence on either phase of the 2% formalin-induced pain. However, at 1% formalin, Noc/OFQ significantly aggravated the second phase at 10 pg but not the first phase at 1 to 1000 pg. This aggravating effect of Noc/OFQ was completely reversed by 10 pg of nocistatin. At 0.3 and 1 microg, Noc/OFQ, but not nocistatin, significantly inhibited both phases of the 2% formalin-induced pain. Suppressive effects of 1 microg of Noc/OFQ on the formalin-induced pain were not affected by 1 microg of nocistatin. These results suggest that Noc/OFQ might be involved in the second phase of the mouse formalin test and that, under such pathophysiological conditions, nocistatin could exhibit antagonism against Noc/OFQ at the spinal level.

Animals↗

Lack of involvement of metallothionein expression in pancreatic carcinogenesis by N-nitrosobis (2-oxopropyl) amine in Syrian hamsters.

The possible involvement of metallothionein (MT) in pancreatic ductal carcinogenesis by N-nitrosobis(2-oxopropyl) amine (BOP) in hamsters was investigated. Hamsters received subcutaneous (s.c.) injections with dissolved BOP to 70 mg/kg body weight (BW) followed 7 days later by 20 mg/kg BW BOP and they were sacrificed at 4, 11, 16 and 27 weeks after the beginning of the experiment. MT expression was studied by immunohistochemistry and MT contents were assayed biochemically. Pancreatic ductal hyperplasias were developed from 11 weeks on and carcinomas from 16 weeks on, the incidence of the latter reaching 73% at the end of experiment. However, while normal appearing proliferating duct cells were sometimes positive, MT expression was not evident in hyperplasia (H), atypical hyperplasia (AH) or carcinoma (C), and MT contents did not significantly differ in pancreas of hamsters receiving saline or BOP at any time point. The results suggest that MT is not involved in pancreatic duct carcinogenesis. However, the presence of MT in proliferating ducts not related to carcinogenesis may suggest some unknown role for MT in cellular homeostasis.

Animals↗