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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 577 records · Page 32Linked to original sources
PubMed1994

Antitumor effect of recombinant human tumor necrosis factor on human testicular tumors heterotransplanted in nude mice.

The antitumor effect of recombinant human tumor necrosis factor (rHu-TNF) on 2 human testicular tumors (embryonal carcinoma, TTSC-1, and teratocarcinoma, TTSC-4) heterotransplanted in nude mice was studied. Therapeutic antitumor effect was observed more evidently in TTSC-1 than TTSC-4 when more than 5 x 10(3) U/mouse of rHu-TNF was administered intratumorally. Complete tumor regression was observed in both TTSC-1 and TTSC-4 after intratumoral administration of rHu-TNF. Histological findings correlated well with the decrease in tumor volume of treated tumors. In contrast to these data, little antitumor effect was observed when the same dose of rHu-TNF was administered intravenously to nude mice bearing these tumors. In conclusion, intratumoral administration of rHu-TNF was a more effective and safe method than intravenous administration against human testicular tumors heterotransplanted in nude mice.

Animals↗
PubMed1994

Protective effects of hydroxychalcones on free radical-induced cell damage.

A number of hydroxychalcones were synthesized to evaluate their protective effects against oxidative cell damage and the production of superoxide anion. The hydroxychalcones which have a 3,4-dihydroxycinnamoyl structure were potent inhibitors of lipid peroxidation in rat liver microsomes. In particular, we found that 2',4',3,4-tetrahydroxychalcone (3) exhibited a potent inhibitory effect on H2O2-induced hemolysis due to an antioxidant effect. In addition, this compound strongly inhibited CCl4-induced cytotoxicity in primary cultured hepatocytes and substantially decreased the production of superoxide anion by rat peritoneal exudate macrophages.

Animals↗
PubMed1994

Synthesis and anti lipid-peroxidation activity of hydroquinone monoalkyl ethers.

A series of hydroquinone monoalkyl ethers was synthesized and evaluated for anti lipid-peroxidation activity in rat liver microsomes. 4-Hexyloxy-2,3,6-trimethylphenol (9), having a low redox potential, as well as ascorbic acid exhibited the strongest anti lipid-peroxidation activity (IC50 = 4.2 x 10(-7) M). Structure-activity relationship studies demonstrated that the inhibitory effect of hydroquinone monoalkyl ethers on lipid peroxidation was increased by the acquisition of an optimum hydrophobicity and decreased by an insufficient or excessive hydrophobicity.

Animals↗
PubMed1994

[A case of temporary severe disequilibrium hypercalcemia].

The patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. Laboratory data on admission revealed severe hypercalcemia of 14.9 mg/dl and renal dysfunction with serum creatinine of 2.9 mg/dl. As reflected by increased urinary excretions of pyridinoline and deoxypyridinoline and suppressed serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D, increased bone resorption seemed to be a main factor for the development of hypercalcemia. The development of hypercalcemia seemed to be acute because of (i) her severe symptoms caused by hypercalcemia and (ii) impaired renal function which improved after normalization of serum calcium. Following combination therapy of saline infusion and furosemide, there was a gradual decrease and later normalization of serum calcium together with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level has remained within the normal range. Measurement of serum factors which have hypercalcemia effects such as PTH, parathyroid hormone-related peptide and cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, hypercalcemia in this patient was regarded as a kind of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and has not recurred despite no treatment, her hypercalcemia developed due to imbalance in calcium regulation but not due to any organic disease.

Acute Disease↗
PubMed1994

[Effects of pravastatin administration for 12 months on serum lipid levels in aged patients with hypercholesterolemia].

To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9 mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220 mg/dl (mean +/- SD aged of 70 +/- 7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265 mg/dl to 216 mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40 mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150 mg/dl. In 168 aged patients on 10 mg/day of pravastatin throughout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r = -0.345, p < 0.001) and age of the subjects (r = -0.208, p = 0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

Aged↗
PubMed1994

[Clinical evaluation on ofloxacin administered once daily in the treatment of acute uncomplicated cystitis].

A comparative study of ofloxacin (OFLX), a new oral quinolone, was carried out at the Department of Urology, Osaka University Hospital and its eighteen affiliated hospitals to evaluate the clinical efficacy and safety of daily dose of 300 mg, given either once daily dose (SID group), or in three divided doses (TID group), in the treatment of acute uncomplicated cystitis in women. Clinical efficacy was evaluated in 42 cases from the SID group, and 43 cases from TID group, respectively, according to the criteria by the Japanese UTI Committee. In the SID group, the clinical efficacy was evaluated as excellent in 29 cases, moderate in 12 and poor in 1, with an overall clinical effectiveness rate of 98%. In the TID group, it was evaluated as excellent in 25 cases, moderate in 17 and poor in 1, with an overall clinical effectiveness rate of 98%. Safety was monitored only by subjective complaints. In the SID group, no subjective side effects appeared (0%). In the TID group, one of the 43 women (2.3%) complained of borborygmus. These findings suggest that there was no significant difference between the two groups in the safety and efficacy of ofloxacin.

Acute Disease↗
PubMed1994

Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese.

An association study of the polymorphism of the angiotensinogen gene, consisting of T-->C transition at nucleotide 704 in exon 2, with essential hypertension in the Japanese population was performed by restriction fragment length polymorphism (RFLP). The allele which contained the Tth 111-I restriction site in the presence of C transition was designated 'a' and the allele that lacked restriction site was designated 'A'. The frequency of aa genotype in our normotensive group was higher than the previously reported values in Caucasians. In spite of the high frequency of the aa genotype in Japanese, the aa genotype was significantly more frequent in 108 hypertensives than in 104 normotensive subjects compared with the two other genotypes (P = 0.009). These results suggested that this molecular variant of the angiotensinogen gene may be a preserved inherited predisposition for essential hypertension in various ethnic groups, including Caucasians and Japanese.

Angiotensinogen↗
PubMed1994

Successfully treated optic nerve infiltration with adult T-cell lymphoma.

A 45-year-old woman with adult T-cell leukemia had a sudden onset of decreased vision with central scotoma in the right eye. Right optic disc edema and thickening of the optic nerve were observed by magnetic resonance imaging. A diagnosis of leukemic infiltration to the optic nerve was made. A course of oral corticosteroid therapy was prescribed and 40 Gy of radiation was administered to the whole brain and right orbit. Her visual acuity recovered from finger counting to 20/20 within 3 weeks. We believe that this patient represents the first report of successfully treated optic nerve infiltration with adult T-cell leukemia caused by human T-lymphotropic virus type-I infection.

Female↗
PubMed1994

[Osteoporosis].

Patients with established osteoporosis visit physicians with various complaints including back pain and weakness of their back, although recent mass screening increases number of osteopenic patients without symptoms. Long-term outcomes of patients with inadequate treatment result in fractures of lumbar spines, femoral necks and/or radial bones. Some patients show friction sound caused by ribs and pelvic bone, and others show skin eruption of abdomen. The psychological problems caused by intolerable pain or fear for the future fractures are also clinically important. The symptomatic improvement are influenced not only by the power of the drugs but also by the psychological condition.

Cardiovascular Diseases↗
PubMed1994

[Exercise and physical therapy in osteoporosis].

Initial studies demonstrated that an adequate amount of continuous exercise such as weight-bearing and aerobic training slow down bone loss, maintain bone mineral density, or even increase bone density in the young adulthood though the magnitude of mechanical loading of the bone. However, it remains unclear whether physical activity is also beneficial for bone health in postmenopausal and elderly women with osteoporosis whose exercise endurance capacity is commonly decreased. Recent longitudinal studies showed that 1-2 years of moderate to intensive exercise can increase postmenopausal bone mass, although the amounts of bone gain are relatively modest and site-specific. Thus, weightbearing exercise should be recommended not only to inhibit loss of bone mass but also to increase muscle strength in the elderly, which definitely lead to prevention of falls and decrease the incidence of new fractures.

Adult↗
PubMed1994

[The role of salvage surgery following chemotherapy in advanced testicular cancer].

Twenty-seven patients with advanced testicular cancer underwent cisplatin-based combination chemotherapy and followed by salvage surgery. Complete necrosis and/or fibrosis (necrosis) was found in 12 (44%) operative specimens, mature teratoma in 5 (19%) and residual cancer in 10 (37%) patients. Ten of the 12 (83%) patients with necrosis and all 5 with mature teratoma were rendered disease-free (NED). Only 6 of the 10 (60%) patients with residual cancer were continuously NED. These findings suggest that if carcinoma is found in the resected specimen, further salvage chemotherapy is required. Salvage surgery should be avoided in patients with elevated serum tumor marker levels.

Adolescent↗
PubMed1994

[Scanning electron microscopic observation on altered fenestration of the choriocapillaris in sodium iodate-treated rats].

Fenestration of the choriocapillaris may be lost and regained in various pathologic conditions. The purpose of this study was to observe the gradual disappearance of fenestrae with the scanning electron microscope. Pigmented rats were treated with an intravenous injection of sodium iodate. Changes in the choriocapillaris were produced by damaging retinal pigment epithelium. The eyes were processed for styrene embedded cracking on the third, fifth, and seventh days. Dense clusters of fenestrae were seen at the luminal surface facing retina on the third day. These clusters were surrounded by protrusion of cellular surface. The clusters of fenestrae were smaller with some variation in size on the fifth and seventh days. The protrusion between the clusters became flatter and wider. Some endothelial cells had a flat surface with tiny clusters of fenestrae. Although there was loss of fenestrae with smaller clusters and some variation in size, the tendency of the fenestrae to cluster was sustained in the same way as during the reformation of fenestrae in the choriocapillaris after laser photocoagulation.

Animals↗
PubMed1994

Linkage disequilibrium and haplotype studies of chromosome 8p 11.1-21.1 markers and Werner syndrome.

Werner syndrome (WS) is an autosomal recessive disorder, characterized as a progeroid syndrome, previously mapped to the 8p 11.1-21.1 region. Because WS is so rare, and because many patients are from consanguineous marriages, fine localization of the gene by traditional meiotic mapping methods is unlikely to succeed. Here we present the results of a search for a region that exhibits linkage disequilibrium with the disorder, under the assumption that identification of such a region may provide an alternative method of narrowing down the location of WRN, the gene responsible for WS. We present allele frequencies in Japanese and Caucasian cases and controls for D8S137, D8S131, D8S87, D8S278, D8S259, D8S283, fibroblast growth factor receptor 1, ankyrin 1, D8S339, and two polymorphisms in glutathione reductase (GSR), covering approximately 16.5 cM in total. We show that three of the markers examined--D8S339 and both polymorphisms in the GSR locus--show strong statistically significant evidence of disequilibrium with WRN in the Japanese population but not in the Caucasian population. In addition, we show that a limited number of haplotypes are associated with the disease in both populations and that these haplotypes define clusters of apparently related haplotypes that may identify as many as eight or nine independent WRN mutations in these two populations.

Ankyrins↗
PubMed1994

The organization of the BCL6 gene.

The chromosomal translocation involving 3q27 has been recently described in B-cell malignancies, especially in diffuse large cell lymphomas. We have previously cloned the breakpoint cluster region of 3q27 designated as the BCL6 locus, previously known as BCL5, and subsequently cloned the cDNA for the BCL6 (we previously reported it as BCL5) gene encoding a novel Cys2-His2 zinc-finger protein, which locates adjacent to the breakpoints and is activated through the translocation. To elucidate whether rearrangements occur within the BCL6 gene, we characterized the genomic structure of the gene. The BCL6 gene encompasses about 26 kilobases (kb) and consists of nine exons. Translation start site is located in exon 3 and zinc-finger motif is distributed in the exons 6 to 9. We have identified at least two types of mRNA alternatively spliced, which contain or do not contain exon 2 of 134 bp coding for the 5' untranslated region. A large intron 1 of 9 kb is not efficiently spliced out, which might result in the creation of minor 10-12-kb transcripts observed in the Northern blot analysis in addition to major 3.8-kb transcripts. The breakpoints are clustered around the first exon, and the putative regulatory region of the BCL6 gene is removed through the translocation, leading to the over-expression of the gene.

Amino Acid Sequence↗
PubMed1994

Oncogenic activation of human R-ras by point mutations analogous to those of prototype H-ras oncogenes.

R-ras, K-rev-1/rap and TC21, are more closely related to prototype H-ras than any other known members of the ras superfamily. We recently isolated a mutationally activated TC21 oncogene from a human ovarian carcinoma cell line. Based upon these observations, we sought to re-examine the transforming potential of R-ras, which was reported earlier to lack transforming capacity. Mutations were introduced into the R-ras gene at codons 38 or 87, analogous to positions 12 and 61, respectively, responsible for H-ras oncogene activation. While both mutations resulted in acquisition of R-ras transforming capacity for NIH3T3 cells the position 61 was shown to be more active. Transfectants expressing either R-ras mutant formed colonies in soft agar and were tumorigenic in vivo. As has been reported for H-ras, R-ras cooperated with c-raf-1 in inducing transformation of NIH3T3 cells. These results imply interactions in R-ras and c-raf-1 signaling pathways. We observed R-ras transcripts of 4.6 and 1.2 kb ubiquitously expressed in each of a variety of tissues examined. All these findings raise the possibility that R-ras, like prototype ras genes, may be mutationally activated as an oncogene in some human malignancies.

3T3 Cells↗
PubMed1994

Expression cDNA cloning of a novel oncogene with sequence similarity to regulators of small GTP-binding proteins.

We generated a cDNA expression library from a human mammary epithelial cell line for detection of novel oncogenes by focus formation assay in NIH3T3 cells. A morphologically unique focus was identified and the transforming plasmid was isolated. The transforming gene, designated TIM, encoded a predicted protein species of 60 kDa containing a Dbl-Homology (DH) motif. This motif is also present in other growth regulatory molecules including Bcr, Cdc24, Vav, Ras-grf, and Ect2 which have been implicated as regulators of small GTP-binding proteins. NIH3T3 cells transfected with TIM expression plasmid showed altered growth properties in vitro and were tumorigenic when injected into nude mice. The 6.5 kilobasepair (kb) transcript of the TIM gene was mainly expressed in kidney, liver, pancreas, lung, and placenta. By analysing a panel of human-hamster somatic cell hybrids, we localized the TIM gene to human chromosome 7.

3T3 Cells↗
PubMed1994

[Study on relationship between intratumoral DNA heterogeneity and clinicopathological findings in colorectal cancer].

We studied the relationship between intratumoral DNA heterogeneity and clinicopathological findings in 85 colorectal cancers. DNA ploidy was analyzed in 5 specimens from different sites of each tumor. When the difference in the DNA index (D.I) between several peaks in the same tumor was more than 0.1, the tumor was considered to consist of heterogeneous subpopulations with different DNA clones. DNA heterogeneity was found in 34 cases (40.0%). There was no relationship between DNA heterogeneity and depth of tumor invasion, lymph node metastasis or stage. The incidence of heterogeneity was significantly higher in the tumor with lower differentiation, liver metastasis or vessel invasion.

Colorectal Neoplasms↗