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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 343 records · Page 19Linked to original sources

Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease.

The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebrovascular disease (CVD) is another atherosclerotic disease; and the effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38), diagnosed by brain computed tomography. Control subjects for the infarction group and the hemorrhage group were randomly selected from 583 subjects matched for age, gender, and history of hypertension with patients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (chi2 = 6.1, P < .05). The AGN/TT genotype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects with ACE/DD genotype (chi2 = 8.0, P < .01, odds ratio; 11.7, 95% confidence intervals: 1.4 to 96.0). There was no significant association between apoE/epsilon4 and CVD. These results suggest that ACE/DD predicts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD.

Adult↗

Hypofluorescent spots in indocyanine green angiography of peau d'orange and fundus.

PURPOSE: Hypofluorescent spots were seen in indocyanine green (ICG) angiography of peau d'orange fundus in eyes with angioid streaks. Origin of the hypofluorescent spots were examined with attention to their correlation with a peau d'orange appearance of the central fundus using a computer-assisted image comparison system. METHODS: ICG angiography was performed in 5 patients having peau d'orange appearance of fundus using a scanning laser ophthalmoscope (SLO) and a digital video-fundus camera. The same central fundus areas corresponding to hypofluorescent spots in an ICG angiogram were then digitally identified in a fluorescein angiogram and in a red-free picture in all 10 eyes of the 5 patients. Monochromatic light observation was also performed with a dark field observation using an SLO to see subretinal or intrachoroidal pigment clumping. RESULTS: In no patient, the areas identified with hypofluorescent spots did show relevant changes in fluorescein angiogram or red-free picture. SLO examination revealed no perfusion defect at the same areas. The dark field observation showed no pigment clumping at the peripapillary and papillomacular bundle regions where hypofluorescent spots were seen. CONCLUSIONS: Hypofluorescent spots seen in ICG angiograms did not show exact consistency with peau d'orange changes in their location and shape. Perfusion defects or blocking by pigments were not a cause of hypofluorescent spots. The scattered hypofluorescent spots were considered to be relevant with irregular affinity of the fundus to ICG dye.

Adult↗

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product.

The activity of DnaA protein, the initiator of chromosome replication in Escherichia coli, is regulated by adenine nucleotide binding; the ATP-bound form, not the ADP-bound form, is active. DnaAcos is a mutant protein that is insensitive to negative regulation by ADP. Initiation of chromosome replication occurs excessively in the dnaAcos mutant at 30 degrees C, a restrictive temperature for growth. To determine the control factors that act independently of adenine nucleotide binding of DnaA, we analysed suppressors from the dnaAcos mutant isolated by Tn5 insertion mutagenesis. Three of the suppressors carried Tn5 in the aroK or aroB gene, the first two cistrons in the dam operon. Complementation tests revealed that the dam gene is responsible for the suppression. Over-replication of the chromosome was inhibited in the dnaAcos aroK::Tn5 double mutant, and initiation of chromosome replication in the dnaA+ aroK::Tn5 mutant was partially inhibited. The aroK(or B)::Tn5 cells contained DnaA molecules at a level similar to that in the parental aroBK+ strain. Moreover, dnaAcos suppression depended on the function of the seqA gene. Thus, Dam activity positively regulates initiation of chromosome replication in vivo. SeqA function seems to be distinguished from the control of DnaA protein by adenine nucleotide binding.

Adenosine Diphosphate↗

Expression of Fas and Fas ligand in renal grafts with acute and chronic rejection in the rat model.

The Fas system-based rejection mechanism has not been studied well in terms of cytotoxic T cell activity in graft rejection. We investigated the Fas and Fas ligand level in renal grafts with acute and chronic rejection in a rat model using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Fas ligand in renal allografts was detected as early as 1 day after transplantation in an acute rejection model. It was highly expressed at day 4 and began to decline at day 6 after transplantation. In contrast, Fas ligand in normal kidneys was almost undetectable. Fas ligand in isografts was increased, but the expression level was much lower than in allografts. Interestingly, when Fas ligand expression began to decline in renal allografts, it increased in the spleens of recipients. Fas ligand expression in chronically rejecting allografts was slightly increased, but it was stronger than in isografts. In contrast to Fas ligand gene expression, Fas was constitutively expressed in isografts, allografts, and normal kidneys. However, the Fas level in renal allografts was higher than in normal kidneys. Our data demonstrated that the Fas system might play an important role in acute and chronic rejection by causing apoptosis, and the spleen may eliminate the lymphocytes strongly expressing Fas ligand after completion of the acute rejection.

Acute Disease↗

Coexpression of multiple Sertoli cell and Leydig cell marker genes in the spontaneous testicular tumor of F344 rat: evidence for phenotypical bifurcation of the interstitial cell tumor.

The development of testicular tumor has been frequently observed in some laboratory rat strains. In the present study, we have further characterized the testicular tumor that spontaneously develops in the F344 rat (F344/Jcl). Tumor cells first appeared in the interstitium and developed into multifocal nodular lesions. In the later stage, the whole testes were occupied by tumor cells that consisted of three different types of cells in morphological appearance: large clear type, small eosinophilic type and intermediate type. To determine the character of these cells, we examined the expression of marker genes for Sertoli cells (e.g., transferrin) and Leydig cells (e.g., 3 beta-hydroxysteroid dehydrogenase 1 (3 beta-HSD 1)). Transferrin and 3 beta-HSD 1 mRNAs were found in all 8 tumor samples analyzed by northern blotting. By in situ hybridization, we observed a substantial amount of 3 beta-HSD 1 mRNA and little or no transferrin mRNA in the large clear cells. In contrast, the small eosinophilic cells showed little or no 3 beta-HSD 1 mRNA and a large amount of transferrin mRNA, suggesting that the tumor was a mixture of at least two types of cells. Other Sertoli cell marker genes, such as cyclic protein 2 and sulfated glycoprotein 2, were expressed in all 8 tumors analyzed, and testin and steel factor (SLF), the c-kit receptor ligand, were also expressed in some of the tumors (testin, 75%; SLF, 25%), while other Leydig cell markers, LH receptor and c-kit, were expressed in 87% and 80% of the tumors, respectively. These results indicate that the spontaneous testicular tumor of F344 rat is of interstitium origin, showing phenotypical bifurcation possibly via transdifferentiation.

3-Hydroxysteroid Dehydrogenases↗

Cessation of spermatogenesis in juvenile spermatogonial depletion (jsd/jsd) mice.

BACKGROUND: Mice homozygous for the jsd (juvenile spermatogonial depletion) allele are sterile because they become azoospermic. The onset of such azoospermia was investigated by histologic analysis of sections of testes from jsd/jsd mice. METHOD: The testes removed from C57BL/6-jsd/jsd mice aged 3 to 10 weeks were examined microscopically. RESULTS: At 3 weeks of age, spermatocytes were seen in most of the seminiferous tubules of jsd/jsd mice. However, the number of tubules that contained spermatids was significantly smaller than that counted in the wild-type mice. Since degenerative figures were not abundant in the jsd/jsd testes, the decreased number of spermatids found in the tubules suggested a longer duration of development from spermatocyte to spermatid in jsd/jsd mice. The abnormality extended to the development of type B spermatogonia, and a decrease in their number became apparent after 6 weeks of age in most of the jsd/jsd tubules. However, as early as 3 weeks of age, a few seminiferous tubules in jsd/jsd mice already contained only Sertoli cells and type A spermatogonia. CONCLUSION: It is assumed that the decrease in type B spermatogonia occurred at various ages and locations. The defect of spermatogenesis in jsd/jsd mice was attributable to aberrations in multiple steps of spermatogenesis.

Aging↗

Transurethral visual laser ablation of the prostate for benign prostatic hyperplasia using a KTP/YAG laser.

BACKGROUND: Transurethral visual laser ablation of the prostate (VLAP) has been established as an alternative method for the treatment of benign prostatic hyperplasia (BPH). However, most VLAP procedures utilize only a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Since a potassium-titenyl-phosphate (KTP) laser offers limited tissue penetration, KTP can be safely utilized to excise part of the obstructing prostatic tissue. This study assessed the interaction between KTP vaporization and YAG coagulative ablation to determine the safety and efficacy of VLAP utilizing a combined KTP/YAG treatment. METHODS: Forty patients with bladder outlet obstruction secondary to BPH were treated with VLAP using a KTP/YAG laser. The laser light was delivered by an angle delivery device. RESULTS: Most cases demonstrated a significant improvement in routine subjective and objective parameters (AUA symptom score, peak flow rate, average flow rate, and amount of residual urine). No significant complications relating to this procedure were reported, however, 4 patients experienced postoperative acute urinary retention. CONCLUSION: KTP/YAG laser ablation of the prostate is safe and effective for the treatment of BPH.

Aged↗

Secondary acute monocytic leukemia occurring during the treatment of a testicular germ cell tumor. A case report and review of the literature.

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors is a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of acute monocytic leukemia occurring in a 44-year-old man who received etoposide-based chemotherapy and radiotherapy for a recurrent, metastatic testicular germ cell tumor. The patient received 14 cycles of systemic chemotherapy for pulmonary and para-aortic lymph node metastases following his initial orchiectomy. The total amount of etoposide this patient received was 6,400 mg/m2. Leukemia occurred 11 years after orchiectomy. A literature review revealed 25 other reported cases of secondary leukemias after treatment for testicular carcinoma. It is not clear whether chemotherapy, radiotherapy or both are responsible for the secondary leukemias seen in these patients.

Adult↗

Renal pelvic cancer with tumor thrombus in the vena cava inferior. A case report and review of the literature.

Renal pelvic cancer with a large vein tumor thrombus is very rare. We report a case of transitional cell carcinoma of the right renal pelvis with tumor thrombus in the inferior vena cava. Based on the radiological findings, the patient was diagnosed having renal cell carcinoma with tumor thrombus in the vena cava preoperatively. Radical nephrectomy with thrombectomy was performed. A literature review of 17 reported cases revealed that 13 cases (76.5%) were diagnosed as renal cancer preoperatively. Prognosis of transitional cell carcinoma with vena cava tumor thrombus is relatively poor compared to that of renal cell carcinoma with a large vein tumor thrombus.

Carcinoma, Renal Cell↗

Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice.

OBJECTIVE: The antitumor effect of CPT-11, a camptothecin derivative, on two human testicular embryonal carcinomas (TTSC-2 and TTSC-3) heterotransplanted into-nude mice was studied. MATERIALS AND METHODS: Tumor-bearing nude mice were given daily intraperitoneal injections of the anticancer drugs in 0.1 ml saline 3 times at 3-day intervals. At the end of the experiments tumors were resected and subjected to light-microscopic observation. RESULTS: When 10, 30 and 50 mg/kg of CPT-11 was administered to tumor-bearing mice intraperitoneally, the antitumor effect of CPT-11 was observed dose-dependently in both TTSC-2 and TTSC-3. When 30 mg/kg of CPT-11 was administered in combination with CDDP, complete tumor regression was observed in both TTSC-2 and TTSC-3 tumors. Histological findings correlated well with the decrease in tumor volume of treated tumors. No mice died after treatment with CPT-11 in a single-agent and combination chemotherapy. CONCLUSION: Chemotherapy with CPT-11 was an effective and safe method against human testicular tumors heterotransplanted in nude mice.

Animals↗

Association of variants in critical core promoter element of angiotensinogen gene with increased risk of essential hypertension in Japanese.

We examined the association between variants in the core promoter element 1 (AGCE1) of the human angiotensinogen gene (AGT), which acts as a critical regulator of AGT transcription, and the risk for hypertension. One hundred and eighty patients with documented essential hypertension and a family history of hypertension and 194 control subjects without hypertension were selected and frequency matched by age and sex. Genomic DNA from leukocytes was analyzed for genetic variants (position: -20 to -18) in AGCE1. The haplotype in AGCE1 was significantly associated with increased risk of essential hypertension (P<.05). The frequency of subjects with homozygous C allele at position -18(CC/C-18T) was significantly higher in case patients than in control subjects (P<.005), and the evaluated odds ratio for hypertension was 4.2 (95% confidence interval [CI]: 1.4 to 12.8, CC/C-18T versus CT/C-18T). The homozygous threonine allele at codon 235 (TT/M235T) in exon 2 of AGT was also associated with hypertension (P<.02; odds ratio, TT versus other genotypes, 1.8; 95% CI, 1.1 to 2.7). According to haplotype analysis between AGT polymorphisms, we identified linkage disequilibrium between M235T and A-20C and between M235T and C-18T. We conclude that C-18T polymorphism in AGCE1 is a genetic risk factor for essential hypertension in the Japanese and is more tightly and directly associated with hypertension than TT/M235T.

Aged↗

Improved separation and determination of phospholipids in animal tissues employing solid phase extraction.

Separation of five glycerophospholipids having different polar groups, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG) and cardiolipin (CL), was investigated by means of solid-phase extraction (SPE) cartridges. First, the phospholipids were retained in an aminopropyl-bonded phase (NH2) cartridge and subsequently eluted as neutral (PC and PE) and acidic (PS, PG and CL) glycerophospholipid fractions. Secondly, a combination of silica gel (SI) cartridge and NH2 cartridge was employed to separate five glycerophospholipids. The polarity of the eluent was responsible for neutral glycerophospholipid separation. Concerning acidic glycerophospholipids, the separation of PG and CL from PS depended mainly on the pH of the eluents, and the separation of PG and CL was affected by the solvent, depending on eluent polarities. Favorable recovery (not less than 95%, for five authentic phospholipids, 10-100 micrograms each) and repeatability (sigma = 2.3 for 10 micrograms ranges) were attained by the present method. This method of separation was applicable to the analysis of phospholipids in biological samples.

Animals↗

Decrease in expression of the master operon of flagellin synthesis in a dnaA46 mutant of Escherichia coli.

We examined the expression of the fliC, fliA and fihD genes in the dnaA46 mutant. In Northern blot analysis, the amounts of fliC, fliA, and flhD mRNA decreased in the dnaA46 mutant growing at 37 degrees C but not at 28 degrees C. The promoter activity of each gene also decreased in this mutant at 37 degrees C. The decrease in expression of the flh D gene was not related to the cAMP-catabolite activator protein (CAP) pathway. We tentatively conclude that DnaA protein is involved in the expression of the flhD gene by a mechanism independent of the cAMP-CAP pathway.

Blotting, Northern↗

Transient DNA relaxation in Escherichia coli induced by nalidixic acid.

We report here the transient relaxation of plasmid DNA by inhibitors of DNA gyrase in Escherichia coli. Relaxation of plasmid DNA in the presence of nalidixic acid, an inhibitor of the A subunit of DNA gyrase, lasted less than 60 min. The effect of nalidixic acid was not observed in a nalA26 mutant, a strain resistant to nalidixic acid due to a mutation in the gyrA gene. Novobiocin, whose target is the B subunit of DNA gyrase, also caused transient DNA relaxation. Resupercoiling of relaxed DNA in the presence of nalidixic acid was inhibited by pretreatment of the cells with chloramphenicol. As mutations of both the rpoH and recA genes did not affect the resupercoiling reaction, this step seems to require protein synthesis that is independent of both heat shock and SOS responses.

Bacterial Proteins↗

Molecular cloning and sequence analysis of the dnaA gene of Staphylococcus aureus.

The dnaA gene of Staphylococcus aureus has now been cloned and sequenced. The deduced amino acid sequence of Staphylococcus aureus DnaA protein is 62% and 39% identical to those of the DnaA protein from Bacillus subtilis and Escherichia coli, respectively. Expression of the dnaA gene of Staphylococcus aureus in Escherichia coli caused lethality in an oriC-dependent manner.

Amino Acid Sequence↗

Localization and functional role of synaptotagmin III in insulin secretory vesicles in pancreatic beta-cells.

Pancreatic beta-cells secrete insulin by Ca2+-triggered exocytosis of insulin-containing large dense-core vesicles. Synaptotagmin is a Ca2+/phospholipid-binding protein and is a good candidate for the Ca2+ sensor for exocytosis of synaptic vesicles in neurons. In the present study, we generated a polyclonal antibody against synaptotagmin III, and found that synaptotagmin III immunoreactivity was present at high levels in insulin-containing pancreatic islet cells and insulin-secreting clonal MIN6 cells. In subcellular fractionations of MIN6 cells, synaptotagmin III was recovered in the vesicular fractions containing both insulin and vesicle-associated membrane protein-2 (VAMP-2), but not in synaptophysin-positive fractions. The secretory vesicles immunoprecipitated by anti-VAMP-2 antibody contained synaptotagmin III and insulin. In addition, treatment of streptolysin-O-permeabilized MIN6 cells with anti-synaptotagmin III antibody significantly inhibited Ca2+-triggered insulin secretion. These results indicate that synaptotagmin III is localized in insulin-containing dense-core vesicles in pancreatic beta-cells, and further strongly suggest that synaptotagmin III is the Ca2+ sensor in the exocytosis of insulin secretory vesicles.

Animals↗

Central distribution of sensory fibers in the facial nerve: an anatomical and immunohistochemical study.

Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injection into the facial nerve of the cat resulted in retrograde labeling in the geniculate and jugular ganglia ipsilaterally. Labeled fibers were found to enter into the brain stem through the intermediate and vagal nerves. These fibers ascended or descended into the dorsal portion of the spinal trigeminal tract and were distributed to the principal sensory nucleus of the trigeminal nerve, marginal layer of the interpolar part of the spinal trigeminal nucleus, nucleus of the solitary tract and ventrolateral portion of the cuneate nucleus. It was of particular interest in the present study that the intensive labeling was present in the medial portion of laminae I-IV of the upper cervical spinal cord. The immunohistochemical study revealed a lot of substance P-immunoreactive neurons in the geniculate and jugular ganglia, and heavy accumulation of immunoreactive fibers in laminae I-II of the upper cervical spinal cord.

Afferent Pathways↗