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Biomedical subjects

T Fujioka

Publications and source records attributed to T Fujioka.

At least 73 records · Page 4Linked to original sources

[A case of congenital hydronephrosis suffering from rupture of the renal pelvis due to trauma].

A 19-year-old male patient was admitted with the chief complaint of left abdominal pain. After receiving a mild punch in the abdomen during boxing exercises, he had severe abdominal pain and was brought to an emergency room. Since abdominal CT scanning revealed the retention of massive fluid in the retroperitoneum, hydronephrotic rupture due to the trauma was diagnosed and nephrectomy was performed. The removed kidney was filled as a result of urinary retention, and congenital hydronephrosis accompanied by the ureteropelvic junction obstruction was macroscopically and pathohistologically diagnosed. Postoperative course was favorable and the patient was discharged on the 10th hospital day.

Adult↗

[Prognostic factors of renal pelvic and ureteral cancer: a multivariate analysis].

We clinicopathologically reviewed 54 cases (40 males and 14 females) of renal pelvic and ureteral cancer examined between 1983 and 1998, in order to determine the impact of prognostic factors. Follow-up ranged from 2 to 173 months (mean, 45.6 months). The age of the patients ranged from 39 to 88 years (mean, 68.9 years). The 1, 3 and 5-year cause-specific survival rates (Kaplan-Meier's method) for all of the patients were 74.6%, 58.4% and 54.5%, respectively. According to univariate analysis, a high grade and high stage of tumor, the presence of lymphatic invasion and positive regional lymph nodes indicated a significantly poor prognosis. On the other hand, multivariate analysis using Cox proportional hazards regression revealed the presence of lymphatic invasion as the most significant predictor of survival. Therefore, patients with lymphatic invasion have a poor prognosis, and the development of effective adjuvant therapy is needed to improve the outcome in these patients.

Adult↗

Yb fiber laser pumped mid-IR source based on difference frequency generation and its application to ammonia detection.

A Yb fiber laser pumped cw narrow-linewidth tunable mid-IR source based on a difference frequency generation (DFG) in a periodically poled LiNbO3 (PPLN) crystal for trace gas detection was demonstrated. A high power Yb fiber laser and a distributed feedback (DFB) laser diode were used as DFG pump sources. This source generated mid-IR at 3 microns with a powers of ~2.5 microW and a spectral linewidth of less than 30 MHz. A frequency tuning range of 300 GHz (10 cm-1) was obtained by varying the current and temperature of the DFB laser diode. A high-resolution NH3 absorption Doppler-broadened spectrum at 3295.4 cm-1 (3.0345 microns) was obtained at a cell pressure of 27 Pa from which a detection sensitivity of 24 ppm m was estimated.

Ammonia↗

[Lymphedema after radical prostatectomy: a case report].

We report a case of intractable lymphedema of the left leg following radical prostatectomy. The 69-year-old male patient complained of difficulty walking, caused by severe lymphedema. Intraarterial autologous lymphocyte transfusion therapy was performed because of failure of conventional conservative therapy, and the leg edema resolved almost completely. However, the treatment did not improve the penoscrotal edema necessitating excision of the edema and skin graft in a separate procedure. The post-operative course was excellent and the patient's performance status improved to 1 from 3.

Aged↗

Nek2 expression and localization in porcine oocyte during maturation.

We studied the role of the Ser/Thr protein kinase Nek2 on meiosis progression by using in vitro porcine oocyte maturation system. Nek2 is a candidate of a mammalian homologue of NIMA, which was found in Aspergillus nidulans as an essential molecule for mitosis progression. We cloned porcine Nek2 cDNA, and examined the mRNA and protein expression levels during meiosis progression. The expression levels did not change through the oocyte maturation, but fluorescence microscopy observation of Nek2 in the oocytes at various maturation steps showed that Nek2 was detected only at metaphase II, but not before metaphase II. At metaphase II, Nek2 was found exclusively on the chromosomes. These results suggest that Nek2 changes the cellular localization during maturation and accumulates on the chromosomes to play a role on the entry and progression of metaphase II.

Amino Acid Sequence↗

Insulin increased cAMP phosphodiesterase activity antagonizing metabolic actions of glucagon in rat hepatocytes cultured with herbimycin A.

The baseline activity of cyclic nucleotide phosphodiesterase 4 was markedly lowered by primary culture of rat hepatocytes with herbimycin A for 4 h [Eur. J. Biochem. 260 (1999) 398-408.]. We now report that insulin added to this preparation of hepatocytes, which had been completely freed of herbimycin, increased the thus lowered phosphodiesterase activity, consequently antagonizing glucagon-induced production of cAMP and activation of glycogen phosphorylase. The insulin receptor beta-subunits and alpha-tubulin were tyrosine-phosphorylated upon the addition of insulin. The phosphorylation of alpha-tubulin afforded conditions unfavorable for microtubule assembly that is responsible for phosphodiesterase inhibition. These effects of insulin observed in herbimycin-pretreated hepatocytes were not inhibited by wortmannin that actually abolished insulin-induced activation of phosphatidylinositol 3-kinase (PtdIns 3-kinase) under the same conditions. The physiological significance of the insulin action not mediated by PtdIns 3-kinase in herbimycin-pretreated hepatocytes is discussed.

1-Methyl-3-isobutylxanthine↗

Flow cytometric analysis of infiltrating cells in the peripheral nerves in experimental allergic neuritis.

Experimental autoimmune neuritis (EAN) is an animal model that shares clinical, pathological and electrophysiological features with the human disease Guillain-Barré syndrome (GBS). In this study, we isolated and characterized by fluorescent activated cell sorter (FACS) phenotype of the inflammatory cells infiltrating cauda equina (CE) of Lewis rats at the active stage of the disease. We found that at this stage of EAN macrophages (Mphi) and alphabeta T cells were two major populations isolated from CE. We also found that among total cell population isolated from CE, gammadelta T and NK cells composed two small but distinct populations, while B cells were negligible. We characterized phenotype of alphabeta T cells in CE as CD45RC(+)CD8(+) (activated cytotoxic lymphocytes) and CD45RC(-)CD4(+) (memory Th cells). The phenotype of gammadelta T cells was found to be consisted of only CD45RC(+)CD8(+) cells. Both alphabeta and gammadelta T cells in CE expressed a higher level of CD25, CD44 and CD54 activation markers compared to the other tissues. Immunohistochemistry demonstrated that gammadelta T cells existed apart from the intense cellular infiltrate. This is the first report on the isolation and FACS analysis of CE-infiltrating cells, contributing a new and alternative approach to study the inflammatory lesions in EAN. We conclude that both alphabeta and gammadelta T cells have a unique activation/inflammatory phenotype required to traffic through and be retained in the peripheral nerves during EAN.

Animals↗

In vivo electrical activity of brainstem neurons in fetal rats during asphyxia.

To see changes in the activity and the sensitivity to glutamate of fetal brain neurons during asphyxia, the electrical activity of brainstem neurons was recorded extracellularly in fetal rats which were still connected with the dams by the intact umbilical cord. In urethan-anesthetized pregnant rats, fetal asphyxia (2-10 min) was induced by occluding the umbilical cord with a surgical clip, while reperfusion of the umbilical blood flow was performed by local application of a relaxant of blood vessels to the occlusion site. The spontaneous discharge of fetal brainstem neurons was suppressed for a long period of time by umbilical cord occlusion. The suppression of the firing occurred 48-150 (78+/-7) s after the start of umbilical cord occlusion, and lasted even after fetal cortical PO(2) recovered to control level after reperfusion. The changes occurred with a marked reduction in spike amplitude. A similar suppression was observed for the spikes induced by iontophoretic application of glutamate, although fetal brainstem neurons were extremely sensitive to glutamate before asphyxia. The suppression of the spontaneous spikes became more notable and longer when asphyxia was repeated. These findings suggest that the long-lasting suppression of fetal neurons during asphyxia may contribute to a reduction of cellular energy requirements in the fetal brain, thereby playing a role in the resistance of fetal neurons to brain damage caused by asphyxia. Furthermore, the reduced sensitivity of fetal neurons to glutamate during asphyxia may also contribute to prevent brain damage due to excitotoxity of glutamate.

Action Potentials↗

Experimental allergic neuritis in the SJL/J mouse: induction of severe and reproducible disease with bovine peripheral nerve myelin and pertussis toxin with or without interleukin-12.

We report a reproducible model of experimental allergic neuritis (EAN) with severe clinical signs and consistent pathological features in mice. Pertussis toxin (PT) in the presence or absence of murine recombinant interleukin-12 (mrIL-12) was used as an adjuvant with bovine peripheral nerve myelin (BPNM) to induce clinical EAN in SJL/J mice. After immunization with a combination of BPNM in complete Freund's adjuvant (CFA) and PT, mice developed severe consistent signs of EAN. The additional treatment of immunized mice with mrIL-12 prolonged the course of EAN characterized by earlier clinical signs of the disease and delayed the recovery stage. Mice injected with BPNM and CFA without PT developed mild clinical signs. Histological examination of the caudae equinae and the sciatic nerves taken from mice with clinical signs of EAN during the recovery stage revealed severe demyelination, remyelination and remnants of mononuclear cell infiltration. Moderate to severe EAN can be induced in SJL/J mice by the injection of a combination of BPNM in CFA and PT. This model can provide a better understanding of mechanism of demyelination in infiltrating peripheral neuropathy.

Animals↗

Prevention of renal cell carcinoma by active vitamin D3.

We studied the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D (Vit D)] in patients with renal cell carcinoma (RCC) and the influence of 1,25(OH)2D3 (Vit D3) on gap junctional intercellular communication (GJIC) during carcinogenesis. The serum Vit D levels were measured by a competitive protein-binding assay using the chromatographic method. Using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, noncytotoxic concentrations of Vit D3 and the tumor promoters N-nitrosodimethylamine (NDMA) and N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested against cultured human renal proximal tubular cells (HRPTCs). GJIC function was assayed by the scrape-loading dye transfer technique. Cx43 mRNA expression was also examined by the reverse transcriptase-polymerase chain reaction (RT-PCR). Serum Vit D levels in patients with RCC were lower than those in controls (p< 0.001). Patients with T3 to T4 (rapid-growth) tumors had lower levels of Vit D than did patients with T1 to T2 (slow-growth) tumors (p < 0.001). Vit D3 enhanced the GJIC function of HRPTCs (p < 0.05), whereas NDMA and EHEN suppressed it (p < 0.05). When the cells were treated with tumor promoters and Vit D3 simultaneously, the GJIC functions remained at pretreatment levels. We also demonstrated Cx43 mRNA expression in RPTECs treated with EHEN and VitD3 simultaneously. These data suggest that a decrease in the serum Vit D level is one of the risk factors for development and progression of RCC, and Vit D3 may prevent RCC by preserving GJIC during carcinogenesis.

Adult↗

Age-associated decrease in plasma cholesterol and changes in cholesterol metabolism in homozygous Watanabe heritable hyperlipidemic rabbits.

We examined the cholesterol metabolism of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model deficient in low-density lipoprotein (LDL) receptors, to clarify the mechanism of the age-associated decrease of plasma total cholesterol, one of the properties of WHHL rabbits. The rabbits were examined at several ages: after weaning at 3 months, at sexual maturation at 6 months, at 12 months, and at 24 months, equivalent to about 35 years of age in humans. Plasma total cholesterol, triglyceride, and phospholipid levels decreased with aging by about 45%. These reductions were mainly dependent on a decrease in the LDL fraction. In the liver microsomal fraction, although there were no age-related changes in the cholesterol concentration and cholesterol 7alpha-hydroxylase (C7H) activity, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity decreased with aging. The lipolytic activity varied with aging. The secretion rate of very-low-density lipoprotein (VLDL) cholesterol as determined by injection of Triton WR-1339 decreased significantly with aging, while the catabolic rate of VLDL cholesterol was about 2-fold higher in the oldest group versus the young groups. From these results, we conclude that the age-associated decrease in plasma cholesterol in WHHL rabbits is related not only to a decrease in the secretion rate of VLDL cholesterol but also to an increase in the catabolic rate.

Aging↗

Induction and adaptation of Fos expression in the rat brain by two types of acute restraint stress.

The present study was designed to examine whether both induction and adaptation of brain Fos expression during acute stress depend on the intensity and duration of stressors. For this purpose, different durations of two types of acute stress, mild (restraint) and severe (immobilization) stress, were employed. Stress-induced Fos expression was analyzed quantitatively by immunohistochemistry. Adaptation of Fos expression to the acute stressors was not apparent in the hypothalamic paraventricular nucleus (PVN) or locus coeruleus (LC) but was observed in the amygdala, hippocampus, and cerebral cortex. A higher level of Fos expression was seen in the PVN, LC, and amygdala, following severe stress than was seen following mild stress. In the hippocampus, the dentate gyrus showed reduced Fos expression in response to stressors, although both mild and severe acute stress increased Fos expression in other regions of the hippocampus. The cingulate cortex showed increased Fos expression during mild stress, whereas long-duration severe stress reduced Fos expression. In the somatosensory cortex, both stressors increased Fos expression. These results indicate that the PVN and LC are relatively resistant to adaptation to acute stress compared to other brain regions. In addition, the PVN, LC, and amygdala may play important roles in the perception of the severity of stress.

Acute Disease↗

Conformational analysis and docking study of potent factor XIIIa inhibitors having a cyclopropenone ring.

A conformational analysis and docking study of potent factor XIIIa inhibitors having a cyclopropenone ring were carried out in an attempt to obtain structural insight into the inhibition mechanism. First, stable conformers of the inhibitors alone were obtained from the conformational analysis by systematic search and molecular dynamics. Next, a binding form model of factor XIIIa was built based on an X-ray crystal structure of the enzyme. Finally, the docking study of the inhibitors into the model's binding site was performed. From the resulting stable complex structures, it was found that the cyclopropenone ring fits the active site located at the base of the binding cavity with high complementarity. The carbonyl oxygen of the cyclopropenone ring formed a hydrogen bond to the indole NH group of Trp279 and the terminal carbon atom of the reactive C=C double bond was in close proximity to the sulfur atom of the catalytic residue, Cys314. This binding mode suggests a possible inhibition mechanism, whereby the cysteine residue reacts with the cyclopropenone ring of the inhibitor, forming an enzyme-ligand adduct. In addition, the higher interaction energies between factor XIIIa and the inhibitors alluded to the probable binding sites of the ligand side chain.

Cyclopropanes↗

Helicobacter pylori infection and gastric carcinoma in animal models.

Many epidemiological studies have shown a strong association between chronic Helicobacter pylori infection and the subsequent development of gastric carcinoma in humans. To confirm this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection has recently been achieved in the Mongolian gerbil model, with results demonstrating that the sequential histopathological changes in the gastric mucosa closely mimic the gastric mucosal changes caused by H. pylori infection in humans. These studies have demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens, such as N-methyl-N-nitroso-urea and N-methyl-N-nitro-N'-nitrosoguanidine and have also demonstrated that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Animals↗

Telomerase activity in human renal cell carcinoma.

PURPOSE: Telomerase activity has been detected in a wide variety of human tumors. The present study evaluated telomerase activity in association with the acquisition of renal cell carcinoma (RCC). METHODS: Telomerase activity was examined in 30 RCC and the adjacent normal kidney tissue, obtained as surgical specimens. The activity was assayed by polymerase chain reaction-based telomeric repeat amplification protocol assay. RESULTS: Among the 30 RCC, 18 (60%) displayed telomerase activity, whereas none of the normal tissue samples exhibited it. Subdivision of the tumors according to telomerase activity did not reveal any obvious difference in distribution with regard to tumor size, stage, histocytological subtype, or DNA-ploidy. However, a statistically significant relationship was found between the frequency of telomerase-positive activity and both serum immunosuppressive acidic protein level in the patient and tumor grade (P<0.05). There was no significant difference in the recurrent-free survival and the disease-specific survival between patients with positive telomerase activity and patients with negative activity. CONCLUSION: The present results indicate that telomerase activity might be related to the progression of RCC and thus a marker of malignant potential.

Aged↗

Therapeutic oral vaccination induces mucosal immune response sufficient to eliminate long-term Helicobacter pylori infection.

We examined the efficacy of therapeutic oral vaccination using Helicobacter pylori-whole cell sonicate and cholera toxin (CT) in mice persistently infected with H. pylori. Efficacy was determined by bacterial culture and microscopic examination of gastric tissues for the persistence of bacteria at 6 weeks after the last vaccination. Vaccination of H. pylori-whole cell sonicate combined with CT eradicated bacteria in 10/16 mice (62.5%). Interestingly, oral vaccination with CT alone also eliminated the bacteria in 8/17 mice (47.1%). However, a therapeutic intraperitoneally administered vaccine failed to eradicate H. pylori from the stomach (1/17 mice, 5.9%). Identification of the type of immunity involved in the eradication process showed that oral vaccination enhanced the antigen-specific IgA in the feces and saliva. The efficacy of eradication of H. pylori correlated well with increases in IgA secretion in mucosal tissue and a higher labeling index of IgA-positive lumina of pyloric glands. Moreover, the expression of IL-4 mRNA in the stomach of mice with eradicated bacteria was higher than in the uneradicated group. Our results suggest that the efficacy of vaccination depends on the mucosal IgA response in the gastrointestinal tract against H. pylori via Th2 cell activation and that therapeutic oral vaccination induces a mucosal immune response sufficient to eradicate long-term infection with H. pylori.

Administration, Oral↗