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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 91 records · Page 5Linked to original sources
PubMed2001

Interstitial photodynamic therapy with rotating and reciprocating optical fibers.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment modality that allows selective destruction of malignant tumor cells. However, because of the difficulty in exposing deeper areas of tumors, the modality has strictly limited indications. In this study, the authors introduce a new method for delivering laser light to a three-dimensional, wide area with the purpose of improving the therapeutic value of PDT. METHODS: Three patients with squamous cell carcinoma of the tongue were treated with the present course. After administering porfimer sodium, laser-proof tubes were inserted through the tumor, and optical fibers were passed through the tubes. Pulse laser was emitted from the obliquely prepared fiber tip and distributed toward the target area while rotating and reciprocating the optical fiber. RESULTS: Two patients achieved a complete response without any complications or functional disabilities. The third patient, however, had a partial response and required surgery. CONCLUSIONS: The results indicate the capability of distributing laser light to an entire area of solid tumor. However, the ideal dose of laser light for the treatment of tumors remains unknown. Interstitial PDT will be more efficacious and reliable after the dosimetry is established.

Aged↗
PubMed2001

In-plane elliptic flow of resonance particles in relativistic heavy-ion collisions.

We analyze the second Fourier coefficient v(2) of the pion azimuthal distribution in noncentral heavy-ion collisions in a relativistic hydrodynamic model. The exact treatment of the decay kinematics of resonances leads to almost vanishing azimuthal anisotropy of pions near the midrapidity, while the matter elliptic flow is in plane at freeze-out. In addition, we reproduce the rapidity dependence of v(2) for pions measured in noncentral Pb+Pb collisions at 158A GeV. This suggests that resonance particles as well as stable particles constitute the in-plane flow and are important ingredients for the understanding of the observed pion flow.

Journal Article↗
PubMed2001

Safety evaluation of hemagglutinating virus of Japan--artificial viral envelope liposomes in nonhuman primates.

We tested, in cynomolgus monkeys, the safety and effectiveness of a hybrid liposome vector, hemagglutinating virus of Japan (HVJ)--artificial viral envelope (AVE) liposomes, for human therapeutic gene transfer in a series of experiments. In a repetitive intramuscular administration study, vehicle control macaques (n = 2), which were treated with HVJ--AVE liposome suspension, received repetitive intramuscular injections of 2 ml of test substance. Human hepatocyte growth factor (HGF) cDNA-inserted expression vector (pUC-SR alpha/HGF) injection animals (n = 2), which were treated with HVJ--AVE liposome suspension containing pUC-SR alpha/HGF, received repetitive intramuscular injection of 2 ml of test substance. General body condition, hematology, blood chemistry, and serum HGF were determined sequentially before treatment and 7, 21, 28, and 29 days after treatment. Elevations in HGF were detected in monkeys injected with pUC-SR alpha/HGF. After this observation period, macaques were killed for autopsy and histological examination. pUC-SR alpha/HGF was detected by polymerase chain reaction (PCR) analysis in the liver, spleen, and at the injection site. In single intravenous administration study, control macaques (n = 4) received a single intravenous injection of 10 ml of physiological saline. Vehicle control animals (n = 5) received a single intravenous injection of 10 ml of HVJ--AVE liposome suspension. DNA-treated animals (n = 7) received a single intravenous injection of 10 ml of HVJ--AVE liposome suspension containing plasmid DNA [pcDNA 3.1(+)]. General body condition, body weight, hematology, blood chemistry, and urine composition were determined sequentially before treatment and 1, 14, 21, and 28 days after treatment. After this observation period, macaques were killed for autopsy and histological examination. pcDNA 3.1(+) was detected by PCR analysis on day 1 in lung, liver, and spleen of all monkeys, in kidney of one of two monkeys, and in heart of one of two monkeys. However, no DNA was detected in any of the tissues examined on days 14, 21, and 28. No virus genomic RNA was detected by reverse transcription (RT)-PCR analysis with HVJ-specific primers. In this series of safety evaluations, the animals tolerated the safety study with no change in body weight or general condition. No hematological changes or alterations in blood chemistry or urine composition was detected. Moreover, no histological changes were observed. This safety evaluation study demonstrates the safety, feasibility, and therapeutic potential of the novel transfection vehicle, HVJ--AVE liposomes, in humans.

Animals↗
PubMed2001

Regulation of dharma/bozozok by the Wnt pathway.

The zebrafish homeobox gene dharma/bozozok (boz) is required for the formation and/or function of the Nieuwkoop center and the subsequent induction of the Spemann organizer. dharma is expressed soon after the midblastula transition in the dorsal blastomeres and the dorsal yolk syncytial layer (YSL). We found that the expression of dharma was upregulated or ectopically induced by misexpression of a Wnt protein and cytoplasmic components of the Wnt signaling pathway and downregulated by the expression of dominant-negative Tcf3. A 1.4-kbp fragment of the dharma promoter region contains consensus sequences for Tcf/Lef binding sites. This promoter region recapitulated the Wnt-dependent and dorsal dharma expression pattern when it was fused to luciferase or GFP. Deletion and point mutant analyses revealed that the Tcf/Lef binding sites were required to drive this expression pattern. These data established that dharma/boz functions between the dorsal determinants-mediated Wnt signals and the formation of the Nieuwkoop center.

Animals↗
PubMed2001

Difference in molecular structure of rod and cone visual pigments studied by Fourier transform infrared spectroscopy.

To investigate the local structure that causes the differences in molecular properties between rod and cone visual pigments, we have measured the difference infrared spectra between chicken green and its photoproduct at 77 K and compared them with those from bovine and chicken rhodopsins. In contrast to the similarity of the vibrational bands of the chromophore, those of the protein part were notably different between chicken green and the rhodopsins. Like the rhodopsins, chicken green has an aspartic acid at position 83 (D83) but exhibited no signals due to the protonated carboxyl of D83 in the C=O stretching region, suggesting that the molecular contact between D83 and G120 through water molecule evidenced in bovine rhodopsin is absent in chicken green. A pair of positive and negative bands due to the peptide backbone (amide I) was prominent in chicken green, while the rhodopsins exhibited only small bands in this region. Furthermore, chicken green exhibited characteristic paired bands around 1480 cm(-1), which were identified as the imide bands of P189 using site-directed mutagenesis. P189, situated in the putative second extracellular loop, is conserved in all the known cone visual pigments but not in rhodopsins. Thus, some region of the second extracellular loop including P189 is situated near the chromophore and changes its environment upon formation of the batho-intermediate. The results noted above indicate that differences in the protein parts between chicken green and the rhodopsins alter the changes seen in the protein upon photoisomerization of the chromophore. Some of these changes appear to be the pathway from the chromophore to cytoplasmic surface of the pigment and thus could affect the activation process of transducin.

Amino Acid Sequence↗
PubMed2001

Regulation of Pim-1 by Hsp90.

The protooncogene Pim-1 encodes serine/threonine protein kinases that are involved in cytokine-mediated cell proliferation and in lymphoma- and leukemogenesis. It is largely unknown how Pim-1 executes its biological effects. Here we show that Pim-1 physically interacts with heat shock protein 90 alpha and beta (Hsp90alpha and beta). The Hsp90-specific inhibitor geldanamycin (GA) induced a rapid degradation of Pim-1 and reduced its kinase activity. The expression of Hsp90alpha was regulated by a signal from the cytokine receptor gp130, as is Pim-1's expression. These results indicate that Hsp90 is coordinately regulated with Pim-1 and is involved in the stabilization and function of Pim-1.

Amino Acid Sequence↗
PubMed2001

Intermolecular DNA interactions stimulated by the cohesin complex in vitro: implications for sister chromatid cohesion.

The establishment of sister chromatid cohesion during S phase and its dissolution at the metaphase-anaphase transition are essential for the faithful segregation of chromosomes in mitosis [1-4]. Recent studies in yeast genetics and Xenopus biochemistry have identified a large protein complex, cohesin, that plays a key role in sister chromatid cohesion [5-10]. The cohesin complex consists of a heterodimeric pair of SMC (structural maintenance of chromosomes) subunits and at least two non-SMC subunits. This structural organization is reminiscent of that of condensin, another major SMC protein complex that drives chromosome condensation in eukaryotic cells [11]. Condensin has been shown to reconfigure and compact DNA in vitro by utilizing the energy of ATP hydrolysis [12]. Very little is known, however, about how cohesin works at a mechanistic level. Here we report the first set of biochemical activities associated with an intact cohesin complex purified from HeLa cell extracts. The cohesin complex binds directly to double-stranded DNA and induces the formation of large protein-DNA aggregates. In the presence of topoisomerase II, cohesin stimulates intermolecular catenation of circular DNA molecules. This activity is in striking contrast to intramolecular knotting directed by condensin [13]. Cohesin also increases the probability of intermolecular ligation of linear DNA molecules in the presence of DNA ligase. Our results are consistent with a model in which cohesin functions as an intermolecular DNA crosslinker and is part of the molecular "glue" that holds sister chromatids together [14].

Adenosine Triphosphatases↗
PubMed2001

Chloride effect on iodopsin studied by low-temperature visible and infrared spectroscopies.

To investigate the chloride effect on the spectral properties of iodopsin, we have prepared an anion-free iodopsin (iodopsin.free) by extensive dialysis of an iodopsin sample against a buffer containing no chloride, and visible and infrared difference spectra between iodopsin.free and its photoproduct at 77 K were recorded. The absorption maximum of iodopsin.free in L-alpha-phosphatidylcholine liposomes was 528 nm, which was almost identical with that of the nitrate-bound form of iodopsin (526 nm, iodopsin.NO(3)), but 43 nm blue-shifted from that of the chloride-bound form of iodopsin (iodopsin.Cl). The iod/batho visible difference spectrum obtained from iodopsin.free was similar in shape to that from iodopsin.NO(3), but not to that from iodopsin.Cl. FTIR spectroscopy revealed that the chromophore vibrational bands and the peptide bonds of the original state in iodopsin.free were identical with those in iodopsin.NO(3) and were also similar to those in iodopsin.Cl except for the ethylenic vibrations of the chromophore. In contrast, those of the batho state in iodopsin.free were similar to those in iodopsin.NO(3) but considerably different from those in iodopsin.Cl. These results suggested that the binding of chloride but not nitrate induces a conformational change in the protein and that the chloride binding site is situated in a position where it directly interacts with the chromophore when the chromophore is photoisomerized. FTIR spectroscopy also revealed that one of the four water bands observed in the batho/iod spectrum of iodospin.Cl is absent in the spectra of iodopsin.free and iodopsin.NO(3). Thus, in contrast to nitrate, a lyotropic anion, chloride would bind to the binding site with water molecule(s) which could form a hydrogen-bonding network with amino acid residue(s) near the chromophore, thereby resulting in the red shift of the absorption maximum of iodopsin.

Amino Acid Sequence↗
PubMed2001

Chromosome condensation by a human condensin complex in Xenopus egg extracts.

13S condensin is a five-subunit protein complex that plays a central role in mitotic chromosome condensation. The condensin complex was originally identified and purified from Xenopus egg extracts and shown to have an ATP-dependent positive supercoiling activity in vitro. We report here the characterization of a human condensin complex purified from HeLa cell nuclear extracts. The human 13S complex has exactly the same composition as its Xenopus counterpart, being composed of two structural maintenance of chromosomes (human chromosome-associated polypeptide (hCAP)-C and hCAP-E) subunits and three non-structural maintenance of chromosomes (hCAP-D2/CNAP1, hCAP-G, and hCAP-H/BRRN) subunits. Human condensin purified from asynchronous HeLa cell cultures fails to reconfigure DNA structure in vitro. When phosphorylated by purified cdc2-cyclin B, however, it gains the ability to introduce positive supercoils into DNA in the presence of ATP and topoisomerase I. Strikingly, human condensin can induce chromosome condensation when added back into a Xenopus egg extract that has been immunodepleted of endogenous condensin. Thus, the structure and function of the condensin complex are highly conserved between Xenopus and humans, underscoring its fundamental importance in mitotic chromosome dynamics in eukaryotic cells.

Adenosine Triphosphatases↗
PubMed2001

In situ telomerase activity in pleural effusions: a promising marker for malignancy.

Telomerase activity in 16 pleural effusions was studied using an in situ telomerase repeat amplification protocol (TRAP) assay on cytospin preparations. Six of nine cytologically malignant specimens contained telomerase-positive cells (67%), and in two further specimens, suspicious positive cells were seen. Two of four atypical specimens contained telomerase-positive cells, whereas two benign cases were telomerase-negative. No mesothelial cells showed telomerase reactivity. Thus, telomerase activity was specific for malignancy and it was always found only in malignant cells. The results suggest that telomerase activity measured with this in situ method can be a valuable complement in the assessment of malignancy in pleural effusions.

Biomarkers, Tumor↗
PubMed2001

Shaping the metaphase chromosome: coordination of cohesion and condensation.

Recent progress in our understanding of mitotic chromosome dynamics has been accelerated by the identification of two essential protein complexes, cohesin and condensin. Cohesin is required for holding sister chromatids (duplicated chromosomes) together from S phase until the metaphase-to-anaphase transition. Condensin is a central player in chromosome condensation, a process that initiates at the onset of mitosis. The main focus of this review is to discuss how the mitotic metaphase chromosome is assembled and shaped by a precise balance between the cohesion and condensation machineries. We argue that, in different eukaryotic organisms, the balance of cohesion and condensation is adjusted in such a way that the size and shape of the resulting chromosomes are best suited for their accurate segregation.

Animals↗
PubMed2001

Enhancement of fibrinolytics with a laser-induced liquid jet.

BACKGROUND AND OBJECTIVE: There are several problems inherent in the treatment of cerebral embolisms, such as the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. There is thus need of a new method of removing a cerebral thrombus more rapidly using smaller amounts of fibrinolytics. STUDY DESIGN/MATERIALS AND METHODS: The liquid-jet generator was made by insertion of an optical fiber (diameter: 0.6 mm) into a balloon catheter (6 Fr). A pulsed holmium (Ho) YAG laser (pulse duration time = 350 micros) was used as a laser source. The maximum penetration depth of a liquid jet generated with this device into a gelatin artificial thrombus was measured at various stand-off distances (L; distance between the optical fiber end and the catheter exit). Based on the result, a stand-off distance of 13 mm was chosen to investigate the enhancement of urokinase (UK) efficacy by only a single operation of the liquid-jet device in artificial thrombi made of human blood. RESULTS: Maximum penetration depth increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. Fibrinolysis rates (%) after incubation with a small amount of UK for 10 and 30 minutes were predominantly raised by a single use of the laser-induced liquid jet (5.4 +/- 2.4 vs. 22.6 +/- 6.1 and 7.3 +/- 3.8 vs. 38.3 +/- 5.6, respectively (mean +/- SD, P < 0.001)). CONCLUSIONS: A laser-induced liquid jet effectively promoted fibrinolysis in vitro with use of only a small amount of fibrinolytics.

Analysis of Variance↗
PubMed2001

Hormonal control of osmoregulation in the channel catfish Ictalurus punctatus.

Prolactin (PRL) is an important hormone for freshwater adaptation in many teleost species. In some euryhaline fishes, growth hormone (GH) and cortisol are involved in seawater adaptation by stimulating ion extrusion. When channel catfish (Ictalurus punctatus) were transferred from fresh water to dilute seawater (300-400 mOsm), their plasma osmolality was always higher than the environmental salinity. In correlation with the increase in plasma osmolality, significant increases in plasma cortisol were observed. However, no effect of ovine GH or cortisol was seen in plasma osmolality or gill Na, K-ATPase activity when the hormones were given during the course of acclimation to dilute seawater. When catfish in fresh water were hypophysectomized, plasma osmolality was significantly decreased by 24 h, reaching a minimum level after 2 days. When they were transferred to dilute seawater, the plasma osmolality of the sham-operated fish was consistently higher than that of environmental water, whereas the osmolality of the hypophysectomized fish was equivalent to the environmental salinity. Ovine PRL restored the plasma osmolality of the hypophysectomized fish in fresh water to the level of sham-operated fish. Cortisol was also effective, but the effect was less pronounced than the effect of PRL. Injection of PRL in combination with cortisol resulted in a marked additive increase in plasma osmolality to a level even above that of the sham-operated fish. Ovine GH was without effect. These treatments in hypophysectomized fish transferred to dilute seawater produced essentially the same results as those in fish in fresh water. Plasma osmolality was also increased after PRL treatment of the intact fish in fresh water. There was a synergistic effect between PRL and cortisol in hypophysectomized fish in dilute seawater as well as in intact fish in fresh water. PRL did not stimulate cortisol secretion either in hypophysectomized fish or in intact fish. In the stenohaline catfish, both PRL and cortisol seem to be involved importantly in ion uptake from the environment not only in fresh water but also in brackish water.

Animals↗
PubMed2001

Stable transformation of Pleurotus ostreatus to hygromycin B resistance using Lentinus edodes GPD expression signals.

It was reported that Pleurotus ostreatus was transformed unstably using recombinant plasmids containing a hygromycin B phosphotransferase gene (hph) under the control of Aspergillus nidulans expression signals, and that the plasmids were maintained extrachromosomally in the transformants. Here we report a stable and integrative transformation of the fungus to hygromycin B resistance, using a recombinant hph fused with Lentinus edodes glyceraldehyde-3-phosphate dehydrogenase expression signals. Restriction-enzyme-mediated integration (REMI) was also tried and increased the transformation efficiency about ten-fold.

Anti-Bacterial Agents↗
PubMed2001

Metachronous neurohypophysical immature teratoma occurring 10 years after total resection of pineal mature teratoma.

An 18-year-old boy presented with an immature neurohypophysial teratoma occurring 10 years after total resection of a mature pineal teratoma through an occipital transtentorial approach in 1989. Thorough histological examination had revealed a mature teratoma. He developed panhypopituitarism and diabetes insipidus in 1999. Magnetic resonance imaging revealed a suprasellar tumor occupying the third ventricle. This tumor was totally resected through a frontobasal approach. Histological examination revealed an immature teratoma. This tumor occurred in a different site from the initial tumor and was considered to be de novo and thus a so-called metachronous germ cell tumor. Patients with completely resected mature teratoma require extended follow-up, including periodic magnetic resonance imaging, because of the risk of such a metachronous germ cell tumor.

Adolescent↗
PubMed2001

Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis.

BACKGROUND: It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS: We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS: The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION: cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

Adult↗