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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 109 records · Page 6Linked to original sources
PubMed1998

Cell kinetics of hemopoietic colony-forming units in spleen (CFU-S) in young and old mice.

The growth potential of the hemopoietic progenitor cells from young and old mice is similar. Previous studies of their cell-kinetics showed no significant differences between them when measured by the incorporation of tritiated thymidine ([3H]TdR). A different approach for exploring stem-cell kinetics in aged animals is provided by another method; the incorporation of bromodeoxyuridine (BrdUrd) during DNA synthesis followed by exposure to near-ultraviolet light (near-UV) kills BrdUrd labelled cells in DNA-synthesis (S-phase). This BrdUrd-near UV cytocide (BUUV) reveals the size of cycling fractions at the level of hemopoietic progenitor cells; it also demonstrates the velocity of the cells entering S-phase when cells are labeled by a continuous infusion of BrdUrd by an osmotic pump, followed by an appropriate colony-assay for each progenitor cell. We compared the cell kinetics of young and old hemopoietic progenitor cells (CFU-S) by this approach. Osmotic pumps were implanted subcutaneously in the backs of young (2 months) and old (22 months) male C57BL/6CrSlc mice for 2, 4, 8, 12, and 16 days to continuously infuse BrdUrd at a flow-rate of 1 mg/h per kg. Cells were harvested from femoral marrow of the infused mice, plated in non-coated bacterial plates, and exposed to a single dose of near-UV at 4000 J/m2. After BUUV cytocide, bone-marrow cells were assayed for 8- and 13-day CFU-S colonies. In the 8-day colonies, the cytocide fraction of CFU-S from young mice increased rapidly, whereas the fraction from old mice showed flatter curves. Both curves reached a plateau at 52.6% for young, and 43.9% for old mice, and then converged 4 days after labeling. In the 13-day colonies, the curve for the aged was much flatter than that for the young; however, the plateaus in both young and old are similar, but at much lower values than earlier, i.e. 24.5% and 16.0%, respectively. The size of the cycling fraction of progenitor cells was close in the two groups during the steady-state cell-cycle. However, the velocity of the cell cycle at a progenitor level was very different, old mice being much slower. Further, within the progenitors, the cell cycle was much slower in the primitive ones and became faster when the stem cells differentiated into mature progenitor cells.

Aging↗
PubMed1998

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth.

PURPOSE: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. METHODS AND MATERIALS: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. CONCLUSION: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.

Adult↗
PubMed1998

A vibriophage, KVP40, with major capsid protein homologous to gp23* of coliphage T4.

The mcp gene encoding the major capsid protein (Mcp) of vibriophage KVP40, a large-tailed DNA phage, was cloned and sequenced. The nucleotide sequence of the mcp gene was 64.4% similar to that of gene 23 of coliphage T4. Analysis of the N-terminal amino acid sequence of purified native Mcp revealed that the mcp gene actually coded for a precursor, pro-Mcp, whose 62 N-terminal amino acids must be removed upon maturation to Mcp. Thus, mature Mcp would consist of 452 amino acid residues and have a calculated molecular mass of 47,561 Da. Comparison of amino acid sequences of Mcp and gp23*, the major capsid protein of T4, demonstrated 61.8% identity and 89.7% similarity between them. In addition, a sequence, TATAAATA, identical to a typical T4 late promoter sequence was seen in the region upstream of the mcp gene. These findings, together with their morphological similarity, suggest that KVP40 and T4 are phylogenetically related.

Amino Acid Sequence↗
PubMed1998

The postspinel phase boundary in Mg2SiO4 determined by in situ X-ray diffraction

The phase boundary between spinel (gamma phase) and MgSiO3 perovskite + MgO periclase in Mg2SiO4 was determined by in situ x-ray measurements by a combination of the synchrotron radiation source (SPring-8) and a large multianvil high-pressure apparatus. The boundary was determined at temperatures between 1400 degrees to 1800 degreesC, demonstrating that the postspinel phase boundary has a negative Clapeyron slope as estimated by quench experiments and thermodynamic analyses. The boundary was located at 21.1 (+/-0.2) gigapascals, at 1600 degreesC, which is approximately 2 gigapascals lower than earlier estimates based on other high-pressure studies.

Journal Article↗
PubMed1998

The guinea-pig skin sensitization test revisited: an evaluation formula to predict possible sensitization levels for eight chemicals used in household products.

In predicting human skin sensitization due to possible risky chemicals, it is not sufficient to evaluate solely the minimum induction dose (MID) or the standard challenge dose (SCD) in the Guinea Pig Maximization Test (GPMT). Nakamura et al. (1994) (Nakamura, A., Momma, J., Sekiguchi, H., Noda, T., Yamano, T., Kaniwa, M., Kojima, S., Tsuda, M., Kurokawa, Y., 1994. A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test. Contact Dermatitis 31, 72-85) previously measured the residual dose of chemicals in the products implicated in human allergic accidents, and stated that '... the level of chemical in the products (direct exposure-dose = DED) was similar to or higher than value of sensitization potency.' However, several of the chemicals listed in their article, show an even lower value of sensitization potency than the DED, although a potential correlation between results of the GPMT and the DED was seemed to be evident; a key question about the essential rule of those parameters therefore remains open. Using the data of Nakamura et al. (1994), we analyzed the functional rules of the three independent parameters, the MID, the SCD, and the DED on which the GPMT is based. Calculations of the degree of allergic reactions elicited in humans provided a range of discrimination constants (D) using the formula; D = DED/(MID*SCD). Possible human allergic accidents may be predicted when the dose of a candidate chemical in a chemical product (equal to DED) exceeds the value; D*(MID*SCD), following the correct evaluation of the MID as well as the SCD.

Allergens↗
PubMed1998

A novel mode of target recognition suggested by the 2.0 A structure of holo S100B from bovine brain.

BACKGROUND: S100B, a small acidic calcium-binding protein, is a member of the S100 protein family and is a multifunctional protein capable of binding several target molecules, such as cytoskeletal proteins and protein kinases, in a calcium-dependent manner. S100B is a homodimer of S100 beta subunits (beta beta) with a total of four calcium-binding motifs called EF hands. S100B is found abundantly in nervous tissue and has been implicated in Alzheimer's disease and Down's syndrome. Structural analysis of S100B in the calcium-bound state is required to gain a better understanding of the conformational changes that occur to S100B upon calcium binding and to elucidate the mode of recognition between S100B and its target molecules. RESULTS: We have determined the three-dimensional structure of holo S100B from bovine brain at 2.0 A resolution by X-ray diffraction. The dimeric S100B molecule is formed by non-covalent interactions between large hydrophobic surfaces on both S100 beta subunits. There are two EF-hand motifs per S100 beta subunit, each of which binds one calcium ion. We observe, in the calcium-bound structure, dramatic changes in the conformation of the terminal helices, from the compact structure in the apo form to a more extended form upon binding calcium. Following these changes, an exposed hydrophobic core, surrounded by many negatively charged residues, is revealed. Cys84 is positioned at an exposed surface of S100B, surrounded by hydrophobic residues, and could form a disulfide bond to tau protein, one of the known target molecules thought to interact with S100B in this way. CONCLUSIONS: The molecular structure of holo S100B suggests a novel mode of target recognition for the S100 family of calcium-binding proteins. Upon calcium binding, dramatic changes occur in the terminal helices of S100B, revealing a large hydrophobic surface, not observed in the apo form. It is through hydrophobic interactions and possibly a Cys84-mediated disulfide bond that S100B is thought to bind its target molecules.

Amino Acid Sequence↗
PubMed1998

An AB block copolymer of oligo(methyl methacrylate) and poly(acrylic acid) for micellar delivery of hydrophobic drugs.

An AB block copolymer of oligo(methyl methacrylate) (oMMA) and poly(acrylic acid) (PAAc) has been synthesized. The block copolymer forms micelles in an aqueous medium, as confirmed by a fluorescence probe technique using pyrene. Doxorubicin hydrochloride was incorporated into the micelle and the release profile of doxorubicin hydrochloride was investigated. Slow and prolonged release of doxorubicin hydrochloride from the micelle was observed. The AB block copolymer micelle can be useful for prolonged mucosal drug delivery of hydrophobic drugs.

Acrylic Resins↗
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 1. Construction of the basic framework.

A novel class of potent, selective, and orally active non-peptide bradykinin (BK) B2 receptor antagonists were designed and synthesized starting from 8-benzyloxyimidazo[1,2-a]pyridine derivative 2. The unique screening lead (2) was discovered by a two-step intentional random screening process, involving recognition of the relationship between BK and angiotensin II (Ang II) and the common structural features. Systematic chemical modification of 2 elucidated the structural requirements essential for B2 binding affinity leading to the identification of 8-[[3-(N-acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]-3-halo- 2- methylimidazo[1,2-a]pyridine skeleton as the basic framework of this new series of B2 antagonists. A molecular modeling study suggested the key role of the N-methylanilide moiety at the 3-position of the 2,6-dichlorobenzene ring to allow these compounds to adopt the characteristic active conformation. The representative lead compounds inhibited the specific binding of [3H]BK to guinea pig ileum membrane preparations expressing B2 receptors, with nanomolar IC50S and also displayed in vivo functional antagonistic activities against BK-induced bronchoconstriction in guinea pigs at an oral dose of 1 mg/kg. Pharmacokinetic studies of compounds 47c and 50b in rats highlighted their excellent oral bioavailabilities, indicating that they represent the first orally active non-peptide B2 antagonists reported to date.

Administration, Oral↗
PubMed1998

Nitric oxide donor decreases neutrophil adhesion in both lung and peritoneum during peritonitis.

BACKGROUND: As nitric oxide (NO) is an antiadhesive molecule, exogenous NO may modulate neutrophil adhesion in organs. This study was designed to examine the effects of the NO donor SNAP (S-nitroso-acetyl penicillamine) on neutrophil adhesion at the inflammatory site and in remote organs, in peritonitis using a fluorescent microscopic method. MATERIALS AND METHODS: In experiment 1, rats (n = 12) were given saline or 10 micrograms/kg of SNAP intravenously followed by continuous infusion of saline, or of 2, 20, or 200 micrograms/kg/h SNAP until sacrifice. Ten minutes after injection of saline or SNAP, 10(7) Escherichia coli were injected into the peritoneal cavity. Five hours after challenge, 10(6) fluorescein-labeled neutrophils were infused. Peritoneal samples, lungs, liver, and kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. In experiment 2, rats (n = 25) were treated with saline or 10 micrograms/kg of SNAP intravenously and infused with saline or 20 micrograms/kg/h SNAP; E. coli was injected as in experiment 1. Before or 5 h after challenge, hemodynamic data were obtained. Then, labeled neutrophils were infused for counting of neutrophil numbers in organs. Arterial blood gas data and the circulating neutrophil number were also determined. RESULTS: Experiment 1. Twenty and 200 micrograms/kg/h SNAP infusions tended to reduce labeled neutrophil numbers in lungs, while all three SNAP doses decreased the peritoneal labeled neutrophil numbers. RESULTS: Experiment 2. Five hours after bacterial injection, SNAP infusion simultaneously decreased both pulmonary and peritoneal labeled neutrophil numbers. SNAP had no effect on hemodynamic and blood gas data, or on circulating neutrophil numbers. CONCLUSION: NO donors may be useful for preventing neutrophil-associated lung injury, but should be used with caution in light of the possible adverse effects on host defense in the peritoneal cavity.

Animals↗
PubMed1998

Loss of imprinting of igf2 in renal-cell carcinomas.

Loss of imprinting (LOI) of the igf2 and h19 genes has been found not only in embryonal tumors but also in common adult cancers. To determine any possible role of genomic imprinting in the development of renal-cell carcinomas (RCCs), we examined the imprinting status of igf2 and h19 in a series of 22 such tumors, and studied its relation to their mRNA expression. Of 14 RCC specimens heterozygous for the ApaI polypmorphism, 7 (50%) showed LOI of igf2. In contrast, for h19 all 9 informative cases maintained imprinting. Furthermore, all 7 cases with LOI transcribed igf2 mRNA at elevated levels, while H19 expression was low regardless of the imprinting status compared with that of background level in each case. These results suggest that LOI of igf2, but not of h19, plays a role in the case of human RCC. However, in contrast to that in Wilms' tumor, LOI in RCC was not associated with any specific down-regulation of h19.

Adult↗
PubMed1998

Acute glucosuria after continuous glucocorticoid loading in the rat in vivo.

We investigated the effects of the continuous infusion of various steroids in rats on renal tubular reabsorption of glucose in vivo to elucidate the pathogenesis of steroid-induced glucosuria. Urinary glucose excretion increased 60 min after administration of dexamethasone (2.38 mM). By 120 min, urinary excretion of glucose was three times higher in the dexamethasone group than in the control group (24.1 +/- 4.6 versus 72.4 +/- 16.7 micromol); the plasma level of glucose did not increase. Dexamethasone had no effect on the resorption of 1,5-anhydro-D-glucitol, which is a glucose-resembling polyol that is actively absorbed by the renal tubules as glucose. Neither estradiol nor progesterone increased urinary excretion of glucose. These findings suggest that continuous administration of a high-dose glucocorticoid selectively influences the glucose reabsorption system in the kidney.

Animals↗
PubMed1998

Recombinant human granulocyte colony-stimulating factor (G-CSF) combined conditioning regimen for allogeneic bone marrow transplantation (BMT) in standard-risk myeloid leukemia.

We previously suggested that using a combined conditioning regimen including rhG-CSF with allogeneic BMT in refractory AML and CML in blast crisis might reduce the rate of relapse and improve disease-free survival, without any major side effects. In this study, we used the same protocol for 10 AML patients in complete remission (CR) and 6 CML patients in the chronic phase (CP). We compared disease-free survival as well as toxic side effects of the regimen with 6 AML patients in CR and 6 CML patients in CP treated with chemoradiotherapy without G-CSF. The conditioning regimen consisted of TBI and high-dose AraC. RhG-CSF was infused continuously at a dose of 5 microg/kg/day, starting 24 hr before the initial dose of total body irradiation (TBI) until the end of AraC therapy. In all 28 cases, there were no early stage deaths due to regimen-related toxicity (RRT). None of the 10 AML cases treated with the G-CSF combined regime relapsed. In 6 AML cases treated conventionally without G-CSF, one patient died of infection and another relapsed. There were no relapses in either CML group. In the combined G-CSF group, one patient died of interstitial pneumonitis 48 days after BMT, while the rest of the CML cases are still alive. There were no relapses with rhG-CSF and no serious adverse effects in terms of RRT, acute graft vs. host disease (GVHD), or leukocyte recovery.

Adult↗
PubMed1998

Primary small cell carcinoma of the esophagus: flow cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the clinical course and effects of histopathologic characteristics of specific tumors including DNA contents and immunohistochemical aspects in patients with small cell carcinoma of the esophagus. METHODS: Medical records of 4 patients who presented with small cell carcinoma of the esophagus were retrospectively reviewed. RESULTS: DNA aneuploidy was observed in 2 cases. Staining for the p53 product was positive in all cases. The average proliferating cell nuclear antigen (PCNA) labeling rate (LR) was 77.6% (64.0-90.8%). The estimated median survival was 42 days for all patients. Distant metastases were observed in 2 of the 4 patients. CONCLUSIONS: Higher PCNA LR of small cell carcinoma may be an unfavorable characteristic of biological behavior. Patients with disseminated disease should have symptomatically palliative operation combined with chemotherapy.

Aged↗
PubMed1998

Optical high-precision three-dimensional position measurement system suitable for head motion tracking in frameless stereotactic radiosurgery.

Head motion is a significant source of therapy-effect degradation in frameless stereotactic radiosurgery (SRS). In this study, a three-dimensional (3-D) optical head motion measurement system and a coordinate transformation algorithm were used to track patient head motion. With this system, head motion in frameless SRS was carefully investigated with a precision of < 0.1 mm. Head motions without any restraint (three cases) and with a Laitinen adapter (four cases) were measured with a data sampling rate of once per second for 30 min. Positions of IR light emission diode markers attached to the head were analyzed by two statistical methods. From these data, mathematically simulated head motions were obtained in each of the three coordinate directions for nonrestraint and Laitinen-adapter SRS. The results show that segmenting a frameless SRS procedure into a sequence of short intervals and repeating registration of the target position for each interval is a good strategy for better therapy precision. This optical 3-D position measurement system is suitable for high-precision head motion tracking in frameless SRS.

Adult↗
PubMed1998

Cadherin-6 in the developing mouse brain: expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry.

Multiple subtypes of the cadherin homophilic cell-cell adhesion molecule are expressed differentially in developing and mature brains, each being expressed in restricted neuronal groups. Cadherin-6 (cad6) is one of such cadherins. Recent studies of cad6 mRNA expression in the postnatal mouse forebrain showed that it occurs in neurons constituting a specific subset of thalamocortical connections. Here we analyzed the localization of cad6 mRNA as well as its protein in the entire central nervous system and also in cranial ganglia of mice at late embryonic to postnatal stages. Our results showed that cad6 is expressed by a limited population of neurons or their precursors, which are synaptically connected to one another, throughout the perinatal stages, and that this expression delineates restricted neuronal circuits from the central to peripheral nervous systems, which include subpathways of the auditory, somatosensory, solitary, vestibular, and olivocerebellar systems. cad6 proteins were detected in these cad6 mRNA-positive neurons on the surface of their cell bodies or dendrites as well as in the cytoplasm. Confocal microscopic analysis revealed that the cad6 protein distribution overlapped that of synaptotagmin in synapse forming areas, suggesting that homotypic cad6 interactions are involved in synaptic connections between neurons expressing this protein. These findings support the idea that cadherin-mediated cell-cell adhesions take part in specific interneuronal connections.

Age Factors↗
PubMed1998

Immediate results and dilatation effect of the vein-covered Palmaz-Schatz stent assessed by intravascular ultrasound.

To evaluate the clinical results of stenting using the vein-covered Palmaz-Schatz (PS) stent by intravascular ultrasound (IVUS). Twenty-eight patients with angina pectoris or confirmed ischemia were entered into this study. Thirteen were allocated to the vein-covered PS stent group and 15 to the normal Palmaz-Schatz stent group. The immediate clinical results in these groups and changes in lumen dimension as assessed by IVUS, were investigated. Acute success was 100% in both groups. There were no immediate complications. Subacute thrombosis occurred in one patient in the vein-covered PS group. In the vein-covered PS group, percent diameter stenosis of the involved coronary artery changed from 70.2% before stenting to 8.8% immediately after and 42.2% at 5 months follow-up. The respective values were 84.5%, 13.4%, and 36.5% in the normal Palmaz-Schatz group. Restenosis in the vein-covered group was 23.1% and in the Palmaz-Schatz group was 20%, showing no significant differences between the two groups. The luminal area in the vein-covered group as assessed by IVUS increased from 3.2 mm2 to 7.4 mm2 (pre to post) and from 3.2 mm2 to 8.2 mm2 in the normal Palmaz-Schatz group. The plaque area decreased from 13.6 mm2 to 10 mm2 (pre to post) in the vein-covered group and from 13.0 mm2 to 9.2 mm2 in the Palmaz-Schatz group. In this study, conducted in a limited number of cases, it is possible to use vein-covered stent like as usual Palmaz-Schatz stent. The vein-covered stent had less dilative effect compared with the Palmaz-Schatz stent. This was probably because of its increased profile but there was no difference in the occurrence of subacute thrombosis or in restenosis rate.

Aged↗
PubMed1998

An immunoelectron microscopic localization of noncollagenous bone proteins (osteocalcin and osteopontin) at the bone-titanium interface of rat tibiae.

This study was designed to investigate by postembedding immunogold method the localization and distribution of osteocalcin (Ocl) and osteopontin (Opn) at the bone-titanium interface in rat tibiae 14 and 28 days postimplantation to determine which bone proteins are present at this interface. Both proteins were widely distributed on the newly formed bone and accumulated predominantly in the region of bone close to the titanium, in electron-dense patches in the bone, and at the osteocytic lacunae. Collagenous osteoid showed little or no labeling for either Ocl or Opn. An amorphous zone (20-50 nm) was interposed between the titanium and interfacial slender cells, osteoid, or bone, and was labeled strongly for Ocl but only weakly for Opn. Furthermore, a second electron-dense layer, the lamina limitans, which faces the titanium, was labeled strongly for Opn but weakly for Ocl. Ocl as a marker protein of osteoblasts was sometimes found in the granules and vesicles of the interfacial cells and extracellularly in their intercellular spaces, close to the titanium. However, Opn was not detected in any granules. This is the first report to show that the amorphous zone contains large amounts of Ocl and small amounts of Opn, and that bone contacts titanium through this Ocl-rich amorphous zone. Furthermore, it is suggested that the interfacial cells seem to be osteoblasts, and that Ocl in the amorphous zone is produced and secreted by these cells and functions with Opn as a regulator of the mineralization front close to the titanium, and as a mediator of cell-matrix and matrix-matrix/mineral adhesion along the titanium.

Animals↗