Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 631 records · Page 35Linked to original sources

PubMed1993

Timing and sequence of hyperthermia in fractionated radiotherapy of a murine fibrosarcoma.

PURPOSE: This study investigated the effect of timing and sequence of hyperthermia on fractionated radiotherapy, since it has been shown that the heat increases the size of hypoxic cell fraction which could affect the effect of subsequent radiation doses. METHODS AND MATERIALS: Animal-tumors were early generation isotransplants of a spontaneous fibrosarcoma, FSa-II, in C3Hf/Sed mice. Tumor response was studied by tumor growth time and TCD50 (50% tumor control dose) assays. The tumor growth time is the time required for one-half of the treated tumors to reach 500 mm3 from the first treatment day. The TCD50 is a radiation dose to control one-half of the treated tumors for 120 days following treatments. One heat treatment at 43.5 degrees C for 45 min was given in a water bath in combination with fractionated doses independently (24 hr interval) or simultaneously (2 min interval). For the normal tissue study, the mouse foot was treated, and the acute foot reaction was scored daily and averaged. The late foot reaction was scored in animals used in the TCD50 assay that developed no recurrence for 120 days. The RD50(2.0) and RD50(5.0), or total radiation doses to induce an average score of 2.0 (complete epilation) and 5.0 (partial foot atrophy) in 50% of treated animals, were calculated. RESULTS: Thermal radiosensitization was most prominent when heat was combined simultaneously with the first or last radiation dose in both the tumor growth time and TCD50 assays. However, the thermal enhancement was greatest when heat was given either with the first or last radiation dose in the TCD50 assay; whereas it was greatest when heat was administered with the last radiation dose in the tumor growth time assay. Both acute and late skin reactions were significantly potentiated by heat administered 24 hr before the first radiation dose. CONCLUSION: A significant observation in this study was that, in both the tumor growth time and TCD50 assays, heat given independently or simultaneously did not result in any therapeutic gain compared to the radiation alone treatment.

Animals↗

PubMed1993

Recognition of specific DNA sequences by the c-myb protooncogene product: role of three repeat units in the DNA-binding domain.

The DNA-binding domain of c-Myb consists of three homologous tandem repeats of 52 amino acids. The structure of the third (C-terminal) repeat obtained by NMR analysis has a conformation related to the helix-turn-helix motif. To identify the role of each repeat in the sequence recognition of DNA, we analyzed specific interactions between c-Myb and DNA by measuring binding affinities for systematic mutants of Myb-binding DNA sites and various truncated c-Myb mutants. We found that specific interactions are localized unevenly in the AACTGAC region in the consensus binding site of c-Myb: The first adenine, third cytosine, and fifth guanine are involved in very specific interactions, in which any base substitutions reduce the binding affinity by > 500-fold. On the other hand, the interaction at the second adenine is less specific, with the affinity reduction in the range of 6- to 15-fold. The seventh cytosine involves a rather peculiar interaction, in which only guanine substitution abolishes the specific binding. The binding analyses, together with the chemical protection analyses, showed that the c-Myb fragment containing the second and third repeats covers the AACTGAC region from the major groove of DNA in such an orientation that the third repeat covers the core AAC sequence. These results suggest that the third repeat recognizes the core AAC sequence very specifically, whereas the second repeat recognizes the GAC sequence in a more redundant manner. The first (N-terminal) repeat, which covers the major groove of DNA only partially, is not significant in the sequence recognition, but it contributes to increase the stability of the Myb-DNA complex. The presence of an N-terminal acidic region upstream of the first repeat, which is important for the activation of c-myb protooncogene, was found to reduce the binding affinity by interfering with the first repeat in binding to DNA.

Base Sequence↗

PubMed1993

Energy transfer processes in Rhodopseudomonas palustris grown under low-light conditions. Heterogeneous composition of LH 2 complexes and parallel energy flow pathways.

Excitation energy flow in the purple photosynthetic bacterium Rhodopseudomonas palustris grown under a low-light intensity was studied by time-resolved fluorescence spectroscopy in the ps time range. This bacterium synthesized the B824 component under this light condition. Time-resolved spectra at 20 degrees C indicated the sequential energy flow in the order of B803, B856, B882 and B900, long wavelength antenna. An emission from B803 was not observed. A remarkable feature was the emission from B824 throughout the measuring time. After the excitation pulse of 100 ps, the spectra did not change any further, indicating the establishment of an equilibrium among components. Based on the energy distribution after equilibrium, parallel energy transfer pathways to LH 1 were suggested; one including B824 integrated in the B803-824-856 complex, and the other, from the B803-856 complex to B882. The latter was the dominant energy flow pathway in this bacterium.

Bacterial Proteins↗

PubMed1993

Thermal stability of the DNA-binding domain of the Myb oncoprotein.

The DNA-binding domain of the c-myb protooncogene product consists of three homologous tandem repeats of 51-52 amino acids (denoted as R1, R2, and R3 from the N-terminal side). In order to analyze conformational and thermodynamic characteristics of the homologous repeats, we have examined the DNA-binding domain by circular dichroism (CD) and differential scanning calorimetry (DSC). The CD spectra for the three individual repeats are significantly different in the fine profiles, indicating subtle differences in their conformations. The melting analyses for the fragments show that the thermal stability of each fragment is different from one another, with the following order of stability: R1(Tm = 61 degrees C) approximately greater than R3(57 degrees C) >> R2(43 degrees C), where R2 is much less stable than the other repeats. The denaturing process for the whole DNA-binding domain, measured by DSC, is characterized by a very broad transition ranging from 30 to 80 degrees C. The denaturation curve can be fit well by a three-state transition with one intermediate state. The transition temperature for the native-to-intermediate transition coincides with the melting temperature of R2, indicating that the intermediate state corresponds to the unfolding of unstable R2. The CD spectrum of the whole domain is almost identical to the sum of the individual spectra. Thus, these results suggest that the individual repeats in the whole DNA-binding domain behave independently in terms of conformation and stability. The addition of DNA to the DNA-binding fragment drastically changed the melting profile, in which the broad transition curve was replaced by a sharp peak at 58 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Time-resolved fluorescence spectroscopy and photolysis of the photoreceptor blepharismin.

Blepharismin is the photoreceptor for the photophobic response in the ciliate Blepharisma japonicum (Scevoli, P., Bisi, F., Colombetti, G., Ghetti, F., Lenci, F., and Passarelli, V. (1987) J. Photochem. Photobiol.: B. Biol. 1, 75-84; Lenci, F., Ghetti, F., Gioffre, D., Heelis, P.F., Thomas, B., Phillips, G.O., and Song, P.-S. (1989) J. Photochem. Photobiol.: B. Biol. 3, 449-453). Blepharismin was solubilized from the red cells with 2% n-octylglucopyranoside. A crude pigment-protein preparation was then successively subjected to Bio-Gel A1.5 filtration, FPLC/hydroxyapatite and FPLC/DEAE ion-exchange chromatography. At least two spectrally distinct forms of blepharismin, with the respective absorbance maxima at 597 +/- 1 and 601 +/- 1 nm, were resolved. The steady state fluorescence emission maxima were at 602.5 and 617.5 nm, respectively. The fluorescence decay curves for these pigments were non-exponential. The major component possesses relatively short fluorescence lifetime (200-500 ps) for the former, according to a global analysis. This analysis suggests that the excited state of the shorter wavelength-absorbing form of blepharismin undergoes primary photoprocess faster than that of the free parental chromophore hypericin. Photolysis of blepharismin in solution yielded a irreversible product, accompanied by a 10-12 nm bathochromic shift of the absorbance maximum. However, the mechanistic nature of the time-resolved fluorescence and the photochemistry of blepharismin remains to be elucidated.

Animals↗

PubMed1993

[Study on the evaluation of recurrence of HCC and the effect after transcatheter hepatic arterial embolization--fluctuations in AFP values].

To determine the usefulness of alpha-fetoprotein (AFP) in determining recurrence of HCC after interventional angiography (IVA) and to define the relation between AFP and the imaging diagnosis of HCC recurrence, changes in AFP values in 160 patients with hepatocellular carcinoma who were treated by IVA > or = two times were classified into four patterns: A: the AFP value was decreased after the first IVA, increased at recurrence and decreased again after the second IVA; B: the AFP value was unchanged after the first IVA, but increased at recurrence and decreased after the second IVA; C: the AFP value was decreased after the first IVA, but was not increased at recurrence; D: the AFP value showed no change. The frequency of each AFP pattern and the diagnosis of recurrence by AFP were determined. The relation between tumor type and AFP was defined. Pattern A was the most frequently detected. In 62.6%, AFP was increased at recurrence (A and B), and there was a positive correlation between changes in the AFP value and the findings of imaging diagnosis. In another 37.5%, AFP was not increased at recurrence (C and D), and therefore, the diagnosis of HCC recurrence by imaging methods was very important.

Aged↗

PubMed1993

Role of peripheral hemopoietic chimerism in achieving donor-specific tolerance in adult mice.

The role of peripheral hemopoietic chimerism in the induction and maintenance of donor-specific tolerance was investigated by our tolerance-inducing method using cyclophosphamide (CP). As has been previously reported, CP injection at a dose of 200 mg/kg to C3H (Thy-1.2, Mls-1b) mice 2 days after priming with 10(8) viable AKR (Thy-1.1, Mls-1a) spleen cells (SC) resulted in both establishment of mixed chimerism and selective elimination of V beta 6+CD4+ T cells in the periphery. When, instead of viable SC, 1300 rad irradiated 10(8) AKR SC were used for priming to C3H mice, CP treatment 2 days after the priming also caused significant but, as compared with priming with nonirradiated viable cells, incomplete elimination of V beta 6+ T cells in the periphery. In these mice, no hemopoietic chimerism was found. In parallel with this incomplete elimination of peripheral V beta 6+ T cells, LN cells of these mice showed reduced but considerable response to AKR SC. However, once hemopoietic chimerism was introduced to these incompletely tolerant mice by an injection with donor-type viable [AKR x C3H]F1 SC 2 days after CP-treatment, LN cells from these newly established chimeras, irrespective of presence or absence of the thymus, became completely nonresponsive to AKR while preserving normal response to BALB/c (third party). This state of nonresponsiveness was accompanied by clonal elimination of the remaining V beta 6+ T cells in the periphery. These results indicate that peripheral chimerism promoted profound tolerance to donor-Mls Ag specifically. Furthermore, from experiments of skin grafting, we demonstrated that tolerance to minor histocompatibility Ag was also achieved in the presence of peripheral hemopoietic chimerism.

Animals↗

PubMed1993

Generation of a novel CD8+ cytotoxic T lymphocyte that requires soluble factor to lyse autologous antigen-presenting cells.

We reported the existence of high and low responders to the streptococcal cell wall antigen (SCW) in the human population. To analyze the mechanism of the low responsiveness to SCW at the cellular level, we established SCW-specific CD4+ T cell lines. During the course of generation of a SCW-specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence of autologous monocytes and IL-2, without SCW. HYCD8 lysed autologous monocytes and Epstein-Barr virus-transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti-HLA class I framework monoclonal antibody and restricted by HLA-B52 or B54 specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCL. It was unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in the presence of soluble factor with low molecular mass (< 10(4) Da) produced mainly by B cells, which could not be replaced by known cytokines and their mixtures. We thus describe novel HLA class I-restricted cytotoxic CD8+ T cells that kill antigen-presenting cells in a soluble factor-dependent manner.

Antibodies, Monoclonal↗

PubMed1993

Muscle cramp as the result of impaired GABA function--an electrophysiological and pharmacological observation.

We investigated the mechanism of cramps in 2 patients: a 48-year-old man with bulbospinal neuronopathy, and a 46-year-old man with amyotrophic lateral sclerosis. Cramps were quite easily induced by volitional exertion and high-frequency stimulation of the peripheral nerves. When an ulnar nerve was blocked with lidocaine at the elbow, no cramp was induced despite the application of high-frequency stimulation at the wrist. Diazepam (GABAA agonist) was effective in the first patient and baclofen (GABAB agonist) in the second, with no cramps induced in spite of increasing stimulation intensity. Impairment of interneurons mediated by GABA as the neurotransmitter is thought to be involved in the mechanism of the cramps.

Amyotrophic Lateral Sclerosis↗

PubMed1993

Chromium and tritiated thymidine releases from target cells are differential events in human monocyte/macrophage-mediated cytotoxicity.

Cytotoxic properties of human activated macrophages were investigated by measuring both 51Cr and [3H]TdR releases from prelabeled target cells. The kinetic study of macrophage-mediated cytotoxicity indicated that 51Cr and [3H]TdR releases showed a distinct time course. Next, when [3H]TdR release was measured as a parameter for cytotoxicity, pretreatment of activated macrophages with either actinomycin D or emetine remarkably decreased their cytotoxicity in a dose-dependent manner. In contrast, the pretreatment with these inhibitors had little effect on 51Cr release. Furthermore, the addition of Zn2+ in the assay medium caused the decrease in [3H]TdR release but not 51Cr release from the target cells. Taken together, our findings indicate that 51Cr and [3H]TdR releases from the target cells are induced by activated macrophages through different cytotoxic mechanisms; the former does not require RNA and protein syntheses in macrophages during coculture, whereas the latter requires them. Our findings also suggest that macrophage-derived nuclease may play an important role for inducing [3H]TdR release from the target cells.

Chromium Radioisotopes↗

PubMed1993

Chondrosarcoma of the nasal septum: surgical considerations on Le Fort I osteotomy.

A case of chondrosarcoma of the nasal septum extending into the entire nasopharynx sphenoid sinus and skull base is presented. These cartilaginous tumors are rate in the head and neck, with only 28 reported in the nasal septum. They arise in tissues known to be formed of cartilage, and in the present case tumour presumably originated from the perpendicular lamina of the septum. The treatment of choice is wide surgical excision, which requires an adequate approach for gaining the widest possible exposure of tumor. Surgical considerations are discussed.

Chondrosarcoma↗

PubMed1993

T-cell repertoire in a strain of transgenic C57BL/6 mice with the HLA-DRA gene on the X-chromosome.

We have established a strain of transgenic mice in which the HLA-DRA gene was integrated into the X-chromosome and the xenogeneic mixed isotype molecule, DR alpha E beta b, was expressed in a cell type-specific manner, although the transgenic DRA gene contained only 268 base pairs of the 5'-flanking region. The DR alpha E beta b molecules expressed in the transgenic mice functioned as major histocompatibility complex (MHC) class II to select T-cell repertoire, and to stimulate mixed lymphocyte reaction. In female transgenic mice homozygous for HLA-DRA (DR alpha-B6-F-homo) and male transgenic mice (DR alpha-B6-M), DR alpha E beta b molecules were expressed in almost all of the MHC class II Ab-positive cells. In contrast, the expression of DR alpha E beta b molecules in female transgenic mice hemizygous for HLA-DRA (DR alpha-B6-F-hemi) was found only in part of the Ab positive cells, and the proportion of cells expressing the DR alpha E beta b molecules varied due to random inactivation of one of the X-chromosomes. Clonal deletions of the T cells and mature thymocytes bearing Tcrb-V5 and Tcrb-V11, which are eliminated from the peripheral repertoire in mice expressing self-superantigen and MHC class II E molecules, were incomplete in DR alpha-B6-F-hemi as compared with those in DR alpha-B6-F-homo, and were correlated with the proportion of DR alpha E beta b-positive spleen cells. These observations suggested that the number of bone marrow-derived cells expressing DR alpha E beta b molecules was critical for clonal deletions of Tcrb-V5+ and Tcrb-V11+ T cells in the thymus.

Animals↗

PubMed1993

Osmoregulation of the fatty acid receptor gene fadL in Escherichia coli.

The fadL gene of Escherichia coli codes for an outer membrane protein that is involved in the uptake of long-chain fatty acids. Uptake is regulated by environmental osmolarity, and decreases when the cells are grown under conditions of high osmolarity. A temperature-sensitive mutant that requires fatty acid for growth at 42 degrees C was unable to grow at the high temperature even in the presence of fatty acid if the medium contained 10% sucrose. Promoter activity of the fadL gene in vivo was repressed by high osmolarity in a FadR repressor null mutant. Furthermore, in vitro transcription of the fadL gene was strongly repressed by the addition of OmpR and EnvZ proteins. The results of gel retardation and DNase I protection experiments indicated that OmpR, after incubation with the protein kinase EnvZ, specifically binds to at least four sites around the fadL promoter, two upstream and two downstream from the transcriptional start site. These results suggest that transcription of the fadL gene is osmotically regulated by the OmpR-EnvZ two-component system.

Bacterial Outer Membrane Proteins↗

PubMed1993

Long-term survival in malignant intracranial germ-cell tumors: a report of two cases and a review of the literature.

The authors report the successful treatment of two cases of malignant germ-cell tumor. A 12-year-old patient with a pineal immature teratoma and increase of alpha-fetoprotein serum levels was treated with total excision and cisplatin, vinblastine, and bleomycin (PVB) in combination given twice. One year later, he had a recurrence of tumor in the right occipital lobe, which was totally removed, and yolk sac tumor was verified. As subsequent adjuvant chemotherapy, PVB was given in four courses over 1.5 years, together with one course of cisplatin-etoposide (PE) therapy. The patient is well 5 years and 9 months after the first operation. In the second case, a 19-year-old patient with a pineal mixed germ-cell tumor, composed of germinoma, yolk sac tumor, and embryonal carcinoma, was treated with total excision, followed by four courses of PVB therapy and one of PE. She has done well in the 4.5 years since the initial treatment. Thus, aggressive extirpation of the lesion and subsequent combination chemotherapy using cisplatin and other multiple drugs, given in at least four courses over 1.5 years, even if tumor markers return to within normal limits, might provide successful treatment for malignant germ-cell tumors.

Adult↗

PubMed1993

The solitary cutaneous metastasis of asymptomatic colon cancer to an operative scar.

Although umbilical or cutaneous metastases from asymptomatic internal malignancies are occasionally documented, the literature contains no report of a solitary cutaneous metastasis to an old operative scar from an asymptomatic internal malignancy. A rare case of colonic cancer presenting as a solitary subcutaneous metastasis to a lower abdominal scar resulting from an open prostatectomy is described in this communication. It was impossible to distinguish this subcutaneous metastasis from a pyogenic granuloma caused by residual sutures without histological evidence. Thus, a granuloma that persists despite repeated treatment may be a possible sign of asymptomatic internal malignancy.

Adenocarcinoma↗

PubMed1993

Immunohistochemical localization of cathepsins B, D and L in the rat osteoclast.

Immunohistochemical localization of cathepsins B, D and L in the osteoclasts of rat alveolar and femoral bones was investigated by using the avidin-biotin-peroxidase complex method for semithin, 1-micron-thick cryosections. Extracellular immunoreactivity for cathepsins B and L was clearly demonstrated along the bone resorption lacunae; the intensity of the extracellular immunoreactivity of cathepsin L was stronger than that of cathepsin B. However, the intracellular immunoreactivity of both cathepsins was weak compared with that of cathepsin D. The intracellular immunoreactivity of cathepsin D in the osteoclasts was clearly observed in the granules and/or vacuoles, but extracellular cathepsin D immunoreactivity was either negligible or not detected along the resorption lacunae. In the adjacent sections stained with anti-cathepsin L or D, extensive extracellular deposition of cathepsin L was found along the bone resorption lacunae, with or without osteoclasts, although the intracellular reactivity of cathepsin L was weak. This is the first morphological study in which cathepsins B and L have been demonstrated to be produced in the osteoclasts and extensively secreted into resorption lacunae, and in which cathepsin D was found to be present in the cells but scantily secreted into the lacunae. These findings suggest that cathepsins B and L directly and effectively participate in the degradation of the bone matrix.

Animals↗

PubMed1993

Submandibular hemangioma as the initial manifestation of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy and occasional hemolysis) is an infrequent but often fatal complication of rapidly growing hemangiomas in infants. We describe a 1-month-old infant with a huge hemangioma involving the left submandibular region associated with a severe consumptive coagulopathy, who was successfully treated with transfusion of blood products, prednisone and radiation therapy. It is stressed that pediatric otorhinolaryngologists should always be aware of the lethal status of this condition in infants.

Combined Modality Therapy↗

PubMed1993

Determination of cyclodextrins in serum by reversed-phase chromatography with pulsed amperometric detection and a membrane reactor.

A high-performance liquid chromatographic method has been developed for the determination of cyclodextrins (CDs) in serum. The method involves solid-phase extraction of CDs, separation on a C18 reversed-phase column using a mixture of water, tetrahydrofuran and methanol as an eluent, eluent pH modification with a cation-exchange membrane reactor surrounded by 1.5 M sodium hydroxide solutions, and pulsed amperometric detection (PAD) with a gold working electrode. The solid-phase extraction on a C18 bonded-silica column was effective for removing the PAD sensitive components in serum. The calibration graphs constructed by internal standard method were linear over the range 6.25-200 pmol of CDs in serum. The detection limits for CDs were about 5 pmol at a signal-to-noise ratio of 3.

Chromatography, High Pressure Liquid↗