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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 685 records · Page 38Linked to original sources
PubMed1993

[Carbon beam irradiation of monolayer cells].

This study was performed to determine the biological effect of carbon beams on mammalian cells (HeLa, RMUG), in comparison with 200 KVp X-rays. Carbon beams were generated by the Riken Ring Cyclotron. An increase in the relative biological effect (RBE) was observed in both cell lines as the LET of the carbon beam increased between 20 and 80 keV/microns. The RBE depended on the size of the irradiation dose at the higher LET region, and increasing the dose from 0.8 Gy to 3.2 Gy decreased the RBE from 2.9 to 2.7. The survival curves of cells irradiated with 20 keV/microns carbon beams showed an initial shoulder. When RMUG was irradiated at 4 Gy with 200 KVp X-rays, the recovery rate between two split doses (6 hour interval) was 1.7. RMUG irradiated with 20 keV/microns carbon beams (4 Gy) showed a recovery rate of 1.4. Recovery between split dose irradiation was observed with both X-ray and carbon beam irradiation; however, the recovery rate was lower with carbon beams. Cells irradiated with LET higher than 40 keV/microns did not show recovery between split doses.

Carbon↗
PubMed1993

Design and synthesis of highly potent and selective cyclic dynorphin A analogs. 2. New analogs.

We have designed and synthesized several cyclic disulfide-containing peptide analogs of dynorphin A (Dyn A) which are conformationally constrained in the putative "address" segment of the opioid ligand. Several of these Dyn A analogs exhibit unexpected apparent selectivities for the kappa and mu opioid receptors(s) of the central vs peripheral nervous systems. Thus, incorporation of conformational constraint in the putative "address" segment of Dyn A analogs has resulted in the kappa/mu opioid receptor ligands [L-Pen5,Cys11]Dyn A1-11-NH2 (4), [Cys5,Cys10]Dyn A1-11-NH2 (5), [Cys5,Cys9]DynA1-11-NH2 (6), and [Cys4,Cys9,Arg10]DynA1-11-NH2(7). All of these analogs possess high kappa and mu opioid receptor affinities for the central receptor (guinea pig brain), but effect only weak potency at peripheral kappa and mu opioid receptors (GPI). In fact cyclic dynorphin A analog 4 shows > 19,000-fold differences between central kappa opioid affinity and potency in the guinea pig ileum (GPI). Additionally analog 4 is not an antagonist in the GPI, suggesting possible receptor differences between these sites. Substitution of Tyr1 by Phe1 in the cyclic 1-11 series gave the analog [Phe1,Cys5,Cys11]Dyn A1-11-NH2 (1) that was surprisingly potent in the guinea pig brain binding assay (IC50 = 15.1 nM) at the kappa receptor, but was inactive in the GPI and mouse vas deferens bioassays. D-Ala2 and Tic4 analogs of 1 had lower affinity at brain kappa receptors and had very weak potencies in the GPI and MVD bioassays. On the other hand, [Cys6,Cys10]DynA1-11-NH2 (8), [Cys8,D-Cys13]DynA1-13-NH2 (9), [D-Cys8,D-Cys12]DynA1-13-NH2 (10), and [D-Pro10,Cys5,Cys13]-Dyn A1-13-NH2 (11) were surprisingly potent in the GPI bioassay, though considerable apparent selectivity for central receptors is still retained. The apparent lack of correlation between the pharmacological profiles observed in smooth muscle and in the brain binding assays, particularly with 1 and 4, may suggest the existence of different subtypes of the kappa and mu opioid receptors in the brain and peripheral systems.

Amino Acid Sequence↗
PubMed1993

Nitric oxide-dependent and -independent neurogenic relaxation of isolated dog urethra.

In the presence of adrenergic and cholinergic blocking agents, transmural electrical stimulation evoked a relaxation in isolated dog urethra precontracted with histamine. The response was abolished by tetrodotoxin, indicating its neurogenic origin. The non-adrenergic and non-cholinergic relaxation developed rapidly and was transient at low stimulation frequencies (< or = 1 Hz). However, at higher frequencies (> or = 5 Hz) the recovery phase of the relaxation became slow and often showed a notch, suggesting the presence of transient and slow components. NG-Monomethyl-L-arginine, a nitric oxide synthase inhibitor, inhibited the transient relaxation but did not affect the relaxation evoked at high stimulation frequencies. NG-Nitro-L-arginine, a more potent nitric oxide synthase inhibitor, abolished the transient relaxation produced at low stimulation frequencies and markedly attenuated the transient component at high frequencies. However, NG-nitro-L-arginine did not affect the slow component. The inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine was reversed by the addition of L- but not D-arginine. Exogenously applied vasoactive intestinal polypeptide (VIP) produced a slowly developing relaxation. The slow relaxation induced by transmural electrical stimulation and VIP was not affected by [4-Cl-D-Phe6,Leu17]VIP, a reportedly competitive VIP antagonist. NG-Nitro-L-arginine did not affect the relaxation induced by VIP and sodium nitroprusside. These results suggest that the non-adrenergic and non-cholinergic relaxation induced by transmural electrical stimulation is composed of nitric oxide-dependent and -independent components in the isolated dog urethra.

Animals↗
PubMed1993

Heat treatment of nuclear extract alters selection of the 3' splice site in pre-mRNA splicing.

We investigated in vitro splicing reaction using an artificially created mRNA precursor containing a single 5' splice site and tandemly duplicated 3' splice sites. We found that the 3' splice site proximal to the 5' splice site is predominantly used under the standard splicing conditions. However, when the preheated nuclear extract was employed, the intermediate in which the distal 3' splice site was selected accumulated exclusively. This shows that heat treatment of nuclear extract abolishes the activity involved in the selection of the 3' splice sites that are in cis-competition for the common 5' splice site. The results presented here suggest the presence of a factor(s) required for the selection of the proximal 3' splice site.

Base Sequence↗
PubMed1993

The human Ig-beta cDNA sequence, a homologue of murine B29, is identical in B cell and plasma cell lines producing all the human Ig isotypes.

The B cell Ag receptor complex consists of at least two disulfide-linked, heterodimeric structures: the clonally restricted membrane Ig (mIg) molecule and the nonpolymorphic Ig-alpha:Ig-beta protein dimer. The latter molecule is encoded by two separate genes, mb-1 and B29. The DNA sequences of murine and human mb-1 and murine B29 have been determined previously. This study describes the sequence of the full-length human cDNA homologue of the murine Ig-beta/B29 message. The human sequence codes for a protein that displays the typical subunit features of a transmembrane member of the Ig superfamily. The transmembrane and intracytoplasmic domains exhibit striking nucleotide and amino acid sequence similarity between the two species. These regions show almost complete conservation of areas presumed to be involved in noncovalent interactions with other members of the receptor complex and with intracellular kinases and cytoskeletal components. The only sequence dissimilarity seen in these presumed critical areas involves the Y-E-G-L-N motif, a potential target for tyrosine phosphorylation. In contrast, the extracellular portion is much more divergent. Inasmuch as similar patterns of species diversity have been reported for Ig-alpha, the Ig-alpha and Ig-beta molecules may have coevolved to maintain species-specific extracellular interactions between one another and with mIg. Similar to the Ig-alpha molecule, the Ig-beta sequence is identical in B lineage cells expressing all five Ig isotypes. However, in contrast to the Ig-alpha molecule, the Ig-beta sequence is expressed at apparently similar levels in terminally differentiated, mIg- plasma cells as well as in mIg+, mature B cells. These data suggest that Ig-beta has functions in addition to those associated with surface mIg expression.

Amino Acid Sequence↗
PubMed1993

Phase I study of DQ-2556, a new parenteral 3-quaternary ammonium cephalosporin antibiotic.

The safety and pharmacokinetic properties of DQ-2556, a new parenteral cephalosporin, were evaluated using healthy volunteers after 5-minute intravenous infusion of doses of 250, 500, 1000, or 2000 mg and a 1-hour infusion of 2000 mg, and an intramuscular dose of 500 mg. The half-lives of DQ-2556 ranged from 1.64 to 2.15 hours. The peak serum concentrations and area under the curve values were linearly correlated to the doses. The mean urinary recoveries were 80.0 to 85.5% of a dose within 24 hours. Salivary concentrations of the drug were low. There was no accumulation of DQ-2556 after 9 administrations every 12 hours. DQ-2556 was well tolerated.

Adult↗
PubMed1993

Manganese superoxide dismutase content and localization in human thyroid tumours.

Manganese-containing superoxide dismutase (Mn-SOD) content and its immunohistochemical localization in human thyroid tumours and some other thyroid diseases were examined and compared with adjacent normal thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used in this study for the measurement of Mn-SOD. The content of Mn-SOD tended to increase in diffuse hyperplasia, adenomatous goitre, and follicular adenoma. In papillary carcinoma, it was significantly higher than in adjacent normal thyroid tissue. Follicular carcinoma also revealed a markedly high Mn-SOD content. In the immunohistochemical study, adjacent normal thyroid tissue showed granular positive staining of Mn-SOD in the cytoplasm. An increase of Mn-SOD was observed in the papillary proliferative lesion of diffuse hyperplasia and in the follicles adjacent to lymphoid tissue in chronic thyroiditis with hypothyroidism. Strong positive staining of Mn-SOD was observed in papillary and follicular carcinomas, whereas in anaplastic carcinoma staining was markedly less intense. These results indicate that the Mn-SOD content varies according to the degree of differentiation of thyroid carcinomas.

Adenoma↗
PubMed1993

Monoclonal IgM, IgG, and IgA human rheumatoid factors produced by synovial tissue-derived, EBV-transformed B cell lines.

In an effort to study disease-related autoantibodies in rheumatoid arthritis (RA), rheumatoid factor (RF)-producing B cell lines were developed from the heterogeneous B cell populations infiltrating the synovial tissue of patients with arthritis. Over 125 EBV-transformed B cell cultures were derived from three patients: one with early pre-erosive RA, one with advanced RA, and one with osteoarthritis (OA). IgM, IgG, and IgA RF-producing B cell lines were found in all three series but with several significant differences. In each of the two RA patients, 22% of the Ig-producing cell lines secreted RF compared to 7% in the OA patient. The isotypes of these RF were mostly IgM in the early RA (62%) and the OA patient (60%) as contrasted to predominantly IgA (75%) and, to a lesser extent, IgG (12.5%) in the advanced RA patient. Analyses of the light (L) chain composition of these RF revealed that 82% of the IgM RF used kappa L chains whereas only 31% of the non-IgM RF used kappa chains. Antigen-binding analyses of these RF revealed that all the synovial tissue-derived RF from the advanced RA patient exhibited antigen binding specificities restricted to a narrow range of gamma globulins. In contrast, the synovial RF of the other two patients were either reactive with a broader spectrum of gamma globulins or reactive with a variety of unrelated antigens. In every instance, the gamma globulin-specific RF were of all three major isotypes whereas the polyreactive RF were restricted to the IgM isotype. These data demonstrate that synovial B cells from both RA and OA patients can produce RF and that significant differences can exist among patients in the percentage of RF generated and their H and L chain isotype distribution. The reversal of the kappa:lambda ratio among the IgG and IgA RF and the more restricted antigen-binding specificities of the IgG and IgA vs IgM RF suggest that a non-stochastic, possibly antigen-driven selection process was involved in their generation. The relevance of these differences in RF precursor frequency, H and L chain distribution, and antigen specificity to these two diseases warrants further investigation.

Aged↗
PubMed1993

Promotion of cell adhesion on fibronectin during adenovirus infection of KB cells.

Cytopathic effects of adenovirus-infected human cells consist of rounding and detachment from the substrate at late times postinfection. It is not known, however, whether any changes in cell adhesion are induced by adenoviruses before cytopathic effects become evident. We show here that attachment and spreading of human adenovirus type 2 (Ad2)-infected KB cells on fibronectin (FN) are, unexpectedly, promoted at intermediate times postinfection. The promotion of spreading by Ad2 is not only on fibronectin but also on laminin and vitronectin. In contrast, Ad2 or Ad5 mutants defective in the E1b 19-kDa function did not lead to a promotion in cell attachment but they led to a promotion in cell spreading. Inhibition of spreading of Ad2-infected KB cells on FN by the peptide Gly-Arg-Gly-Asp-Ser-Pro is partial, although it is complete in uninfected KB cells. We found, however, that Ad2 infection does not significantly change the levels of expression of beta 1 integrin mRNA and FN receptor polypeptides. Our results thus suggest that adenovirus infection leads to a promotion in adhesion through influencing integrin molecules without altering the quantity and/or through activation in the cytoskeleton or some other pathway.

Adenoviridae Infections↗
PubMed1993

Indium-111-labelled liposomes: dosimetry and tumour detection in patients with cancer.

Neutral phospholipid vesicles (VesCan), which had been prepared for clinical use, were loaded with 37 MBq indium-111 and administered to seven patients with malignant tumours. The median lipid dose was 2.0 mg/kg. Sequential images showed rapid blood clearance at the early stage, with homogeneous uptake of 111In-labelled VesCan (111In-labelled V-liposomes) in the liver and spleen. Dosimetric estimates for these organs were 1.2 and 1.5 mGy/MBq, respectively, with a whole-body exposure dose of 0.076 mGy/MBq. Total renal excretion of 111In was less than 10% of the injected dose, occurring mainly as 111In-EDTA in three patients. Gamma camera images 24-48 h after administration revealed increased activity in the tumours of four patients. 111In-labelled V-liposomes may enable the demonstration of the tumour site without toxicity and with radiation doses comparable to other radionuclide imaging techniques.

Aged↗
PubMed1993

Hypothalamic-pituitary-adrenal axis function in children with attention-deficit hyperactivity disorder.

Examined hypothalamic-pituitary-adrenal axis (HPA axis) function in 30 children with attention-deficit hyperactivity disorder (ADHD) by measuring the diurnal variation and response to the dexamethasone suppression test (DST) of saliva cortisol. Normal diurnal saliva cortisol rhythm was found in only 43.3% of the ADHD children. DST showed suppression in 46.7% of the ADHD children. An abnormal diurnal rhythm and nonsuppression to the DST were more frequent in the severely hyperactive group than in the mildly were more frequent in the severely hyperactive group than in the mildly hyperactive group of children with ADHD. These results suggest abnormalities in HPA axis function in some children with ADHD, especially those exhibiting severe hyperactivity.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

The presence of a common antigen between human gastric cancer cells and OK-432.

Twenty two surgical specimens of gastric cancer resected after administration of OK-432 for the skin reaction test were examined to determine whether the cancer cells had the same antigens as OK-432, a product of hemolytic streptococcus cells. When the tissues were stained by the PAP method with anti-Su streptococcus antibody used as the primary antibodies, the common antigens were demonstrated in 10 (45.5%) of the 22. The presence or absence of the common antigens was independent of the degree of skin reaction to OK-432, and the relations of the common antigens to other host responses were not clear in this study. This is the first report for the presence of such common antigens between human gastric cancer and OK-432.

Adult↗
PubMed1993

Role of 5-HT1A receptors in the forced swimming wheel test in reserpine-treated mice.

The antidepressant-like effect of 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a selective 5-HT1A receptor agonist, was studied in the forced swimming wheel test in reserpine-treated mice. 8-OH-DPAT and the antidepressant imipramine, dose-dependently increased the number of turns of a water wheel made by mice. This effect of imipramine (30 mg/kg, i.p.) was enhanced by reserpine treatment 24 hr before the test. The effect of 8-OH-DPAT (0.3 mg/kg, i.p.) was also enhanced in reserpine-treated mice. This enhanced effect of 8-OH-DPAT was blocked by pretreatment with the 5-HT1A receptor antagonists, (-)-propranolol (3 mg/kg, i.p.) and NAN-190 (1 mg/kg, i.p.), but was not blocked by a beta-blocker, (-)-atenolol (3 mg/kg, i.p.). 8-OH-DPAT did not affect locomotor activity in the reserpinized mice and did not affect the reduction of monoamine content induced by reserpine. These results suggest that the effect of 8-OH-DPAT in increasing the number of turns of the wheel made by mice was exerted through a 5-HT1A receptor and that this effect did not reflect only changes in the locomotor activity of the mice.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Surfactant apoprotein A secretion by human tracheobronchial epithelial cells.

To determine whether surfactant apoproteins are produced locally by the airway walls, we used a two-site simultaneous immunoassay with monoclonal antibodies and measured the surfactant apoprotein-A (SP-A) content in media cultured with human airway explants or cultured epithelial cells. Tracheobronchial explants were cultured for 2 successive periods (periods I and II). Significant SP-A concentrations were detected in both periods. Methacholine (MCh) or isoproterenol (ISP), added to the medium at the beginning of period II, reduced the ratio of SP-A concentration in period II to that in period I, compared to samples without treatment. The SP-A concentration in the medium at the confluent period of cultured epithelial cells was significantly higher than at the mid-period, indicating that SP-A secretion is dependent on the cell number. The supernatant from explants stimulated by MCh was capable of reducing SP-A secretion from cultured epithelial cells. Immunohistochemical study of SP-A using monoclonal antibody demonstrated positive immunoperoxidase staining in the cytoplasm of epithelial cells. Further, Western blots of electrophoresed proteins from epithelial cells showed the characteristic properties of SP-A. These findings indicate that tracheobronchial epithelium can secrete SP-A.

Apolipoproteins A↗
PubMed1993

Effects of oestrogen on hypothalamic beta-endorphin in ovariectomized and old rats.

Immunocytochemical beta-endorphin (beta-EP) staining and ultrastructural observations in the hypothalamus were compared in normal mature female rats, ovariectomized rats, and aged female rats. The effects of oestradiol benzoate (EB) on the hypothalamus were studied. The female Wistar rats were divided into seven groups, as follows: 40-day-old rats (Mature), 54-day-old rats ovariectomized at 40 days (Ovx), rats ovariectomized at 40 days and injected with 0.1 mg EB daily for 7 days (Ovx + e) rats ovariectomized and injected with one dose of 1 mg EB (Ovx + E), 500-day-old (Old), old rats injected with 0.1 mg EB daily for 7 days (Old + e), and old rats injected with 1 mg EB (Old + E). In the Ovx and Old groups, beta-EP-positive cells in the arcuate nucleus were rarely seen, as compared with the Mature group. The staining of beta-EP-positive cells in Ovx + e was slightly recovered and that in Ovx + E was almost completely recovered. However, no recovery of beta-EP-positive cells was seen in the Old + e or Old + E groups. The number of nerve fibers in the median eminence were reduced in both the Ovx and Old groups, as compared with the Mature group. There was no relationship between changes in these numbers and oestrogen replacement in the Old group, but in the Ovx group oestrogen replacement brought about recovery of these numbers. The number of glial cells increased after oestrogen replacement in both the Ovx and Old groups. The frequency of giant mitochondria in the neurons in the arcuate nucleus decreased after oestrogen replacement in the Old group.

Aging↗
PubMed1993

Fc gamma receptor-mediated biological activities of human leukemic cell lines and their modulation by transforming growth factor-beta 1 and interleukin 6.

Previously we reported that transforming growth factor-beta 1 (TGF-beta 1) remarkably enhanced the differentiation of human leukemic cell lines, HL-60 and THP-1, in the presence of 1 alpha,25-dihydroxyvitamin D3 (VD3) and also that it induced Fc receptor for immunoglobulin G (Fc gamma R), type IIIB, in the presence of retinoic acid (RA). The present study revealed that TGF-beta 1 enhanced the Fc gamma RI- and Fc gamma RII-mediated antibody-dependent cellular cytotoxicity (ADCC) of the cells differentiated in the presence of VD3 and RA. However, production of active oxygen molecules was suppressed by TGF-beta 1. On the other hand, IL-6 stimulated production of active oxygen molecules and ADCC of the cells treated with VD3 and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the levels of cell surface Fc gamma RI and Fc gamma RII were not clearly correlated with the ADCC. The TGF-beta 1/VD3-treated HL-60 cells were able to synthesize mRNAs for TGF-beta 1 and TNF-alpha, although TNF-alpha protein was not detectable. These results suggest that TGF-beta 1 has a bifunctional role, either stimulatory or inhibitory, in the modulation of macrophage activities through Fc gamma Rs and that IL-6 stimulates certain macrophage activities in mature cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1993

Anti-CD23 monoclonal antibodies: comparisons of epitope specificities and modulating capacities for IgE binding and production.

A large battery of anti-CD23 mAb were compared for their epitope specificities and for their abilities to alter both IgE binding to cell-associated CD23 and IgE production in vitro in response to three sets of stimulants. The nine mAb tested can be divided into four families which define four antigenic epitopes (A-D) of CD23. Of these four families, two bind antigenic sites, (A and D) that appear to lie outside the IgE ligand binding site and two bind sites (B and C) that appear to be located within or close to this site, as determined by the abilities of appropriate mAb to alter IgE binding to CD23. The effects that these mAb had on IgE secretion by normal peripheral blood mononuclear cells (PBMNC) varied depending on the stimulant employed to induce IgE production. Interactions with epitope A, which was found to lie outside the ligand binding site and to be made more accessible by binding of mAb to other epitopes, had different effects on IgE production than interactions with the other epitopes. Indeed, mAb binding to this epitope lead to as much as a 10 fold enhancement in IgE biosynthesis induced by IL-4 alone or by IL-4 + hydrocortisone whereas interactions at the other sites resulted in almost complete inhibition of IgE production. In addition, mAb reactive with epitopes B and C had minimal effects on IgE production induced by IL-4 + anti-CD40 mAb whereas interactions at epitope A consistently enhanced IgE production. Finally, no apparent direct correlation was found between the ability of individual anti-CD23 mAb to alter IgE binding to cell-associated CD23 and their ability to modulate IgE production by PBMNC. These studies suggest that IgE binding to cell-associated CD23 does not have a major role in the de novo synthesis of IgE that involves CD23 interactions. In addition, the different effects that binding to epitope A vs B or C have on IgE synthesis suggest that molecular interactions between distinct portions of the CD23 molecule and other cell surface molecules expressed on the same B cell or adjacent communicating cells may lead to divergent cellular effects on IgE production. Finally these studies imply that only epitope A is involved in the generation of an IgE response through the CD40 pathway.

Animals↗