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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 199 records · Page 11Linked to original sources
PubMed1993

Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study.

BACKGROUND: The failure rate with radiation therapy alone for Stage III cervical cancer is quite high, and therefore other modalities are being pursued as adjuvants to radiation therapy in hopes of improving the results. METHODS: A randomized, controlled, comparative study on the efficacy and safety of radiation therapy combined with LC9018 (a biologic response modifier prepared from heat-killed Lactobacillus casei YIT9018) was conducted using 228 patients with Stage IIIB cervical cancer. RESULTS: LC9018 enhanced tumor regression (P < 0.1) by radiation after both 30 Gy of external radiation and at the completion of radiation therapy. The combination therapy also prolonged survival and the relapse-free interval (P < 0.05) compared to radiation alone. Analysis of survival using the Cox proportional hazard model indicated that use of LC9018 was a significant factor related to survival duration. Major side effects of combined LC9018 included fever and skin lesions at the injection site, but no severe symptoms were noted. Radiation-induced leukopenia was significantly less severe (P < 0.05) in the LC9018-combined group than in the radiation-alone group, suggesting that this agent might help to prevent leukopenia during radiation therapy. CONCLUSIONS: LC9018 was shown to be an effective agent for adjuvant immunotherapy when combined with radiation therapy.

Adjuvants, Immunologic↗
PubMed1993

Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog, impairs memory consolidation in mice.

Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high selectivity and affinity for mu-opioid receptors, was administered intracerebroventricularly to mice before or immediately after training in a one-trial step-down type passive avoidance task. The pre- and post-training administration of TAPA (0.3 and/or 3 ng) impaired retention performance 24 h after training. In particular, the post-training administration of TAPA was much more effective because a lower dose (0.3 ng) of TAPA exclusively inhibited retention performance. The amnesic effects of TAPA were reversed by the mu-selective opioid antagonist beta-funaltrexamine (5 micrograms, i.c.v.). In addition, TAPA (0.3 and 3 ng) had no effects on nociceptive responses in a tail-flick test or on behavioral responses to electric shock during training. These results suggest that activation of mu-opioid receptors impairs passive avoidance learning, resulting in a dysfunction of memory consolidation, without affecting other behavioral responses.

Amino Acid Sequence↗
PubMed1993

[Plain MR imaging of breast lesions: a study using 3 mm slice thickness].

MR images of 66 patients with palpable breast masses were reviewed. The histological diagnoses were 46 carcinomas and 20 benign lesions. T1- and T2-weighted sagittal images were obtained with a 3 mm slice thickness, 15 cm field of view and 256 x 192 matrix using a 10 cm receiver coil in a 1.5 Tesla system. Thirty-three carcinomas and 12 benign masses were detected on T1-weighted images. Thirty-five carcinomas and 12 benign lesions were detected on T2-weighted images. Thirty-nine carcinomas and 14 benign lesions were detected on T 1- and/or T2-weighted images. High signal areas on T2-weighted images were found in 22 carcinomas and 5 benign lesions. Low signal areas on T2-weighted images were found in 12 carcinomas and 5 benign lesions. Fine spicules were found on T1-weighted images around 13 carcinomas, but were not found around any benign lesions. This result suggested that the fine spicules might be the only useful finding to differentiate malignancy on MR images without contrast medium.

Adult↗
PubMed1993

[Atherectomy with over-the-wire type catheter for femoro-popliteal artery stenosis: initial and eight month follow-up results].

Percutaneous atherectomy using Atherotrack was performed in 5 patients with symptomatic femoro-popliteal artery stenosis. All patients were men and ages ranged from 37 to 70. Four lesions were atherosclerotic and 1 lesion was post-operative anastomotic stenosis following traumatic popliteal artery injury. There was no technical failure and all lesions were successfully dilated with no or minimal residual stenosis. API returned within normal limit and patients were symptom-free immediately after the procedure. We experienced no major complication related to this procedure. Excised specimen included thickened fibrous intima, atherosclerotic materials, calcification, internal elastic lamina and fibrous media. Follow-up DSA 5 months after procedure showed good patency in 4 cases, and they remained free from symptoms in this follow-up period. In those patients, lesions were generally short and eccentric, run-off was good, and only thickened intimal tissue was obtained. Those factors seem to promise long-term patency and to be good indications of atherectomy. Restenosis as well as recurrence of claudication, however, developed in one patient with DM, who had long, tight, complex stenosis and poor run-off. Considerable amount of medial tissue was found in this specimen. We suspect that those factors were associated with reduced long-term patency rates.

Adult↗
PubMed1993

[A clinical and pathological study of non-Hodgkin's lymphoma of the nasal cavity and paranasal sinuses].

We studied 30 patients with early stage malignant lymphomas involving the nasal cavity and/or paranasal sinus who were treated between 1972 to 1991 in Hokkaido University Hospital. The mean age of the patients was 60.6 yr, and the male-to-female ratio was 2.6. The predominant histologic type was diffuse large cell type (n = 23). Treatment policy differed depending on time: radiotherapy (RT) alone between 1972 and 1980 (n = 15), RT followed by modified CVP or CHOP between 1981 and 1988 (n = 10) and BACOP followed by RT between 1989 and 1991 (n = 5). Overall five-year survival was 53%. Better survival was observed in patients with B-cell type (72%), smaller mass (tumor limited to the unilateral nasal cavity or paranasal sinus) (76%), and patients who were treated with combination chemotherapy (BACOP) followed by RT (100%). Eleven patients experienced recurrence. Four of nine local recurrences were in patients with T-cell lymphoma. CNS relapse was observed in three patients with T-cell lymphoma. We conclude that T-cell lymphoma arising at the nasal cavity and/or paranasal sinus needs careful follow-up for its high frequency of local and CNS relapse. More intensive treatment such as prophylactic whole brain RT, intrathecal administration of MTX or third generation chemotherapy (e.g. MACOP-B) might improve survival in these patients.

Adolescent↗
PubMed1993

Geranylgeranylacetone used as an antiulcer agent is a potent inducer of differentiation of various human myeloid leukemia cell lines.

Low concentrations of geranylgeranylacetone (GGA), known as an antiulcer agent (Teprenone), induces differentiation of various human myeloid leukemia cell lines. The cell lines examined in the present study were myeloblastic ML1, histiocytic U937, promyelocytic HL60, and multipotential K562. All of these cell lines were induced to differentiate by 20 microM GGA, as measured by NBT staining. Neither polyprenylacetones, with more or fewer isoprene units than the geranylgeranyl group, nor polyprenylalcohols had no differentiation-inducing activity. GGA used in combination with RA or TNF-alpha increased ML1 cell differentiation. The present results suggest that GGA may be a useful agent in differentiation therapy of leukemia.

Cell Differentiation↗
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↗