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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 919 records · Page 51Linked to original sources

Improvement in the therapeutic efficacy of an asthma-inducing sea squirt antigen termed DIIIa by its polymerization in hyposensitization of sea squirt allergy.

Polymerization using glutaraldehyde markedly improved the apparently low efficacy of an asthma-inducing sea squirt antigen, DIIa (MW 9,980), in hyposensitization therapy on patients with sea squirt allergy. A product (poly-DIIa-G) comparable to Gi-rep (MW 106,000) in MW-distribution showed high therapeutic efficacy comparable to the most effective therapeutic antigen, Ei-M, which was paralleled by a significant increase in the allergen-specific IgG titer in most of the successfully hyposensitized patients as assayed using Ei-M as the target antigen. Another product (poly-DIIa-E) comparable to Ei-M (MW 22,800) in MW also showed a high but slightly lower therapeutic efficacy relative to poly-DIIIa-G with an apparent increase in the specific IgG titer in some patients. However, no significant change in the IgG titer was detected in most patients unsuccessfully treated with intact DIIIa. On the other hand, no significant change was detected in the IgE titer specific to the target antigen in the patients, except in a few cases where the change was independent of the therapeutic effect. The apparent correlation between the increase in the specific IgG titer and the enhancement of the therapeutic effect suggested that polymerization enhanced the immunogenicity of DIIIa and resulted in a significant improvement in the therapeutic efficacy through an additional induction of the specific IgG capable of competing, as a blocking antibody, with the specific IgE for an asthma-inducing antigen, like DIIIa, in patients treated with the polymerized antigens.

Animals↗

[Phenytoin induced agranulocytosis: direct and T cell-mediated mechanisms].

A 57-year-old male was admitted to our hospital because of high fever and dyspnea. He had convulsive attacks after the operation for subarachnoid hemorrhage. He received an anticonvulsant, Hydantol F (Phenytoin + Phenobarbital), for 20 days before hospitalization. The white cell count on admission was 900/microliters without any neutrophils. Pseudomonas was demonstrated from blood cultures. After the anticonvulsant was discontinued and potent antibiotics were administered, his symptoms improved. Neutrophils appeared in the peripheral blood. We investigated the effect of phenytoin on the granuloid precursors using in vitro colony assay (CFU-C) after recovery from agranulocytosis. There was substantial decrease in CFU-C colony numbers when phenytoin or peripheral T-lymphocytes incubated with phenytoin was added in the culture. The addition of sera from acute phase did not affect the colony formation. These results suggested that direct toxic effect of the drug and cellular immunity played an important role in phenytoin induced agranulocytosis.

Agranulocytosis↗

Revision of residual deformities after operations for duplication of the thumb.

We treated thirty-six patients (thirty-eight thumbs) who had residual deformity after ablation of a duplicated thumb. The deformities were classified into three groups: interphalangeal (eight thumbs), metacarpophalangeal (sixteen thumbs), and zigzag (fourteen thumbs). The indication for operation was primarily cosmetic; only eight patients had a functional disability, and that was mild. At the most recent follow-up, the results were rated good except for three fair results in the group that had an interphalangeal deformity, two fair results in the group that had a metacarpophalangeal deformity, and two poor and seven fair results in the group that had a zigzag deformity.

Adult↗

[The changes in EEG, evoked potentials and neurological recovery after global brain ischemia in dogs].

Electroencephalography (EEG), evoked potentials and neurological recovery score were compared between 10 min and 15 min transient global brain ischemia in 18 dogs. The transient global brain ischemia was induced by occluding aorta, superior and inferior caval veins. The grade of EEG (1: normal approximately 5: flat) 2 hrs after ischemia was significantly lower with the 10 min ischemic group (n = 9) than with the 15 min group (n = 9) (3.7 +/- 0.5 vs 4.1 +/- 0.3, P less than 0.05). The rate of reappearance in evoked potential waves 2 hrs after ischemia was higher with the 10 min ischemic group than with the 15 min group (auditory brainstem response 5 wave: 100% vs 33%, middle latency response Pa wave: 80% vs 0%, somatosensory evoked potential N2 wave: 83% vs 78%, N3 wave: 67% vs 33%). The neurological recovery score (0: death approximately 100: normal) 7 days after ischemia was significantly higher with the 10 min group than with the 15 min group (58 +/- 34 vs 27 +/- 23, P less than 0.05). In both groups, there was a significant correlation (r = +0.85, P less than 0.01) between the total score of EEG and evoked potential waves (0: no wave appeared approximately 6: all waves appeared) 2 hours after ischemia and the neurological recovery score 7 days after ischemia. These results suggest that the neurological recovery after transient global brain ischemia would be estimated by EEG and evoked potential waves.

Animals↗

[Clinical study of drug accumulation in gastric cancer after preoperative intra-arterial EA'P injection therapy].

In order to deliver a high concentration of anti-cancer drugs in tumor tissue, preoperative intra-arterial injection therapy using Etoposide (VP-16), Pirarubicin (THP-ADM) and Cisplatin (CDDP), was used for 22 patients with resectable advanced gastric cancer. The concentration of VP-16, Adriamycin (ADM) and platinum (Pt) were measured in cancer tissue, normal mucosa and lymphnodes without metastasis at the greater curvature, which were gathered operatively and in serum just before operation. Student's t test was performed with their data. The mean concentration of VP-16 was less than the detectable limit in all tissues and in serum. The mean concentration of ADM in cancer tissue was significantly higher than in normal gastric mucosa, in lymphnodes without metastasis, and in serum. The mean concentration of platinum in cancer tissue was higher than those in lymphnodes, normal mucosa, and serum, but no significant differences were noted among them. It was concluded that the intra-arterial injection of THP-ADM and CDDP was an effective method to maintain a high concentration of ADM and Pt in gastric cancer tissue. However, intra-arterial injection of VP-16 was not useful.

Antineoplastic Combined Chemotherapy Protocols↗

Disposition and effect of the new thromboxane synthetase inhibitor 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid in man.

The disposition of a new thromboxane synthetase inhibitor, 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904) upon administration of a single 200-mg oral dose to normal Japanese volunteers was studied. DP-1904 proved to be rapidly absorbed from the gastrointestinal tract and converted to its ester glucuronide, which appeared in plasma within 30 min after dosing. The AUCs of DP-1904 and its ester glucuronide were 7.23 +/- 0.54 and 7.93 +/- 0.86 micrograms.h/ml (mean +/- S.E., n = 5), respectively. Both compounds were also eliminated very rapidly from the body (half-lives greater than 60 min). The primary route of elimination was renal, with 52.1 +/- 2.2 and 37.6 +/- 1.6% of the dose being excreted in the urine as the unchanged form and the glucuronide conjugate within 48 h, respectively. The cumulative fecal excretion rates of DP-1904 up to 48 h after dosing were approximately 0.5%. The main metabolite of DP-1904 in humans was DP-1904 glucuronide. Serum thromboxane (TX) B2 levels were reduced more than 98% within 1 h after dosing. There was still more than 75% suppression of serum TXB2 levels at 12 h after dosing. At 72 h TXB2 concentrations returned to control levels. These data indicate that DP-1904 is a potent and long-acting thromboxane synthetase inhibitor.

Adult↗

[Results of radiation therapy for medulloblastoma].

Results of radiation therapy for cerebellar medulloblastoma at Kyoto University Hospital were reviewed. Between 1962 and 1988, 30 patients with histologically-proven medulloblastoma completed radiotherapy. Before 1971, the treatment volume was either the posterior fossa only or posterior fossa plus spinal axis, but after 1972, it was extended to include the entire neuraxis. The mean dose was 48 Gy to the posterior fossa, 36 Gy to the whole brain, and 25 Gy to the spinal axis. The 5-year survival rate and 5-year relapse-free survival rate estimated by the Kaplan-Meier's method were 36% and 37%, respectively, for total cases, but were as high as 79% and 80%, respectively, for the recent 10 patients. This improvement in the treatment results appeared to be due to extensive tumor resection and improved radiotherapy technique, and not to the use of chemotherapy. The prognosis was significantly better in patients treated with craniospinal irradiation than in those otherwise treated. There was a trend towards better survival in patients who received 50 Gy or more to the posterior fossa or 24 Gy or more to the spinal axis, compared to the patients who received lower doses to each site. No significant morbidity of radiotherapy was seen. Four of the six surviving patients who were treated below age 12 have a mental retardation and/or a short stature, but one patient treated at age 5 has a normal growth and a good intelligence. From these analysis, it is recommended to irradiate craniospinal axis and posterior fossa up to 25-35 Gy and 50-55 Gy, respectively.

Adolescent↗

Malignant lymphomas of bone in Japan.

Thirty-four cases of primary non-Hodgkin's lymphoma (NHL) of bone collected from hospitals in Japan were histologically and immunohistologically reviewed, and the results were compared with those in Western countries. There were no remarkable differences in age, sex, and the distribution of bone tumors between Japanese and Western cases. Sixteen cases (47%) diagnosed previously as "reticulum cell sarcoma" were reclassified as diffuse NHL of large cell (seven cases), mixed type (four cases), immunoblastic type (three cases), clear cell type (one case), and multilobated type (one case). The cases with small lymphocytic type with plasmacytoid features (lymphoplasmacytic type) were more common in Japan (35% of our cases) than in Western countries. The distribution of histologic subtypes, except for lymphoplasmacytic and T-cell lymphomas, in the current cases was similar to that in Western countries. However, immunohistochemistry showed that Japanese cases contained a much higher frequency of T-cell lymphoma (10% of all cases) than Western cases. Histologic grade according to the Working Formulation correlated well with clinical stage. There may be a tendency towards better prognosis with lower grade tumors, but this was not statistically significant.

Adolescent↗

Sugar sequences of allergenically active oligosaccharide alcohols isolated from a large-molecular-size sea squirt antigen termed H-antigen.

O-Glycosidically linked oligosaccharide chains were liberated as oligosaccharide alcohols (HPG-beta 2) by beta-elimination treatment from a glycopeptide fraction (HPG, Mr ca. 10(5)) that was isolated from a Pronase digest of a large-size sea squirt antigen termed H-antigen (Mr 10(6)-2 X 10(7)). After HPG-beta 2 was divided into a neutral (HPG-beta 2-N) and an acidic (HPG-beta 2-A) fraction, 11 neutral saccharitols were isolated from HPG-beta 2-N, and their sugar sequences were determined by methylation/GC-MS, FAB-MS, and/or DI/EI-MS. By skin tests specific to patients with sea squirt allergy, it was found that six saccharitols were allergenically active but five were inactive. Furthermore, active saccharitols were all of branched structure containing two nonreducing terminal GalNAc (t-GalNAc) residues, whereas the inactive saccharitols contained one or no t-GalNAc. Since the allergic reaction in skin should depend on the crosslinking of IgE antibodies by certain allergens carrying two or more epitopes, three types of N-acetylgalactosaminyl disaccharide units, GalNAc1----2Fuc1----, GalNAc1----3/4GalNAc1----, and GalNAc1----3/4GlcNAc1----, were nominated as the major components of the allergy-specific epitopes in the active saccharitols. Such multiplicity of the epitope structures might reflect the polyclonality of the specific IgE antibodies.

Allergens↗

Neurite outgrowth from mouse neuroblastoma and cerebellar cells induced by the protein kinase inhibitor H-7.

The protein kinase inhibitor H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) or staurosporine was found to induce neurite outgrowth from mouse neuroblastoma N18TG2 cells and cultured cerebellar cells by light microscopy. Examination by electron microscopy revealed some morphological differences between the neurites of N18TG2 cells induced by H-7 and dB-cAMP, in which H-7 formed longer and thinner neurites and more abundant localized varicose structures along neurites than dB-cAMP. These results indicate that protein kinase inhibitor itself can act as a potent stimulus for inducing neurite outgrowth in a different manner from dB-cAMP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Monoclonal antibody that binds to both the prenatal and postnatal astroglia in rodent cerebellum.

A monoclonal antibody (MAb), generated by immunizing mice with homogenized guinea pig cerebellum, labeled cerebellar astroglia including perikarya, radial fibers and veil-like processes in adult rats, mice and guinea pigs. Cell bodies and processes of the immature radial glia in the ventricular neuroepithelium of fetal mice cerebellum were definitely stained by the MAb on the 14th day of gestation. The astroglial components continued to show selective immunoreactivity to the MAb after the 14th day of gestation.

Animals↗

Calcitonin gene-related peptide regulates calcium current in heart muscle.

The influx of Ca2+ due to the transmembrane calcium current, ICa, has a fundamental role in cardiac pacemaker activity, in the action potential plateau and in excitation-contraction coupling. Both sympathetic and parasympathetic neurotransmitters can modulate ICa. Recent studies indicate that in both the cardiovascular and the central nervous systems, nerve varicosities exist that contain a novel non-adrenergic, non-cholinergic peptide--calcitonin gene-related peptide (CGRP). Although CGRP is known to exert strong positive inotropic and chronotropic effects, as well as to cause vasodilation, very little is known about the ionic mechanisms of these effects. Here we report that CGRP dramatically increases ICa in single heart cells. Although this CGRP-induced increase in ICa resembles the effect of beta-adrenergic agonists, our results demonstrate some significant differences between the effects of CGRP and these agonists: (1) the increase due to CGRP cannot be blocked by beta-adrenergic antagonists; (2) the CGRP-induced effect is transient; and, (3) CGRP can inhibit isoproterenol-stimulated ICa. Our results provide the first electrophysiological evidence that CGRP can significantly modulate ICa in the heart, and suggest a new additional mechanism for the neurogenic control of cardiac function.

Action Potentials↗

The human alpha 2(XI) collagen (COL11A2) chain. Molecular cloning of cDNA and genomic DNA reveals characteristics of a fibrillar collagen with differences in genomic organization.

We have isolated three overlapping cDNA clones encoding the pro alpha 2(XI) collagen chain from a human chondrocyte cDNA library. Together, the cDNAs code for 257 uninterrupted Gly-X-Y triplets (almost 80% of the triple helical domain) and about 200 amino acid residues of the carboxyl telopeptide and carboxyl propeptide. The identification of the clones as pro alpha 2(XI) cDNAs was based on the complete identity between the amino acid sequences of three tryptic peptides derived from human alpha 2(XI) collagen and the cDNA-derived sequence. We have also sequenced six exons within a human genomic alpha 2(XI) cosmid clone. This sequence shows that although type XI collagen belongs to the fibril-forming class of collagens, there are substantial differences in exon sizes at the 3' end of the gene when comparing the alpha 2(XI) gene with those of human types I, II, and III collagens. Finally, pro alpha 2(XI) cDNA has been used as a probe to determine the location of the gene by in situ hybridization of chromosome spreads. The results demonstrate that the gene is located close to the region p212 on chromosome 6. Northern blot analysis shows that the gene is expressed in cartilage but not in adult liver, skin, and tendon.

Amino Acid Sequence↗

Cancer superimposed on adult T-cell leukemia.

Forty-three patients with adult T-cell leukemia (ATL), admitted to the hospital from 1982 to 1987, were studied. Five of those were found to have additional cancer; two of the five had two additional kinds of cancers besides ATL. During the same period, in contrast, the authors encountered only three patients with some superimposed cancer among 155 cases of hematologic malignancies which had no association with human T-cell lymphotropic virus type I (HTLV-I). These facts strongly suggest that HTLV-I infection is not only associated with ATL, but it is likely to increase the incidence of other types of malignancy as well.

Aged↗

Interaction between cholinergic neurons and substance P or calcitonin gene-related peptide terminals of the rat sacral intermediolateral nucleus: double immunostaining at the light and electron microscopic levels.

The relationships both between cholinergic neurons and substance P (SP) and between cholinergic neurons and calcitonin gene-related peptide (CGRP) terminals were examined in the rat sacral intermediolateral nucleus at the light and electron microscopic levels by means of double-immunostaining methods. Cholinergic neurons were labeled by a monoclonal antibody to choline acetyltransferase (CAT) with the avidin-biotin technique and stained bluish-green by indolyl-beta-galactoside reaction products with beta-galactosidase as a marker. On the same sections, SP or CGRP fibers were labeled by polyclonal antisera to SP or CGRP after application of the peroxidase-antiperoxidase (PAP) method and stained brown by the p-dimethylaminoazobenzene (DAB) reaction. After embedding in Epon, light and electron microscopic sections were examined. At the light microscopic level, CGRP-like immunoreactive (CGRP-I) fibers and SP-like immunoreactive (SP-I) fibers were found to pass through the lateral edge of the dorsal horn and then into the dorsal region of the sacral intermediolateral nucleus. In addition, SP-I fibers also extend from the dorsolateral funiculus into the entire sacral intermediolateral region. At the electron microscopic level, many axosomatic and axodendritic synapses were found between CAT-I structures and SP-I terminals in the intermediolateral nucleus, whereas most of the CGRP-I terminals in this area made axodendritic synapses with CAT-I dendrites. These results indicate that cholinergic neurons in the sacral intermediolateral nucleus receive direct synaptic input from SP-I and CGRP-I terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of reverse transcriptase activity by a flavonoid compound, 5,6,7-trihydroxyflavone.

5,6,7-Trihydroxyflavone (baicalein) is a potent inhibitor of the activities of reverse transcriptases from murine leukemia viruses (MLV) (Rauscher and Moloney strains) and human immunodeficiency virus (HIV). Under the reaction conditions specified for each of the MLV- and HIV-reverse transcriptases, both enzyme activities were inhibited by more than 90% in the presence of 2 micrograms/ml baicalein. The mode of the inhibition by baicalein was competitive with respect to the template.primer, (rA)n.(dT)12-18, and noncompetitive to dTTP substrate. Ki value of baicalein for the MLV-reverse transcriptase was determined to be 0.37 microM.

Binding, Competitive↗

Prognostic significance of Ki-67 reactivity in soft tissue sarcomas.

Proliferative activity of soft tissue sarcomas (STS) in 34 cases was estimated by immunohistochemical procedures (avidin-biotin complex [ABC] method) with monoclonal antibody Ki-67 which reacts with a nuclear antigen expressed in all phases of cell cycle except G0. In 20 of 34 cases (59%), varying numbers of Ki-67-positive tumor cells were detected with a range from 5 to 382 per 10 high power fields (HPF) (mean 57.2/10 HPF). Ki-67 index (the number of Ki-67-positive tumor cells/10 HPF) positively correlated with mitotic count (r = 0.428, P less than 0.02), cellularity (r = 0.447, P less than 0.01), and histologic grade (r = 0.473, P less than 0.01). The Ki-67 low index group (less than 50/10 HPF) showed more favorable prognosis than the high index group (more than 50/10 HPF) (P less than 0.005). Three cases with low mitotic count and unfavorable prognosis were proved to be the Ki-67 high index group (142-382/10 HPF). These results indicated that reactivity of tumor cells for Ki-67 is a useful prognostic marker in the patients with STS, and might be used as one of the histologic factors for the grading of STS.

Adolescent↗

Differences in prognostic factors between leukemia and lymphoma type of adult T-cell leukemia.

Prognostic factors affecting the survival of adult T-cell leukemia (ATL) patients were analyzed in three groups: total cases, leukemia type cases, and lymphoma type cases. Factors found to be important overall, i.e. for total cases, were leukocyte count, ATL cell ratio in the peripheral blood, serum calcium levels and lactate dehydrogenase (LDH) level. Of those, LDH level proved not significant when evaluated separately for leukemia type or lymphoma type cases. Leukocyte count and ATL cell ratio were significant in leukemia type patients, whereas it was serum calcium level that was significant in lymphoma type; there were mutually exclusive sets of factors for the two groups. Thus, prognostic factors for ATL patients should be considered separately for each type of the disease.

Adult↗