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Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 397 records · Page 22Linked to original sources

Prenatal ethanol exposure affects the activity and mRNA expression of neuronal membrane enzymes in rat offspring.

In order to elucidate molecular mechanisms underlying brain dysfunction in offspring exposed to ethanol in utero, subclinical doses of ethanol that do not have apparent structural effect on the offspring were administered intraperitoneally to pregnant rats at various gestational stages. We measured the activity of membrane marker enzymes and the level of mRNA of myelin proteins of the offspring brain. The activity of a myelin specific enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased in ethanol-exposed offspring. This effect was not related to the period of gestation or the dose of ethanol. Perikaryonal enzymes, acetylcholinesterase and Na+, K(+)-ATPase, were significantly affected in groups exposed to ethanol at early fetal stage and in high doses. Expression of mRNAs of CNP and myelin basic proteins decreased significantly in the ethanol-treated group, with abnormal developmental profile suggesting a relationship with delayed myelination in offspring exposed to ethanol in utero. The present findings suggest that in spite of the low doses of ethanol that do not cause clinical symptoms in the offspring, prenatal exposure to ethanol affects the level of mRNA of membrane enzyme proteins in the offspring brain, consequently causing a corresponding reduction in enzyme activity, that may lead to neuronal dysfunction. In a separate study, blood ethanol levels were found to reach a maximum level within 30 min after injection and be undetectable after 5 to 10 h. No accumulation effects due to daily injection were observed.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Lysis of autologous tumor cells by large granular lymphocytes in patients with acute leukemia in complete remission: correlation between lytic activity and clinical outcome.

In order to evaluate the effect of specific immune response on prognosis in acute leukemia, we investigated the correlation between the lysis of autologous tumor cells (ATC) by lymphocytes and prognosis. Peripheral mononuclear cells (PMC) from most patients with acute leukemia in complete remission (CR) do not exhibit cytotoxic activity against fresh-frozen ATC, although they have adequate cytotoxic activity against K562 cells. When the large granular lymphocyte (LGL) fraction was used in this study, we observed lysis of ATC in 17 (43.6%) of 39 patients with acute leukemia (12 (42.9%) of the 28 patients with acute myelogenous leukemia (AML) and 5 (45.5%) of the 11 patients with acute lymphocytic leukemia (ALL)). With regard to prognosis, the lytic activity of the LGL fraction did not reflect the duration of CR. The median CR duration in AML patients was 13 months for the lysis-positive group and 11 months for the lysis-negative group. No significant correlation was also found between lytic activity of the LGL fraction and overall survival in each patient. However, the lysis-positive group tended to have a longer survival, the median overall survival being 48 months for the lysis-positive group vs 12 months for the lysis-negative group. The prolonging of overall survival in the lysis-positive group was attributed to a high rate of induction of second remissions in this group. Long-term patient survival in the two groups did not differ.

Adolescent↗

Translocation (3;21)(q26;q22) in treatment-related acute leukemia secondary to acute promyelocytic leukemia.

We performed cytogenetic studies in a patient with treatment-related acute leukemia (t-AL) to identify the associated chromosomal changes. Metaphase analysis revealed a t(3;21)(q26;q22) translocation. Acute promyelocytic leukemia (APL) had been diagnosed 4 years earlier and the patient had received intensive induction chemotherapy and sequential post-induction therapy that included agents that targeted DNA-topoisomerase II (topo II). This case suggests an association between previous therapy with topo II inhibitors and development of t-AL associated with a balanced aberration involving the 3q26 and 21q22 bands.

Acute Disease↗

Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes.

To study the contribution of putative perforin-independent mechanism in the antigen-specific target destruction by cytotoxic T lymphocytes CD8+ CTL lines were established from spleen cells of chimeric mice produced by injecting perforin (-/-) embryonic stem cells into blastocysts of RAG-2(-/-) mice. When tested on normal concanavalin A blasts, these perforin-deficient cytotoxic T lymphocyte lines were found to be capable of inducing antigen-specific target cell lysis accompanied by DNA degradation. In contrast, with target cells carrying a mutation in Fas molecule, perforin-independent cytotoxicity was not detectable. These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis.

Animals↗

[Positive rates of Neisseria gonorrhoeae and Chlamydia trachomatis on pharynx and rectum of patients with gonococcal or chlamydial genital infections].

In an attempt to know the applicability of non-cultural detection technique for N. gonorrhoeae and C. trachomatis on pharyngeal and rectal swabs, the swabs taken from N. gonorrhoeae- and C. trachomatis-free subjects were tested by Gonozyme, Chlamydiazyme, Ideia Chlamydia, Gen-Probe and Gen Probe Pace 2. As N. gonorrhoeae- and C. trachomatis-free subjects, the castrated males older than age 70, with known prostate cancer treated at least for 6 months with anti-androgens who were seronegative for C. trachomatis and had a history of Ofloxacin treatment in the last 3 months and whose pharyngeal and rectal swabs were negative for N. gonorrhoeae, were subjected for study. The false negative rates were for N. gonorrhoeae from the pharynx by Gonozyme 57.7%, by Gen-Probe 0%, by Gen-Probe Pace 2 0%, from rectum by Gonozyme 0%, by Gen-Probe 0% by Gen-Probe Pace 2 0%, for C. trachomatis from pharynx by Chlamydiazyme 93.8%, by Ideia Chlamydia 8.3%, by Gen-Probe 0%, by Gen-Probe Pace 2 0%, from rectum by Chlamydiazyme 94.4%, by Ideia Chlamydia 70.9%, by Gen-Probe 20.0% and by Gen-Probe Pace 2 0%. To investigate the incidence of pharyngeal and rectal infection by N. gonorrhoeae among the patients with gonococcal genital infection, as well as pharyngeal and rectal infection by C. trachomatis among the patients with chlamydial genital infection, pharyngeal and recal swabs obtained from the patients with genital infection by N. gonorrhoeae or C. trachomatis were tested by Gen-Probe Pace 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome.

Scott syndrome is a bleeding disorder associated with an isolated defect in expression of membrane coagulant activity by stimulated platelets. This defect represents a decrease in platelet membrane binding sites for coagulation factors Va and VIIIa, reflecting diminished surface exposure of phosphatidylserine (PS). To gain insight into the cellular and genetic basis for this disorder, B-lymphocytes from a patient with Scott syndrome and from normal donors were immortalized by EBV-transformation, and tested for their capacity to expose plasma membrane PS in response to the Ca2+ ionophore, A23187. Upon incubation with A23187, EBV-lymphoblasts derived from normal donors consistently induced surface expression of PS in > 70% of all cells, as detected by membrane association of the PS-binding proteins, factor Va or annexin V. PS exposure in these cells was maximal after 5 min, and saturated at < 100 microM external free [Ca2+]. By contrast, < 30% of Scott syndrome lymphoblasts exposed PS, and saturation was not observed at > 1 mM external free [Ca2+]. Single-cell clones derived from the Scott lymphoblasts all exhibited a diminished response to A23187 comparable with that of the parental cells, suggesting that all lymphocytes from this patient share this membrane abnormality. Hybridomas prepared by fusion of Scott lymphoblasts with the myeloma cell line UC-LUC showed responses to Ca2+ ionophore comparable to those observed for normal lymphoblasts and for hybridomas prepared by fusion of normal lymphoblasts with UC-LUC. This correction of the Scott abnormality suggests possible complementation of an aberrant gene(s) responsible for this disorder.

Annexin A5↗

Indonesian medicinal plants. IX. Chemical structures of gongganosides A, B, and C, three new quinovic acid glycosides from the bark of Bhesa paniculata (Celastraceae).

Three new quinovic acid glycosides, named gongganosides A (1), B (2), and C (3), were isolated from the bark of Bhesa paniculata (Celastraceae), an Indonesian medicinal plant collected in Sumatra Island. The chemical structures have been elucidated on the basis of chemical and physicochemical evidence as quinovic acid 3-O-beta-D-xylopyranosyl(1-->3)-alpha-L- rhamnopyranoside for 1,28-O-beta-D-glucopyranosylquinovic acid 3-O-alpha-L-rhamnopyranoside for 2, and 28-O-beta-D-glucopyranosyl-quinovic acid 3-O-beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranoside for 3.

Carbohydrate Sequence↗

Primary ocular and central nervous system malignant lymphoma first manifested as uveitis: possible role of single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine in the diagnostic procedure.

A case of primary ocular and central nervous system malignant lymphoma was reported which was first manifested as bilateral uveitis ten months before the neurological symptoms appeared. The lesion of lymphoma in the central nervous system was clearly demonstrated as a heavy accumulation of N-isopropyl-123I-p-iodoamphetamine by single photon emission computed tomography. Since most brain tumors reportedly show a low uptake of N-isopropyl-123I-p-iodoamphetamine, single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine could be helpful in making the diagnosis, as well as in visualizing primary central nervous system malignant lymphoma.

Adult↗

Expression and localization of mRNA for epidermal growth factor and epidermal growth factor receptor in human cholesteatoma.

The roles of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in the proliferation and progression of the epithelium of middle ear cholesteatoma were studied. An attempt was made to elucidate the site and degree of localization of the EGF mRNA and EGF-R mRNA in the epithelium of the cholesteatoma by means of the non-radioactive in situ hybridization method. Ten cholesteatoma specimens excised during operations and six normal skin specimens (control) collected from the external ear canal were used in this study. The signal of the EGF mRNA was slightly expressed in part of the basal cells in only one of the six control specimens, while the signal was strongly expressed along the basal cells of the cholesteatoma epithelium in five of the ten specimens. The signal of the EGF-R mRNA was observed along the basal cell layer in five of the six control specimens, while the signal was strongly expressed in all layers of the cholesteatoma epithelium in all ten specimens. The expression was especially marked in the basal cell layer. These findings suggest the possibilities that abnormal expression of the EGF-R mRNA in nearly entire epithelial layers of cholesteatoma is due to overexpression of EGF-R gene, and that there is a mechanism of epithelial basal cell proliferation through an autocrine regulatory system via EGF and EGF-R.

Base Sequence↗

Brain abscess due to infection with Entamoeba histolytica.

We successfully treated a serious case of Entamoeba histolytica infection showing brain abscess, meningitis, and liver abscess by oral administration of metronidazole, intramuscular injection of dehydroemetine, and drainage of the brain abscess. The diagnosis of amebic brain abscess was based on a combination of clinical symptoms and signs, computed tomography and magnetic resonance imaging findings, a positive serologic test result for E. histolytica, a dramatic response to anti-amebic drugs after an ineffective therapeutic history with antibacterial drugs, and application of the polymerase chain reaction method.

Administration, Oral↗

[CAMBO-VIP for advanced diffuse large cell lymphoma (LSG classification)--a long-term follow-up study].

Twenty-two patients with advanced diffuse large cell lymphoma (LSG classification) were treated with the combination chemotherapy of cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission and 2 patients had partial remission. With a median follow-up of 52 mos, 3 patients relapsed (17%), and 2 patients died. The actuarial overall survival and relapse-free survival at 4 years were estimated to be 90% and 83%, respectively. Myelosuppression was severe, but transient. No serious infection was seen, and no platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in WHO grading) was seen in one patient each, but no treatment-related fatalities were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for advanced diffuse large cell lymphoma.

Adolescent↗

[Increased blood cell destruction during vigorous regeneration of bone marrow after CAMBO-VIP chemotherapy for non-Hodgkin's lymphoma].

Alternating non-cross-resistant chemotherapy has been induced for the treatment of non-Hodgkin's lymphoma (NHL) with the aim of cure, even in advanced cases. We formulated a new high dose regimen, CAMBO-VIP, which was a weekly treatment. They were administered during alternate weeks for a total period of 12 weeks. We obtained high response rate and prolonged disease-free survival with this regimen. We noticed the elevation of serum LDH level in some patients at or shortly after the completion of CAMBO-VIP treatment. LDH elevation was not associated with liver function abnormality in terms of elevation of GOT or total bilirubin. All of these patients were in complete or partial response with no evidence of tumor progression. An LDH isozyme study which was done at the time of LDH elevation showed elevation of both LDH1 and LDH2. Interestingly serum haptoglobin was undetectable in all 6 patients measured at the time of LDH elevation. Reticulocytosis and leukoerythroblastosis in peripheral blood were also observed in all of these patients. These abnormalities including LDH elevation returned to normal within a rather short period, usually within 1 to 3 weeks. From these observations, it is most likely that these abnormalities were due to excessive blood cell destruction, which was observed in association with rapid recovery from myelosuppression.

Adolescent↗

Improvement of impaired brain monoamine metabolism by the cognition-enhancing agent nefiracetam after microsphere-induced cerebral embolism in rats.

Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide DM-9384, CAS 77191-36-7), a pyrrolidone (cyclic GABA) derivative, is a newly developed cognition-enhancing (nootropic) agent. In the present study, the effects of nefiracetam on cerebral monoamine metabolism in rats after microsphere-induced cerebral embolism have been examined. For cerebral embolization, microspheres were injected into the left internal carotid artery. Nefiracetam (3, 10 and 30 mg/kg p.o.) was administered daily to the animals for 13 days from the 9th day after the operation. The levels of DA, DOPAC and HVA in the control (embolism-induced, but untreated) group were significantly decreased compared with those of the normal (non-operated) group. In animals treated with nefiracetam (3 mg/kg p.o.), these monoamine levels were higher than controls in the cortex and hippocampus, whereas they were not significantly changed in the striatum. 5-HT contents in the control group significantly decreased from normal levels in the cortex and hippocampus, on which nefiracetam at various doses had no effect. The levels of 5-HIAA in the control group also decreased, which were, however, significantly increased by 3 mg/kg of nefiracetam. The results suggest that nefiracetam has improving actions on the dysfunction of the dopaminergic and serotonergic systems induced by cerebral embolism.

3,4-Dihydroxyphenylacetic Acid↗

[Pharmacokinetics of paclitaxel in experimental animals. Part 1. Blood level].

The plasma disposition of paclitaxel in rabbits (7 mg/kg, 1 h i.v. inf.) was biphasic with half-lives of 0.36 and 6.36 h, and AUC was 9.46 micrograms.hr/ml. K12 value was larger than K21 and V2 was larger than V1, suggesting that paclitaxel had a favorable distribution profile in tissues. In S 180 bearing male ICR mice (30 mg/kg, i.v. bolus), the biphasic plasma disposition was also observed. The half-lives and AUC were 0.25 h, 2.23 h and 117.93 micrograms.hr/ml. Paclitaxel distributed widely in plasma rather than blood cells. The biliary level of paclitaxel in the enlarged gallbladder of ICR mice was markedly high, about 10-fold higher than the urinary level and 100-fold higher than the plasma level. The bioavailability with oral administration to ICR mice was poor. AUC(oral)/AUC(i.v.) ratio in the bile, liver, tumor and plasma was 18.91, 6.71, 0.83 and 0.45%, respectively.

Administration, Oral↗

[Pharmacokinetics of paclitaxel in experimental animals. Part 2. Tissue distribution].

In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.

Animals↗