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Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 163 records · Page 9Linked to original sources
PubMed2000

[Treatment of hepatic veno-occlusive disease after bone marrow transplantation with recombinant human tissue plasminogen activator (rh-tPA)].

Ten children were treated with recombinant human tissue plasminogen activator (rh-tPA) for severe hepatic veno-occlusive disease (VOD) that developed after bone marrow transplantation. Treatment with rh-tPA was begun a median of 22 days (range; 13-127 days) after transplantation. Seven of 9 (78%) evaluable patients had complete resolution of their VOD. Four patients had hemorrhagic complications, and 2 of them died because of pulmonary hemorrhage and subdural hemorrhage, respectively. Although rh-tPA seems to be an effective therapy for established VOD, further studies will be necessary to determine its safety as well as the optimal dosing regimen.

Adolescent↗
PubMed2000

Consensus Conference on the Treatment of Aplastic Anemia.

This article presents guidelines for the diagnosis and treatment of aplastic anemia (AA) established by a consensus panel of investigators from various countries. The panel used the scientific evidence presented during the Consensus Conference forum and found in the scientific literature to prepare guidelines categorized as immunosuppressive therapy, unrelated bone marrow transplantation in patients with AA, and myelodysplasia/acute myeloid leukemia after immunosuppressive therapy.

Anemia, Aplastic↗
PubMed2000

[Clinical features of essential thrombocythemia in three children].

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.

Aspirin↗
PubMed2000

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis.

AIMS: Imbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may be involved in the breakdown of articular cartilage matrix of the temporomandibular joint (TMJ). In this study, MMPs, TIMPs, and MMP-1/TIMP-1 complex levels were examined in TMJ synovial fluid samples aspirated from TMJ osteoarthritis (OA) patients (2 males, 8 females; mean age, 29.7 years) and asymptomatic control subjects (2 males, 8 females; mean age, 23.6 years) to determine the likelihood of increased proteolytic activity in the OA joints. METHODS: The various types of MMPs and TIMPs were detected by Western blotting with monoclonal antibodies and gelatin zymography. The MMP-1/TIMP-1 complex level was measured by an enzyme-linked immunosorbent assay kit. All aspirates were first analyzed for total protein content and then individually diluted to make the total protein levels equivalent. RESULTS: The mean MMP-1/TIMP-1 complex concentration in the synovial fluids of the OA patients was 3.92 +/- 1.39 ng/mL; this value was significantly lower (P < 0.05) than the value from control subjects (5.46 +/- 1.32 ng/mL). Matrix metalloproteinase-1 (52 kDa), MMP-3 (57 kDa), TIMP-1 (28 kDa), and TIMP-2 (26 kDa) were detected in all of the normal and the OA samples. However, MMP-1 (28 kDa), MMP-2 (72 kDa), MMP-3 (45 kDa), and MMP-9 (83 kDa) were detected in higher concentration in the OA samples. CONCLUSION: These findings suggest a strong association between the OA-active joints and the presence of biologically active forms of known tissue degradation enzymes (MMP-1, MMP-3, and MMP-9).

Adolescent↗
PubMed2000

[Progressive paralysis of divergence in an adult with midbrain angioma].

A 37-year-old woman was admitted to the hospital with the complaint of progressive horizontal diplopia of six years' duration when viewing distant objects. On admission she had a slight left convergent strabismus. Homonymous diplopia was present beyond 50 cm and increased on distance fixation. Both eyes were fully mobile in the horizontal plane with a mild decrease in the velocity of horizontal eye movement to the left, and slight impairment of upward eye movement. The left eye did not fully adduct during convergence. The right pupil was slightly larger than the left. Prism cover test showed 6 delta esophoria at 30 cm and 14 delta esophoria at 5 m. The Hess chart showed a convergent deviation. MRI revealed a small right-side paramedian lesion of the midbrain tegmentum lying ventral to the aqueduct of Sylvius, at the level between the superior colliculi and the intercollicular area. A venous angioma with arteriovenous shunts in the right midbrain was diagnosed by angiography. We suggest that lesions that damage the divergence neurons in the tegmentum of the midbrain and also interrupt the supranuclear fibers having an inhibitory effect on the convergence neurons may produce homonymous diplopia on distant fixation combined with the esotropia.

Adult↗
PubMed2000

Improvement of growth of Plasmodium falciparum fresh clinical isolates by using an established serum-free medium, GIT.

In the present study, we have tried to establish continuous cultures of fresh clinical isolates of P. falciparum by using a serum-free medium, GIT. To examine the ability of GIT to support the parasite growth, the growth of various P. falciparum isolates including two laboratory strains of P. falciparum, FCR3 and K1 was compared in both of GIT and RPMI 1640 medium supplemented by 10% human serum (RPMI-HS). Growth rates of various P. falciparum expressed as fold increases were compared in GIT and RPMI-HS, and the maximum growth rates of P. falciparum were 72 in GIT and 35 in RPMI-HS during the culture for 8 days. Growth rate of the clinical isolates varied individually in both culture media, with average growth rates of parasites being 15.9 in GIT and 8.8 in RPMI-HS, respectively (not significant). Growth rates of FCR3 and K1 strains were 28.0 and 6.6 in GIT, and 10 and 7.5 in RPMI-HS. After 30 days culture of P. falciparum in GIT, 9 of 12 clinical isolates still continuously propagated but other three isolates disappeared. Despite variation of the P. falciparum isolates in their abilities to multiply in GIT, our experiments suggested that GIT is useful for culture of fresh clinical isolates of P. falciparum that are derived from geographically distinct areas as well as laboratory strains used commonly in laboratory research.

Animals↗
PubMed2000

[Effect of Nippostrongylus brasiliensis induced alterations in T helper cell subsets on Plasmodium berghei infection in mice].

OBJECTIVE: To observe the anti-P. berghei ability of C57BL/6 mice after infected with Nippostrongylus brasiliensis alterations in T helper cell subsets in the course of Plasmodium infection, and the effect of the alteration on host's prognoses. METHODS: C57BL/6 mice were infected with Nippostrongylus brasiliensis subcutaneously, 3 wk later, the mice were injected with Plasmodium berghei intraperitoneally. The parasitemia was monitored daily. On days 0, 3 and 9, RNA from the spleens of infected mice was prepared for PT-PCR to analyse the changes of IFN-gamma and IL-4 mRNA during the infection course. RESULTS: Compared with control group, the peak-reaching time of parasitemia in the experiment group was delayed, and the bearing capacity of mice to malaria infection and the surviving time increased obviously. The IL-4 level in the experiment group was higher than that in the control group on day 0 of P. berghei infection, but all raised abnormally in both groups at the early stage of the infection; while IFN-gamma level in the experiment group was higher than that in the control group on day 3 after infection, and then began to reduce to some extent on day 9 of the infection in the experiment group. CONCLUSION: T helper cell subsets play an important role in antimalarial immunoregulation in mice.

Animals↗
PubMed1999

Scanning gene expression during neuronal cell death evoked by nerve growth factor depletion.

Depletion of nerve growth factor (NGF) from differentiated, neuronal PC12 cells causes a form of programmed cell death that stems from the attenuation of NGF receptor signaling and the resultant expression of certain genes required for cell death. To better understand the associated molecular events, we surveyed the changes in gene expression in PC6-3 cells, a subline of PC12, caused by depletion of NGF. Using restriction landmark cDNA scanning, we assessed the expression patterns of as many as 15,000 gene species, and 30 genes were isolated whose expression was altered in the absence of NGF. Of the 20 genes up-regulated in the absence of NGF, including transcription factor LRF-1/ATF3, most were also up-regulated during the programmed death of cortical neurons caused by Ca2+ ionophore. Their function may thus be a general feature of programmed neuronal cell death. In contrast, with one exception, expression of down-regulated genes was NGF-dependent and therefore diminished in the absence of NGF but unaffected by Ca2+ ionophore. These findings confirm that global investigation of the features of up- and down-regulated genes should add substantially to our understanding of the regulation of programmed neuronal cell death and the mechanisms involved.

Animals↗
PubMed1999

Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens.

Infection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-gamma than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-gamma in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.

Animals↗
PubMed1999

Similarity relations of DNA and RNA polymerases investigated by the principal component analysis of amino acid sequences.

The principal component analysis based on the physicochemical properties of amino acid residues is applied to DNA and RNA polymerases to assign the sequence motifs for the polymerization activities of these proteins. After the reconfirmation of the sequence motifs of families A and B of DNA polymerases indicated previously, it elucidates the sequence motifs for the polymerization activity of DNA polymerase III (family C) by the similarity to the polymerization center of multimeric DNA dependent RNA polymerases. This identification proceeds to clarify the sequence motifs for polymerization activities of primases; eukaryotic and archaebacterial primases carry motifs similar to those of family C, while the motifs of eubacterial primase fall into the category of the motifs in family B DNA polymerases such as alpha, delta, epsilon and II. This finding means that DNA dependent RNA polymerases are also divided into groups corresponding to three families, A, B and C, because the monomeric DNA dependent RNA polymerases in phages are reconfirmed to carry sequence motifs similar to those of family A DNA polymerases. Furthermore, the three families of polymerization motifs are found to fall within the variation range of polymerization motifs displayed by many RNA dependent RNA polymerases, suggesting a close evolutionary relation between them. The sequence motifs for polymerization activities of reverse transcriptase and telomerase seem to be the intermediate between family A DNA polymerase and some RNA dependent RNA polymerases, e.g., from Leviviridae. On the contrary, the sequence fragments similar to the nucleotidyltransferase superfamily including DNA polymerase beta are not found in any RNA dependent RNA polymerase, suggesting their other lineage of polymerization motifs.

Amino Acid Sequence↗
PubMed1999

SH1 (cysteine 717) of smooth muscle myosin: its role in motor function.

To determine if a thiol group called SH1 has an important role in myosin's motor function, we made a mutant heavy meromyosin (HMM) without the thiol group and analyzed its properties. In chicken gizzard myosin, SH1 is located on the cysteine residue at position 717. By using genetic engineering techniques, this cysteine was substituted with threonine in chicken gizzard HMM, and that mutant HMM and unmutated HMM were expressed in biochemical quantities using a baculovirus system. The basal EDTA-, Ca(2+)-, and Mg(2+)-ATPase activities of the mutant were similar to those of HMM whose SH1 was modified by N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (IAEDANS). However, while the chemically modified HMM lost the function of the light chain phosphorylation-dependent regulation of the actin-activated ATPase activity, the mutant HMM exhibited the normal light chain-regulated actin-activated ATPase activity. Using an in vitro motility assay system, we found that the IAEDANS-modified HMM was unable to propel actin filaments but that the mutant HMM was able to move actin filaments in a manner indistinguishable from filament sliding generated by unmutated HMM. These results indicate that SH1 itself is not essential for the motor function of myosin and suggest that various effects observed with HMM modified by thiol reagents such as IAEDANS are caused by the bulkiness of the attached probes, which interferes with the swinging motion generated during ATP hydrolysis.

Amino Acid Sequence↗
PubMed1999

TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor.

A series of mutants with deletion in the extracellular portion of TrkB were expressed transiently and stably in mammalian cells to examine the brain-derived neurotrophic factor (BDNF)-binding properties of TrkB. We found that these binding activities were retained by the TrkB deletion mutant (TrkBDelta4) lacking most of the extracellular portion, cysteine-rich cluster 1 and 2, leucine-rich motif and most of the first immunoglobulin-like domain (Ig1). Furthermore, the results of the neurotrophin selectivity, the equilibrium binding constant, auto-phosphorylation and BDNF dependent cell survival indicate that TrkBDelta4 acts as a functional BDNF receptor comparable to wild-type TrkB. Thus, our findings showed that only the carboxyl-terminal half of the extracellular portion of TrkB, which includes the Ig2 domain, is essential for the functional BDNF receptor.

3T3 Cells↗
PubMed1999

Physical interaction between retinoic acid receptor and Sp1: mechanism for induction of urokinase by retinoic acid.

Induction of urokinase plasminogen activator (uPA) by retinoic acid (RA) is the initial event preceding certain subsequent biological changes in vascular endothelial cells. We investigated the molecular mechanism by which RA stimulates the expression of uPA, which lacks a canonical RA receptor (RAR)-responsive element, in bovine and human aortic endothelial cells. Upon stimulation with RA, mRNA levels of RARalpha and beta transiently increased in parallel with the induction of uPA, and this increase was inhibited by cycloheximide. Results of transient transfection of RAR/RXR cDNAs and experiments using specific agonists and antagonists suggested that uPA induction is dependent upon RAR (initially, RARalpha) with the help of RXRalpha. Deletion analysis of the uPA promoter suggested that RAR/RXR acts on GC box region within the uPA promoter. This was further supported by inhibition of Sp1 binding to this region. Coimmunoprecipitation studies, glutathione S-transferase pull-down experiment, and mammalian two-hybrid assays suggested a physical interaction between RAR/RXR and Sp1. Furthermore, gel shift studies showed that the binding of Sp1 to the uPA GC box is significantly potentiated in the presence of RARs/RXRs. Finally, Sp1 and RAR/RXR synergistically enhanced the transactivation activity of the uPA promoter. These results suggest that (1) RA induces RARs mainly via RARalpha and that (2) RAR/RXR physically and functionally interact with Sp1, resulting in a potentiation of uPA transcription.

Animals↗
PubMed1999

KW-5092, a novel gastrokinetic agent, facilitates luminal serotonin release from the guinea-pig colon.

The present study was designed to determine the influence of KW-5092 ((1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2- imidazolidinylidene) propanedinitrile fumarate), a novel gastroprokinetic agent on intraluminal serotonin (5-hydroxytryptamine, 5-HT) release which reflects the release of 5-HT from enterochromaffin cells, using the luminally perfused isolated guinea-pig proximal colon in vitro. 5-HT was determined by high-performance liquid chromatography with electrochemical detection. KW-5092 (1-10 microM) concentration-dependently caused an increase in the luminal 5-HT outflow. In the presence of atropine (0.2 microM) or tetrodotoxin (0.3 microM), the stimulatory action of KW-5092 (10 microM) was inhibited by 94% and 74%, respectively. These results suggest that KW-5092 stimulates intraluminal 5-HT release from luminally perfused proximal colon of the guinea-pig via the stimulation of cholinergic neurons. Because 5-HT is recognized as an important messenger substance in the control of intestinal motility, this stimulatory effect could be considered as an indirect action of KW-5092 that may contribute to its prokinetic effects.

Animals↗
PubMed1999

Identification of a novel kinase-like gene induced during neuronal cell death.

When deprived of neurotrophic factors, neuronal cells undergo a form of programmed cell death that involves a cascade of gene expression. To better understand this cascade, we screened the genes induced during programmed cell death evoked in neuronal PC6-3 cells by NGF-depletion and discovered a novel gene, NIPK (Neuronal cell death Inducible Putative Kinase), that contains a kinase-like domain. Expression of NIPK was also induced in cultured sympathetic neurons by NGF deprivation and in cortical neurons exposed to the Ca2+ ionophore, A23187. In contrast, NIPK was not induced during non-neuronal cell death evoked by serum or growth factor deprivation, or by treatment with methyl methanesulfonate, an agent that causes cell death by damaging DNA. Taken together, these findings suggest that NIPK is involved in programmed cell death via a pathway that is present in neurons but is absent in non-neurons.

Amino Acid Sequence↗