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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 289 records · Page 16Linked to original sources
PubMed1998

BAZF, a novel Bcl6 homolog, functions as a transcriptional repressor.

The BCL6 gene, which has been identified from the chromosomal translocation breakpoint in B-cell lymphomas, functions as a sequence-specific transcriptional repressor. We cloned a novel Bcl6-homologous gene, BAZF (encoding Bcl6-associated zinc finger protein). The predicted amino acid sequence of BAZF indicated that the BTB/POZ domain and the five repeats of the Krüppel-like zinc finger motif are located in the NH2-terminal region and the COOH-terminal region, respectively. BAZF associated with Bcl6 at the BTB/POZ domain and localized in the nucleus. Since zinc finger motifs of BAZF were 94% identical to those of Bcl6 at the amino acid level, BAZF bound specifically to the DNA-binding sequence of Bcl6 and functioned as a transcriptional repressor. The repressor activity was associated with both the BTB/POZ domain and the middle portion of BAZF. The 17-amino-acid sequence in the middle portion was completely conserved between BAZF and Bcl6, and the conserved region was critical for the repressor activity. Expression of BAZF mRNA, like that of Bcl6 mRNA, was induced in activated lymphocytes as an immediate-early gene. Therefore, the biochemical character of BAZF is similar to that of Bcl6 although the tissue expression pattern of BAZF differs from that of Bcl6. This is apparently the first report of a gene family whose members encode zinc finger proteins with the BTB/POZ domain.

Amino Acid Sequence↗
PubMed1998

Indomethacin interferes with EGF-induced activation of ornithine decarboxylase in gastric cancer cells.

BACKGROUND/AIMS: Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation. METHODS: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells. RESULTS: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. CONCLUSION: Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.

Adenocarcinoma↗
PubMed1998

Induction of protection against tetanus toxin in mice by tetanus toxoid-liposome conjugate.

Tetanus toxoid (Ttd) was coupled to liposomes via glutaraldehyde. Intraperitoneal injection in BALB/c mice with Ttd-liposomes induced a substantial amount of anti-Ttd IgG antibody production and an extremely low level of anti-Ttd IgE antibody production. Mice immunized with Ttd-liposomes were successfully protected against a subsequent challenge with a lethal dose of tetanus toxin (Ttx). On the other hand, aluminum hydroxide-adsorbed Ttd (Ttd-alum) and plain Ttd solution induced the production of both IgG and IgE antibodies against Ttd. Moreover, secondary immunization with Ttd-liposomes in mice, in which anti-Ttd IgE antibody production was induced by Ttd-alum led to enhanced anti-Ttd IgG and a limited anti-Ttd IgE antibody production. When Ttd-liposome preparation was lyophilized, the efficacy of Ttd-liposomes was maintained for 6 months at 37 C, suggesting that this vaccine preparation would be stable without refrigeration. These results demonstrate the potential ability of Ttd-liposome conjugates to produce a tetanus vaccine which provides protection against (Ttx) while inducing the least amount of anti-Ttd IgE antibodies.

Animals↗
PubMed1998

Induction of protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 in mice by shiga-like toxin-liposome conjugate.

We have previously reported that purified Shiga-like toxins (SLT), SLT-I and SLT-II coupled with liposomes induced a substantial amount of anti-SLT-I and anti-SLT-II IgG antibody production, respectively, in mice. The levels of anti-SLT antibody in the sera of SLT-liposome-immune mice correlated well with the protection against subsequent challenge with SLT. In this study, mice were immunized intraperitoneally with the mixture of SLT-I-liposome and SLT-II-liposome and protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 was evaluated. All of the mice that received immunization with the mixture of SLT-I-liposome and SLT-II-liposome were protected against subsequent intravenous challenge with 10 LD50 of either SLT-I or SLT-II. Eight weeks after primary immunization, mice were inoculated intragastrically with 10(9) CFU of E. coli O157:H7 strain 96-60. All SLT-liposome-immune mice tested survived without any apparent symptom while control mice died within 5 days. In addition, as shown by other antigen-liposome conjugates, SLT-liposome induced undetectable anti-SLT IgE antibody production while they induced substantial amounts of anti-SLT IgG antibodies. These results suggest that SLT-liposome conjugate may serve as a candidate vaccine that induces protection against cytotoxin-producing E. coli infection.

Animals↗
PubMed1998

Suppressive effects of SP-A on ionomycin-induced IL-8 production and release by eosinophils.

Recent studies have demonstrated that pulmonary surfactant protein (SP)-A plays a potential role in modifying inflammation and immune function. To see whether SP-A could modify IL-8 production and release by eosinophils stimulated with ionomycin, SP-A purified from surfactant recovered from patients with alveolar proteinosis was added to eosinophils isolated by the negative-selection method with immunomagnetic beads, and cultured for 24 h. The concentrations of IL-8 in the cell-free supernatants and cell lysates were then measured by ELISA. SP-A attenuated the production of IL-8 by eosinophils in a concentration-dependent manner. SP-A also attenuated the release of IL-8 from the eosinophils. The addition of SP-A antibody (PE10) reversed these effects of SP-A completely. These data suggest that SP-A may have the potential to modify allergic inflammation by inhibiting the release and production of IL-8 by eosinophils.

Antibodies, Monoclonal↗
PubMed1998

Molecular screening of uncoupling protein 2 gene in patients with noninsulin-dependent diabetes mellitus or obesity.

Uncoupling protein 2 (UCP2), a member of the family of mitochondrial carrier proteins, has been implicated in the control of whole-body energy balance. The coding region of the human UCP2 gene has now been shown to comprise six exons, and the sequences of the exon-intron boundaries were determined. With the use of this sequence information, 25 Japanese patients with obesity and noninsulin-dependent diabetes mellitus (NIDDM) and 25 subjects with simple obesity were screened for mutations in the entire coding region of UCP2 by PCR and single-strand conformation polymorphism analysis. Two nucleotide polymorphisms resulting in Ala55 --> Val and Ala232 --> Thr substitutions were detected. With the use of PCR and restriction fragment length polymorphism analysis, the allele frequencies for each of these polymorphisms were determined in 210 Japanese patients with NIDDM, 42 obese individuals, and 218 normal control subjects. The frequency of the Val55 allele did not differ significantly among the NIDDM group (46.0%), the obesity group (48.8%), and the normal control group (48.4%). The Thr232 allele was detected in only three subjects, who were heterozygotes and in the NIDDM group (allele frequency, 0.7%). However, expression in yeast of the human wild-type UCP2 protein and UCP2 containing Thr232 revealed no difference in functional activity. These results indicate that the Ala55 --> Val and Ala232 --> Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.

Adult↗
PubMed1998

Thyrotropin secreting pituitary adenoma effectively treated with octreotide.

We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma, who was diagnosed based on the lack of inhibition of serum TSH despite an increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The pituitary adenoma was, however, inoperable due to chronic respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d. resulted in inhibition of serum TSH and free T4 to euthyroid levels and considerable shrinkage of the pituitary tumor. These effects were continued over 8 months after the start of octreotide therapy without any adverse effects. These findings add further evidence that octreotide is useful for treating inoperable TSH secreting pituitary adenoma.

Adenoma↗
PubMed1998

Expression of deoxycytidine kinase (dCK) gene in leukemic cells in childhood: decreased expression of dCK gene in relapsed leukemia.

Competitive RT-PCR was used to determine the quantitative variation in the expression of deoxycytidine kinase (dCK) gene in childhood leukemic cells. The degree of dCK gene expression varied over a 50-fold range. In two cases in which both primary and relapsed leukemic cells were analysed, decreased expression of dCK gene was found in relapsed leukemic cells. The sequence variation analysis using bisbenzimide/polyethylene glycol electrophoresis demonstrated no sequence alteration of dCK cDNA in all cases. These results indicate that the expression of dCK gene varies in patients and suggests decreased expression of the dCK gene as one of the mechanisms responsible for clinical resistance to ara-C.

Adolescent↗
PubMed1998

Specific induction of hepatocellular adenomas by transplacental administration of ENU in the tsc2 gene mutant (Eker) rat.

Eker rats develop dominantly inherited renal carcinomas (RCs), with hereditary mutation, and following somatic mutation (Knudson's second hit) at tuberous sclerosis gene (Tsc2). We document the effect of transplacental administration of N-ethyl-N-nitrosourea to Eker (Eker/+) and non-Eker (+/+) rats (same genetic background). Although we observed no difference in the number of preneoplastic GST-P positive foci between Eker and non-Eker rats, interestingly we observed the specific development of hepatocellular adenomas only in Eker rats. The Tsc2 gene mutation might thus influence the phenotype of preneoplastic initiated hepatocytes.

Adenoma, Liver Cell↗
PubMed1998

[Low-dose levodopa therapy of autistic disorder: evaluation of clinical effectiveness].

Based upon the hypothesis that brain monoamine metabolism is disorganized in some children with an autistic disorder, we tried low dose levodopa therapy (0.5 mg/kg/day) proposed by Segawa, et al. We treated 20 patients with an autistic disorder diagnosed according to DSM-IV, and evaluated the effectiveness. A double blind cross over method was applied in this study because of the small number of patients. Drug effects were observed carefully by the psychologists and pediatric neurologists using an evaluation sheet consisting of twenty items. No significant effectiveness was observed in this study, although four cases (20%) showed some improvement. In conclusion, administration of low dose levodopa to autistic children resulted in no clear clinical improvements of autistic symptoms.

Autistic Disorder↗
PubMed1998

[Unexpected anuria during Miles' operation in a renal-transplant patient].

We report a case of 33-yr-old-male after orthotopic renal transplantation 18 years ago, presenting with sudden anuria during Miles' operation. This anuria was caused by temporal compression of the transplanted kidney by retractor, neither by acute renal failure, the rejection nor the damage of the ureter by the surgical procedure. This case indicates that in the anesthetic management after renal transplantation, we have to be careful about renal dysfunction due to surgical procedure or positioning, in addition to side effects and pharmacokinetics of drugs used perioperatively.

Adult↗
PubMed1998

[Subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with SMANCS].

Recently, subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein has been performed to treat hepatic infarction in subregion hepatocellular carcinoma (HCC). Here, we report subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with styrene maleic acid neocarzinostatin lipiodol (SMANCS) (SMANCS-TAE under balloon occlusion of the corresponding hepatic vein). This study included 9 patients with HCC who underwent SMANCS-TAE under balloon occlusion of the corresponding hepatic vein. In all patients, the therapeutic effects (TE) were evaluated according to the criteria of direct response to liver cancer treatment on abdominal computed tomography (CT) 3 weeks after surgery. In 7 patients who could be followed for more than one year, there was no postoperative relapse at the site of treatment. Furthermore, this procedure facilitated the detection of accumulation of SMANCS not only in the tumor but also in the subregion of the tumor in patients with HCC involving immature arterial tumor neoplastic vessels. In patients with large HCC complicated by severe heart failure showing a poor general condition, this procedure allowed treatment to be completed without complication. SMANCS-TAE under balloon occlusion of the corresponding hepatic vein, which can also embolize the portal vein by applying targeting chemotherapy with SMANCS, may cause necrosis not only in the tumor but also in noncancerous liver tissues. This procedure may be an indication for a larger number of cases than standard TAE, facilitating more complete local treatment.

Antineoplastic Agents↗
PubMed1998

In situ hybridization with biotinylated tyramide amplification: detection of human papillomavirus DNA in cervical neoplastic lesions.

A novel peroxidase-mediated amplification system, which is based on the deposition of biotinylated tyramide (BT) molecules, was recently described for immunohistochemistry and in situ hybridization (ISH). We report here a highly sensitive ISH system combined with a microwave prehybridization treatment and BT enhancement after hybridization. Our ISH with BT amplification can detect human papillomavirus (HPV) 16 DNA signals in the fixed SiHa cell, suggesting the ability to detect single or few copies of HPV DNA. To confirm its diagnostic usefulness, we used our ISH with BT amplification to detect HPV 16 DNA in 81 cases of cervical neoplastic lesions, which had been used for routine pathologic diagnosis. Of 81 tumors, 47 (58%) showed HPV 16 DNA, of which 29 and 18 were cervical intraepithelial neoplasia (CINs) and invasive cancers, respectively. In almost all of the invasive cancers positive for HPV 16 DNA, ISH revealed a basic dot signal pattern in the nuclei, suggesting that HPV DNA integrated into tumor cell DNA. On the other hand, low-grade CINs displayed a diffuse, mainly episomal, signal pattern, which decreased in frequency with increased grade of CIN. Our ISH with BT amplification is highly sensitive and can be used to detect various genes and their expressions.

DNA, Viral↗
PubMed1998

[Evaluation of routine blood cell counts in predicting the mobilization of CD34 positive cells].

The collection of peripheral blood stem cells (PBSC) is a crucial step for successful PBSC transplantation. Routine hematological parameters utilized for predicting the optimal timing of collection include white blood cell (WBC) counts, high fluorescence ratio (HFR) of reticulocytes, and platelet counts. We compared these parameters with the CD34-positive rates in the peripheral blood. In regimen with high-dose chemotherapy where the WBC count at nadir was lower than 1,000/microliter, we found that the maximum mobilization of PBSC was observed on the day when the WBC count reached 10,000/microliter. This coincidence was within about one day (mean 0.44, standard deviation 0.53). However, the reliability of the WBC count as a marker of PBSC mobilization varied among different harvest regimens. In the regimen with regular-dose chemotherapy where the WBC count at nadir was above 1,000/microliter, we could not find such a tight coincidence between the WBC count and PBSC mobilization. These results suggested that, in some situations, the measurement of the CD34-positive rate is mandatory for an efficient PBSC collection. We also found that the number of CD34-positive cells in the peripheral blood correlated (x) well to the amount of the CD34-positive cells actually harvested (y) (y = 0.524x + 0.249, r = 0.787). Thus, rapid fluorescence activated cell sorter (FACS) analysis of peripheral CD34-positive rates seemed to be extremely useful to predict the yield of PBSC collection.

Adult↗