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Biomedical subjects

N Hanada

Publications and source records attributed to N Hanada.

At least 55 records · Page 3Linked to original sources
PubMed1996

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-gamma and has been in complete remission for more than 6 years.

We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.

Antineoplastic Agents↗
PubMed1995

Specific inhibitors of vacuolar type H(+)-ATPases induce apoptotic cell death.

Concanamycin A and bafilomycin A1 are known as strong inhibitors of the vacuolar type H(+)-ATPases in vitro. These inhibitors exhibited cytotoxic effects on twelve cell lines in cell viability assay. On the other hand, the F1F0-type H(+)-ATPase inhibitor oligomycin and the E1E2-type H(+)-ATPase inhibitor vanadate showed no cytotoxic effect. We show here that concanamycin A and bafilomycin A1 induce a significant increase in the proportion of fragmented DNA in agarose gel electrophoresis. Flow cytometric cell cycle analysis of WEHI 231 cells stimulated with concanamycin A revealed the increased percentage of apoptotic cells with hypodiploid DNA. These findings indicate that cell death induced by specific inhibitors of vacuolar type H(+)-ATPases occurs through apoptosis.

Animals↗
PubMed1995

Up-regulation of ICAM-1 expression on human dermal fibroblasts by IFN-beta in the presence of TNF-alpha.

Unstimulated human fibroblasts show low or undetectable ICAM-1 expression. Interferon-beta (IFN-beta) at concentrations of 10, 100, and 1000 IU/ml in the presence of tumor necrosis factor-alpha (TNF-alpha) significantly increased the ICAM-1 expression of fibroblasts in a dose-dependent manner. Treatment with IFN-beta alone, however, did not up-regulate the ICAM-1 expression. Furthermore the attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated fibroblasts was increased. This augmented attachment was partly inhibited by anti-ICAM-1 antibody. These results suggest that IFN-beta and TNF-alpha may cooperatively modulate the attachment of PBMCs in the dermis.

Cell Adhesion↗
PubMed1995

In vitro comparative study of the antitumor effects of human interferon-alpha, beta and gamma on the growth and invasive potential of human melanoma cells.

We have studied the effects of interferon (IFN)-alpha, beta, and gamma in vitro on the growth and invasive potential of human melanoma SK-MEL-118 cells. The antiproliferative effects of IFNs were assessed by a quantitative regrowth assay in which cells were treated with IFNs at concentrations of 10(2), 10(3) or 10(4) IU/ml for 3 days (until day 4) and then further incubated without IFNs for 7 days (until day 11). The growth inhibitory effect of each IFN on melanoma cells was dose- and time-dependent. Among these three types of IFNs, however, IFN-beta exerted the strongest inhibitory effect on cell growth. To assess the anti-invasive effect of each IFN on melanoma cells, we employed an in vitro assay system using matrigel-coated Transwell chambers. When cells were treated with 10(2), 10(3), or 10(4) IU/ml of the three types of IFNs for 24 hours, the amount of tritiated thymidine incorporated into melanoma cells were treated for 24 hours with 10(4) IU/ml of IFN-beta or gamma prior to the assay, the number of cells that invaded the filter decreased by 40%; this decrease was only 10% with the same amount of IFN-alpha. Simultaneous addition of IFNs during the invasion assay was not effective in any combination. Only when the cells were pretreated with IFNs, antiinvasive effects against melanoma cells were exerted. IFN-alpha was less inhibitory than IFN-beta or gamma on proliferation and not at all inhibitory on invasion. Considering both the antiproliferative and antiinvasive effects of IFNs, our results suggest that IFN-beta has the strongest antitumoral effect on human melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1995

Evidence for apoptosis of murine macrophages by Actinobacillus actinomycetemcomitans infection.

The gram-negative bacterium Actinobacillus actinomycetemcomitans is considered an important etiological agent in periodontal diseases. In this study, we show that A. actinomycetemcomitans strains are cytotoxic for the murine macrophage cell line J774.1. On the other hand, Porphyromonas gingivalis strains, other gram-negative oral species implicated in adult periodontitis, showed weak cytotoxic effects. For this to occur, A. actinomycetemcomitans had to gain entry into the macrophages, since cytotoxicity was prevented by cytochalasin D. We demonstrate that cell death induced by A. actinomycetemcomitans Y4 occurs through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether the cytotoxicity induced by A. actinomycetemcomitans Y4 could be modulated by the protein kinase inhibitors H7 and HA1004. Apoptotic cell death induced by A. actinomycetemcomitans Y4 was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals of protein kinases may regulate apoptosis induced by A. actinomycetemcomitans Y4. The ability of A. actinomycetemcomitans to promote the apoptosis of macrophages may be important for the initiation of infection and the development of periodontal diseases.

Actinobacillus Infections↗
PubMed1995

An antigenic peptide inducing cross-reacting antibodies inhibiting the interaction of Streptococcus mutans PAc with human salivary components.

A 190-kDa surface protein antigen (PAc) of Streptococcus mutans, in particular the A region of this molecule, may be implicated in the induction of dental caries via an interaction with salivary components. For this reason, it was probably used successfully as an antigenic component for experimental vaccination to prevent dental caries in animals. While developing a synthetic peptide vaccine for dental caries, as reported herein, we have identified a unique peptide, TYEAALKQYEADL, as a candidate vaccinal immunogen. The amino acid sequence of this peptide completely corresponds to the sequence of a B-cell epitope in the A region of PAc and additionally contains its own T-cell epitope for B10.D2 mice within the molecule. This peptide strongly induces the production of only cross-reacting antibodies against PAc. In addition, as demonstrated by surface plasmon resonance analysis using the BIAcore system, these cross-reacting antibodies inhibit approximately 50% of the binding of fluid-phase salivary components to immobilized recombinant PAc.

Adult↗
PubMed1995

Assessment of malocclusion of Japanese junior high school pupils aged 12-13 years in Iwate prefecture according to the Dental Aesthetic Index (DAI).

The purpose of this investigation is to grasp the actual condition of malocclusion in Japanese junior high school pupils using the Dental Aesthetic Index (DAI). A total of 218 junior high school pupils aged 12-13 years were examined according to DAI. About 40% of the subjects had incisal crowding. The percentage of subjects with incisal spacing was 24%, and 71% of them had diastema of 1 mm or more. The percentage of subjects with anterior irregularity on the upper and lower arch was 39% and 33%, respectively. The percentage of subjects with anterior maxillary overjet and mandibular protrusion of 1 mm or more was 85% and 6% respectively. Dislocation by more than a half-cusp in the proximal or distal relationship in the molars was observed in 26% of all subjects. Mean +/- SD of DAI score was 25.3 +/- 7.3.

Adolescent↗
PubMed1995

Membrane-associated interleukin-1 on macrophages stimulated with Actinobacillus actinomycetemcomitans lipopolysaccharide induces osteoclastic bone resorption in vivo.

The effect of paraformaldehyde-fixed murine macrophage P388D1 cells stimulated with Actinobacillus actinomycetemcomitans Y4 lipopolysaccharide (membrane-associated interleukin-1) on osteoclastic bone resorption was investigated. Both the number of osteoclasts and the bone resorption surfaces increased considerably along the inside of the marrow space of mouse calvaria when membrane-associated interleukin-1 mediated by A. actinomycetemcomitans Y4 lipopolysaccharide were injected into the subcutaneous tissues overlying the central calvaria of 4-week-old C3H/HeJ mice. Membrane-associated interleukin-1 caused hypercalcaemia when injected into C3H/HeJ mice twice a day for 2 days. The calvaria of C3H-HeJ mice injected with membrane-associated interleukin-1 contained less mineral than those of the control mice. These results suggest that membrane-associated interleukin-1 on macrophages stimulated with A. actinomycetemcomitans Y4 lipopolysaccharide plays an important role in inflammatory osteoclastic bone resorption in periodontal diseases.

Aggregatibacter actinomycetemcomitans↗
PubMed1994

[A case of Fusobacterium necroforum sepsis].

A 26-year-old man was admitted to our hospital with a 10-day history of sore throat, high fever, and right knee joint pain. On physical examination, the pharynx was considerably inflamed, and the right knee joint was swollen and extremely tender. Chest radiography showed multiple, bilateral nodules and masses with pleural effusions. Fusobacterium necorforum grew from samples of blood, pleural effusion, and pus taken from the knee joint. The patient was treated with intravenous clindamycin, ventilatory support, and continuous chest and knee joint drainage. His condition progressively improved and he was discharged on the 66th hospital day. A disease caused by an oropharyngeal infection with secondary suppurative thrombophlebitis of the internal jugular vein, and complicated by multiple metastatic infections is called postanginal septicemia, or Lemierre syndrome. Before the discovery of antibiotics, this disease usually was fatal. The widespread use of antibiotics for treat oropharyngeal infections may have caused a number of reported cases. Lemierre syndrome is an uncommon complication of oropharyngeal infection, and it may be fatal if diagnosis is delayed. Careful attention must be directed to patients with oropharyngeal infection who have signs and symptoms that suggest metastatic infection.

Adult↗
PubMed1993

Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II.

Crigler-Najjar syndrome (CN) type II is characterized by severe chronic nonhemolytic unconjugated hyperbilirubinemia due to reduced hepatic bilirubin UDP-glucuronosyl-transferase (UGT) activity. Two bilirubin UGT isozymes, UGT1A and UGT1D, have been identified. We analyzed the DNA sequence of the bilirubin UGT genes in a 5-year-old Japanese male patient with CN type II, who had consanguineous parents. Point mutations were found on exons 1 of the UGT1A and UGT1D genes. The abnormalities were single nucleotide substitutions of G by A and of T by C at base position 211 of UGT1A cDNA and at base position 395 of the UGT1D, respectively. We found another single nucleotide substitution of T by G on exon 5 common to both genes at base position 1456 of the UGT1A cDNA or 1459 of the UGT1D cDNA. These three mutations result in changes of glycine to arginine and of tyrosine to aspartic acid at amino acid positions 71 and 486 of the UGT1A protein, and of leucine to proline and of tyrosine to aspartic acid at amino acid positions 132 and 487 of the UGT1D protein, respectively. Our patient was homozygous for all defects and his parents and elder brother were heterozygous for all defective alleles. The findings suggest that the CN Type II is inherited as an autosomal recessive trait.

Adult↗
PubMed1993

Identification of human T cell hybridoma-derived macrophage activating factor as interleukin-2.

Macrophages are activated by a two-step mechanism involving at least two kinds of factors, a priming and a triggering factor, to become cytotoxic to various tumor cells. In the present study, we purified macrophage-activating factor for cytotoxicity I (MAF-C I), defined as a priming macrophage activating factor (MAF), by about 1,600-fold from the culture supernatant of a human T cell hybridoma, H3-E9-6, by a series of chromatographic procedures. We identified MAF-C I activity released from H3-E9-6 cells as interleukin-2 (IL-2) from the following findings. (i) The physicochemical properties of MAF-C I and IL-2 were almost identical. (ii) Purified MAF-C I active fraction also showed T cell proliferating activity. (iii) MAF-C I activity in the purified fraction was completely neutralized by anti-IL-2 antibodies. (iv) Human recombinant IL-2 (rIL-2), at a suboptimal dose, and lipopolysaccharide (LPS) synergistically induced monocyte-mediated cytotoxicity.

Cytotoxicity, Immunologic↗
PubMed1993

Nucleotide sequence analysis of the gtfT gene from Streptococcus sobrinus OMZ176.

The gtfT gene and its upstream region isolated from the Streptococcus sobrinus OMZ176 chromosomal DNA were sequenced. The gtfT gene was preceded by a potential Shine-Dalgarno sequence. The gtfT gene product, glucosyltransferase (GTF), displays a typical gram-positive bacterial signal peptide sequence and both an active site peptide sequence and carboxy-terminal repeats typical of GTFs. The signal sequence is similar to those of other known GTF proteins. The putative active-site peptide sequence of this enzyme was DGIRVDAVD, which was different by one amino acid from the active-site peptide sequence derived from two different types of the S. sobrinus GTFs reported previously (G. Mooser, S. A. Hefta, R. J. Paxton, J. E. Shively, and T. D. Lee, J. Biol. Chem. 266:8916-8922, 1991). The gtfT gene product has three repeated sequences of 51 to 52 amino acids and a partial repeat of 18 amino acids. Another open reading frame (ORF) was detected in the region immediately upstream of the gtfT gene. The upstream ORF showed substantial DNA homology with the gtfS gene isolated from Streptococcus downei MFe28. The inferred amino acid sequence of the upstream ORF has four repeating units and has extensive homology with the repeated peptides coded by the S. downei gtfS gene. These results suggested that the gtfT gene was a typical gtf gene isolated from the mutans streptococci and that the two gtf genes were located in tandem on the chromosomal DNA of S. sobrinus OMZ176.

Amino Acid Sequence↗
PubMed1993

DNA sequence of the glucosyltransferase gene of serotype d Streptococcus sobrinus.

A glucosyltransferase (GTF) gene was cloned into Escherichia coli from serotype d Streptococcus sobrinus OMZ176. Transformed E. coli strain MI expressed water-insoluble glucan synthesizing activity. Restriction enzyme map of pGT31 extracted from MI shows that the enzyme gene exists in the 6.4-KB PstI-fragment inserted into pBR322 vector. DNA sequence analysis indicates that a single ORF (530-5,300) is located in the PstI-fragment. The putative amino-acid composition (1,590 residues) resembles those of other GTF-I enzymes obtained from serotype g S. sobrinus and serotype h Streptococcus downei. However, at the same positions of the sequence, 18 and 142 amino-acid residues are different between serotype d and g, and serotype d and h GTF-I enzymes, respectively. The differences between serotype d and h GTF-Is are distributed in N and C-terminal regions.

Amino Acid Sequence↗
PubMed1993

[Aniline-induced methemoglobinemia monitored by pulse oximetry].

A case of aniline-induced methemoglobinemia is reported. When the pulse oximeter reading (SpO2) was 80%, the oxygen saturation measured by a co-oximeter (SaO2) was 61.2%, the oxygen saturation calculated from PaO2 values was 98.9% and methemoglobin level was 38.8%. After methylene blue injection, methemoglobin level decreased gradually. With a decrease of methemoglobin level, SpO2 approached SaO2. If disparity between SpO2 and the oxygen saturation calculated from PaO2 values is noted, the presence of methemoglobinemia must be suspected. In clinical situations, the pulse oximeter permits the continuous noninvasive monitoring of oxygen saturation. It is necessary, however, to consider the potential errors in pulse oximetry.

Adult↗
PubMed1993

Four different types of glucans synthesised by glucosyltransferases from Streptococcus sobrinus.

Four different kinds of glucosyltransferases (GTFs) were purified from the cariogenic bacterium Streptococcus sobrinus AHT. One of them (GTFP3) produced water-insoluble glucan with the alpha-1,3 linkage, exclusively. The others (GTFP1, P2 and P4) produced water-soluble glucans. GTFP2 produced oligosaccharides with linear 1,6-alpha-D-glucan structure. Since GTFP1 and P4 produce similar molecular weight glucans, the structural differences between these glucans remain unclear. To clarify the difference between GTFP1 and P4 products, the glucan structures were investigated by methylation analysis with gas liquid chromatography and gas liquid chromatography-mass spectrometry. The glucan synthesised by GTFP1 was 1,6-alpha-D-glucan with a high percentage (25.9 mol%) of 1,3-alpha-D-linked units. The other glucan synthesised by GTFP4 contained 1,6-alpha-D-glucan with 1,3,6-alpha-D-glucose (18.5 mol%).

Glucans↗
PubMed1993

[A case of T-cell lymphoma showing multiple nodular shadows and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody].

A 42-year-old man, born in Chiba prefecture, was admitted to our hospital because of multiple nodular shadows on chest X-ray film and an elevated titer of human T-lymphotropic virus type I (HTLV-I) antibody. The pulmonary lesion was diagnosed as T-cell lymphoma by open lung biopsy. There has been only one previous report of T-cell lymphoma showing multiple nodular shadows on chest X-ray. The elevated titer of HTLV-I antibody strongly suggested that the present case was one of adult T-cell lymphoma.

Adult↗