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Biomedical subjects

K Naito

Publications and source records attributed to K Naito.

At least 163 records · Page 9Linked to original sources
PubMed1997

HUB1, a novel Krüppel type zinc finger protein, represses the human T cell leukemia virus type I long terminal repeat-mediated expression.

We have shown that human T-cell leukemia virus type I (HTLV-I) gene expression is negatively regulated by the U5 repressive element (U5RE) of its long terminal repeat (LTR). To isolate factors binding to U5RE, we screened a cDNA expression library by south-western blotting with a U5RE probe. Screening 2 x10(6) clones gave a positive clone with a 3.8 kb insert encoding a novel 671 residue polypeptide, named HTLV-I U5RE binding protein 1 (HUB1), with five zinc finger domains and a Krüppel-associated box like domain; HUB1 may be related to a repressor belonging to the Krüppel type zinc finger protein. A 4.0 kb mRNA for HUB1 is ubiquitously expressed among all human tissues tested. HUB1 recognizes the TCCACCCC sequence as a core motif and exerts a strong repressive effect on HTLV-I LTR-mediated expression. A new repressive domain, named HUB1 repressive (HUR) domain, was identified, rather than the Krüppel-associated box like domain. The N-terminal region upstream of HUR domain seemed to be also indispensable to the repression. Thus, we propose that HUB1 is a new type repressor and plays an important role in the HTLV-I U5-mediated repression.

Amino Acid Sequence↗
PubMed1997

A site-specific DNA endonuclease specified by one of two ORFs encoded by a group I intron in Dictyostelium discoideum mitochondrial DNA.

The second intron (DdOX1/2.2) of Dictyostelium discoideum cytochrome oxidase subunit 1/2 fused gene has two free-standing ORF genes (Dd ai2a and Dd ai2b) in a loop, which have similar amino acid sequences and are homologous to aI4 DNA endonuclease (I-SceII) of Saccharomyces cerevisiae. To elucidate the functions of these ORFs, we cloned the ORFs into an expression vector and introduced the composite vectors into E. coli. The expression of Dd ai2a in E. coli caused growth inhibition and degradation of the E. coli genomic DNA. To determine whether Dd ai2a protein is a homing type DNA endonuclease, the ability to cleave the homing site of its intron in vivo was examined. Dd ai2a cleaved only one strand of intronless DNA sequence at the site which coincides with the I-SceII cleavage recognition site. We suppose that Dd ai2a functions actually as a homing type DNA endonuclease in D. discoideum mitochondria by virtue of other factors. To obtain further information about the relationship between the existence of introns and the mating system, we carried out in vitro self-splicing assay and polymerase chain reaction analysis using 13 strains of the cellular slime mold.

Animals↗
PubMed1997

Cytokine-mediated antitumor effect of OK-432 on urinary bladder tumor cells in vitro.

Fatal complications from the intravesical instillation of bacillus Calmette-Guérin (BCG) for the treatment of superficial urinary bladder tumors have been reported. OK-432, an immunomodulating agent like BCG, may be an effective and safe agent for the treatment of urinary bladder tumors. We investigated the cytokine-mediated antitumor effect of OK-432 on established human bladder cancer cell lines (T24 and KK-47) in vitro. Peripheral blood mononuclear cells (PBMCs) from a healthy volunteer were cultured with OK-432 for various periods, and the culture supernatants were used as conditioned media. Cytokines in the culture supernatants were quantified. The antitumor effect of OK-432 was evaluated by colony-forming assays, using the conditioned media as the culture media. The colony survival of T24 and KK-47 cells was significantly inhibited by conditioned media from 24-h cultures of PBMCs incubated with OK-432 at concentrations of 0.05 and 0.1 Klinische Einheit (KE)/ml. Conditioned media from PBMCs cultivated with OK-432 for 7 days at 0.01 and 0.05 KE/ml also significantly inhibited the colony survival of both cell lines. Higher concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were detected in conditioned media cultivated with OK-432 for 24 h than in media from PBMCs alone. However, higher concentrations of interferon gamma (IFN gamma) were detected in conditioned media cultivated with OK-432 for 7 days. Approximately 90% of the inhibition of KK-47 cells by the 24-h conditioned media was neutralized by an anti-TNF monoclonal antibody. The inhibition of T24 cells was neutralized approximately 50% by the same antibody. The inhibition of T24 and KK-47 cells by 7-day conditioned media was completely neutralized by an anti-IFN gamma monoclonal antibody. The cultivation of PBMCs with OK-432 inhibited the production of granulocyte-colony-stimulating factor (G-CSF) by PBMCs. The inhibition may play a role in the mechanism of the antitumor effect of OK-432. Urinary bladder tumor cell lines have different sensitivities to cytokines. The cytokines induced by OK-432 vary with the concentration of OK-432 and the culture period. It is suggested that in intravesical instillation of OK-432 for treatment of urinary bladder tumor, the optimal dose and interval of instillation should be considered.

Antibodies, Monoclonal↗
PubMed1997

Pelvic exenteration for the treatment of gynecological malignancies.

Twenty-three patients undergoing pelvic exenteration for primary and recurrent gynecological malignancies from 1976 to 1994 are reported. Fifteen patients underwent total pelvic exenteration, 3 underwent anterior exenteration, and 5 underwent a posterior procedure. Eight patients had exenteration as their primary treatment (primary group), and 15 underwent exenteration as secondary treatment (recurrent group). In the primary group, two patients developed recurrence and died of it at 6 and 20 months after operation. Five patients are still being followed up and are alive without disease. Four of these 5 patients have survived more than 5 years. In the recurrent group, 12 patients were followed up and three died of complications during the early years. Seven patients died of cancer with the mean survival time of 16.6 months. The mean age, average operating time, and mean blood loss in the primary and recurrent groups were 57 vs. 53 years, 8 hours and 20 min vs. 8 hours and 10 min, and 4,120 vs. 4,190 ml, respectively. The overall cumulative 5-year survival rate was 34.7%, being 68.6% in the primary group and 16.7% in the recurrent group. It is noteworthy that the 5-year survival rate was 51.3% in the patients who had surgical margins free of disease. In conclusion, pelvic exenteration should be considered an acceptable therapeutic option when appropriately selected.

Adult↗
PubMed1997

Current advances in rhinomanometry.

Current advances in rhinomanometry were reviewed in this paper. Active posterior rhinomanometry with a "head-out" body plethysmography may be the least invasive method currently available for measuring nasal patency. In general, active anterior rhinomanometry with a face mask or a nasal nozzle has been employed in various studies throughout the world. Nasal resistance as calculated from the equation R = 0.78 (delta P/V)1.33 at any points on a pressure/flow curve, or averaged nasal resistance may be the most suitable expression for nasal patency. Values for nasal resistance at delta P 100 Pa in Japanese patients or delta P 150 Pa in Caucasians have been widely employed as standard objective data for nasal obstruction, although rhinomanometric results sometimes do not agree with subjective evaluation of nasal obstruction. Nasal airflow acceleration or peak flow index during nasal breathing at rest can be applied as warranted to confirm an objective diagnosis of symptomatic nasal obstruction. Further, nationality and anthropological characteristics can be related to the severity and type of stuffiness.

Humans↗
PubMed1997

Strain-related differences in Sephadex bead-induced airway hyperresponsiveness and inflammation in rats.

OBJECTIVE: The aim of this study was to compare Sephadex G-200 (Sephadex)-induced airway hyperresponsiveness (AHR) and pulmonary eosinophilia among some rat strains. MATERIALS: Sprague-Dawley (SD), Brown-Norway (BN), Fischer 344 (Fischer), Lewis and Wistar-Kyoto (WKY) rats were used. METHODS: Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Measurement of AHR using serotonin and bronchoalveolar lavage (BAL) was performed on day 7. RESULTS: The Lewis strain exhibited significant AHR to Sephadex but the BN, Fischer and WKY strains did not. Additionally, the degree of AHR in Lewis rats was smaller than in SD rats throughout the study. Eosinophils in BAL fluid, however, increased in each strain, and the magnitude of the response was BN > Lewis > WKY > Fischer. Both the AHR and pulmonary eosinophilia in Lewis rats were inhibited by dexamethasone (0.1 mg/kg, p.o. x3). CONCLUSION: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.

Animals↗
PubMed1997

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Adult↗
PubMed1997

Study on the mechanism of immunopotentiating antitumor effect of 6-MPG, a water-soluble derivative of 6-mercaptopurine.

We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6-yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6) cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the secondary tumor growth was diminished by prior treatment of the primed animals with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay). Treatment of the spleen cells with anti-CD8 antibody plus complement diminished the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did not, indicating that CD8-positive cells are responsible for potentiation of the tumor immunity. These results suggest that the antitumor effect of 6-MPG against the secondary tumor is elicited by augmenting tumor specific T-cell production.

Adenocarcinoma↗
PubMed1997

The effect of L-menthol stimulation of the major palatine nerve on subjective and objective nasal patency.

To determine whether L-menthol stimulation of the major palatine nerve can affect nasal patency, we noted subjective and measured objective nasal patency before and after L-menthol stimulation of the palatal mucosa. L-Menthol stimulation of the palatal mucosa enhanced nasal sensation of airflow but nasal resistance was unaffected. By contrast, L-menthol stimulation after local anesthesia of the palatine nerve or of the nasal mucosa substantially diminished the subjective response of increased nasal patency but without affecting objective nasal patency. It is suggested that the effect of both direct stimulation by L-menthol of the major palatine nerve and its vapor action on the sensory nerve endings of the nasal mucosa produce an increase in the sensation of nasal patency without an increase in objective nasal patency.

Administration, Oral↗
PubMed1997

Amount of mpl on bone marrow haemopoietic precursor cells from healthy volunteers and patients with refractory anaemia.

Using a non-isotopic ligand binding assay using multi-colour flow cytometry, we quantitatively examined the amount of mpl in megakaryocyte-platelet lineage cells. Firstly, we quantified the amount of mpl on cell lines. Mpl gene-transfected BaF3 cells expressed a large amount of mpl, whereas original BaF3, K562, HL-60 and NOMO-1 cells showed no mpl. In bone marrow cells from healthy volunteers, mpl was expressed on CD34+ cells from the very early stage of differentiation when they had no CD38 antigen. The amount of mpl increased with differentiation to CD34+ CD41+ cells, but decreased with further differentiation to CD34- CD41+ cells. In CD34+ CD41+ cells the amount of mpl varied according to cell size: abundant in large cells, moderate in medium-size cells and a little in small cells. In bone marrow cells from patients with refractory anaemia (RA), the amount of mpl was decreased compared with that in bone marrow cells from healthy volunteers. When analysed by the same CD phenotype and same cell size, the amount of mpl was less in RA patients compared with that in healthy volunteers in all phenotypes and sizes tested. The proportion of large CD34+ CD41+ cells was less in RA patients than in normal volunteers.

ADP-ribosyl Cyclase↗
PubMed1997

Two short peptide sequences repeated three times in carrot beta-tubulin.

There are two repeated peptides, [S,T,Y]QQ[Y,M] and MFR[R,X][V,K], which appear three times each in the region corresponding to the third exon of carrot beta-tubulins. The former peptide is flanked on both sides by a pair of identically charged groups and the latter includes two or three basic amino acids in it. The sequences are generally conserved well among the eukaryotes except for fungi, in which one of the peptides, SQQY, does not exist.

Amino Acid Sequence↗
PubMed1997

The pharmacologic profile of 606A, a novel angiotensin II receptor antagonist.

The pharmacologic profile of a novel angiotensin I (AT1) receptor antagonist 606A was studied in various in vitro and in vivo preparations. The 606A showed a high affinity at AT1 receptors [inhibition constant (Ki), 12.8 +/- 0.4 nM] in rabbit adrenal cortical membrane and a low affinity to AT2 receptors (Ki, > 1 mM) in bovine cerebellar membrane, indicating potent and selective AT1 properties. In the guinea pig aorta, 606A reduced the maximal angiotensin II-induced contraction (pD'2, 9.06 +/- 0.04), whereas EXP3174 showed suppression of the maximum response and a shift to the right of the concentration-response curve at lower and higher concentrations, respectively (conventionally calculated pd'2, 8.61 +/- 0.23). The 606A had no effects on KC1-, norepinephrine-, serotonin-, and endothelin-1-induced contractions or any agonist activities. In anesthetized dogs, 606A inhibited the angiotensin II-induced pressor response 35 times more potently than losartan. In renal hypertensive rats and spontaneously hypertensive rats (SHRs), 606A decreased systolic blood pressure 10 and 3 times more potently than losartan, respectively, without any chronotropic effects. By repeated administration of 606A to SHRs for 2 weeks, an augmentation of the hypotensive effect was observed No rebound phenomena occurred after discontinuation. These results indicate the 606A is a potent AT1-selective insurmountable angiotensin II receptor antagonist having more potent angiotensin II receptor antagonistic and hypotensive effects than losartan in in vivo models. 606A is suggested to be a useful agent for the treatment of patients with hypertension.

Angiotensin II↗
PubMed1997

Transitional cell carcinoma of the renal pelvis with vena caval tumor thrombus.

We report a case of transitional cell carcinoma of the renal pelvis with vena caval tumor thrombus. To our knowledge only 14 cases of transitional cell carcinoma of the renal pelvis protruding into the vena cava have been reported. The literature regarding these cases is reviewed, and the differential diagnosis of this tumor from renal cell carcinoma is discussed.

Carcinoma, Transitional Cell↗
PubMed1997

Efficacy of continuous subcutaneous infusion therapy using interferon alpha and the possible prognostic indicator of TNF-alpha in renal cell carcinoma.

BACKGROUND: In an attempt to improve efficacy by escalating the dose and maintaining higher serum concentrations over a long period of time, this study examines continuous interferon alpha (IFN alpha) subcutaneous infusion therapy in patients with renal cell carcinoma (RCC). METHODS: Seven of 11 patients with RCC had evaluable metastatic lesions. A highly purified natural human IFN alpha was injected subcutaneously via an infuser pump for 5 consecutive days, followed by a 2-day rest period (25 million IU/week). The treatment was continued for a period of 15 weeks. Serum concentrations of IFN alpha, IL-1 alpha, IL-1 beta, TNF-alpha, and IFN gamma were measured at intervals throughout the study period. RESULTS: Two of the 7 patients with evaluable lesions achieved a partial response (overall response rate, 29%), while 1 achieved a partial response only to lung metastasis. These 3 cases were defined as responders. No difference was found in the concentration of serum IFN alpha between responders and nonresponders, however, a significantly higher concentration of serum TNF-alpha was observed in responders (P < 0.05, Mann-Whitney U test). Five cases (45%) had moderate to severe adverse effects, including depression (n = 1), eyeground hemorrhage (n = 2), and general fatigue (n = 2). CONCLUSION: Appropriate patient selection may be necessary for subcutaneous continuous infusion therapy for the treatment of metastatic RCC. Also, the serum concentration of TNF-alpha measured during the course of treatment reflected well on the outcome of IFN alpha therapy.

Adult↗
PubMed1997

Effect of oral adsorbent AST-120 on cyclosporin absorption in rats.

The oral adsorbent AST-120 is used to inhibit the progression of renal failure by adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is administered to patients receiving immunosuppressive medicines, it is important to study the effect of AST-120 on the amount of these and other drugs absorbed. We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and investigated the effect of oral administration of AST-120 on the absorption of cyclosporin in rats. The in-vitro adsorption ratios of AST-120 for cyclosporin were more than 80%. When pure cyclosporin powder was administered with AST-120, blood cyclosporin concentrations were significantly higher than when cyclosporin was administered alone. When cyclosporin dissolved in medium-chain triglyceride was administered to rats by intramuscular injection there was no significant difference in the blood cyclosporin concentration of rats given combined AST-120 and cyclosporin and those given cyclosporin alone. There was no significant difference between the serum concentration of total bile acids, in rats receiving combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving orally solely a solution of cyclosporin dissolved in olive oil. These results suggest that oral administration of AST-120 accelerates the absorption of orally administered cyclosporin from the gastrointestinal tract and does not affect the metabolism of cyclosporin. When a solution of cyclosporin in olive oil is administered orally, however, oral administration of AST-120 has no influence on cyclosporin absorption and does not affect the enterohepatic circulation of bile acids.

Absorption↗
PubMed1997

Development of lung eosinophilic inflammation by the infusion of IL-5-producing T cell clones.

To delineate the critical role of T cells on asthma, we tested whether eosinophilic inflammation of the bronchial mucosa is induced by transfer of IL-5-producing T cell clones, in the absence of antigen-specific immunoglobulins (IgE, A and G). Ovalbumin-specific T cell clone, FI5, that produced IL-5 upon challenge with relevant antigen was established. Eosinophilic inflammation of the lung occurred when unprimed mice were transferred with FI5 and challenged by the inhaled antigen. Eosinophil infiltration was completely suppressed by the administration of anti-IL-5 neutralizing antibody, indicating the essential role of IL-5. We concluded that the existence of IL-5-producing helper T cells is sufficient for the development of airway eosinophilic inflammation.

Animals↗
PubMed1997

Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones.

Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa. Accumulating evidences suggest that activated T cells and T cell cytokines play critical roles in the local accumulation and activation of eosinophils. To further delineate the critical role of T cells on asthma, we tested the possibility whether eosinophilic inflammation of the bronchial mucosa is induced by transferred T cell clones, in the absence of antigen-specific immunoglobulins (IgE, A, and G). Ovalbumin-specific Th2 clones were established and cytokine profiles were determined. Eosinophilic inflammation accompanied with airway hyperresponsiveness occurred only when unprimed mice were transferred with IL-5 producing Th2 clones and challenged by the inhalation of relevant antigen. Increase of IL-5 concentration in bronchoalveolar lavage fluid (BALF) was detected after the challenge, indicating the local production of cytokines by the transferred T cells, and preceded the appearance of the airway eosinophilia. Eosinophil infiltration was completely suppressed by the administration of anti-IL-5 neutralizing antibody, indicating the essential role of IL-5 in this model. The intensity of the eosinophil accumulation in vivo correlated well with the capacity of the T cell clones to produce IL-5 in vitro. We concluded that the existence of IL-5-producing helper T cells is sufficient for the development of the eosinophilic inflammation at the bronchial mucosa upon inhalation challenge of the relevant antigen.

Animals↗