Biomedical subjects

K Hiyama

Publications and source records attributed to K Hiyama.

At least 37 records · Page 2Linked to original sources

PubMed1999

Expression of C-C chemokines in bronchoalveolar lavage cells from patients with granulomatous lung diseases.

To determine the role of C-C chemokines in the pathogenesis of granulomatous lung diseases, we studied the mRNA levels of C-C chemokines, regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 in bronchoalveolar lavage (BAL) cells obtained from patients with sarcoidosis (n = 17), hypersensitivity pneumonitis (HP) (n = 4), and cryptogenic fibrosing alveolitis (CFA) (n = 10) using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The mRNA levels of RANTES, MIP-1alpha, and MIP-1beta in BAL cells were significantly correlated with the lavaged lymphocyte proportion, and a significant inverse correlation was observed between the mRNA level of MIP-1beta and the CD4/CD8 ratio of lavaged lymphocytes. Among the three diseases, the mRNA levels of RANTES and MIP-1alpha were significantly higher in the patients with sarcoidosis or HP compared with those in the patients with CFA. The level of MIP-1beta mRNA was significantly higher in the HP patients compared with that in the patients with sarcoidosis or CFA. No significant differences were observed in the level of MCP-1 mRNA among the three diseases. Thus, RANTES and MIP-1alpha were suggested to be important in the pathogenesis of granulomatous inflammation in sarcoidosis and HP. MIP-1beta might play an important role in the pathogenesis of HP, mediating the recruitment of lymphocytes specific to HP.

Adult↗

PubMed1999

Asymmetric reduction of hydroxyacetone to propanediol in immobilized halotolerant microalga Dunaliella parva.

Cells of the halotolerant microalga Dunaliella parva immobilized in calcium-alginate gel showed morphological characteristics and photosynthetic activity similar to those of free cells. The photosynthetic activity in immobilized cells fell only about 20% during 2 weeks incubation at 5 degrees C in the light. The asymmetric reduction of hydroxyacetone to (R)-propanediol was first examined in batch reactions with both free and immobilized cells. Since the activity of immobilized cells was as high as that of free cells, the optimum conditions for the column reactor were investigated using immobilized cells. The productivity of propanediol in immobilized cells increased in proportion to increases in the light intensity, suggesting that NADPH regenerated through photosynthesis was used for the asymmetric reduction. Electron microscopic observation of thin sections of immobilized cells after the reaction suggested that NADPH used for asymmetric reduction in the dark was produced through the metabolism of starch granules. The use of a CaCO3-free medium in the column reactor markedly prolonged the period of reductive activity and photosynthesis.

Journal Article↗

PubMed1999

A case of group II non-specific interstitial pneumonia developed during corticosteroid therapy after acute respiratory distress syndrome.

Non-specific interstitial pneumonia/fibrosis (NSIP) is a relatively new entity among idiopathic interstitial pneumonias. This disease is pathologically characterized by varying proportions of interstitial inflammation and fibrosis that appear to occur over a single, short period of time, and is clinically characterized by a generally good prognosis. Although corticosteroid therapy is widely considered to be effective for treatment of this disease, we report a case of Group II NSIP which developed during treatment with corticosteroid 4 months after acute respiratory distress syndrome (ARDS). This case suggests that any group of NSIP may be developed after ARDS, and that low-dose corticosteroid treatment is not sufficient to prevent the development of NSIP.

Female↗

PubMed1999

Expression of transforming growth factor-beta1 and tumour necrosis factor-alpha in bronchoalveolar lavage cells in murine pulmonary fibrosis after intraperitoneal administration of bleomycin.

OBJECTIVE: We previously observed increased expression of interleukin-1beta, platelet-derived growth factor-A, and insulin-like growth factor-I in bronchoalveolar lavage (BAL) cells during the development of pulmonary fibrosis after an intraperitoneal administration of bleomycin in mice. The purpose of this study was to investigate the roles of tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 in this model. METHODOLOGY: We investigated the mRNA expression levels of TNF-alpha and TGF-beta1 in BAL cells of Institute for Cancer Research mice after 10 days of the intraperitoneal administration of bleomycin with or without treatment with a specific neutrophil elastase inhibitor, ONO-5046 x Na. RESULTS: On day 1 but not on days 15 and 29, the relative amount of TGF-beta1 mRNA in the bleomycin-treated mice was significantly decreased compared with control mice. In the mice treated with both bleomycin and ONO-5046 x Na intermediate values for TGF-beta1 were obtained. No significant differences in TNF-alpha expression were observed in any of the treatment groups. CONCLUSIONS: These results suggest that a reduced expression of TGF-beta1 in BAL cells in the early phase may be important during the development of murine pulmonary fibrosis induced by an intraperitoneal administration of bleomycin.

Animals↗

PubMed1999

New monoclonal antibodies against the epithelioid cells in sarcoid granulomas.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Extensive investigations of granulomas have suggested several possible causes, but these are still controversial. We previously developed an anti-Kveim monoclonal antibody, IHY-1, which reacts with sarcoid granulomas as well as with epithelioid cells of various granulomatous diseases including tuberculosis. In the present study, we developed 2 new anti-Kveim monoclonal antibodies, IHY-2 and IHY-3, which react with epithelioid cells in sarcoidosis but not in tuberculosis. These antibodies reacted with a small population of alveolar macrophages in sarcoidosis and hypersensitivity pneumonitis by flow cytometry, as well as with most epithelioid cells in sarcoid granulomas by immunoperoxidase technique, suggesting that these cells expressed the antigen present in the Kveim reagent. Although the antigens recognized by these antibodies have not yet been identified, these monoclonal antibodies might become useful tools to elucidate the etiology of sarcoidosis.

Animals↗

PubMed1999

Dermatomyositis associated with rapidly progressive fatal interstitial pneumonitis and pneumomediastinum.

We describe two cases of dermatomyositis (DM), which subsequently developed into rapidly progressive fatal interstitial pneumonitis and pneumomediastinum during steroid therapy. Both cases showed the classical cutaneous manifestations of DM, but the muscular symptoms were absent or mild. Both rapidly progressive interstitial pneumonitis and pneumomediastinum can occur in DM showing less inflammatory changes in the muscles. Patients with this form should be treated with extreme caution.

Adult↗

PubMed1999

Thiopurine methyltransferase genotype and the toxicity of azathioprine in Japanese.

OBJECTIVE: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including Azathioprine (AZA). It has been reported that the level of AZA toxicity is dependent on the TPMT genotypes in Caucasian individuals; we thus investigated this relationship in Japanese. METHODS: The TPMT genotype was determined using peripheral blood cell DNA obtained from 36 Japanese patients with rheumatic diseases who were treated with AZA, by polymerase chain reaction (PCR) technique. Duration of AZA administration, white blood cell counts before and after AZA administration, and side effects were investigated in each subject, and were compared between the patients with or without TPMT mutation. RESULTS: The TPMT allelotype was TPMT*1/TPMT*1 in 33 (91.7%) and TPMT*1/TPMT*3C in 3 (8.3%) individuals. All 3 patients (100%) with the mutant TPMT allele (TPMT*3C) discontinued AZA treatment due to leucopenia while only 4 patients (12%) without mutant TPMT alleles showed leucopenia (p=0.0049, Fisher's exact test). However, leucopenia developed relatively late in patients with mutant TPMT. CONCLUSION: The TPMT mutant allele, TPMT*3C, also exists in Japanese individuals, and the bone marrow toxicity of AZA is likely stronger in patients with this mutant allele.

Azathioprine↗

PubMed1999

Sarcoidosis associated with connective tissue diseases: report of 3 cases.

Disease activity in Japanese sarcoidosis patients is generally mild. However, the pulmonary sarcoidosis coexisting with connective tissue disease is likely to be progressive. We report here three cases of sarcoidosis coexisting with connective tissue diseases, who developed pulmonary manifestations from stage II to stage III.

Aged↗

PubMed1999

Telomerase activity in the synovial tissues of chronic inflammatory and non-inflammatory rheumatic diseases.

Telomerase is a ribonucleoprotein complex which can compensate for telomeric loss originating from each cell division, and its activation plays a critical role in cellular immortality. We previously found that telomerase is activated not only in immortal cancer cells but also in activated lymphocytes. To assess the diagnostic significance of telomerase activity in RA synovial tissues, we quantitatively examined telomerase activity in synovial tissue samples obtained from 47 patients with RA, 31 with osteoarthritis (OA), and 23 with other joint diseases. Telomerase activity in synovial tissues was detected in 28 of 47 (59.6%) patients with RA, including monoarticular-type RA, but in none of those with other joint diseases except one case each of synovial chondromatosis and OA. Thus, the specificity of telomerase activity in synovial tissues for RA among joint diseases was 96.3% (52/54). In RA samples, the telomerase activity was detected in 14 of 27 (51. 9%) patients with total joint replacement, 7 of 12 (58.3%) open synovectomy cases, and 7 of 8 (87.5%) arthroscopic synovectomy cases. Detection of telomerase activity in synovial tissues is considered to be useful for diagnosis of RA, including monoarticular-type RA, or active inflammation with lymphocyte infiltration, and arthroscopy can be applied for this purpose.

Arthritis, Rheumatoid↗

PubMed1999

Alternative splicing, but not allelic loss, of the FHIT gene increases with development of lung cancer.

The FHIT gene is considered to be a tumor suppressor gene, its role and inactivation mechanism remain unclear. We analyzed FHIT gene aberrations in 64 lung cancer tissues and found that the appearance of the aberrant FHIT transcripts depends on the condition of RT-PCR and high telomerase activity, shortened telomere length, and advanced pathological stage were likely associated with the prevalence of aberrant FHIT transcripts, but not with allelic loss of the FHIT gene. These observations would indicate that an additional unknown gene may exist, which is more responsible for the allelic loss around the FHIT gene locus.

Acid Anhydride Hydrolases↗

PubMed1999

Rapid detection of MYCN gene amplification and telomerase expression in neuroblastoma.

Amplification of the MYCN gene and high telomerase activity predict a poor prognosis for the patients with neuroblastoma. We used PCR techniques for rapid detection of MYCN gene amplification and human telomerase reverse transcriptase (hTERT) expression in neuroblastoma specimens. The detection of MYCN gene amplification is based on differential PCR in which three primer pairs were used to coamplify a 178-bp fragment of target MYCN gene with two reference gene fragments, a 237-bp of p53 exon 7 and a 120-bp of beta-globin exon 3, in a single tube of 40 surgically resected tumor samples. MYCN amplification was identified by this differential PCR in all 10 samples carrying more than 10 copies (already known to have MYCN gene amplification by Southern blot analysis). There were no false-negative or false-positive cases, and the relative intensity of MYCN bands in the differential PCR correlated significantly with the copy number determined by Southern blot analysis (y = 0.99, P<0.0001). This protocol was also applicable in the biopsy or aspirated samples, as well as the paraffin-embedded tissues, and in detecting intratumoral heterogeneity. Using RT-PCR procedures, hTERT mRNA expression was detectable in all 13 tumors with high telomerase activity. These nonradioisotopic PCR-based protocols for detecting MYCN gene amplification and hTERT mRNA expression are rapid and reliable and are likely to be useful to determine the biological behavior of neuroblastoma.

Biomarkers, Tumor↗

PubMed1999

Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma.

Inoperable adenocarcinoma in colon or lung shows resistance to conventional anti-cancer therapy. For these cancers, the feasibility of transcriptionally targeted killing of carcinoembryonic antigen (CEA)-producing adenocarcinoma cells was investigated. Adenovirus vectors carrying a CEA promoter to express E. coli lacZ (AdCEALacZ) or herpes simplex thymidine kinase (AdCEATK) were made and their in vitro and in vivo tumoricidal effects on CEA-producing or non-producing colon and lung cancer cells were evaluated. In vitro infection with AdCEALacZ showed significantly higher CEA promoter-driven lacZ expression in CEA-producing adenocarcinoma cells including VMRC-LCD and LoVo than in CEA-non-producing cells. AdCEATK-infected LoVo showed higher sensitivity to ganciclovir than control vector-infected LoVo or AdCEATK-infected HeLa both in vitro and in subcutaneously implanted tumors of nude mice. Moreover, total tumor elimination in vivo was achieved by either pre-infection of as few as 30% of cells comprising tumors or by direct in vivo injection of AdCEATK to pre-established LoVo tumors. In addition, CEA promoter-driven lacZ expression in LoVo cells was enhanced by the addition of interleukin-6 (IL-6) in vitro. These results provide a rationale for CEA-promoter-driven, adenovirus-mediated gene therapy for CEA-producing adenocarcinomas in colon and lung with reduced toxicity to normal cells.

Adenocarcinoma↗

PubMed1999

Two asymptomatic cases with sarcoidosis demonstrated sequential evolution from radiographic stage I to III within five years.

There are no guidelines regarding the treatment of pulmonary sarcoidosis. Generally, oral corticosteroids are considered the first-line treatment for symptomatic patients with pulmonary sarcoidosis. We report here two Japanese cases with pulmonary sarcoidosis who demonstrated sequential evolution from radiographic stage I to III within five years. Although these two cases had no symptoms, persistent, progressive pulmonary involvements were observed on chest X-ray. Considering the effectiveness of corticosteroids on patients with radiographic type II or III sarcoidosis reported by the British Thoracic Society, corticosteroid therapy might be a choice even in asymptomatic cases, if they demonstrate developing pulmonary involvement.

Adrenal Cortex Hormones↗

PubMed1999

Pranlukast, a cysteinyl leukotriene antagonist, reduces serum eosinophil cationic protein levels in patients with asthma.

Cysteinyl leukotrienes (cysLTs) are considered to be important mediators involved in bronchial asthma and the ensuing eosinophilic inflammation. We evaluated the effects of pranlukast, a potent and selective cysLT receptor antagonist, on the clinical course and serum eosinophil cationic protein (ECP) levels of 10 asthmatic patients. A four-week administration of pranlukast increased the morning peak expiratory flow (PEF) (p = 0.007) and decreased as-needed beta 2-agonist use (p = 0.021). Changes in the morning PEF inversely correlated with those in the serum ECP levels (r = -0.80, p = 0.0057). These results suggest that cysLTs are important mediators involved in eosinophilic inflammation, a major pathophysiologic feature of bronchial asthma in humans.

Adolescent↗

PubMed1998

Rheumatoid arthritis associated with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinct clinicopathologic entity, which is characterized by chronic recurrent sinopulmonary infection and inflammation. We describe 3 patients with rheumatoid arthritis (RA) associated with DPB and consider that DPB is one of the bronchopulmonary manifestations associated with RA.

Aged↗

PubMed1998

Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis.

OBJECTIVE: To determine whether the presence of telomerase activity in synovial tissues could provide insights into the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue samples obtained from patients with RA or osteoarthritis (OA) were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was detected in over half the RA synovial tissues (14/25, 56%) but in no OA synovial tissue samples (0/15). Telomerase activity was detected in the mononuclear cells isolated from telomerase-positive RA synovial tissue, but not in cultured adherent cells. In RA synovial tissue with positive telomerase activity mononuclear cell infiltration levels were increased (p < 0.001). In addition, patients with RA with positive telomerase activity had undergone joint operations at an earlier age (p = 0.030) and more often (p = 0.023) compared to those without telomerase activity. CONCLUSION: Telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA. Clinically, the presence of telomerase activity in RA may be an indicator of a more aggressive phenotype.

Aged↗

PubMed1998

[Relationship between telomere length and clinical and biological characteristics of the cancers with telomerase reactivation].

Activation of telomerase and stabilization of telomeres are considered to be necessary for immortalization of human tumor cells. Telomerase activity and telomere lengths were examined in adult and childhood cancer tissues. High telomerase activity was detected in over 40% samples. In these cases, the lengths of telomeres varied in wide range and the short telomere length significantly correlated with high proliferative index. The patients with short telomeres demonstrated poorer prognosis than other patients. These findings suggest that the short telomeres might be related with the malignant potential in cancers with high telomerase activity.

Adult↗

PubMed1998

[Telomerase activity as a novel marker of lung cancer].

Telomerase activity is found in more than 80% of human malignant neoplasms, including lung cancer. Markers with high incidence in malignant samples and very low incidence in benign samples are useful in clinical diagnosis of cancer. Thus, telomerase activity in clinical materials may become a novel tumor marker of existing lung cancer cells. Moreover, since activation of telomerase is associated with cellular immortality and its activity level is quite different between lung cancer tissues, the activity level may become an indicator of some biological features in lung cancer.

Biomarkers, Tumor↗