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Biomedical subjects

H Miyazawa

Publications and source records attributed to H Miyazawa.

At least 19 recordsLinked to original sources
PubMed2006

Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp.

This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type patients in response rates (78 vs 14%, P = 0.0017), and MST (15.4 vs 11.1 months, P = 0.0135). A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259, P = 0.036). This research showed the need for screening for EGFR mutations in NSCLC patients.

Adult↗
PubMed2006

Isolated osteochondroma near the mandibular angle.

A benign tumour of osseous and cartilaginous origins, osteochondroma generally develops in osseous tissue and is frequently found near the end of long bones. It is relatively rare in the oral and maxillofacial region but is common in the mandibular condyle and coronoid process in the pediculate form. This is a report on a rare case of osteochondroma in soft tissue near the mandibular angle without pedicle to the bone.

Adult↗
PubMed2006

Relevance of callosal and periventricular MRI lesions to oligoclonal bands in multiple sclerosis.

OBJECTIVES: To evaluate the association between callosal or periventricular lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in Japanese patients with multiple sclerosis (MS). MATERIALS AND METHODS: Brain magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging was added to the routine MRI studies. RESULTS: Among the 34 patients, 20 (59%) were OB positive. Among the 20 patients with OB-positive MS, 17 (85%) had callosal lesions, although only two (14%) of 14 OB-negative MS patients had callosal lesions. The periventricular lesion area was significantly larger in the OB-positive patients compared with the OB-negative patients. CONCLUSIONS: The present study clearly demonstrated a strong association between the periventricular lesions and OB in Japanese MS. Certain OB-related immune mechanisms may contribute to the development of callosal and periventricular lesions in MS. OB may be an important factor to understand the pathomechanisms of MS lesions.

Adult↗
PubMed2004

Sore throat and hoarseness after total intravenous anaesthesia.

BACKGROUND: Sore throat and hoarseness are common complications, but these have not been studied after total i.v. anaesthesia. METHODS: We prospectively studied 418 surgical patients, aged 15-92 yr, after total i.v. anaesthesia with propofol, fentanyl and ketamine to assess possible factors associated with sore throat and hoarseness. RESULT: We found sore throat in 50% and hoarseness in 55% of patients immediately after surgery. This decreased to 25% for sore throat and 24% for hoarseness on the day after surgery. Both sore throat and hoarseness were more common in females and when lidocaine spray had been used. Cricoid pressure during laryngoscopy was inversely associated with the risk of sore throat. CONCLUSION: Knowledge of these factors may reduce postoperative throat complications, and improve patient satisfaction.

Adolescent↗
PubMed2001

Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells treated with an anthrax toxin fusion protein.

As a novel and safe vaccine strategy, the anthrax toxin-mediated antigen delivery system composed of lethal factor (LF) fusion protein and protective antigen (PA) has been studied to prime hepatitis C virus (HCV) core-specific cytotoxic T lymphocytes (CTLs) in vivo. The core epitope fused to LF (LF-core) together with PA induces a negligible core-specific CTL response in mice, whereas core-specific CTL are effectively primed in mice by injecting dendritic cells (DCs) treated in vitro with LF-core and PA. These findings imply that LF fusion protein plus PA in combination with dendritic cells may be useful for a novel T cell vaccine against HCV infection.

Animals↗
PubMed2001

Purification and characterization of an autoregulatory substance capable of regulating the morphological transition in Candida albicans.

The yeast Candida albicans has a distinguishing feature, dimorphism, which is the ability to switch between two morphological forms: a budding yeast form and a multicellular invasive filamentous form. This ability has been postulated to contribute to the virulence of this organism. Studies on the morphological transition from a filamentous to a budding yeast form in C. albicans have shown that this organism excretes an autoregulatory substance into the culture medium. This substance was extracted and purified by normal-phase and reversed-phase HPLC. The autoregulatory substance was structurally identified as 3,7,11-trimethyl-2,6,10-dodecatrienoate (farnesoic acid) by NMR and mass spectrometry. Growth experiments suggest that this substance does not inhibit yeast cell growth but inhibits filamentous growth. These findings have implications for developmental signaling by the fungus and might have medicinal value in the development of antifungal therapies.

Candida albicans↗
PubMed2001

Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines.

BACKGROUND: Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate-type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate-type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined. METHODS: Serum samples were taken from 28 children who showed allergic nonimmediate-type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate-type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate-type reaction as one occurring within 1 h after vaccination. RESULTS: Of 10 children who showed immediate-type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate-type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination. CONCLUSION: These results suggest that some children who showed allergic nonimmediate-type reactions to JE vaccine were sensitized to gelatin.

Antibody Specificity↗
PubMed2001

Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis.

The natural occurrence of Japanese cedar [Cryptomeria japonica (CJ)] pollinosis has been reported in Japanese monkeys (Macaca fuscata). The present study was designed to investigate seasonal changes in immunological reactions to CJ pollen allergens in monkeys with CJ pollinosis. Blood samples were collected from six monkeys with CJ pollinosis before and after CJ pollen season. Seasonal changes in specific IgE and IgG to major allergens (Cry j 1 and Cry j 2) were observed before and after CJ pollen season. The humoral responses decreased significantly before CJ pollen and increased after CJ pollen season. Similar seasonal changes in peripheral blood mononuclear cells proliferative responses to CJ allergens were observed before and after CJ pollen season. These humoral and cellular immune responses might serve as a biomarker for assessing new immunotherapies for monkeys with pollinosis.

Allergens↗
PubMed2001

E2F regulates growth-dependent transcription of genes encoding both catalytic and regulatory subunits of mouse primase.

DNA polymerase alpha-primase is one of the principal enzymes involved in eukaryotic chromosomal DNA replication. Mouse DNA polymerase alpha-primase consists of four subunits with molecular masses of 180, 68, 54 and 46 kDa. Protein and mRNA expression levels of the four subunits are up-regulated in a coordinated manner in response to growth stimulation. We have previously analysed the transcription of the 180 kDa (p180) and 68 kDa (p68) subunits, which form the DNA polymerase catalytic complex, and found that growth-dependent regulation of transcription of the mouse p180 and p68 genes is mediated by a common factor, E2F, while the basal transcription of the genes is regulated by different transcription factors. We characterized the transcriptional regulation of the 54 kDa (p54) and 46 kDa (p46) subunits, which form the DNA primase catalytic complex. We isolated genomic clones spanning the 5'-flanking regions of the p54 and p46 genes and showed, using transient expression and gel mobility shift assays, that the basal transcription of p54 is controlled by Sp1 and GA-binding protein, as is the basal transcription of the p180 gene. The basal transcription of p46 is controlled by unknown factor(s) which were bound to the upstream sequence. The variant E2F sites close to the transcription initiation sites of the p54 and p46 genes had no basal promoter activity, but were essential for the growth-dependent transcription of both genes. The promoter regions of the four subunits of mouse DNA polymerase d-primase complex share several common features. The coordinated transcription of all four subunits in response to growth stimulation appears to be controlled by E2F.

3T3 Cells↗
PubMed2001

Follicular cyst in a patient with myotonic dystrophy: a case of cyst with differentiation toward follicular infundibulum, isthmus, inner root sheath, and hair.

We report a case of follicular cyst, which developed in a patient with myotonic dystrophy (MyD). Histopathologically, the cyst showed infundibular and trichilemmal keratinization, inner root sheath differentiation, aggregation of basaloid cells, and pilomatricoma-like changes in the pericystic connective tissue. These findings have been reported in follicular cysts with Gardner's syndrome (GS). Interestingly, pilomatricoma is known as one of the skin diseases associated with MyD, though there have been no reported cases of cyst formation with differentiation toward portions of hair follicle in a MyD patient. In our case, we hypothesized that the cyst might be derived from embryonic follicular germinative cells or follicular stem cells under the genetic influence of the MyD gene, as observed in follicular cysts in patients with GS.

Adult↗
PubMed2001

Lesions in lateral hypothalamic areas increase splenocyte apoptosis.

OBJECTIVE: The lateral hypothalamic area (LHa) is involved in various functions such as feeding, drinking, sexual and reward behavior, among others. Recently, we demonstrated that the LHa can regulate cellular immunity in the spleen. In experiments involving the LHa, it was noticed that the spleen shrinks noticeably after LHa destruction. To explore this phenomenon further, the effect of LHa lesioning on splenocyte apoptosis was investigated. METHODS: Male Wistar-King-Aptekman rats underwent bilateral lesioning of their LHa and consequent spleen weights, splenocyte numbers and apoptosis were measured. For the detection of splenocyte apoptosis, both ELISA, which measures DNA fragmentation within the splenocytes, and flow cytometry, which measures the percentage of apoptotic lymphocytes in the spleen, were used. RESULTS: In the LHa-lesioned rats, spleen weights and the number of splenocytes decreased significantly within 24 h. Additionally, in the spleen, lymphocyte apoptosis significantly increased compared to the control after 6 h. CONCLUSION: These results suggest that the LHa may play a role in immunoregulation by affecting lymphocytes in the spleen through apoptosis and may be relevant to the pathway of stress-induced apoptosis.

Animals↗
PubMed2000

Transcription of the catalytic 180-kDa subunit gene of mouse DNA polymerase alpha is controlled by E2F, an Ets-related transcription factor, and Sp1.

We have isolated a genomic DNA fragment spanning the 5'-end of the gene encoding the catalytic subunit of mouse DNA polymerase alpha. The nucleotide sequence of the upstream region was G/C-rich and lacked a TATA box. Transient expression assays in cycling NIH 3T3 cells demonstrated that the GC box of 20 bp (at nucleotides -112/-93 with respect to the transcription initiation site) and the palindromic sequence of 14 bp (at nucleotides -71/-58) were essential for basal promoter activity. Electrophoretic mobility shift assays showed that Sp1 binds to the GC box. We also purified a protein capable of binding to the palindrome and identified it as GA-binding protein (GABP), an Ets- and Notch-related transcription factor. Transient expression assays in synchronized NIH 3T3 cells revealed that three variant E2F sites near the transcription initiation site (at nucleotides -23/-16, -1/+7 and +17/+29) had no basal promoter activity by themselves, but were essential for growth-dependent stimulation of the gene expression. These data indicate that E2F, GABP and Sp1 regulate the gene expression of this principal replication enzyme.

3T3 Cells↗
PubMed2000

Cloning and characterization of the 5'-upstream sequence governing the cell cycle-dependent transcription of mouse DNA polymerase alpha 68 kDa subunit gene.

We have isolated the genomic DNA fragment spanning the 5-end and the first four exons encoding the 68 kDa subunit (p68) of the mouse DNA polymerase alpha-primase complex [corrected]. The p68 promoter region lacks TATA and CAAT boxes, but contains a GC-rich sequence, two palindrome sequences and two putative E2F-binding sites [corrected]. A series of transient expression assays using a luciferase reporter gene indicated that a region from nucleotide position -89 to -30 (-89/-30) with respect to the transcription initiation site is crucial for basal transcription of the p68 gene in proliferating NIH 3T3 cells. In particular, part of the GC-rich sequence (-57/-46) and the palindrome (-81/-62) elements were necessary for promoter activity, both of which share homology with the E-box sequence. Gel mobility shift assays using NIH 3T3 nuclear extracts revealed that the upstream stimulatory factor, known as an E-box-binding protein, binds to these sites. Moreover, we observed binding of E2F to two sites near the transcription initiation site (-11/-3 and +9/+16). A transient luciferase expression assay using synchronized NIH 3T3 cells in G(0)phase revealed that these E2F sites are essential for transcription induction of the p68 gene after serum stimulation, but are dispensable for basal transcription. These results indicate that growth-dependent regulation of transcription of the mouse p68 and p180 genes is mediated by a common factor, E2F; however, basal transcription of the genes, interestingly, is regulated by different transcription factors.

3T3 Cells↗
PubMed2000

Sensitization to gelatin in children with systemic non-immediate-type reactions to varicella vaccines.

BACKGROUND: We recently found that four children who experienced systemic immediate-type reactions to varicella vaccine with gelatin had anti-gelatin IgE. We also found systemic non-immediate-type allergic reactions, which mainly consist of systemic cutaneous signs, appearing several hours or more after the vaccination. OBJECTIVE: To investigate the relationship between immune responses to gelatin and non-immediate-type reactions to gelatin-containing varicella vaccines, we measured anti-gelatin IgE and IgG in the sera of the children with these allergic reactions. METHODS: Serum samples were taken from 21 children who showed non-immediate-type reactions to varicella vaccines. As a positive control, serum samples were taken from 33 children who showed immediate-type reactions to varicella vaccine and had anti-gelatin IgE. As a negative control, serum samples were taken from 50 children who showed no reaction to the vaccine. We then examined anti-gelatin IgE and IgG in sera of the children. RESULTS: Of 21 children with non-immediate-type reactions, two (10%) had anti-gelatin IgE and six (29%) had anti-gelatin IgG. In the positive control group, all 33 children with immediate-type reactions had anti-gelatin IgG as well as IgE. In the negative control group, all 50 children who showed no allergic reaction to varicella vaccines had neither anti-gelatin IgE nor IgG. CONCLUSIONS: These results suggest that the possibility exists that some non-immediate-type reactions to varicella vaccine are caused by immune reactions to gelatin.

Angioedema↗