[Positional cloning of the causative gene for the Medaka mutation, double anal fin (Da), defective in dorsoventral patterning].
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Biomedical subjects
Publications and source records attributed to M Ohtsuka.
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OBJECTIVE: To evaluate the relationship between vertebral bone mass and tooth loss and jaw bone mass in elderly Japanese women. METHODS: Mandibular cortical bone mass, alveolar bone height and number of teeth present (total, anterior, and posterior) were compared with the 3rd lumbar vertebral bone mineral density (L3BMD), measured by dual energy computed tomography (DEQCT), in 90 Japanese women by means of multiple regression analysis, controlling for body mass index, menopausal status, years since menopause and self-reported periodontal condition. RESULTS: Mandibular cortical bone mass and number of posterior teeth were associated with both alveolar bone height and L3BMD, but there was no association between alveolar bone height, number of anterior teeth present and L3BMD. CONCLUSION: Our results suggest that the loss of posterior teeth may be associated with a decrease not only in alveolar bone height, but also alveolar bone mineral density (BMD). The latter may be related to a decrease of lumbar vertebral BMD.
Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.
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Patients with hydroa vacciniforme (HV)-like eruptions and malignant potential have been reported from Asia and Mexico, and those patients frequently had an associated latent Epstein-Barr virus (EBV) infection. In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV-related RNAs in biopsy specimens from cutaneous lesions. Cutaneous lesions of all six children with typical HV contained EBV-encoded small nuclear RNA (EBER)+ cells in 3-10% of the dermal infiltrates, whereas no Bam HI-H, l-fragment (BHLF) mRNA, or transcripts encoding EA-D antigen, were detected. No EBER + cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. Polymerase chain reaction amplification confirmed the presence of EBV DNA sequences in five of six biopsy specimens from the patients. Latent EBV infection is associated with the development of cutaneous lesions of HV.
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The binding characteristics of the class 1 antiarrhythmic agents, cibenzoline, disopyramide, disopyramide metabolite (the main active metabolite of disopyramide in humans), and pirmenol, for human muscarinic receptors (m1-m3) stably expressed in Chinese hamster ovary cells (CHO) were investigated by binding assay with [3H]N-methylscopolamine ([3H]NMS) as a ligand. All of these agents inhibited the specific [3H]NMS binding to membrane preparations in a concentration-dependent manner. The potencies of affinity of these agents for m1, m2, and m3 receptors (compared by IC50) were disopyramide > pirmenol > disopyramide metabolite > cibenzoline, pirmenol > cibenzoline > disopyramide > disopyramide metabolite, and disopyramide > disopyramide metabolite > pirmenol > cibenzoline, respectively. Some competition curves of cibenzoline, disopyramide, and pirmenol were shallow, and Hill coefficients of these curves differed from unity, suggesting that these agents have allosteric binding characteristics for human muscarinic receptors. The m2-selective ratios to m1 (IC50 m1/IC50 m2) and m3 (IC50 m3/IC50 m2) of cibenzoline were 4.0 and 16, and those of pirmenol were 6.5 and 43, respectively, whereas those of disopyramide and its metabolite ranged from 0.46 to 1.6, suggesting that cibenzoline and pirmenol exerted high selectivity to the m2 receptor. We conclude that (a) all class 1 antiarrhythmic agents in this study have inhibitory effects on human m1, m2, and m3 receptors, and some of those binding may show allosteric characterization; (b) disopyramide and its metabolite have similar affinity to m1 to m3 receptors; and (c) cibenzoline and pirmenol have high m2-selective ratios to m1 and m3.
Double anal fin (Da) is a medaka with an autosomal semidominant mutation that causes mirror image duplication of the ventral region concentrating on the caudal region. The chromosomal location of the Da gene and its sequence have remained unknown. We constructed a medaka linkage map as a first step to approach positional cloning of the gene. The segregation analysis was performed on the basis of genetic recombination during female meiosis using 134 random amplified polymorphic DNA (RAPD) markers, 13 sequence-tagged sites (STSs), 15 polymorphic sequences from known genes, and the Da gene. One hundred forty-six markers from the above markers segregated into 26 linkage groups. The size of the genome was estimated to be 1776 cM in length. We identified four syntenic regions between medaka and zebrafish (and human) by mapping the known genes and found one of them to be located in close proximity to the Da gene. By mapping the region surrounding the Da gene in high resolution, two markers were detected flanking the Da gene at 0.32 and 0.80 cM. The detected markers providing a vital clue to initiate chromosome walking will lead us to the definite location of the Da gene.
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A 44-year-old man was admitted to the hospital with dyspnea on exertion. Chest radiographs and pulmonary function tests showed evidence of pulmonary emphysema. Serum alpha 1-antitrypsin (alpha 1-AT) could not be detected by nephelometry, immuno-electrophoresis, or iso-electric focusing. However, allele-specific PCR revealed a genotype homozygotic for an alpha 1-AT deficient variant of the Siiyama allele. An elder sister of the proband was also a homozygous carrier of the Siiyama allele. The amino acid sequence for normal alpha 1-AT variants had been substituted by Arg101-Val213-Glu376 in the proband, demonstrating that the alpha 1-antitrypsin-deficient Siiyama variant in this pedigree was derived from M 1 (Val213).
Combined antitumor activity of CPT-11 and 5-fluorouracil (5-FU) was evaluated in a human cultured cell line derived from lung cancer. After 24 h culture with SN-38 followed by 5-FU 24 h, synergistic effect was observed in the cell line. In addition, the antitumor effect of this combination was studied in in vivo experiments using Donryu rat with Yoshida sarcoma cells. CPT-11 and 5-FU synergistically inhibited tumor growth. There was no significant increase of toxicity as assessed by the body weights. These results might support for the combination with 5-FU and CPT-11 in a chemotherapy for cancer.
The association between systemic lupus erythematosus (SLE) and malignancy has been controversial in the literature. We report a case of lung cancer in a 50-year-old woman with a 4-year history of SLE. She underwent surgery at a pathological stage of T2N2M0, but she eventually died of rapid recurrence of the cancer in the abdomen resulting in massive haemorrhage from the inferior vena cava (IVC). Immunological disorders related to SLE are thought to contribute to rapid progression of the malignancy.
We report a case with metastatic small cell lung cancer which first manifested with biliary obstruction due to metastasis. Prognosis of patients presenting with jaundice due to hepatic parenchyma involvement is thought to be poor. However, the patient was successfully treated with percutaneous transhepatic biliary drainage and combination chemotherapy with reduced dosage. We believe this to be the first such case report, despite the frequency of metastasis to the liver from small cell lung cancer.
We evaluated the apoptosis of neutrophils during the resolution of acute pulmonary inflammation induced by exposure to ozone. The inflammatory response was assessed in rat lungs 0, 1, 3, and 7 days after 4-h exposure to air or 2 ppm ozone. Analysis of bronchoalveolar lavage fluid demonstrated significant increases in albumin concentrations on days 0 and 1 and in the number of lavageable neutrophils on days 0, 1, and 3, indicating the presence of acute pulmonary inflammation. These parameters returned to control values on day 7, which suggests that the acute pulmonary inflammation induced by ozone was reversible. On days 1 and 3, but not on day 0, the neutrophils showed morphologic evidence of apoptosis. Based on morphologic analysis, the proportion of apoptotic neutrophils was 23.3 +/- 2.2% on day 1 and 55.7 +/- 3.2% on day 3. Terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL), in contrast, revealed that the proportion of apoptotic cells was 59.7 +/- 9.1% on day 1 and 68.0 +/- 4.3% on day 3. On day 3, light microscopy and electron microscopy demonstrated engulfment of the neutrophils by macrophages. These findings indicate that the apoptosis of neutrophils followed by their engulfment by macrophages contributes to the clearance of neutrophils from the sites of inflammation. Moreover, TUNEL detected apoptotic neutrophils with greater sensitivity compared with morphologic assessment.