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Biomedical subjects

G Nishimura

Publications and source records attributed to G Nishimura.

At least 19 recordsLinked to original sources

Feminizing Wolbachia in an insect, Ostrinia furnacalis (Lepidoptera: Crambidae).

Wolbachia, which forms a group of maternally inherited bacteria in arthropods, often cause reproduction alterations in their hosts, such as cytoplasmic incompatibility, parthenogenesis, male-killing, hybrid breakdown and feminization. To date, Wolbachia-induced feminization has been reported only in isopods. Here we report that a Wolbachia strain feminizes an insect host, Ostrinia furnacalis. Among 79 wild females of O. furnacalis examined, Wolbachia infection was detected in 13 females. Twelve of the 13 infected females produced all-female progenies, and this trait was maternally inherited. Tetracycline treatment of thelygenic matrilines resulted in the production of all-male progenies. The present findings indicate that the Wolbachia infection induces feminization of genetic males in O. furnacalis. Differences in the Wolbachia-induced feminization in O. furnacalis and that in isopods are discussed along with the differences in sex determination mechanisms between insects and isopods. Phylogenetic analysis of the wsp gene sequence of Wolbachia suggests independent evolutionary origins for the Wolbachia-induced feminizations in O. furnacalis and in isopods. Our findings over 5 years suggest that the infection has been maintained at a low prevalence in the O. furnacalis population.

Animals↗

Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer.

BACKGROUND AND STUDY AIMS: Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. We report on the utility of laparoscopy and its indications in the detection of peritoneal metastasis in gastric cancer. PATIENTS AND METHODS: A total of 39 patients with gastric cancer underwent laparoscopy and peritoneal cytology investigation in our department, between April 1992 and April 2000. Laparoscopic diagnosis for peritoneal metastasis (LP-P) was determined through macroscopic, pathological and cytological diagnoses. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound before laparoscopy. Carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA125 levels in serum and peritoneal fluid were measured using enzyme immunoassay. RESULTS: Laparoscopic diagnosis for peritoneal metastasis gave negative results in 21 patients and positive results in 18. All the patients with negative LP-P findings underwent surgery; 18 of the 21 patients showed no peritoneal metastasis, but three were diagnosed as having peritoneal metastasis, one at the pouch of Douglas and two at the mesentery. The diagnosis of all the patients with positive LP-P findings was finally confirmed as correct. The specificity, sensitivity, and accuracy of laparoscopy for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 86 % (18/21, 95 % CI 0.64 - 0.97), and 92 % (36/39, 95 % CI 0.79 - 0.98), respectively. The specificity, sensitivity, and accuracy of diagnostic imaging for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 38 % (8/21, 95 % CI 0.18 - 0.62), and 67 % (26/39, 95 % CI 0.50 - 0.81), respectively. All of the 11 patients showing high levels of serum CA125 (equal to or more than 35 U/ml) had peritoneal metastasis whereas 17 of the 26 patients with low levels of serum CA125 (less than 35 U/ml) did not ( P < 0.001). CONCLUSIONS: The sensitivity of laparoscopy for peritoneal metastasis was much higher than that of diagnostic imaging. Laparoscopy and serum CA125 level both predicted peritoneal metastasis, but the degree, volume, or distribution of peritoneal metastasis was disclosed only by laparoscopy. Laparoscopy is a useful way of detecting peritoneal metastasis in gastric cancer, and patients with an elevated level of serum CA125 are the best candidates for laparoscopy.

Adult↗

Confirmation of genetic homogeneity of syndactyly type 1 in an Iranian family.

Syndactyly type 1 (SD1) is the most common type of syndactyly, inherited in an autosomal dominant fashion and characterized by complete or partial webbings between the third and fourth fingers and/or between the second and third toes. We recently encountered an Iranian family in which 33 members in six generations were affected with SD1. As a locus of SD1 in a German family has recently been assigned to chromosome 2q34-q36, we performed a linkage analysis of the Iranian SD1 in order to know whether the disorder is genetically homogeneous. With the analysis on 15 affected and 16 unaffected persons in the Iranian family, using dinucleotide repeat polymorphisms as markers, we mapped the SD1 locus to 2q34-q36 with a maximum LOD score of 6.92 at a recombination fraction straight theta = 0.00 (penetrance = 1.00) for the D2S2179 locus. The result not only confirmed the gene assignment, but also suggests genetic homogeneity of the disease.

Alleles↗

Regulation of apoptosis by respiration: cytochrome c release by respiratory substrates.

Cytochrome c release from mitochondria is essential for apoptosis. Using human myelogenous leukemia ML-1a, its respiration-deficient and reconstituted cells, we demonstrated that respiratory function is essential for tumor necrosis factor-induced cytochrome c release. In a cell free system using mitochondrial fraction from ML-1a, initiation of respiration by substrates for complexes I, II, and III but not IV released cytochrome c, suggesting that reduction of coenzyme Q or complex III is essential for cytochrome c release. In the same system, disruption of mitochondrial outer membrane was neither enough nor the cause for cytochrome c release by succinate. These observations define an early pathway in which a change in respiration releases cytochrome c.

Apoptosis↗

Spondylar dysplasia in type X collagenopathy.

BACKGROUND: The type X collagen gene (COL10A1) is currently known as the disease-causing gene of metaphyseal dysplasia type Schmid (MDS), whereas a mutation of COL10A1 has been reported to cosegregate with a disease phenotype of mild spondylometaphyseal dysplasia (SMD) in a Japanese family. OBJECTIVE: To elucidate whether or not spondylar dysplasia is common in patients with mutations of COL10A1. MATERIALS AND METHODS: We re-evaluated the radiological manifestations in six patients with mutations of COL10A1, who had been previously reported as having MDS. RESULTS: Two of six patients showed mild platyspondyly in infancy and early childhood. In both patients, the spondylar dysplasia tended to normalize with age, but mild alterations of the vertebral bodies persisted, even into late childhood. The other radiological manifestations of both patients were identical to those of MDS. CONCLUSION: Our observation suggests that mild spondylar dysplasia may not be uncommon in MDS.

Bones of Upper Extremity↗

Patterson-Lowry rhizomelic dysplasia: a potentially lethal bone dysplasia?

We report a Japanese boy, who is considered as having Patterson-Lowry rhizomelic dysplasia, a rare, as yet undefined, skeletal dysplasia. The diagnosis was warranted by the constellation of skeletal abnormalities - mild platyspondyly, hypoplastic ilia, broad proximal femora with prominent lesser trochanters, mild brachymetacarpalia and, most importantly, rhizomelic shortening of the upper limbs with lateral bowing, medial cortical thickening, and medial metaphyseal notching of the humeri. Our patient, unlike previously reported patients, had respiratory distress and died suddenly of unknown cause in late infancy. Our experience may imply the heterogeneity or phenotypic variability of Patterson-Lowry rhizomelic dysplasia.

Abnormalities, Multiple↗

Severe cervical kyphosis in osteopathia striata with cranial sclerosis: case report.

We report a 29-month-old girl with osteopathia striata with cranial sclerosis (OS-CS), who showed several unusual manifestations, including short stature, muscular hypotonia, short lingual frenulum, an accessory ear and a granuloma at the oral edge. The most unusual distressing finding was severe cervical kyphosis with a dysplastic cervical spine. MRI revealed impingement of the upper spinal cord. To clarify the mode of inheritance of this disease in this patient, we performed a methylation-specific PCR analysis. It eventually showed random inactivation of X-chromosomes, suggesting an autosomal dominant trait.

Bone Diseases, Developmental↗

Low-intensity fetal lungs on MRI may suggest the diagnosis of pulmonary hypoplasia.

BACKGROUND: Pulmonary hypoplasia is a common cause of neonatal death. Despite the recent advances in prenatal diagnosis with US, the diagnosis of pulmonary hypoplasia is difficult. The recent application of fast MR imaging may provide additional valuable information. OBJECTIVE: To evaluate pulmonary hypoplasia in the fetus with MRI. MATERIALS AND METHODS: The subjects comprised 23 fetuses (18-40 weeks' gestation), including major anomalies diagnosed on fetal ultrasonography (n = 20), maternal abnormality (n = 2) and one normal twin. MRI was performed with a 1.5-T magnet and half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences. MR images were interpreted by three radiologists with special attention to the intensity of the lungs. The lung-to-liver intensity ratio was calculated by means of region-of-interest (ROI) analysis. The diagnosis of pulmonary hypoplasia depended on clinical, surgical and autopsy findings. RESULTS: All fetuses with normal pulmonary development showed high intensity in the lung except for one fetus at 24 weeks' gestational age. All fetuses with pulmonary hypoplasia showed lung of low intensity. CONCLUSIONS: Low-intensity fetal lung on MRI imaging indicates pulmonary hypoplasia after 26 weeks' gestation.

Female↗

Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome.

Proximal symphalangism is an autosomal-dominant disorder with ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive deafness. These symptoms are shared by another disorder of joint morphogenesis, multiple synostoses syndrome. Recently, it was reported that both disorders were caused by heterozygous mutations of the human noggin gene (NOG). To date, seven mutations of NOG have been identified from unrelated families affected with joint morphogenesis. To characterize the molecular lesions of proximal symphalangism, we performed analyses of NOG in three Japanese individuals with proximal symphalangism. We found three novel mutations: g.551G>A (C184Y) in a sporadic case of symphalangism, g.386T>A (L129X) in a familial case of symphalangism, and a g.58delC (frameshift) in a family with multiple synostosis syndrome. Characteristic genotype-phenotype correlations have not been recognized from the mutations in the NOG gene.

Abnormalities, Multiple↗

SHOX haploinsufficiency and overdosage: impact of gonadal function status.

Since its discovery in 1997, knowledge about the SHOX gene has rapidly increased. In this review, we summarise clinical features and diagnostic and therapeutic implications in SHOX haploinsufficiency and overdosage. SHOX haploinsufficiency usually results in mesomelic short stature and Turner skeletal features, including Madelung deformity with puberty, in subjects with normal gonadal function. Thus, identification of early or mild signs of Madelung deformity is pivotal for the diagnosis, and gonadal suppression therapy may serve to mitigate the clinical features. By contrast, SHOX overdosage usually leads to long limbs and tall stature resulting from continued growth into the late teens in subjects with gonadal dysgenesis. Thus, the combination of tall stature and poor pubertal development is the key to diagnosis, and oestrogen therapy can help the prevention of unfavourably tall stature as well as the induction of sexual development. These findings, in conjunction with skeletal assessment in Turner syndrome and expression analysis during human embryogenesis, imply that SHOX functions as a repressor for growth plate fusion and skeletal maturation in the distal limbs and, thus, counteracts the skeletal maturing effects of oestrogens.

Female↗

The inhibitory effects of TNP470 on tumour growth of head and neck carcinoma cell producing interleukin-8.

The anti-tumour effect of the angiogenic inhibitor TNP470, sigma-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo using KB cells, one of the human head and neck carcinoma cell lines that produce interleukin(IL)-8. In the in vitro study, the combination treatment of TNP470 and anti-IL-8 antibody significantly reduced the proliferation of KB cells. In the in vivo studies, TNP470 administration by any route (intratumoral: i.t., intraperitoneal: i.p., intravenous: i.v.) reduced the tumour volume significantly, compared to the control group. Among the groups administered TNP470, the anti-tumour effect was strongest in the it group. Furthermore, the concurrent treatment of anti-IL-8 antibody and TNP470 also maximally reduced the tumour volume. The combination therapy of TNP470 and anti-IL-8 antibody was very effective. These results suggest that combination therapy of TNP470 and anti-IL-8 antibody could be beneficial for solid tumours, such as head and neck cancer.

Angiogenesis Inhibitors↗

Immunization against intestinal bacterial endotoxin prevents alcoholic fatty liver in rats.

Accumulating evidences indicate that an endotoxin originating from intestinal gram-negative bacteria may be involved in alcohol-induced liver injury including fatty liver. Therefore, whether immunization against intestinal bacterial endotoxin blocked fatty liver induced by chronic alcohol and diet including much-unsaturated fatty acid was investigated in rats. The titer of antibody against the endotoxin increased significantly after 13 weeks of continuous immunization. Daily alcohol treatment was initiated at 12 weeks and continued for 4 weeks. Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and triglyceride (TG) levels increased significantly in non-immunized rats receiving alcohol, but not in immunized rats. Continuous alcohol treatment gradually decreased the survival rate to 60% from 13 days after beginning administration in non-immunized, but not immunized, rats. A histochemical study revealed that continuous treatment with alcohol and unsaturated fatty acids caused fatty liver in non-immunized, but not immunized, rats. This study strongly supports the hypothesis that alcohol-induced fatty liver is due to a circulating endotoxin, and suggests that immunization for endotoxin prevent the alcoholic fatty liver.

Alanine Transaminase↗

Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma.

S100A4 has been implicated in invasion and metastasis of cancer, but prognostic significance of its expression in esophageal squamous cell carcinoma remains unclear. In this study, we examined the expression of S100A4 by Western blot analysis and immunohistochemistry in surgically resected esophageal squamous cell carcinoma. The relationship between S100A4 tissue status and clinicopathological findings was analyzed to assess the prognostic significance of S100A4 in esophageal squamous cell carcinoma. The S100A4 protein level was significantly higher in tumor tissue than in corresponding normal esophageal mucosa (p<0.05) in 22 cases of esophageal carcinoma by Western blot analysis. S100A4 expression was detected in 25% of 52 cases of esophageal squamous cell carcinoma by immunohistochemistry and correlated with the depth of invasion (p<0.05). Patients with S100A4-positive carcinoma had significantly poorer prognosis than those with S100A4-negative carcinoma, which was also true in the cases with deep invasion of the primary cancer (T3, T4) (p<0.01 and p<0.05, respectively). Moreover, S100A4 tissue status remained the only independent prognostic parameter in the multivariate analysis. Our results suggest that S100A4 may play a key role in the progression of esophageal carcinoma and that immunohistochemical detection of S100A4 in the primary tumor may be useful for the prediction of a poor prognosis.

Adult↗

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

Apoptosis↗