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Biomedical subjects

G Nishimura

Publications and source records attributed to G Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed2000

Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata.

Chondrodysplasia punctata (CDP) is a heterogeneous group of skeletal dysplasias characterized by stippled epiphyses. A subtype of CDP, X-linked dominant chondrodysplasia punctata (CDPX2), known also as Conradi-Hünermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. The cause of CDPX2 was unknown until recent identification of mutations in the gene encoding Delta(8),Delta(7) sterol isomerase emopamil-binding protein (EBP). Twelve different EBP mutations have been reported in 14 patients with CDPX2 or unclassified CDP, but with no evidence of correlation between phenotype and nature of the mutation. To characterize additional mutations and investigate possible phenotype-genotype correlation, we sequenced the entire EBP gene in 8 Japanese individuals with CDP; 5 of them presented with a CDPX2 phenotypes. We found EBP mutations in all 5 CDPX2 individuals, but none in non-CDPX2 individuals. Three of these CDPX2 individuals carried novel nonsense mutations in EBPand the other two, separate missense mutations that had been reported also in different ethnic groups. Our results, combined with previous information, suggest all EBP mutations that produce truncated proteins result in typical CDPX2, whereas the phenotypes resulted from missense mutations are not always typical for CDPX2. Patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Delta(8), Delta(7) sterol isomerase. X-inactivation patterns of the patients showed no skewing, an observation that supports the assumption that inactivation of the EBP gene occurs at random in affected individuals.

Adolescent↗
PubMed2000

Therapeutic efficiency of IL-2 gene transduced tumor vaccine for head and neck carcinoma.

Transduction of the human interleukin-2 (IL-2) gene into tumor cells was carried out in order to develop a new immunotherapy for advanced head and neck carcinomas with a poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using a defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. A high level of IL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2 producibility of irradiated KB/IL-2 cells was almost the same as that of non-irradiated cells. In the tumor establishment model in nude mice, IL-2 and interferon-gamma (IFN-gamma) at high concentrations were detected in the sera of mice transplanted with KB/IL-2 cells. The spleen cells of nude mice transplanted with KB/IL-2 cells exhibited high cytotoxic activity compared to those from mice transplanted with KB cells and from untreated mice. Three of five mice transplanted with KB/IL-2 cells rejected tumors. In the treatment of established tumors, therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumor growth were blocked by anti-asialo GM1, anti-human IL-2 and anti-IFN-gamma antibodies. Immunohistochemical observation revealed the presence of asialo GM1(+) cells among the KB/IL-2 cells in tumors transplanted into nude mice.

Animals↗
PubMed2000

Alteration of beta-catenin expression in esophageal squamous-cell carcinoma.

beta-catenin regulates cadherin-mediated cell-cell adhesion and also functions as a signaling molecule. In this study, we examined the expression pattern of E-cadherin, alpha-catenin and beta-catenin in 22 cases of esophageal squamous-cell carcinoma by Western-blot analysis. Expression of E-cadherin, alpha-catenin and beta-catenin was lower in carcinomas than in normal esophageal mucosa in 4 cases (18.2%) for E-cadherin, 6 cases (27.3%) for alpha-catenin and 9 cases (40.9%) for beta-catenin. Expression of beta-catenin was not always correlated with that of E-cadherin. Over-expression of beta-catenin was observed in 3 cases (13.6%). Of 3 cases that presented with over-expression of beta-catenin, 2 showed cytoplasmic staining by immunohistochemistry. Nuclear localization of beta-catenin was observed in one case that had higher beta-catenin level in tumor tissue (1.4-fold higher than normal mucosa). The genomic DNA sequences of the beta-catenin and the APC gene were analyzed. No mutation of the beta-catenin gene was observed in any cases. Silent mutation of the APC gene was found in all the cases that showed over-expression or nuclear localization of the beta-catenin protein. These results indicate that alterations of the cadherin-catenin complex may play an important role in a sub-set of esophageal carcinogenesis. Furthermore, it is suggested that beta-catenin over-expression is not caused by genetic alteration of either the beta-catenin or the APC gene.

Blotting, Western↗
PubMed2000

Intrafamilial phenotypic variability in Engelmann disease (ED): are ED and Ribbing disease the same entity?

We report on clinical and radiologic manifestations in a 3-generation Japanese family with Engelmann disease (ED) or progressive diaphyseal dysplasia. A large variation of phenotype was remarkable among 12 affected family members. Of the 12 patients, 7 had full manifestations of ED, such as bilateral, symmetrical diaphyseal sclerosis of long bones with myopathy and limb pain, whereas the other 5 exhibited only segmental (rhizomelic and/or mesomelic) involvement and asymmetric diaphyseal sclerosis without any clinical symptoms. The phenotype of the latter group of patients resembled Ribbing disease (RD). We propose that ED and RD represent phenotypic variation of the same disorder.

Adult↗
PubMed2000

Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease.

Camurati-Engelmann disease (CED, MIM 131300) is an autosomal dominant, progressive diaphyseal dysplasia characterized by hyperosteosis and sclerosis of the diaphyses of long bones. We recently assigned the CED locus to an interval between D19S422 and D19S606 at chromosome 19q13.1-q13.3, which two other groups confirmed. As the human transforming growth factor-1 gene (TGFB1) is located within this interval, we considered it a candidate gene for CED.

Base Sequence↗
PubMed2000

Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3.

Camurati-Engelmann disease (CED [MIM 131300]), or progressive diaphyseal dysplasia, is an autosomal dominant sclerosing bone dysplasia characterized by progressive bone formation along the periosteal and endosteal surfaces at the diaphyseal and metaphyseal regions of long bones and cranial hyperostosis, particularly at the skull base. The gene for CED, or its chromosomal localization, has not yet been identified. We performed a genomewide linkage analysis of two unrelated Japanese families with CED, in which a total of 27 members were available for this study; 16 of them were affected with the disease. Two-point linkage analysis revealed a maximum LOD score of 7.41 (recombination fraction.00; penetrance 1.00) for the D19S918 microsatellite marker locus. Haplotype analysis revealed that all the affected individuals shared a common haplotype observed, in each family, between D19S881 and D19S606, at chromosome 19q13.1-q13.3. These findings, together with a genetic distance among the marker loci, indicate that the CED locus can be assigned to a 15.1-cM segment between D19S881 and D19S606.

Camurati-Engelmann Syndrome↗
PubMed2000

Bicycle spoke injuries in the lower extremity.

This study reports the authors' 5-year experience with treating lower extremity injuries in bicycle passengers caused by the spokes. This patient group was selected from 716 lower extremity injuries that received treatment at our outpatient plastic surgery clinic. A total of 26 patients were treated during the study. Patients ranged from 2 to 19 years old, with a mean age of 5.6 years. The authors treated more female passengers (62 percent) than male passengers. The right foot (52 percent) was involved more often than was the left. Most patients were injured in the afternoon, from 2 to 7 PM (62 percent), and between May and October (77 percent). The rear wheel (89 percent) injured the majority of patients. The Achilles tendon was the most common site of injury (63 percent). The typical types of wounds observed included the following: type I, laceration with partial avulsion of skin and subcutaneous tissue (41 percent) and laceration forming a distally based flap (33 percent); type II, abrasions with ecchymoses and friction burn from the shearing effect of the spokes creating a partial- to full-thickness skin defect (26 percent). Of the type I injuries, full-thickness skin lacerations (33 percent) were closed primarily. Partial-thickness skin lacerations, abrasions, ecchymoses, and skin defects (67 percent) were treated conservatively with wound irrigation and dressing. The wound healing time for type I injuries was 29 days; for type II injuries, it was 27 days. These healing times were prolonged compared with healing by first intention. No significant difference was found in healing time when comparing both types of injury. Four patients required hospitalization. No patient required skin grafting. No fractures were noted because these patients were selected from the outpatient plastic surgery clinic and did not include patients from the emergency room. Since the first report of bicycle spoke injuries a half-century ago, prevention has not improved.

Achilles Tendon↗
PubMed2000

Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation, and CNS structural anomalies: another observation.

We report a Japanese girl with brachycephaly, a wide forehead, hypertelorism, macroblepharon with eyelid colobomas, ectropion, a broad nasal root, a depressed nasal tip, macrostomia, a small and grooved chin, ear anomalies, a structural anomaly of the corpus callosum, dilatation of the fourth ventricle, a urogenital sinus, and mental retardation. Cause and inheritance are unknown.

Abnormalities, Multiple↗
PubMed2000

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma.

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma was developed. After transplantation of KB cells into nude mice, the mice were given tiracoxib, a selective cyclooxygenase (COX)-2 inhibitor, probucol, an antioxidant, and S-1, an oral pro-drug of 5-fluorouracil (5-FU), or combinations of two of them. The combined administration of tiracoxib with probucol significantly inhibited the tumor growth. The angiogenesis in this group was markedly reduced. Tiracoxib and probucol did not affect the intratumoral concentration of 5-FU when coadministered with S-1. The combined use of tiracoxib and probucol is thus a candidate for use in maintenance therapy after the primary therapy for patients with advanced head and neck carcinoma.

Animals↗
PubMed2000

PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells.

The aim of this study was to examine whether a specific PPARgamma ligand can inhibit the growth of human pancreatic cancer cells through induction of terminal differentiation. PPARgamma was expressed in five human pancreatic cancer cell lines: Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. Treatment of these cells with a specific PPARgamma ligand, thiazolidinedione (TZD), resulted in inhibition of both cellular and clonogenic growth, and G1 cell cycle arrest. Finally, thiazolidinedione treatment resulted in induction of p21WAF-1 and increased expression of differentiation markers. These results suggest that thiazolidinedione treatment inhibits growth and induces cellular differentiation in pancreatic cancer cells and thereby reduces their development in favor of differentiated and stable cell phenotype.

Adenocarcinoma↗
PubMed2000

[Antitumor effect of the angiogenesis inhibitor, TNP470, on squamous cell carcinoma cells in head and neck cancer].

The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p < 0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.

Angiogenesis Inhibitors↗
PubMed2000

[A case of stage IVb (H2P0N4T4) gastric cancer successfully treated with neoadjuvant chemotherapy (PMFE therapy)].

A 69-year-old man was examined at our hospital because of a sense of upper abdominal fullness. He was diagnosed as having stage IVb (H2P0N4T4) gastric cancer and treated with neoadjuvant chemotherapy. One course of the regimen consisted of 10 mg CDDP (day 1-5), 10 mg MMC (day 1), 250 mg 5-FU (day 1-20) and 50 mg ETP (day 6, 7). The patient underwent the regimen three times in succession. After the chemotherapy, his hepatic metastases showed necrotic changes and the swelling of the para-aortic lymph nodes disappeared on a CT scan. A histological examination revealed that the cancer cells had completely vanished both at the site of the hepatic tumor and the para-aortic lymph nodes. This combination chemotherapy, named PMFE therapy, is considered effective without serious side effects for gastric cancer in patients with non-curative factors.

Adenocarcinoma↗
PubMed2000

[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.

Administration, Oral↗
PubMed2000

[A case of a combined aortectomy with dissection of recurrent paraaortic lymph nodes of sigmoid colon cancer].

A combined aortectomy was performed on a patient with recurrence of sigmoid colon cancer in the paraaortic lymph nodes. The 48-year-old woman was found to have tumor recurrence in the lymph nodes in the area between the aortic bifurcation and the paraaortic area, accompanied by left hydronephrosis, four years after surgery for sigmoid colon cancer (H0, P0, ss, n3, stage IIIb). No metastasis to distant areas was detected at that time. The woman thus underwent a reoperation. Intraoperatively, the aortic bifurcation and the lymph nodes were seen as a mass. The mass involved the left common iliac vein and the left ureter, as well. Therefore, we resected the area from the aortic bifurcation to the bilateral common iliac arteries, the left common iliac vein, the left ureter and the left kidney en bloc, and replaced them with a Y-shaped graft. One year after the reoperation, a tumor metastasis to the liver was detected, and a partial hepatectomy was performed. At present, the patient is being managed at our outpatient clinic. The results suggest that extended resection, involving the aorta as well, is sometimes useful when dealing with tumor recurrence in the paraaortic lymph nodes, unaccompanied by blood-borne metastasis.

Aorta↗
PubMed1999

Analysis of interaction between chaperonin GroEL and its substrate using fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy (FCS) provides information about translational diffusion properties of fluorescent molecules in tiny detection volume and allows the analysis of binding processes of biomolecules in homogeneous solution. In this study, FCS was used to measure equilibrium binding constants of disulfide-reduced apo-alpha-lactalbumin (rLA), denatured pepsin, and apo-cytochrome c (apo-cyt c) bound by chaperonin GroEL at different salt concentrations. The results indicate that apo-cyt-c has a much stronger affinity to GroEL than denatured pepsin and rLA have. Titration experiments of GroEL to each substrate with various concentrations of four kinds of salts (K+, Na+, Ca2+, and Mg2+) show that the binding constant of denatured pepsin and rLA to GroEL depends on the salt concentration. The dependence of denatured pepsin binding to GroEL on salt concentration is much stronger than that of rLA. However, the interaction of positively charged apo-cyt c with GroEL is not affected by the salt concentration. Furthermore, the divalent cation promotes the binding of GroEL to denatured pepsin and rLA more strongly than does the monovalent cation.

Animals↗
PubMed1999

New brittle bone disorder: report of a family with six affected individuals.

We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications.

Adult↗
PubMed1999

Young-Simpson syndrome: further delineation of a distinct syndrome with congenital hypothyroidism, congenital heart defects, facial dysmorphism, and mental retardation.

Young-Simpson syndrome is a rare congenital disorder, characterized by congenital hypothyroidism, congenital heart defects, facial dysmorphism, cryptorchidism in males, hypotonia, mental retardation, and postnatal growth retardation. We describe the cases of a 5-year-old boy and a 7-year-old girl with a similar constellation of symptoms and compared them with previously reported patients.

Brain↗