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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 343 records · Page 19Linked to original sources

A schwannoma of the cecum: case report and review of Japanese schwannomas in the large intestine.

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.

Aged↗

The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24-q32.

Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal dominant skeletal dysplasia characterized by dwarfism, shortening of the forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation. We studied a Thai family in which 15 members in 3 generations were affected with MDK. With reference to the breakpoints of a balanced translocation [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a skeletal dysplasia that appears similar to MDK, a linkage analysis was performed in the Thai family using 50 CA-repeat markers mapped to nearby regions (2q22-q34 and 8p24-p21) of the translocation breakpoints. The results clearly ruled out a linkage of MDK to marker loci at the 8p24-p21 region, whereas all nine affected members available for the study shared a haplotype at four loci (D2S2284, D2S326, D2S2188, and D2S2314) spanning about 22.7 cM in the 2q24-q32 region. The computer-assisted two-point linkage analysis revealed maximum logarithm of odds (lod) scores of 4.82, 4.21, 4.82, and 4.21 (theta = 0) at these loci, respectively. These data indicated that the MDK locus is in the vicinity of D2S2284 and D2S2188 loci that are most likely mapped to 2q24-q32.

Chromosome Mapping↗

Both positive and negative portal venous and hepatic arterial glucose gradients stimulate hepatic glucose uptake after the same amount of glucose is infused into the splanchnic bed in conscious dogs.

We studied the effects of both positive and negative portal venous and hepatic arterial glucose gradients on hepatic glucose uptake after the same amount of glucose was administered into the portal vein and/or hepatic artery. Studies were performed on eight unrestrained conscious dogs with catheters in the portal vein, hepatic vein, gastroduodenal artery, superior mesenteric vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Glucose was infused as follows: protocol 1, 55.6 micromol/kg/min into the portal vein for the first 90 minutes; protocol 2, 27.8 micromol/kg/min into both the portal vein and hepatic artery for the next 90 minutes; and protocol 3, 55.6 micromol/kg/min into the hepatic artery for the last 90 minutes. The portal venous and hepatic arterial plasma glucose gradient was 2.1+/-0.3, -3.0+/-0.5, and -7.1+/-0.6 mmol/L, the rate of hepatic glucose uptake divided by the administered glucose load was 46%+/-11%, 42%+/-10%, and 57%+/-8%, net hepatic glucose uptake was 25.4+/-5.9, 23.5+/-5.6, and 31.6+/-4.6 micromol/kg/min; and the fractional hepatic extraction of glucose was 10.7%+/-2.2%, 11.6%+/-2.5%, and 15.0%+/-2.1%, respectively (mean+/-SEM of three points at 60, 75, and 90 minutes in each protocol). The rate of hepatic glucose uptake divided by the administered glucose load, net hepatic glucose uptake, and fractional hepatic extraction of glucose did not change significantly despite the various portal venous and hepatic arterial glucose gradients. We also studied the effect of the same amount of intraportal glucose infusion for 240 minutes on net hepatic glucose uptake. From 60 to 240 minutes, net hepatic glucose uptake did not change significantly. In conclusion, the liver took up a large amount of glucose administered into the portal vein and/or hepatic artery, regardless of positive or negative portal venous and hepatic arterial glucose gradients. Augmentation of hepatic glucose uptake is not dependent on the signal of the positive or negative portal venous and hepatic arterial glucose gradient.

Animals↗

Histopathologic and radiographic findings of the simple bone cyst.

OBJECTIVE: The purpose of this study is to examine the correlation between histopathologic and radiographic findings and to discuss the cause of the simple bone cyst. STUDY DESIGN: Histopathologically, we classified 53 simple bone cysts into two types. Type A has a connective tissue membrane and type B has a partially thickened wall with dysplastic bone formation. Radiographically, we evaluated the following: margin, radiolucency, or radiopacity, relationship with tooth apices, bucco-lingual bone expansion, and displacement of the mandibular canal. RESULTS: Bone expansion and radiopacity were closely related to histopathologic findings although there was no correlation between the histopathologic findings and radiographic margin, relationship with tooth apices, and displacement of mandibular canal. Local recurrence was more likely to be observed in patients diagnosed as having type B than type A lesions. CONCLUSIONS: Type A and type B bone cysts may have different causes. Cysts determined radiographically to be radiopaque, those diagnosed as type B histopathologically, and cysts that have been treated surgically should all be followed by radiographic examinations.

Adolescent↗

An analysis of the prognostic significance of p53 status for squamous cell carcinoma of the oral cavity treated by radiotherapy.

The status of the p53 gene in biopsy specimens was analyzed to determine whether it is predictive of the outcome of radiotherapy of squamous cell carcinomas of the oral cavity. Biopsy materials were obtained from 45 patients, and the p53 status of each patient was determined using a single-strand conformation polymorphism analysis. Fourteen of the patients were treated with radiation therapy alone; the other 31 patients underwent radiotherapy in combination with surgery or chemotherapy. Twenty-seven patients had tumors with wild-type p53 and 18 patients had a tumor with mutant p53. The initial tumor response was not significantly different between these two groups. Kaplan-Meier survival plots (log-rank test) showed that the probability of survival was not significantly different between two groups although the patients with mutant p53 had a tendency for longer survival (P = 0.2941). However, among the patients with stage III/IV tumors (n = 24), those with a wild-type p53 status tended to have longer survivals.

Adult↗

Inflammatory responses to ischemia and reperfusion in skeletal muscle.

Skeletal muscle ischemia and reperfusion is now recognized as one form of acute inflammation in which activated leukocytes play a key role. Although restoration of flow is essential in alleviating ischemic injury, reperfusion initiates a complex series of reactions which lead to neutrophil accumulation, microvascular barrier disruption, and edema formation. A large body of evidence exists which suggests that leukocyte adhesion to and emigration across postcapillary venules plays a crucial role in the genesis of reperfusion injury in skeletal muscle. Reactive oxygen species generated by xanthine oxidase and other enzymes promote the formation of proinflammatory stimuli, modify the expression of adhesion molecules on the surface of leukocytes and endothelial cells, and reduce the bioavailability of the potent antiadhesive agent nitric oxide. As a consequence of these events, leukocytes begin to form loose adhesive interactions with postcapillary venular endothelium (leukocyte rolling). If the proinflammatory stimulus is sufficient, leukocytes may become firmly adherent (stationary adhesion) to the venular endothelium. Those leukocytes which become firmly adherent may then diapedese into the perivascular space. The emigrated leukocytes induce parenchymal cell injury via a directed release of oxidants and hydrolytic enzymes. In addition, the emigrating leukocytes also exacerbate ischemic injury by disrupting the microvascular barrier during their egress across the vasculature. As a consequence of this increase in microvascular permeability, transcapillary fluid filtration is enhanced and edema results. The resultant increase in interstitial tissue pressure physically compresses the capillaries, thereby preventing microvascular perfusion and thus promoting the development of the no-reflow phenomenon. The purpose of this review is to summarize the available information regarding these mechanisms of skeletal muscle ischemia/reperfusion injury.

Capillary Permeability↗

Predicting chemotherapeutic response to small-cell lung cancer of platinum compounds by thallium-201 single-photon emission computerized tomography.

Thallium-201 single-photon emission computerized tomography (SPECT) was used to clarify the relationship between 201Tl uptake and the response in chemotherapy to platinum compounds in 21 patients with small-cell lung cancer. 201Tl-SPECT scans were obtained twice: at 15 min (early scan) and 120 min (delayed scan) after an intravenous injection of 111 MBq (3 mCi) of thallium-201 chloride. We obtained the uptake ratio from each scan and calculated the retention index:uptake ratio = region of interest uptake/contralateral normal lung uptake; retention index = (delayed ratio - early ratio)/early ratio. After 201Tl scintigraphy, 12 patients received chemotherapy consisting of platinum compounds and nine were treated with chemoradiation. Among patients receiving only chemotherapy, the retention index correlated with the responses to chemotherapy. In an in vitro study, ouabain, an inhibitor of the Na,K-ATPase pump, reduced sensitivity to cisplatin and inhibited intracellular thallium uptake in the small-cell lung cancer cell line. These studies suggest that 201Tl-SPECT is a useful indicator of response to chemotherapy with platinum compounds in small-cell lung cancer, and that Na,K-ATPase is commonly involved in transporting both thallium and platinum compounds into cancer cells.

Aged↗

Phenotypic diversity of neurofibromatosis 2: association with plexiform schwannoma.

AIMS: Plexiform schwannoma (PS) is a rare variant of benign schwannoma characterized by a multinodular and plexiform growth pattern. In contrast to plexiform neurofibroma. PS is not associated with neurofibromatosis 1 (NF-1; von Recklinghausen's disease) and has no propensity for malignant transformation. The purpose of this study was to clarify the relationship between PS and the entities of neurofibromatosis 2 (NF-2; bilateral acoustic neurofibromatosis) and schwannomatosis. METHODS AND RESULTS: Six cases of PS associated with NF-2 or meningioma were retrospectively studied clinicopathologically and immunohistochemically. Four cases of PS were found among the patients with NF-2, and all of these had multiple PSs; three cases also had multiple schwannomas of the spinal nerve roots and two of these had meningioma. Two other patients had meningioma, but not NF-2. Four patients were male and two were female. The ages ranged from 18 to 52 years (mean 29.6 years). Histologically, PS showed the histological features that have been previously described, i.e. schwannoma composed of a predominant Antoni A-type component with a plexiform growth pattern. Immunohistochemically, the tumour cells were positive for S100 protein. Each nodule was surrounded by perineural cells which were positive for epithelial membrane antigen. CONCLUSIONS: It is important to recognize that PS could be associated with NF-2 or meningioma. The combination of PS and meningioma may be a 'formes frustes' of NF-2, and is clinically overlapped with schwannomatosis.

Adolescent↗

Pulmonary blastoma in an adult. A case with rapid progression.

A case of biphasic type pulmonary blastoma in a 59-year-old man is reported. Although the tumour was radically resected, there was rapid metastasization to the neck, mediastinum, liver and multiple bones. Despite radiotherapy, the patient died about 14 months postoperatively. Close follow-up and aggressive chemotherapy should be considered for such tumours.

Combined Modality Therapy↗

A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation.

About 100 amino acid residues in the C-terminal region are conserved among human, rat and murine CD30, a member of the tumor necrosis factor receptor (TNFR) superfamily, and can be separated into three subdomains with relatively higher conservation (D1, D2 and D3). Activation of NFkappaB by CD30 was shown to be mediated through interaction of TNFR-associated factor (TRAF) 1, 2 and 5 with the D2 and D3 subdomains. However, the function of the other conserved subdomain, D1, remained to be determined. Deletion of the D2 and D3 subdomains abolished interactions with TRAF2 and 5 but it did not affect NFkappaB activation. Reporter gene assays using deletion and mutant constructs of CD30 revealed that the D1 subdomain is sufficient for NFkappaB activation, without interaction with TRAF2 or 5, and that each subdomain alone can activate NFkappaB. Electrophoretic mobility shift assays revealed constitutive and CD30-induced NFkappaB activation in stable transformants of 293 cells expressing CD30 or a deletion mutant lacking D2 and D3 subdomains. Deletion of C-terminal 19 amino acid residues of the D1 subdomain abolished activation of NFkappaB. Substitution of alanine for one of the two threonine residues (amino acid position 524 and 529), one of which is a potential phosphorylation site in the D1 subdomain, also abolished the NFkappaB activation. Overexpression of the TRAF domain of TRAF2 or 5 had a dominant negative effect on the NFkappaB activation mediated by the D1 subdomain, thereby suggesting involvement of TRAF proteins in the signaling. Thus, the C-terminal 100 amino acid region of CD30 is composed of three independent functional subdomains, two of which contain binding sites for TRAF proteins. A novel domain in the cytoplasmic tail mediates NFkappaB activation, without direct interaction of TRAF2 or 5. Our observations suggest involvement of an unknown TRAF protein(s) in the signal transduction pathway of CD30.

Binding Sites↗

Expression of a synthetic gene for initiation factor 4E-binding protein 1 in Escherichia coli and its interaction with eIF-4E and eIF-4E x m7GTP complex.

An artificial gene coding for the human initiation factor (eIF) 4E-binding protein 1 (4E-BP1) was chemically synthesized and cloned. Although the expression of the 4E-BP1 gene alone has not yet been accomplished, the gene was expressed in Escherichia coli [BL21(DE3)] as a fusion gene with the glutathione-S-transferase (GST) gene using a prokaryotic gene fusion vector (pGEX-4T-2), which contains a gene sequence coding the cleavage site for a specific protease, alpha-thrombin. The fusion gene product was purified to homogeneity by glutathione Sepharose-4B affinity column chromatography. It was shown by m7GTP- and glutathione-affinity chromatography that the binding ability of 4E-BP1 to eIF-4E is nearly the same as that to the eIF-4E x m7GTP complex, implying different binding sites of eIF-4E and its nonallosteric obligation for 4E-BP1 and mRNA cap structure. In contrast with the binding of eIF-4E to the mRNA cap structure, where some functional amino acids play an important role in the binding, the binding to 4E-BP1 was suggested to occur via multiple nonspecific interactions.

Amino Acid Sequence↗

Characterization of a human small-cell lung cancer cell line resistant to a new water-soluble camptothecin derivative, DX-8951f.

DX-8951f, a water-soluble and non-pro-drug analogue of camptothecin, exhibits a strong inhibitory action on DNA topoisomerase I (Topo I) and in vitro cytotoxicity against various human cancer cell lines. In order to elucidate the mechanisms of its cytotoxicity, we established a DX-8951f-resistant cell line, SBC-3/DXCL1, from human small cell lung cancer cells (SBC-3) by stepwise exposure to DX-8951f. SBC-3/DXCL1 cells were approximately 400 times more resistant to DX-8951f than parent cells. The SBC-3/DXCL1 cells showed a high degree of cross-resistance to other Topo I inhibitors such as CPT-11, SN-38 and camptothecin, but not to non-Topo I targeting agents such as cisplatin, adriamycin, etoposide, and vincristine. The mechanisms of resistance of SBC-3/DXCL1 cells to DX-8951f were examined. Intracellular accumulation of DX-8951f by SBC-3 and SBC-3/DXCL1 cells did not differ significantly. Although the Topo I activity of nuclear extracts obtained from SBC-3/DXCL1 cells was the same as that of the parent cells, the Topo I of SBC-3/DXCL1 cells was resistant to the inhibitory effects of DX8951f and SN-38. Immunoblotting using anti-Topo I antibody demonstrated similar protein levels of Topo I in SBC-3 and SBC-3/DXCL1 cells. The active Topo I protein of SBC-3/DXCL1 was eluted by a high concentration of NaCl (0.4 N) compared with that of SBC-3 (0.3 N). DX-8951f stabilized the DNA-Topo I cleavable complex from SBC-3 cells, as measured by Topo I-mediated cleavage assay. In SBC-3/DXCL1 cells, DX-8951f also stabilized the DNA-Topo I complex, but with a 10-fold lower efficiency. These results suggest that a qualitative change in Topo I contributes, at least partially, to the resistance to DX-8951f in SBC-3/DXCL1 cells. Therefore, SBC-3/DXCL1 cells may have a unique mechanism of resistance to Topo I-directed antitumor drugs.

Antineoplastic Agents, Phytogenic↗

Human tumor growth suppression by apoptosis induced with anti-ErbB-2 chimeric monoclonal antibody.

We established an anti-ErbB-2 mouse-human chimeric monoclonal antibody (MoAb), CH401, which was able to kill cancer cells overexpressing the ErbB-2 protein in vitro. The analysis of the killing mechanism indicated that MoAb CH401 might be the first anti-erbB-2 mouse-human chimeric MoAb which can induce the apoptosis of cancer cells, since morphological changes and DNA fragmentation were recognized in MoAb CH401-treated cells. The ErbB-2 receptor appears to have two opposing functions: acting as a receptor both for a growth factor and for an apoptotic factor. Our results indicate that MoAb CH401 treatment may prove to be very useful for cancer therapy.

Animals↗

Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma.

Hepatocyte growth factor (HGF) is a heterodimeric polypeptide growth factor that has pleiotropic roles, including those of mitogen, motogen and morphogen. The HGF receptor is characterized as a c-Met proto-oncogene product (c-Met), which is a heterodimeric tyrosine kinase receptor. Hepatocyte growth factor acts as a mediator between the mesenchymal and epithelial tissues because HGF is produced by mesenchymal cells and c-Met is mainly expressed on various epithelial cells. Furthermore, the HGF/c-Met system plays an important role in embryogenesis and the regeneration of various organs. Synovial sarcoma (SS) are unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c-Met was examined by immunohistochemistry in SS specimens from 12 patients (six each of biphasic and monophasic fibrous types). Immunohistochemical coexpression of HGF and c-Met was demonstrated in the epithelial component of five biphasic SS, while only c-Met was expressed in the epithelioid nests of three monophasic fibrous SS. The spindle cell component was negative for HGF and c-Met. In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed in spindle cells, while vimentin was positive predominantly in the spindle cell component. The areas expressing HGF and c-Met corresponded to distinct epithelial structures; however, HGF and c-Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS. Considering the morphogenic effect of HGF, which has been known to be one of its most important roles, the unique immunohistochemical localization of HGF and c-Met in SS suggests that the HGF/c-Met system may be closely related to the formation of epithelial (glandular) structures in biphasic SS.

Adolescent↗

Atypical decubital fibroplasia in a young patient with melorheostosis.

A case of atypical decubital fibroplasia of the right forearm arising in a 25-year-old male with melorheostosis is presented. The diagnosis of melorheostosis involving the right-sided bones was made by radiographical studies, and the patient has been obliged to use crutches due to the contracture and limited range of motion of the right leg. Two painless masses occurred in the subcutis of the posterior aspect of the right forearm over the excrescences of the underlying ulna due to melorheostotic deformity. Grossly, ill-defined firm masses, which measured 3 x 6 x 1.5 cm and 4 x 5 x 1 cm, respectively, were white and intermingled with yellow fatty tissue. Histologically, the lesions consisted of a proliferation of plump fibroblastic cells with abundant collagenous stroma. Vascular proliferation and occasional eosinophilic degeneration of the collagen fibers were also seen. The gross and histological features were those of atypical decubital fibroplasia (ischemic fasciitis). Immunohistochemically, the plump fibroblastic cells were positive for vimentin, but negative for desmin, muscle specific actin, and alpha-smooth muscle actin. Chondroid metaplasia was focally noted and round-shaped cells within this area were positive for S-100 protein. This lesion seemed to be a fibroblastic response against the long-standing, intermittent ischemia of the subcutaneous tissue between the bony excrescences due to melorheostosis and the weight-bearing forces of the crutch.

Adult↗

[A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory Mycosis in Kyoto].

During the 7 years from 1990, thirty-two patients (20 in male and 12 in female, mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To clarify the essential points for early diagnosis of pulmonary cryptococcosis, we reviewed the clinical records and chest images. Three patients had a past history of pulmonary tuberculosis and eleven patients had underlying disorders such as malignancy, chronic pulmonary diseases and so on, but no HIV infection, which would affect this disease. Eighteen patients did not have any past history nor complications. The symptoms such as cough, sputum, chest pain and fever were generally of low-grade, 14 patients had no symptom at diagnosis. Except of some patients with severe infections and severe underlying disorders, laboratory findings such as inflamatory and nutritious markers were almost within near the normal range. On plain chest X-ray films the distribution of lesions was almost in proprtion to the volume of the lobes. The multifocal nudular and/or infitrative shadows wer observed in about 2/3 cases and single lesion in about 1/3. The width of lesions were minimal except of one case with interstitial pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the lesions were almost located in the outer zone, the lesions which were adjacent to the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the nodular/infitrative shadows were observed in three cases. Pulmonary cryptococcosis is air-borne and almost a chronic infection except in AIDS patients, so careful planning for examination is essential with considerations of the characteristics of clinical and imaging features of this infection.

Adult↗

Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status.

AIMS: To correlate vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma with the clinicopathological characteristics and prognosis; and to assess whether p53 gene status is associated with VEGF expression in human cancers. METHODS: Tumour specimens from 45 patients with oral squamous cell carcinomas were examined. Expression of VEGF was determined using an immunohistochemical method, and a tumour was considered positive when more than 5% of the neoplastic cells showed VEGF immunoreactivity. The p53 gene status was screened using a polymerase chain reaction--single strand conformation polymorphism analysis. RESULTS: VEGF positive staining was detected in 19 (42.2%) of the 45 cases. VEGF immunoreactivity did not correlate with the histological degree of tumour differentiation, clinical stages, or lymph node metastasis. The patients with VEGF positive tumours had a significantly worse prognosis than those with VEGF negative tumours. The five year overall survival rate of the VEGF negative patients was 76.5%, as compared with 48.8% for the VEGF positive patients. No significant association between VEGF expression and the p53 gene status of the tumours was found. CONCLUSIONS: VEGF is a good prognostic indicator of the survival of patients with oral squamous cell carcinoma. The p53 gene status does not seem to be associated with VEGF expression in these cancers.

Adult↗

HLA and HPA typing in idiopathic thrombocytopenic purpura patients treated with Kami-kihi-to.

We performed human leukocyte antigen (HLA) and human platelet antigen (HPA) in patients with Kami-kihi-to-responsive idiopathic thrombocytopenic purpura. The HLA-A2, A61 and Cw1 were significantly increased in responders compared with nonresponders, as were HLA DRB1 *0901, DRB1 *1502, and DPB1 *0501. In contrast, HLA DPB1 *0201 and DPB1 *0901 were significantly decreased in responders. The a/b genotype of HPA-2 and a/a genotype of HPA-3 were markedly increased in nonresponders, and anti-GPIb antibody was also increased. These results suggest that HLA, HPA, and anti-GP antibody studies may predict the response of idiopathic thrombocytopenic purpura to Kami-kihi-to.

Antigens, Human Platelet↗