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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 271 records · Page 15Linked to original sources

Noninvasive evaluation of myocardial ischemia in Kawasaki disease: comparison between dipyridamole stress thallium imaging and exercise stress testing.

The sensitivities of dipyridamole stress thallium 201 single photon emission computed tomography (SPECT) and treadmill exercise testing in the detection of myocardial ischemia were compared. Thirty-eight patients with Kawasaki disease and 11 age-matched controls participated in the study. Fifteen of the 38 patients with Kawasaki disease had marked coronary artery stenosis (> 75%) in at least one vessel. SPECT scans were obtained immediately after dipyridamole infusion and 4 hours later. The sensitivity of SPECT for detection of coronary stenosis was 80% (12/15), whereas that of treadmill exercise testing was only 33% (5/15) (p < 0.001). Although the sensitivity of SPECT significantly exceeded that of treadmill exercise testing among patients with coronary stenosis in only one vessel (p < 0.05), such benefits were not found for patients with stenosis in two or three vessels. These findings suggest that dipyridamole stress SPECT has a higher degree of sensitivity in the detection of myocardial ischemia than does treadmill exercise testing, especially for patients with single-vessel disease.

Child↗

Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions.

The p16 protein (p16) is a cyclin-dependent kinase (CDK) inhibitor that decelerates the cell cycle by inactivating the CDKs that phosphorylate retinoblastoma (Rb) protein. Recent biological studies have revealed that p16 expression is markedly influenced by the status of Rb expression, and p16 overexpression has been demonstrated in cervical cancers because of functional inactivation of Rb by human papillomavirus (HPV) E7 protein. To clarify the relationship between p16 overexpression and HPV infection in cervical carcinogenesis, immunohistochemical analysis of p16 and detection of HPV by in situ hybridization and polymerase chain reaction were performed on 139 formalin-fixed and paraffin-embedded samples of cervical and genital condylomatous and neoplastic lesions. Marked overexpression of p16 protein, ie, diffuse and strong immunostaining, was observed in all cervical cancers and preneoplastic lesions with infection by high- and intermediate-risk HPVs, ie, subtypes 16, 18, 31, 33, 52, and 58. Condylomata acuminata and low-grade squamous intraepithelial lesions with infection by low-risk HPV such as HPV-6/11 showed focal and weak immunohistochemical staining for p16. Our results clearly showed that the mode of p16 expression in lesions with high- and intermediate-risk HPVs differed from its expression in lesions with low-risk HPVs and thus might be attributable to differences in functional inactivation of Rb protein by different HPVs.

Condylomata Acuminata↗

Leiomyosarcoma in soft tissue: examination of p53 status and cell proliferating factors in different locations.

The biological behavior of soft tissue leiomyosarcoma varies with its location: tumors in deep soft tissue show a worse prognosis than those in superficial soft tissue. In this study, we analyzed cell proliferating factors (mitotic and Ki-67 indices) and the p53 status of both types of leiomyosarcoma (37 cases) to evaluate the possibility that these factors may serve as indicators in prognosis. Expression of both of the cell proliferating factors were higher in the superficial type, but these differences were not significant. The incidence of abnormal p53 detected by immunohistochemistry and mutation analysis was also higher in the superficial type, but, again, no significant difference was observed. Abnormal p53 and a high Ki-67 index in the deep type, and a large tumor size (>6 cm) in the superficial type may be useful as prognostic factors. Interestingly, all of the superficial cases who died of the disease showed abnormal p53. In conclusion, these two types of leiomyosarcoma are essentially the same, and their location remains a good prognostic factor. Furthermore, abnormality of the p53 gene was related to a poor prognosis regardless of the tumor's anatomic location.

Adult↗

Effects of acute or prolonged administration of cabergoline on parkinsonism induced by MPTP in common marmosets.

The effects of a single treatment or chronic administration of cabergoline (1-[(6-allylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino)p ropyl]-3-ethyl-urea), a potent, long-lasting dopamine receptor agonist, on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in common marmosets were studied. The administration of 0.2 mg/kg or a higer dose of cabergoline began to reverse parkinsonism-like symptoms 60 min after a subcutaneous injection, and showed steady and constant effects throughout the observation period. For prolonged administration, 0.2 mg/kg cabergoline was injected daily for 22 consecutive days. Locomotor activity in MPTP-treated animals increased until it reached its peak on the third day, then it gradually decreased. Akinesia scores, rating the quality of movements, were also improved, and the improvement was sustained up to the last day of chronic administration. None of the animals developed abnormal behaviors after either acute or chronic administration. These results suggest that cabergoline has long-acting effects in the marmoset model of parkinsonism, and that it will be a useful agent for the treatment of Parkinson's disease, particularly in cases with fluctuating motor disabilities.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Microbial contamination of 'sterile water' used in Japanese hospitals.

We examined the following samples of water from 10 hospitals for microbial contamination: water obtained using an ultra filtration system (UF water), a reverse osmosis system (RO water), a water distillation system (distilled water) and tap water. UF water and RO water are used for handwashing before surgery, and distilled water for the preparation of drugs. All 10 samples of tap water examined were contaminated with < 10 colony forming units (cfu)/mL. Thirteen (68%) of 19 samples of UF water, nine (53%) of 17 samples of RO water and 15 (79%) of 19 samples of distilled water were contaminated with 10(1)-10(4) cfu/mL. The majority of micro-organisms were non-fermentative bacteria such as Sphingomonas paucimobilis and CDC gr. IV C-2. Japanese hospitals commonly use UF water and RO water for preoperative handwashing under the assumption that it is sterile. Our results suggest, however, that these types of water are inferior microbiologically to tap water. Distilled water from the dispensary was also contaminated with micro-organisms. The available chlorine content of tap water was 0.17-0.42 ppm and that of UF water (from tap water) 0-0.06 ppm. There was no available chlorine in RO water or distilled water (each from tap water). The reduction or disappearance of available chlorine appears to be associated with microbial contamination of UF water, RO water and distilled water.

Chlorine↗

Bilateral facial palsy caused by bilateral masked mastoiditis.

Acquired simultaneous bilateral facial palsy caused by bilateral masked mastoiditis in a 25-month-old girl is reported. After the administration of antibiotics for 10 days for treatment of bilateral acute otitis media, overt signs of otitis media diminished as bilateral facial palsy ensued. For diagnosis of masked mastoiditis, brain magnetic resonance imaging was of significant value in our case. The findings in this case suggest that masked mastoiditis should be considered as a cause of bilateral facial palsy, as well as unilateral facial palsy.

Anti-Bacterial Agents↗

Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI-1 chimeric mRNA.

We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the PNET/Ewing's sarcoma family, arising in the left ovary of a 29-year-old woman. Microscopically, the tumor was composed of solid nests and sheets of monotonous, primitive, small round cells with a few rosettes, making it difficult to distinguish from small cell carcinoma of the ovary. Immunohistochemically, the tumor cells showed intense cell-membranous immunoreactivity for MIC2 protein (CD99). A short-term cell culture and karyotypic analysis revealed the tumor to possess a balanced t(11;22)(q24;q12) chromosomal translocation that is highly specific for tumors of the PNET/Ewing's sarcoma family. In addition, EWS/FLI-1 chimeric mRNA that originated from the characteristic chromosomal translocation was detected by reverse transcription-polymerase chain reaction. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the ovary may have been mistakenly diagnosed as small cell carcinomas of the ovary.

12E7 Antigen↗

Prostaglandins in the stomach: an update.

Prostaglandins (PGs) are responsible for regulation of various physiologic activities in many tissues and organs, including the stomach. Recent studies have shown new crucial roles of PGs in the stomach. Activation of inflammatory cytokines and neutrophils may cause acute gastric mucosal lesions and recurrence of ulcers, which are induced by noxious stimuli such as nonsteroidal antiinflammatory drugs (NSAIDs), stress and Helicobacter pylori (H. pylori). These phenomena are PG-dependent because exogenous PGs reverse them. PG deficiency and H. pylori may worsen the quality of ulcer healing in terms of inflammatory responses, which are related to future ulcer recurrence. Neutrophils, monocytes/macrophages, and adhesion molecules are involved in the mechanism of recurrence caused by inflammatory cytokines. PGs accelerate ulcer healing, possibly via angiogenesis, epithelial cell proliferation, production of growth factors such as hepatocyte growth factor and transforming growth factor beta, reconstruction of extracellular matrices, and suppression of inflammatory cell infiltration, in addition to gastroprotective mechanisms. The PG synthase cyclooxygenase (COX) has two forms, COX-1 and COX-2. COX-2, but not COX-1, contributes to ulcer healing. Moreover, recent studies suggest the involvement of COX-2 in development of gastric and colon carcinoma. This may be linked to the chemopreventive effect of NSAIDs.

Humans↗

Does traumatic subarachnoid hemorrhage caused by diffuse brain injury cause delayed ischemic brain damage? Comparison with subarachnoid hemorrhage caused by ruptured intracranial aneurysms.

OBJECTIVE: To examine whether traumatic subarachnoid hemorrhage (TSAH) caused by severe diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome, as does aneurysmal subarachnoid hemorrhage (ASAH). METHODS: We examined 99 patients with diffuse brain injury with TSAH and 114 patients with ASAH. Computed tomographic (CT) findings, cerebral blood flow, and neurological outcomes were assessed during the acute and subacute phases and were compared between the two groups. RESULTS: The distribution of subarachnoid hemorrhage on the CT scans differed between the two groups. Unlike ASAH, TSAH was not limited to cisterns surrounding the circle of Willis but extended to supratentorial regions and interhemispheric fissures. Computed tomography-detected subarachnoid hemorrhage disappeared very early with TSAH and gradually with ASAH. In the ASAH group, mean cerebral blood flow decreased to 75% of normal during the acute phase and decreased a further 10% during the subacute phase. In the TSAH group, mean cerebral blood flow decreased to 85% of normal during the acute phase and increased slightly during the subacute phase. Neurological deterioration and in-hospital death peaked on Day 0 in association with TSAH and showed twin peaks in association with ASAH. The incidence of low-density areas on the CT scans was significantly higher with ASAH than with TSAH. All low-density areas on the CT scans of patients with ASAH corresponded to vascular territories, but low-density areas on the CT scans of patients with TSAH were rarely associated with vascular territories and contained deep-seated or gliding contusion types. CONCLUSION: The findings suggest that the incidence of vasospasm is low in association with TSAH and that the cause is different compared with ASAH. There is no evidence that the presence of TSAH in cases of diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome.

Acute Disease↗

Generation of metastatic variants of Eker renal carcinoma cell lines for experimental investigation of renal cancer metastasis.

We and others have demonstrated that a mutation in Tsc2 is the rate-limiting step for renal carcinogenesis in the Eker rat model. Although inactivation of Tsc2 results in development of renal tumors, it is not sufficient for metastatic renal cell carcinomas (RCs) in the Eker rat. To investigate the additional genetic event(s) necessary for cancer metastasis, we have established highly metastatic S-Lk9d-SLM cell lines from a non-metastatic RC cell line (Lk9dL) by co-implantation with a foreign body (gelatin sponge). Since these cell lines were remarkably different in metastatic performance (all and none, respectively) despite having the same genetic background, they should be useful experimental tools to investigate metastasis-promoting events in renal carcinogenesis.

Animals↗

Oesophageal hiatal hernia-induced hydropneumothorax.

The patient presented with acute and constant abdominal pain. He had had a lobectomy of the left lung three months before. On the 4th day in hospital the pain increased and he went into temporary shock. The next day a hydropneumothorax and incarcerated stomach were revealed by chest X-ray and computed tomography. He was transferred to the University Hospital immediately and underwent an operation. The diagnosis was an incarcerated para-oesophageal hernia with hydropneumothorax and perforation of the stomach. As a para-oesophageal hernia may be fatal, it is important to diagnose and treat it early.

Abdominal Pain↗

Coexpression of HGF and c-Met/HGF receptor in human bone and soft tissue tumors.

To understand the interaction between hepatocyte growth factor (HGF) and its receptor c-Met on various bone and soft tissue tumors, their expressions were investigated by western blot analysis, immunohistochemistry and enzyme immunoassay. Western blot analysis revealed that c-Met protein was expressed in 21 (38.8%) of 54 tumors, which detailed to seven (25.9%) of 27 bone tumors and 14 (51.8%) of 27 soft tissue tumors. Most malignant fibrous histiocytomas (MFH) and all neurofibromas expressed c-Met protein. The highest expression of c-Met protein was seen in a case of biphasic synovial sarcoma, where its immunoreactivity was localized only on the epithelial component and not on the sarcomatous component. By enzyme immunoassay for HGF, all but one MFH showed HGF production and the mean level of HGF was the highest among the tumors investigated. Neurofibromas and osteosarcomas had the next highest mean levels of HGF production, respectively. Coexpression of HGF and c-Met was observed in 19 (35.2%) of 54 tumors and was frequently observed in neurofibroma, followed by MFH and synovial sarcoma. Although the mode of interaction between HGF and c-Met varies among the various bone and soft tissue tumors including MFH, their signaling system may play an important role in the development and progression of bone and soft tissue tumors.

Blotting, Western↗

c-Met expression of thyroid tissue with special reference to papillary carcinoma.

It has become clear that papillary carcinomas of the thyroid often express the receptor for c-Met/hepatocyte growth factor (HGF) receptor, but little is known about the role of the HGF and c-Met system in the pathogenesis of thyroid carcinoma. In this study, the expression of c-Met/HGF receptor was evaluated in thyroid tissue by western blot and immunohistochemistry, and compared with the concentration of HGF. Clinicopathological characteristics were also compared. Fifteen of 20 papillary carcinomas (75%) showed c-Met bands of 145 kDa. No or only a low frequency of c-Met expression was detected in healthy thyroid tissue (0/5), thyroiditis or Basedow's disease (0/2), adenomatous goiters (0/8), follicular adenomas (1/9, 11%) and undifferentiated carcinomas (0/2). These results were confirmed by immunohistochemistry, but a relatively higher frequency of c-Met expression was detected in adenomatous goiters (25%), follicular adenoma (44%) and papillary carcinoma (100%) using formalin-fixed and paraffin-embedded materials. A strong immunoreaction for c-Met was observed in the tumor cytoplasm of papillary carcinomas among the fibrous tissues situated at the periphery of the tumor. The densitometrically measured expression of c-Met had no relation to tumor stage in papillary carcinoma, but did correlate to the concentration of HGF in papillary carcinomas. In conclusion, in thyroid lesions, c-Met was highly expressed specifically in the cytoplasm of papillary carcinomas. c-Met expression was not related to the aggressiveness of the tumor but was related to the concentration of HGF, which was probably derived from the stroma. Also, the c-Met system might play a role in the pathogenesis of papillary carcinoma of the thyroid.

Adenoma↗

Characterization of a newly established human acinic cell adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line.

Human acinic cell adenocarcinoma cell (HACC) line was established from the pleural effusion that contains metastatic tumor cells of acinic cell adenocarcinoma of papillary and microcystic type originating from the parotid gland. The HACC cells grew in an adherent monolayer with a doubling time of 66 h. Implanted tumor of SCID mice revealed similar histological findings to that of the primary tumor. The HACC cells produced mucin and expressed epithelial markers as well as alpha1-antitrypsin and lysozyme, whereas salivary peptide P-C was expressed in cultured HACC cells but not in the primary and implanted HACC cell tumors. S-100 protein was also expressed in both the primary tumor and HACC cell line. Neither amplification of common oncogenes nor expression of p53 was observed. The receptor for epidermal growth factor (EGF) was expressed, indicating EGF and transforming growth factor-alpha (TGF-alpha) enhanced the growth of the HACC line. Unexpectedly, tumor necrosis factor-a (TNF-alpha) also enhanced the growth of the HACC line significantly. However, there was no evidence of autocrine growth using these growth factors. In contrast, TGF-beta1 inhibited the growth of the HACC cell line through apoptosis. The HACC cell line has features similar to both acinar and intercalated ductal cells of the salivary gland. Epidermal growth factor, TGF-alpha and TNF-alpha are potential growth factors for the HACC cell line. The HACC cell line may be a good model for studying the biological behavior of salivary gland neoplasms.

Animals↗

Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia.

Both p16 and retinoblastoma (Rb) proteins are important tumor suppressors that regulate the cell cycle. The status of both proteins in invasive cervical cancer and cervical intraepithelial neoplasia (CIN) has not yet been examined. The aim of this study was to investigate the expression of p16 and Rb proteins by immunohistochemistry using 98 formalin-fixed and paraffin-embedded samples of various cervical neoplastic lesions. Strong immunoreactivity for the p16 protein was observed in both the nuclei and cytoplasm of all CIN and invasive cancer cases except several low-grade CIN lesions. Expression of Rb protein was also demonstrated in the scattered nuclei of neoplastic and normal cells in all cases investigated. The results suggest that the deletion or mutational inactivity of both p16 and Rb proteins may be a rare event in cervical carcinogenesis. Moreover, overexpression of the p16 protein may be a useful diagnostic marker for cervical neoplastic lesions on routine laboratory screening.

Adenocarcinoma↗

Case report: a mixed tumor of the vagina.

We report a case of a mixed tumor arising in the vagina of a 64-year old woman. Microscopically, the tumor was composed of stromal-type spindle cells and nests of mature squamous cells embedded in myxomatous stroma. We examined the tumor immunohistochemically, ultrastructurally, and cytogenetically. Based on the results, we discuss the histogenesis of this rare tumor.

Adenoma, Pleomorphic↗