Evidence for reciprocal regulation of pro- and anti-inflammatory lymphokines in rat nephrotoxic serum (NTS) nephritis.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M Fukunaga
Publications and source records attributed to M Fukunaga.
[Efficacy of combination chemotherapy with mitoxantrone, vincristine, prednisolone (MVP) for recurrence of breast cancer].
Fourteen patients with recurrent breast cancer were treated with a combination of mitoxantrone (10 mg/m2 iv, day 1), vincristine (1 mg/m2 iv, day 1) and prednisolone (30 mg/day day 1-7). Cycles were repeated every 4 weeks and all patients received more than 3 cycles. The objective response rate was 70.0% (7 of 10). In two patients, the treatment has been continued now for more than one year. In these 2 patients, the duration of response is more than 40 weeks. The toxicity was primarily myelosuppression. Five of 14 patients (35.7%) had leukopenia of Grade 3 and 4. These patients received G-CSF therapy and recovered well from leukopenia. Nausea and vomiting were well tolerated, probably by prednisolone. This regimen was especially superior in the maintenance of quality of life because hair loss was much less compared to CAF (cyclophosphamide, ADM, 5-fluorouracil) treatment. In conclusion, MVP treatment is highly effective and safe for the treatment of recurrent breast cancer.
Adult↗
Stimulatory effect of 8-Epi-PGF2 alpha, an F2-isoprostane, on endothelin-1 release.
8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane produced in vivo by a cyclooxygenase-independent, free radical-catalyzed lipid peroxidation mechanism. It exhibits renal vasoconstrictor effects by binding to a receptor related to, but distinct from, that of thromboxane A2 (TxA2). In cultured bovine aortic endothelial cells (BAECs), competitive binding assays using [3H]-8-epi-PGF2 alpha indicated the existence of two distinct binding sites. The Kd values were similar to those of cultured rat aortic smooth-muscle cells, suggesting that the high- and the low-affinity binding sites represent isoprostane and TxA2 receptors, respectively. 8-Epi-PGF2 alpha dose-dependently stimulated endothelin-1 (ET-1) secretion from BAECs. These increases were partially inhibited by a TxA2 receptor antagonist, consistent with the premise that isoprostanes and TxA2 recognize closely related receptors. The presence of specific binding sites for F2-isoprostanes on endothelial cells widens the scope of the possible pathophysiologic significance of these eicosanoids, released during oxidant injury, to include alteration of endothelial cell biology. The release of ET-1 by 8-epi-PGF2 alpha may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2 alpha in patients with hepatorenal syndrome.
Animals↗
A frequent alteration of p53 gene in carcinoma in adenoma of colon.
In general, colorectal carcinoma is thought to originate mainly from adenoma, and this pathway is called the adenoma-carcinoma sequence. Carcinoma in adenoma is an appropriate model for analysis of this mechanism, because adenoma and carcinoma tissues coexist in the same polyp and the carcinoma is thought to have originated from the surrounding adenoma. Expression of the p53 protein was analyzed in 36 cases of carcinoma in adenoma in the colon by immunohistochemistry using an anti-human p53 monoclonal antibody (PAb1801). Alterations of the p53 gene were analyzed by the polymerase chain reaction for microanalysis of normal mucosa, adenoma, and carcinoma from histological slides. Mutations were assessed by the polymerase chain reaction-single strand conformation polymorphism analysis and identified by DNA sequencing in some cases. Loss of heterozygosity was studied by polymerase chain reaction-restriction fragment length polymorphism analysis. Positive staining for p53 was detected in three (8%) of 37 adenomas and 20 (53%) of 38 focal carcinomas. One (7%) of 15 adenomas with mild dysplasia, three (14%) of 22 adenomas with moderate dysplasia, and 16 (42%) of 38 focal carcinomas had a mutation in exon 5 through exon 8 of the p53 gene. As for allelic loss in the p53 gene locus, only one adenoma with moderate dysplasia had loss of heterozygosity, whereas six (40%) of 15 focal carcinomas had loss of heterozygosity. Of those tumors (3 of 37 adenomas and 20 of 38 focal carcinomas) that reacted with PAb1801, 78% (18 of 23) showed genetic alterations. Among 52 tumors which showed negative staining, five tumors had a p53 mutation and four of them were nonsense mutations. Putting all of these results together, 71% (24 of 34) of the cases underwent p53 gene and protein alterations during the conversion from adenoma to focal carcinoma. These data clearly indicate that genetic alterations of p53 are involved mainly in the malignant transformation from adenoma to focal carcinoma in colon carcinogenesis. In addition, some cases show heterogeneity of the p53 gene in carcinoma in adenoma of the colon. There may be other pathways than p53 responsible for malignant change in the colon.
Adenocarcinoma↗
Immunohistochemical study of p53 in gastric carcinoma.
The authors had previously reported that the accumulation of p53 is clearly demonstrable in microwave-fixed, paraffin-embedded sections of colorectal carcinomas. In the present paper, the authors performed an immunohistochemical study of p53 in gastric carcinomas prepared by microwave irradiation. Using a monoclonal antibody (PAb1801), nuclear p53 was detected in 22 of 45 (49%) cases of gastric carcinoma, and no staining for p53 was demonstrated in the adjacent normal epithelium, including areas of intestinal metaplasia. The incidence of p53 accumulation was not affected by clinical features, such as tumor stage, depth of invasion, and metastasis; however, positivity for p53 was significantly higher in intestinal-type carcinomas (56%) than in diffuse-type (27%) carcinomas. Furthermore, a large number of carcinoma cells expressed p53 in the intestinal-type, but only a few cells were positive for p53 in the diffuse-type. The results of the present immunohistochemical study of p53 accumulation in gastric carcinomas suggest that gene alterations of p53 are not rare in gastric carcinomas and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach.
Gastric Mucosa↗
Lyme disease spirochetes in Japan: enzootic transmission cycles in birds, rodents, and Ixodes persulcatus ticks.
The ixodid tick, Ixodes persulcatus, serves as a vector of Borrelia species associated with Lyme disease in Hokkaido, Japan. The migratory birds of genera Emberiza and Turdus and the woodland rodents of genera Apodemus and Clethrionomys are the wildlife reservoirs. To systemize the enzootic transmission cycles, borreliae isolates were classified by ribosomal RNA gene restriction fragment length polymorphism (RFLP) analysis. Most (> 60%) isolates from the bird-feeding I. persulcatus larvae belonged to Borrelia garinii; the rest were classified as RFLP ribotype group IV (unknown species). In contrast, no B. garinii were found among isolates from rodent-feeding I. persulcatus larvae. These isolates were classified as Borrelia afzelii, group IV, and group V (unknown species). These observations suggest that two enzootic cycles in nature (bird-tick and rodent-tick) maintain borreliae specifically. The group IV species, which was predominant among clinical isolates from Lyme disease patients in Hokkaido, appears to be the most important pathogen for humans.
Animals↗
Penile verrucous carcinoma with anaplastic transformation following radiotherapy. A case report with human papillomavirus typing and flow cytometric DNA studies.
We report a case of penile verrucous carcinoma with anaplastic transformation after radiotherapy. A 49-year-old man with penile verrucous carcinoma initially underwent excision and chemotherapy followed by radiotherapy when the carcinoma recurred locally. Twenty-four months after the completion of radiotherapy, the verrucous cancer transformed to an anaplastic spindle-cell carcinoma, which resulted in his death 10 months after diagnosis. Autopsy confirmed a huge hemorrhagic recurrent lesion and lung metastases. In situ hybridization with biotinylated DNA probes did not detect any type of human papillomavirus (HPV) (types 6/11, 16/18, and 31/33/51) in either the primary or the anaplastic tumor. Immunohistochemical HPV capsid antigens were also negative in both lesions. A flow cytometric analysis, using paraffin-embedded materials, showed a diploid DNA content in the excised verrucous carcinoma and an aneuploid content in the anaplastic tumor. This patient most likely had radiation-induced transformation of an anaplastic carcinoma. Wide excision and, if necessary, amputation, are preferred to radiotherapy.
Carcinoma↗
Comparative studies on Borrelia afzelii isolated from a patient of Lyme disease, Ixodes persulcatus ticks, and Apodemus speciosus rodents in Japan.
The genospecies Borrelia afzelii was isolated from a patient of Lyme disease in Hokkaido, Japan, for the first time, by culturing the minced erythema lesion in BSK II medium. Two analytical methods, rRNA gene restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) using the specific primer set to amplify the 16S rRNA gene, revealed that this clinical isolate belongs to the group of B. afzelii. In our culture collection of spirochetes, part of the isolates from Ixodes persulcatus ticks, and from Apodemus speciosus rodents, were also classified as B. afzelii. These results strongly suggest that the agent pathogenic to humans is maintained in "rodent-tick" transmission cycle.
Adult↗
Pulsed field gel electrophoresis analysis of Borrelia burgdorferi sensu lato isolated in Japan and taxonomic implications with Lyme disease spirochetes.
Genomic DNAs of Borrelia burgdorferi sensu lato isolates obtained in Japan sharing different rRNA gene ribotypes were digested with rare-cutter restriction endonucleases and the fragments obtained were separated by pulsed field gel electrophoresis (PFGE). The sizes of large restriction cleavage bands with MluI endonuclease were quite similar among isolates in each ribotype group. On the other hand, the PFGE profiles obtained with the other enzymes (NruI, Sal I or SplI) were rather divergent, and Japanese isolates were distinguishable from the United States and European isolates. The Japanese isolates classified as ribotypes group II (Borrelia garinii) and III (B. afzelii) showed different PFGE patterns from that of European isolates. The isolates grouped into ribotype IV revealed distinctively different PFGE profiles. These results indicate that the Japanese isolates may be genetically divergent and distinct from the United States and European isolates.
Borrelia burgdorferi Group↗
Borrelia japonica in nature: genotypic identification of spirochetes isolated from Japanese small mammals.
Spirochetes were isolated from earlobe tissues of shrews (Sorex unguiculatus, Sorex caecutiens, and Crocidura dsienezumi), voles (Clethrionomys rufocanus), and mice (Apodemus argenteus and Apodemus speciosus) captured in various localities in Japan. The isolates were identified as Borrelia japonica by rRNA gene restriction fragment length polymorphism analysis. The data suggest that these small mammals are candidates of reservoir hosts for B. japonica.
Animals↗
Histopathologic study of partial hydatidiform moles and DNA triploid placentas.
Sixty-two placentas with a triploid DNA content, which were analyzed by flow cytometry using paraffin-embedded tissues, were histologically investigated. These placentas were histologically classified as follows: 51 partial hydatidiform moles (PM), two hydropic abortuses and nine non-hydropic placentas. The DNA indices of the triploid peaks were between 1.41 and 1.60. Histologically, two populations of normal and edematous villi, vesicular villous edema with cistern formation, focal syncytiotrophoblastic hyperplasia with vacuolation, and villous scalloping with trophoblastic inclusion were almost always observed in the PM, but no single pathologic feature was specific for PM. The two entities, PM and triploid placenta, overlapped. Not all triploid gestations are PM and not all PM moles are triploid as shown in previously reported diploid or tetraploid PM. Although no patient with triploid PM developed persistent disease in this series, follow up of triploid PM is required as long as its true biological potential remains unclear. Flow cytometry is a reliable aid in the diagnosis of PM.
Abortion, Spontaneous↗
Ossifying subcutaneous tumor with myofibroblastic differentiation: a variant of ossifying fibromyxoid tumor of soft parts?
Immunohistochemical, ultrastructural, and flow cytometric studies were performed on an ossifying soft-tissue tumor, presumed to be a variant of ossifying fibromyxoid tumor of soft parts, which was located in the subcutis of the left buttock of a 76 year old Japanese woman. Histologically, this was a benign-looking spindle, oval, or round cell lesion, having a fibrous capsule with a discontinuous rim of bone as seen in typical cases. However, this lesion was also characterized by a high degree of cellular proliferation in storiform and whorl arrangements, extensive ossification, osteoid and metaplastic bone formation and absence of myxoid features. In an immunohistochemical study using formalin-fixed, paraffin-embedded sections, many tumor cells expressed vimentin, S-100 protein, Leu-7, neuron specific enolase, and desmin. Ultrastructurally, this neoplasm consisted of fibroblast-like cells and myofibroblast-like cells. This tumor had an aneuploid DNA content. No recurrence has been observed for 16 months. These results suggest that the neoplastic cells may show the phenotypic expressions of myofibroblast and also osteogenic differentiation.
Aged↗
Effects of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture.
The effect of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture was investigated to characterize growth regulating factors of the liver in neonates and to confirm whether the stimulatory factor is human hepatocyte growth factor (hHGF). Neonatal serum stimulated DNA synthesis of both adult and suckling rat hepatocytes. The stimulatory effect was dose-dependent up to 20% in volume. The molecular weight of the stimulatory substance in neonatal serum was between 12,500 and 25,000, as estimated by gel filtration. Its activity was stable after heating at 56 degrees C for 20 min, but was lost after heating at 90 degrees C for 30 s, and easily passed through S- or heparin-Sepharose columns. The concentration of hHGF quantified by ELISA was too low to stimulate DNA synthesis in vitro. Biological and biochemical properties of the growth stimulatory activity in neonatal serum differed from that of hHGF. The presence of other growth factors in human neonatal serum for suckling and adult hepatocytes was suggested.
Animals↗
[The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer].
Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.
Acid Phosphatase↗
[The mechanism of biochemical modulation in methotrexate/5-fluorouracil sequential chemotherapy].
5-fluorouracil (5-FU)/methotrexate (MTX) sequential chemotherapy is one of the standard regimen for the treatment of gastric cancer. Though this combination therapy is highly effective, the mechanism is still unclear. In this study, we investigated the relationship between antitumor activity and the inhibition of thymidylate synthase and between antitumor activity and incorporation of 5-FU into RNA (F-RNA) in mice bearing Sarcoma-180 treated by tegafur alone (100 mg/kg) or by the combination of MTX (42 mg/kg) and tegafur (100 mg/kg). A new method for the determination of F-RNA of tumor tissue samples was used. Briefly, RNA fractions containing incorporated 5-FU were extracted by KOH hydrolysis. FUra in RNA fractions was released by HCl hydrolysis and its levels were determined by GC-MS. The results showed that the F-RNA levels were significantly elevated by the pretreatment of MTX. According to this result, it is suggested that the measurement of F-RNA levels together with the determination of FUra concentration and the inhibition rate of thymidylate synthase were considered as a good means for the evaluation of antitumor efficacy of FUra. We concluded that the impairment of RNA metabolism played a major role in the antitumor activity of MTX/5-FU combination.
Animals↗
[Quantification of bone mineral density].
To evaluate the skeletal state of bone pathophysiology in metabolic bone diseases including osteoporosis, various non-invasive bone mineral quantifying methods have been developed recently, and used clinically. As each bone quantifying method differs in its principle of measurement, the index obtained, the site of measurement, precision, data-acquisition time, and radiation dose, the characteristics of and problems with these methods should be kept in mind. Among these bone quantifying methods, the fundamental performance of dual-energy X-ray absorptiometry (DXA) is excellent, and it is the most popular bone quantifying method at present. In this paper, the role of bone quantifying methods in the diagnosis of osteoporosis, the actual procedure of measurement by DXA, the relation between bone mineral densities at different sites of measurement, the importance of longitudinal measurements, and the relation to bone metabolic parameters were reviewed.
Absorptiometry, Photon↗
Vascular smooth muscle actions and receptor interactions of 8-iso-prostaglandin E2, an E2-isoprostane.
8-iso-PGE2, an E2-isoprostane, decreased GFR and RPF dose-dependently in rats, but with lesser potency than 8-epi-PGF2 alpha, an F2-isoprostane. This effect was abolished by SQ29,548. 8-iso-PGE2 displaced [3H]SQ29,548 or [125I]BOP binding in aortic smooth muscle cells with the affinity rank order of SQ29,548 > = I-BOP > U46,619 > 8-iso-PGE2 > PGF2 alpha, while it activated phospholipase C with a potency greater than those of I-BOP or U46,619 and lesser than that of 8-epi-PGF2 alpha. We concluded that 8-iso-PGE2 is a renal vasoconstrictor linked to phosphoinositide metabolism. Its vascular smooth muscle contractile actions are likely mediated through activation of putative thromboxane A2 receptor-like "isoprostane receptors."
Animals↗
Soft tissue vascular tumors. A flow cytometric DNA analysis.
BACKGROUND: The clinical behavior of soft tissue vascular tumors is difficult to predict on histologic grounds alone. METHODS: To assess the usefulness of DNA flow cytometry in predicting the biologic behavior of these tumors, the authors studied 51 soft tissue vascular tumors by DNA flow cytometry of paraffin-embedded tissue. RESULTS: All 20 capillary hemangiomas, one epithelioid hemangioma, two spindle cell hemangioendotheliomas, and two benign hemangiopericytomas had a diploid DNA content. Of the 20 patients with angiosarcomas, their ages ranged from 9-80 years (mean, 44.0 years), and the mean follow-up period was 16.5 months. Ten tumors (including two postmastectomy angiosarcomas) were cutaneous, six were deep soft tissues, and four were from other sites. These tumors were classified histologically into three types: sinusoidal (n = 10), capillary (n = 7), and mixed type (n = 3). Thirteen of the angiosarcomas (65%) were diploid, and seven (35%) were aneuploid. Three patients with angiosarcoma had lung metastases at initial diagnosis, and seven had them later in the course. Nine patients died of their disease within a period of 18 months after the initial diagnosis. All five patients with malignant hemangiopericytoma died of their disease. Three of these lesions had a diploid DNA content, and two had an aneuploid content. Although it was found that all benign and intermediate-grade malignant tumors were diploid, there were no significant correlations among histologic type, DNA ploidy, and clinical outcome in angiosarcomas and malignant hemangiopericytomas. CONCLUSIONS: Based on this study, DNA analysis has limited value in predicting the biologic behavior of malignant vascular tumors of the soft tissue.
Adolescent↗