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Biomedical subjects

J Matsumoto

Publications and source records attributed to J Matsumoto.

At least 19 recordsLinked to original sources

Expression and diversity of Echinococcus multilocularis AgB genes in secondarily infected mice: evaluating the influence of T-cell immune selection on antigenic variation.

The T-cell-mediated immune response exhibits a crucial function in the control of the intrahepatic proliferation of Echinococcus multilocularis larvae in mice and humans, both being natural intermediate hosts of the parasite. Antigen B (AgB), a metabolized Echinococcus spp. lipoprotein, contributes to the modulation of the T-cell immune response, and distinct sites of the corresponding AgB1, AgB3 and AgB4 genes were shown to be under positive selection pressure. Since several AgB gene variants are present in a single Echinococcus metacestode, we used secondary E. multilocularis infections in BALB/c and in athymic nude mice (devoid of T-cell responses) to analyze the effect of the cellular immune response on the expression and diversity of EmAgB1-EmAgB4 genes. We demonstrated hereby that EmAgB transcripts were less abundant in nude mice during the early phase of infection (at one month post-infection), and that EmAgB2 is simultaneously down-regulated when compared to the other three genes. A negative relationship exists between the level of transcription and diversity of EmAgB genes. Moreover, no excess of non-synonymous substitutions was found among the distinct EmAgB alleles from a single host. Together, these results pointed to the effect of purifying selection, which seemed to eliminate the detrimental AgB variants generated during the development of the metacestode within the peritoneal cavity of its intermediate host.

Animals↗

14-3-3- and II/3-10-gene expression as molecular markers to address viability and growth activity of Echinococcus multilocularis metacestodes.

The present study aimed to search for and characterize parasite molecules, whose expression levels correlate with the viability and growth activity of Echinococcus multilocularis metacestodes. We focused on the expression profiles of 2 parasite-derived genes, 14-3-3 and II/3-10, as putative molecular markers for viability and growth activity of the larval parasite. In experiments in vivo, gene expression levels of 14-3-3 and II/3-10 were relatively quantified by real-time reverse transcription-PCR using a housekeeping gene, beta-actin, as a reference reaction. All three reactions were compared with growth activity of the parasite developing in permissive nu/nu and in non-permissive wild type BALB/c mice. At 2 months p.i., the transcription level of 14-3-3 was significantly higher in parasites actively proliferating in nu/nu mice compared to parasites moderately growing in wild type mice. Immunoblotting experiments confirmed at the protein level that 14-3-3 was over-expressed in parasites derived from nu/nu mice at 2 months p.i. In vitro treatment of E. multilocularis with an anti-echinococcal drug nitazoxanide resulted in a significant decrease of both 14-3-3 and II/3-10 transcription levels found after 8 days of treatment, which correlated with the kinetics of a housekeeping gene, beta-actin. The conclusion is that 14-3-3, combined with II/3-10, exhibits good potential as a molecular marker to assess viability and growth activity of the parasite.

14-3-3 Proteins↗

[Metastatic sternal tumor from thyroid papillary carcinoma; report of a case].

A 68-year-old male was referred to our department for treatment of a metastatic sternal tumor in the manubrium sterni. Primary lesion was papillary carcinoma of the left lobe of the thyroid gland. Total thyroidectomy, cervical lymph node dissection, resection of manubrium sterni with concomitant resection of bilateral clavicles, 1st ribs and 2nd ribs, and chest wall reconstruction using Marlex Mesh were performed on January 29, 2001. Considering relatively good prognosis and good response to multimodality therapy, surgical resection of sternal metastatic lesion from differentiated thyroid cancer seems to be a choice of therapy as a part of multimodality approach, including surgery, radioiodine and external radiation therapy, to thyroid cancer with systemic spread.

Adenocarcinoma, Papillary↗

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.

Adult↗

Cost-effectiveness associated with the diagnosis and staging of non-small-cell lung cancer.

OBJECTIVE: We evaluated how much time and money could be saved without compromising overall results in treating lung cancer. SUBJECTS AND METHODS: We retrospectively evaluated 318 patients for T- and M-factors and 335 for N-factor. If bronchoscopy failed to diagnose a mass lesion believed to be malignant in x-ray computed tomography (CT), we proceeded to direct thoracotomy without needle or video-assisted biopsy. When mediastinal nodes were negative in CT, we proceeded to direct thoracotomy without mediastinoscopy. We searched routinely for distant metastasis with brain and abdominal CTs and bone scans. RESULTS: Lesions suspected of malignancy in CT were pathologically malignant in 93%. A total of 82.8% of patients with CT-negative mediastinum were without metastasis. The remainder, with metastasis, had a postoperative 5-year survival of 23.5%. Brain CT scans were positive in only 2.2%, abdominal CT scans in 2.4%, and bone scans in 5.0%, for patients with a cT1/T2 non-cN2 lesion. CONCLUSION: Brain and abdominal CT scans and bone scans may be omitted for cT1/T2 and non-cN2 lesions in CT. CT-negative mediastinum then leads to direct thoracotomy. The vast majority of patients may thus undergo surgery earlier with less physical and financial burden. The cost saving was calculated to be 59.4% per cT1/T2 non-cN2 patient, or US$666,815, for population evaluated based on cost-effectiveness.

Adult↗

Increased Fas antigen in uremia accelerates adhesion of mononuclear cells to endothelial and sinovial cells via stimulated hyaluronan production.

We examined influences of increased soluble Fas (sFas) and hyaluronan in uremia on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness. Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronary artery smooth muscle cells (CASMC), and MNC were prepared in this study. In cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyaluronan was added to media at medium change. After 1 day, Fas-positive cells were calculated by fluorescence-activated cell sorting. Uremic level of sFas enhanced Fas-positive cells in all cell lines (P < 0.01) not in CASMC. On the contrary, hyaluronan inhibited Fas expression in all cell lines (P < 0.05). In culture with uremic serum, Fas were induced in all cell lines. At this time, the hyaluronan levels of the supernatant were measured and hyaluronan production was estimated. In contrast to the results using sFas supplement, hyaluronan production was increased in culture with sFas and uremic sera. MNC adhesiveness was increased in synovocytes and HUVEC lines by adding hyaluronan or sFas. Higher adherent cell numbers were recognized when both sFas and hyaluronan were added to the media. A most remarkable increase in cell numbers was observed in uremic MNC suspension as compared with that of MNC from healthy subjects. In conclusion, these results indicate that increased sFas in uremia stimulates apoptosis and hyaluronan production. Both sFas and hyaluronan are responsible for accelerated MNC adhesiveness in uremia.

Adhesiveness↗

Inactivate the remaining p53 allele or the alternate p73? Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants.

Several reports have noted epidemiological differences in the prevalence or prognostic significance of p53 mutants with arginine (R) or proline (P) at the codon 72 polymorphism (R72/P72) in certain cancer types, but the biological significance of these variants is unclear. The ability of p53 mutants to interact with and inactivate the p53 homolog p73 was recently reported to depend on the conformational state of the p53 protein and the residue at codon 72. Since the conformation of p53 mutants may influence their ability to transdominantly inhibit wild-type p53, we tested whether there was a correlation between the amino acid at codon 72 and the transdominance of p53 alleles found in tumors. The transdominance test was performed using a simple yeast transcription assay, and the amino acid at codon 72 was determined by sequencing. A total of 100 p53 mutants were tested. Compared with the germline frequency (R:P = 427:297), an extreme bias in favor of the R72 allele was observed with recessive mutants (R:P = 50:7, P < 0.0002), whereas no selection for the R72 allele was seen with transdominant mutants (R:P = 23:20). p53 and p73 are known to transactivate overlapping sets of target genes. We interpret the R72 bias with recessive mutants as evidence that decreased activation of p53 target genes provides a selective growth advantage to tumor cells during the stage of tumorigenesis in which a wild-type and mutant p53 allele coexist. We suggest that transdominant p53 mutants achieve this by inactivation of the remaining wild-type p53 allele, whereas recessive p53 mutants achieve it through inactivation of p73.

Alleles↗

A novel C-type lectin regulating cell growth, cell adhesion and cell differentiation of the multipotent epithelium in budding tunicates.

We have isolated two Ca(2+)-dependent, galactose-binding polypeptides from the budding tunicate, Polyandrocarpa misakiensis. Based on their partial amino acid sequences, full-length cDNAs were cloned. One of them was identical with a tunicate C-type lectin (TC14-2) reported previously. The other was a novel C-type lectin, referred to as TC14-3. In living animals, they appeared to be coupled. This complex of lectins, when applied in vitro to tunicate multipotent cells of epithelial origin, blocked cell proliferation and induced cell aggregation. The aggregates expressed a homolog of the integrin alpha-chain and other differentiation markers specific for epithelial cells. Recombinant TC14-3 could reproduce all the activities of native lectins by itself, which was accelerated by recombinant TC14-2. The inhibitory activity of TC14-3 on cell growth was completely abolished by the addition of 50 microM D-galactose. Anti-TC14-3 monoclonal antibody showed that the antigen was expressed constitutively by the multipotent epithelial and mesenchymal cells. These results provide evidence that in P. misakiensis a C-type lectin plays a novel, cytostatic role in regulating cell growth, cell adhesion and cell differentiation during asexual reproduction.

Amino Acid Sequence↗

VUF-K-8788, a periphery-selective histamine H1 antagonist with anti-pruritic activities.

The pharmacological properties of 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investigated in vitro and in vivo. VUF-K-8788 inhibited [3H]-mepyramine from binding to the cell membrane of lung parenchyma (Ki value: 5.0 nM) and the histamine-induced contraction of isolated guinea pig ileum (pA2: 9.71) without affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and passive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-8788 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respectively). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed in rats. In experiments on the effects on the central nervous system, VUF-K-8788 at 1 mg/kg, p.o. hardly antagonized the H1 receptor at all in the cerebral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. These results suggested that VUF-K-8788 would be useful in the treatment of allergic disorders such as atopic dermatitis and eczema.

Animals↗

Symptomatic solitary xanthogranuloma occupying the cavernous sinus. Case report.

The authors report the first case of a solitary xanthogranuloma of the cavernous sinus without systemic manifestation. A 43-year-old woman experienced decreased visual acuity on the right side in association with papilledema and a visual field defect. She was alert and no other neurological sign was observed. She had no family history of hyperlipoproteinemia and no cutaneous and/or systemic xanthomatous lesions. Skull x-ray films showed an enlarged right superior orbital fissure. Computerized tomography revealed a low-density oval mass 2 x 3 cm in diameter in the right cavernous region that was compressing the right optic nerve in the lateral to medial direction. This mass exhibited isointensity on T1-weighted and mixed-pattern hyperintensity on T2-weighted magnetic resonance images with diffuse contrast enhancement. Cerebral angiography demonstrated fine staining in the margin, originating from the right middle meningeal artery. These neuroimaging findings closely mimicked those associated with trigeminal neuroma. The lesion was partially removed via a right-sided zygomatic approach, and her symptoms improved. Clinical characteristics and histopathological features of this rare case are discussed.

Adult↗

[Thymidine phosphorylase expression in hepatic metastasis from colorectal carcinoma].

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), and has angiogenic activity. It has been reported that a higher level of dThdPase activity is associated with an unfavorable patient prognosis. The activity of dThdPase was investigated in 15 patients who underwent hepatectomy for hepatic metastasis from colorectal carcinoma, and an assessment was made as to whether its expression was correlated with the prognosis. The dThdPase activity was significantly higher in the patients with extrahepatic metastasis after hepatectomy (n = 5) than in those without extrahepatic metastasis (n = 10) (168.2 +/- 50.8 vs 95.1 +/- 35.2 Unit/mg prot., p < 0.05). This dThdPase activity could be a significant prognostic indicator, and was useful in predicting the extrahepatic recurrence after hepatectomy for hepatic metastasis from colorectal carcinoma.

Colorectal Neoplasms↗

Decreased absorption and retention rates of magnesium in the rats fed on spinach-supplemented diets: possible explanations.

We studied the bioavailability of magnesium (Mg) in spinach after boiling with distilled water, using Mg-deficient growing male rats. The rats were fed a semipurified diet (Mg:0.063 per cent (w/w)) for 3 days. then a Mg-deficient diet (Mg:0.001 per cent (w/w)) for 5 days. They were then divided randomly into 7 groups of 6 rats each, and fed the semipurified diet (Mg: 0.063, 0.045 or 0.027 per cent (w/w)), or the spinach-supplemented diet (10 per cent (w/w) dried and powdered spinach after boiling with distilled water for 3 min at 100 degrees C). The Mg content of the diets supplemented with spinach grown on chemical nutrients, and on manure from pigs, cattle and fowl, was 0.069, 0.051, 0.043 and 0.036 per cent (w/w), respectively. Water intake and volumes of urine and faeces were significantly greater in the rats fed the spinach-supplemented diets than in those fed the semipurified diets. Apparent absorption of Mg, and urinary and faecal excretions of Mg were directly related to Mg intake: no significant difference was observed amongst the groups. Both the ratios of Mg absorption and retention were significantly lower in the rats fed diets supplemented with spinach than in those fed semipurified diets. The plasma Mg level was directly related to Mg intake in the rats fed the semipurified diets and the spinach-supplemented diets. However, the plasma Mg level in the rats fed spinach grown organically on manure from fowl tended to be higher than in the other groups. From these results, it was concluded that bound Mg in spinach was effectively utilized by Mg-deficient rats, however, the absorption and retention rates of Mg in rats fed diets supplemented with spinach were decreased. Possible explanations were discussed.

Animals↗

A case of primary leiomyosarcoma of the chest wall successfully resected under the video-assisted thoracoscopic approach.

We report a case of a 62-year-old woman with primary leiomyosarcoma of the chest wall which was successfully resected under the video-assisted thoracoscopic approach. The disease was found during the treatment for a malignant melanoma of the left heel. On the preoperative CT images, the lesion was suspected to be a metastasis of the malignant melanoma. The thoracoscopic surgery revealed that the tumor originated from the parietal pleura, and it was resected with a 5-mm margin of normal pleura. Histopathologically, the tumor was diagnosed as low-grade leiomyosarcoma. Since no residual tumor cells were proven in the resected margins histologically, further resection was not performed. At present, she is alive and well with no sign of recurrence of leiomyosarcoma two years and one month after operation. Thoracoscopic surgery is worth trying for accurate diagnosis of and effective treatment for a chest lesion without apparent invasion of the chest wall on the preoperative CT images.

Biopsy↗

Results from surgical treatment for thymoma. 43 years of experience.

OBJECTIVE: The biological behavior of thymoma and its prognosis after surgical intervention remain still controversial. The efficacy of surgical treatment for thymoma was investigated by examining long-term follow-up data. SUBJECTS AND METHODS: Follow-up data for patients undergoing surgical resection of histopathologically-confirmed thymoma between 1954 and 1997 were obtained and were retrospectively analyzed. Clinical staging was based on Masaoka's staging system, and histological classification on Rosai's proposed criteria. RESULTS: Data for 140 patients were collected. Sixty-four patients had stage I, 32 had stage II, 28 had stage III, and 16 had stage IV thymoma. There were significant differences in survival between patients with stage I and stage III, stage I and stage IV and stage II and stage III disease, but not between those with stage I thymoma and stage II thymoma. No significant difference in survival was observed between the 56 patients with myasthenia gravis (MG) and the 84 without MG. The 38 patients classified as having a predominantly-epithelial thymoma had a poorer prognosis than the 41 with a predominantly-lymphocytic thymoma. Until 1975, there were four patients with stage I thymomas who later showed recurrence, compared with 21 among those with stage II, III and IV diseases. Since 1976, extended thymectomy with thymomectomy under median sternotomy has been adopted as the standard operation for a thymoma, and there has been no recurrence in stage I patients. CONCLUSIONS: Patients with stage III or IV invasive thymoma have a poorer prognosis and a higher recurrence rate than those with encapsulated thymoma, and patients with a predominantly-epithelial thymoma have a poorer prognosis than those with a predominantly-lymphocytic thymoma. Extended thymectomy with thymomectomy under median sternotomy can be considered as adequate treatment for a stage I thymoma. Myasthenia gravis does not appear to affect the prognosis of patients with a thymoma.

Adult↗

Malaria infection induces rapid elevation of the soluble Fas ligand level in serum and subsequent T lymphocytopenia: possible factors responsible for the differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection.

The intraerythrocytic stage of the simian malaria parasite Plasmodium coatneyi (CDC strain) was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, including four Japanese macaques (Macaca fuscata) and three cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria and eventually became moribund, while the infected cynomolgus macaques, natural hosts of the parasite, exhibited no severe manifestation of disease except anemia and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4(+) and CD8(+) T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible at least in part for the T lymphocytopenia. Furthermore, soluble Fas ligand levels in sera of the infected Japanese macaques increased gradually to a markedly high level of 28. 83 +/- 10.56 pg/ml (n = 4) when the animals became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or elevated soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.

Animals↗