Biomedical subjects

M Nishitani

Publications and source records attributed to M Nishitani.

At least 19 recordsLinked to original sources

PubMed2001

Granule-dependent killing of Toxoplasma gondii by CD8+ T cells.

Immunization of mice with live bradyzoites of a low-virulent Beverley strain of Toxoplasma gondii has been shown to increase CD8+ T-cell mediated immunity against a highly virulent RH strain. We found that preimmunization with an RH homogenate further enhanced this immunity. Using this model, we investigated the mechanism of CD8+ T-cell mediated protection against T. gondii infection. Splenic cells from mice immunized with RH homogenate and live bradyzoites stimulated apoptosis of RH-infected J774A.1 macrophages in vitro, and at the same time, the immunization significantly suppressed the proliferation of parasites within macrophages, as assessed by measuring 3H-uracil uptake by the parasites. Splenic cells from the immunized mice produced larger amounts of interferon-gamma (IFN-gamma) than did naive splenic cells; however, the production of nitric oxide (NO) by RH-infected macrophages was not enhanced. The elimination of CD8+ T cells from splenic cells significantly reduced their inhibitory action on parasite proliferation as well as their cytotoxic activity against RH-infected macrophages, but it did not affect the production of IFN-gamma. Treatment of CD8+ T-enriched splenic cells from the immunized mice with concanamycin A, but not an anti-Fas ligand monoclonal antibody, significantly reduced their anti-proliferative and killing capabilities, suggesting that the CD8+ T cells induced by immunization with RH antigen and live bradyzoites of the Beverley strain may exert protection against T. gondii infection at least in part through granule-dependent cytotoxic activities.

Animals↗

PubMed2001

[Ectopic prostatic tissue in retrotrigone of the bladder: a case report].

We herein report a case of ectopic prostatic tissue in the retrotrigone of the bladder. A 35-year-old man was referred to our hospital because of bladder tumor which was incidentally discovered on abdominal ultrasonography (US). US and computed tomography (CT) showed a tumor in the bladder wall 1.5 cm in diameter. Magnetic resonance imaging (MRI) revealed an invasive bladder tumor. Cystoscopy showed a non-papillary, wide-based tumor in the retrotrigone of the bladder. Transurethral resection of bladder tumor was carried out and pathological findings showed ectopic prostatic tissue. This is the 8th case of ectopic prostatic tissue in the Japanese literature.

Adult↗

PubMed2000

Expression of vascular endothelial growth factor isoforms and platelet-derived endothelial cell growth factor in bladder cancer.

We analyzed the expression of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) isoforms and platelet-derived endothelial cell growth factor (PDECGF) mRNA in bladder cancer. We also attempted to determine if correlation exists between their expression level and conventional clinical variables in patients with bladder cancer. Tissues obtained from 60 patients with bladder carcinoma were used for analysis. Expression levels of VEGF isoforms and PDECGF were examined using reverse transcription-polymerase chain reaction (RT-PCR). Correlations between the expression levels of each VEGF isoform and PDECGF and histopathologic findings were evaluated. Four VEGF isoforms corresponding to VEGF121, 165, 189, and 206 were detected in bladder cancer tissue by RT-PCR. Gene expression of all VEGF isoforms as a ratio of the target to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) showed no correlation with pathologic stage of bladder cancer. However, with regard to relative expression levels of VEGF isoform, which is the ratio to the sum of total VEGF isoforms, the levels of VEGF206 and VEGF189 in tumor samples of grade pT2 or higher were significantly lower than those in tumors of grade pT1 or lower (P<.05). In contrast, the levels of VEGF121 in >/=pT2 tumors tended to be higher than those in </=pT1 tumors (P=.056). The expression level of PDECGF as a ratio to GAPDH in pT2</= tumors was significantly higher than that in either pTa or pT1 tumors (P<.05). Moreover, a higher expression level of PDECGF was observed in G3 tumors than in G1 tumors (P<.05). The results indicated that gene expression of VEGF isoforms do not play a significant role in tumor progression or invasion; however, the distribution of VEGF isoforms may play a role in tumor progression of bladder cancer. A high expression level of PDECGF correlated significantly with the tumor progression of bladder cancer.

Journal Article↗

PubMed2000

Nonequivalent nucleotide trapping in the two nucleotide binding folds of the human multidrug resistance protein MRP1.

Multidrug resistance protein 1 (MRP1) and P-glycoprotein, which are ATP-dependent multidrug efflux pumps and involved in multidrug resistance of tumor cells, are members of the ATP binding cassette proteins and contain two nucleotide-binding folds (NBFs). P-glycoprotein hydrolyzes ATP at both NBFs, and vanadate-induced nucleotide trapping occurs at both NBFs. We examined vanadate-induced nucleotide trapping in MRP1 stably expressed in KB cell membrane by using 8-azido-[alpha-(32)P]ATP. Vanadate-induced nucleotide trapping in MRP1 was found to be stimulated by reduced glutathione, glutathione disulfide, and etoposide and to be synergistically stimulated by the presence of etoposide and either glutathione. These results suggest that glutathione and etoposide interact with MRP1 at different sites and that those bindings cooperatively stimulate the nucleotide trapping. Mild trypsin digestion of MRP1 revealed that vanadate-induced nucleotide trapping mainly occurs at NBF2. Our results suggest that the two NBFs of MRP1 might be functionally nonequivalent.

ATP-Binding Cassette Transporters↗

PubMed2000

Cytokine gene therapy for cancer with naked DNA.

Plasmid DNA vectors (naked DNA) can easily be purified and transferred in vivo by intramuscular or intradermal injection. Naked DNA is stable in vivo, and long-term expression of the encoded protein is seen without chromosomal integration. Gene gun-mediated delivery of an expression plasmid is slightly more complicated but more efficient. These techniques have been applied to DNA vaccination or cytokine gene therapy for various diseases, including infections, autoimmune disorders, and cancer. We review cytokine gene therapy for cancer with naked DNA in animal models and present our preliminary data on gene gun-mediated in vivo transfection with the interleukin-12 gene in a murine renal cancer model. Because of its safety, simplicity, and low cost, cytokine gene therapy with naked DNA may become an important cancer treatment.

Animals↗

PubMed2000

CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major.

The roles of gamma delta T, NK and NKT cells in an early stage of protective immunity against infection with Leishmania major were investigated. Further, the contribution of these innate cells to the expression of 65 kDa heat shock protein (HSP65) in host macrophages was examined, since we found previously that this expression prevents apoptotic death of infected macrophages and is a crucial step in the acquisition of protective immunity against infection with various obligate intracellular protozoa including L. major. C57BL/6 and DBA/2 mice were found to be resistant against the infection on the basis of the parasite burden in their regional lymph nodes, and to strongly express HSP65 in their macrophages, whereas BALB/c mice were susceptible and barely expressed the HSP65. In those resistant mice, CD4(+) NKT cells prominently increased in their regional lymph node and were the main effector cells at least for an early stage of the protective immunity and for the HSP65 expression, whereas this subset did not increase in susceptible BALB/c mice. Further, neither gamma delta T nor NK cells in resistant mice contributed to those protective immune responses. The NKT cell subset bore CD3, CD4, TCR alpha beta, IL-2R beta and NK1.1 but scarcely asialo-GM(1). Moreover, this effector subset was confirmed to be V(alpha)14 NKT cells by using J(alpha)281(-/-) mice.

Animals↗

PubMed2000

[Analysis of serum soluble interferon alpha/beta receptor levels in patients with urological diseases].

PURPOSE: In order to define the clinical significance of serum soluble Interferon alpha/beta receptor (sIFN alpha/beta R) levels, we determined sIFN alpha/beta R concentrations in serum of patients with urological benign and malignant diseases. MATERIALS AND METHODS: Serum sIFN alpha/beta R levels were measured in normal control (n = 22), patients with benign diseases (n = 50) included urolithiasis (n = 16), prostatic hypertrophy (n = 13), and malignant diseases included bladder cancer (n = 49), renal cell carcinoma (n = 30) and prostate cancer (n = 36) by the enzyme linked immunosolbent assay (ELISA) using monoclonal and polyclonal antibodies. The levels of serum sIFN alpha/beta R was correlated with the results of other hematoserological examinations, and clinical or pathological characters of each urological malignancies. RESULTS: The serum sIFN alpha/beta R levels (pg/ml) of patients with urolithiasis (2,370.6 +/- 640.6, p = 0.0002), benign prostatic hypertrophy (2,121.1 +/- 550.6, p = 0.0103), bladder cancer (2,512.3 +/- 1,012.3, p = 0.0006), renal cell carcinoma (2,686.4 +/- 1,510.9, p = 0.0046), prostate cancer (3,188.7 +/- 1,788.0, p = 0.0003) showed significantly higher values than those of controls (1,709.5 +/- 346.7). Moreover, we found statistically significant correlations among serum creatinine (Cr) levels and sIFN alpha/beta R levels. However, there were no correlations between the sIFN alpha/beta R levels and clinical stage, or histological grade in the patients with bladder cancer or prostate cancer, whenever the levels of sIFN alpha/beta R were corrected by serum Cr levels. On the other hand, high level of corrected serum sIFN alpha/beta R was observed in patients with high stage or high grade renal cell carcinoma, but not significant statistically. CONCLUSIONS: Elevated serum sIFN alpha/beta R was observed in patients with urological disease. Further examinations should be necessary to determine the clinical usefulness of serum sIFN alpha/beta R.

Adolescent↗

PubMed1998

Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancer.

BACKGROUND: Matrix metalloproteinase-2 (MMP-2), which degrades the extracellular matrix or the basement membrane, has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-2, its inhibitor (tissue inhibitor of metalloproteinase-2 [TIMP-2]), and its activator (membrane-type matrix metalloproteinase-1 [MT1-MMP]) in tumor invasion or as a prognostic factor in patients with bladder carcinoma, the authors investigated the expression of MMP-2, TIMP-2, and MT1-MMP in patients with bladder carcinoma. METHODS: Tissues obtained from 41 patients with bladder carcinoma were used for analysis. Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate dehydrogenase was examined by reverse transcriptase-polymerase chain reaction analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP expression and histologic findings or patient outcome were evaluated. RESULTS: Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2< or = bladder tumors than in pT1a tumors (MMP-2: P < 0.0005; TIMP-2: P < 0.005). Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression, all were strongly associated with decreased survival (MMP-2: P < 0.0001; TIMP-2: P < 0.0001; and MT1-MMP: P < 0.005). Even within the radically cystectomized muscle invasive pT2< or = tumor group, patients with a high expression of any of these three genes had a worse prognosis than those with low expression (MMP-2: P < 0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). CONCLUSIONS: MMP-2 and TIMP-2 are believed to contribute to the invasive properties of bladder carcinoma. The authors report that expression of MMP-2, TIMP-2, and MT1-MMP are useful prognostic indicators in patients with bladder carcinoma and may be helpful in designing treatment protocols.

Aged↗

PubMed1998

Intradural spinal hibernoma: case report.

BACKGROUND: Hibernoma is a rare, benign tumor arising from vestigial remnants of brown adipose tissue. It usually affects muscle and subcutaneous tissue and is asymptomatic and slow growing. METHODS: A review of the worldwide literature contains about 110 cases of hibernomas. However, only two cases (including our case) of hibernoma located in the intradural spine have been reported. We present an extremely rare case of intradural extramedullary spinal hibernoma and summarize the magnetic resonance imaging (MRI) findings of the lesion. CASE DESCRIPTION: A 35-year-old woman suffered from motor weakness and numbness of the left upper extremity. Cervical spinal MRI revealed an intradural extramedullary mass at C7. She underwent surgery via the posterior approach and the lesion was completely removed. Histopathologic examination showed multivacuolated cells with centrally placed nuclei, and the diagnosis of hibernoma was made. CONCLUSIONS: Because the CT and MRI findings of hibernoma are almost same as those of other lipomatous tumors, a surgical specimen of this tumor is necessary to establish the correct diagnosis. Early diagnosis and total resection are necessary as some cases showed malignant features or rapid growth. Etiologically, the tumor may have developed by the ectopic growth or migration of adipose tissue.

Adult↗

PubMed1998

Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase families in noninvasive and invasive tumors transplanted in mice with severe combined immunodeficiency.

OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS: Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.

Aged↗

PubMed1997

Multiple intramedullary spinal sarcoidosis: case report.

BACKGROUND: According to past reported cases, spinal intramedullary sarcoidosis has the radiologic characteristics of a single enhanced lesion with cord swelling. However, it is difficult to make a diagnosis using only radiologic examinations. Including our case, 20 cases have been reported of intramedullary spinal sarcoidosis. Only six cases were diagnosed as primary spinal sarcoidosis. We present a rare case of multiple spinal intramedullary sarcoidosis without cord swelling. CASE DESCRIPTION: This 63 year-old man was afflicted with progressive paraparesis and numbness of the lower extremities. Magnetic resonance imaging showed intramedullary lesions without cord swelling. The patient underwent biopsy for diagnosis and the specimen showed a noncaseating granuloma mainly composed of epitheloid cells. Postoperative corticosteroid therapy was effective and the lesion disappeared 1 month after the operation. CONCLUSIONS: Biopsy is a less invasive method and is useful for early diagnosis. Early diagnosis is important for spinal sarcoidosis so that high-dose corticosteroid therapy can be commenced while the lesion still has a good chance of being successfully treated.

Humans↗

PubMed1995

Comparison of the selectivity of anti-varicella-zoster virus nucleoside analogues.

We compared the selectivity of six anti-varicella-zoster virus (VZV) drugs, which are clinically available or of which clinical efficacy for the treatment of VZV infections has been reported. Sorivudine (BV-araU) had the most potent anti-VZV effect in the plaque inhibition assay, followed by brivudine (BVDU) and 5-propynyl-arabinofuranosyluracil (Pry-araU). All test compounds, except vidarabine (AraA), had only a very weak effect on human embryonic lung cell growth. The selectivity indexes (ID50 for cell growth/ED50 for VZV plaque inhibition) of BV-araU, BVDU, and Pry-araU were > 1,000,000, 20,000, and > 10,000, respectively, while those of acyclovir and penciclovir ranged from 600 to 800. AraA was much less selective than any of the other drugs tested. We measured the amount of [3H] thymidine incorporated into the acid-insoluble fraction of VZV-infected cells to determine the ability of these drugs to selectively inhibit viral DNA synthesis. [3H]Thymidine incorporation was markedly inhibited by all anti-VZV compounds, except BVDU. Treatment of infected cells with drugs from 32 to 38 hr after infection inhibited the DNA synthesis to the same extent as VZV plaque formation, except that AraA inhibited the DNA synthesis at a lower dose than for VZV plaque formation. DNA synthesis in non-infected growing cells was inhibited to the same extent as cell growth. A particularly high selectivity index for the inhibition of DNA synthesis was noted for BV-araU, which was defined as the ratio of inhibitions of DNA synthesis in VZV-infected and non-infected. The highest selectivity indexes were recorded for BV-araU > Pry-araU > acyclovir > or = penciclovir > AraA.

Antiviral Agents↗

PubMed1995

[Value of PSA/gamma-Sm ratio (P/S ratio) for diagnosis of prostate cancer in patients with urinary retention].

It is known that serum prostate specific antigen (PSA) in urinary retention due to benign prostatic hypertrophy (BPH) increase. To evaluate prognostic value of the ratio of serum PSA to gamma-seminoprotein (P/S Ratio) for prostate cancer (PC) in patients with urinary retention, we have studied the P/S Ratio at the initial examination in 33 patients with untreated PC (10 with and 23 without urinary retention) and 193 patients with untreated BPH (38 with and 155 without urinary retention) histopathologically diagnosed at our hospital between January, 1992 and December, 1993. The results were as follows: 1) The mean P/S ratio of PC patients was significantly higher than that of BPH patients in both groups with and without urinary retention. 2) When the cut off value of P/S Ratio was determined to be 1.35, the highest efficiency, 59.3% was obtained in the group without urinary retention. The sensitivity and specificity were 65.2% and 91.0%. 3) In the group with urinary retention, the efficiency was also the highest, 80.0% with a cut off value of 1.35. The sensitivity and specificity were 80.0% and 100%. 4) In all patients, the efficiency was 64.6%, the sensitivity was 69.7%, and the specificity was 92.7% with a cut off value of 1.35. 5) Positive rate of serum PSA in BPH patients with urinary retention was 47.4% and that in BPH patients without urinary retention was 17.4%. The mean P/S ratio of the BPH patients with urinary retention was significantly lower than that of BPH patients without urinary retention, which suggested that the serum free PSA increase in the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

[High flow priapism after perineal trauma, successfully treated by unilateral embolization of the internal pudendal artery: a case report].

We reported a case of 45-year-old patient with high flow priapism secondary to arteriovenous fistula produced by perineal trauma. Diagnosis was based on the results of gasometry in cavernous blood, cavernography and pudental arteriography. Although conservative treatment had been tried, complete resolution of priapism was not obtained. We could successfully treat the priapsim by percutaneous temporary embolization of the right internal pudendal artery with Gelatin. Erection and sexual function, after 2 months of treatment, was normal. The rationale for the use of this embolization in the treatment of high flow priapism and its etiology was discussed.

Embolization, Therapeutic↗

PubMed1995

[Evaluation of the efficacy of recombinant human erythropoietin (rHuEPO) administration on penile erection in males undergoing hemodialysis and effect on pituitary-gonadal function].

Recombinant human erythropoietin (rHuEPO) was administered to males undergoing hemodialysis, and its effects on penile erection and hypothalamus-pituitary-gonadal hormone levels were studied. The subject consisted of 18 males undergoing hemodialysis ranging in age from 22 to 58 years (mean 45.3 years). Chronic glomerulonephritis was present in 16, and diabetic nephropathy in 2, as underlying disease. rHuEPO was administered intravenously at 1,500 U 3 times a week with a target to increase the Ht value to 25% or above. Penile erection was evaluated subjectively by a questionnaire based on a visual analogue scale and objectively by semi quantitative measurement of nocturnal penile tumescence (NPT) using an erectometer. Of the 18 patients, subjective improvements in penile erection were observed in 13 (72%), and objective improvements in NPT were observed in 10 (56%). The administration of rHuEPO may alleviate hyperprolactinemia but was found to have no effect on the FSH, LH, Zn, or HS-PTH level. rHuEPO was suggested to be fairly effective for the treatment of sexual disorders.

Adult↗

PubMed1995

[High flow priapism following a straddle-injury-induced arteriocavernosal fistula: a case report].

A 26-year-old man with high flow priapism after blunt perineal trauma, is described herein. Patient evaluation included intracavernal blood-gasometry, cavernography, color flow Doppler sonography. The blood-gasometry showed pH 7.413, pO2 77.9 mmHg, pCO2 41.0 mmHg, HCO2- 26.1 mmol/L, BE 2.0 mmol/L. By direct cavernosography, pooling of contrast agent was seen at the root of the penis. Color flow Doppler sonography revealed pulsatile, turbulent flow within left corpus cavernosum. Our case was diagnosed as high flow priapism from these findings. Detumescence was not achieved by an alpha-adrenergic agent. Superselective embolization of the deep artery of the penis with autologous blood clot was performed with good results. Our case demonstrates that this procedure is a safe and effective therapy for high flow priapism and that erectile function can return to normal.

Adult↗

PubMed1994

Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone.

Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.

Antigens, Viral↗

PubMed1994

In vitro and in vivo anti-herpes viral activities and biological properties of CV-araU.

We compared the in vitro and in vivo antiviral effects against herpes simplex virus type 1 (HSV-1) and other biological properties of 1-beta-D-arabinofuranosyl-5-[(E)-2-chlorovinyl]uracil (CV-araU) and 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU, sorivudine). Both CV-araU and BV-araU exhibited antiviral activities against HSV-1 in the cell culture derived from mouse, though the activities were lower than those seen in human cells. For intraperitoneal and intracerebral infections in mice with HSV-1 strain WT-51, both compounds, administered twice daily, were effective in increase in the survival rate at doses of 15 mg/kg and 30 mg/kg, respectively. In pharmacokinetic analysis, both drugs were absorbed well in the rat gastrointestinal tract following oral administration. There was no difference between the metabolism of orally administered CV-araU and BV-araU in rats. High levels of the corresponding base were found in plasma after oral administration of CV-araU and BV-araU, but much lower base levels were seen after intravenous doses. Both drugs were resistant to degradation by rat liver enzymes.

3T3 Cells↗