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Biomedical subjects

K Shigeno

Publications and source records attributed to K Shigeno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein.

Spicamycin is a potent inducer of differentiation of human myeloid leukemia cells (HL-60) and murine myeloid leukemia cells (M1). One of the spicamycin derivatives, KRN5500, shows a broad spectrum of antitumor activity against human tumor xenografts in nude mice. In this study, we first investigated the differentiation efficacy of spicamycin and KRN5500 in HL-60 and acute promyelocytic leukemia cell line, NB4, and found that low concentrations of both compounds induced differentiation to a small extent in both cell lines, but markedly induced apoptosis in NB4 cells. Further investigation in a myeloid leukemia cell line, NKM-1, a lymphoma cell line, Daudi, and a multiple myeloma cell line, NOP-1, showed that high concentrations of both compounds also induced apoptosis in these cells. The 50% inhibitory concentration (IC(50)) determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that myeloid cells were more sensitive to both compounds than lymphoid cells, and spicamycin was more potent than KRN5500. Western blot analysis of Bcl-2, Bcl-xL and Bax expression and immunofluorescence analysis of promyelocytic leukemia (PML) protein indicated that apoptosis induced by spicamycin and KRN5500 was associated with down-regulation of Bcl-2 expression and modulation of PML protein. Thus, spicamycin and KRN5500 may be useful for the treatment of myeloid and lymphoid neoplasms.

Antibiotics, Antineoplastic↗
PubMed2000

Artificial trachea and long term follow-up in carinal reconstruction in dogs.

We have already reported successful carinal reconstruction of the trachea with an observation period of 1 - 2 years. In this study, we evaluate the long-term safety and efficacy of the reconstruction after 5-years of follow-up. The Y-shaped Marlex mesh tube was reinforced with a polypropylene spiral and coated with atelocollagen made from porcine skin. The prosthesis was 60 mm long with an outer diameter of 18 mm. Replacement of the tracheobronchial bifurcation was preformed through a right thoracotomy in a beagle dog. Bronchoscopical examination and sampling of the tracheal epithelium was performed periodically to check the function of cilia. The implanted prothesis was promptly infiltrated by the surrounding connective tissue and completely incorporated by the host trachea and bronchus. Bronchoscopically, sufficient epithelization was confirmed from the upper to the lower site of anastomosis. After 5 years neither stenosis nor dehiscence was observed. In spite of there being mesh-exposure at the luminal surface, the dog had no clinical symptoms until sacrifice for pathological examination. The bent frequency of the cilia was maintained within the normal range, indicating functional recovery of the regenerating airway. Our tracheal prosthesis is promising for clinical repair of the tracheobronchial bifurcation.

Animals↗
PubMed2000

Regeneration of the junctional epithelium and connective tissue after transplantation of detergent-processed allo-teeth.

The authors have developed a new artificial dental implant and evaluated it in a dog model in terms of its potential to produce: I) regeneration of junctional epithelium; II) regeneration and attachment of connective tissue. The implants were constructed from allo-teeth. We removed the cell components from the periodontal ligaments of these teeth with a detergent (1% TritonX-100); the remaining acellular periodontal ligament acted as an extracellular matrix upon which regeneration and attachment could proceed. We placed 10 of these implants in the just-extracted sites of three beagle dogs. We observed regeneration of both junctional epithelium and connective tissue at all implant sites after 3 months. The connective tissue was attached in all cases. Use of the acellular periodontal ligament as an extracellular matrix may facilitate regeneration of host periodontal ligament tissue, thus contributing to recovery of host immunological defense and long-term oral function.

Animals↗
PubMed1999

Clinical significance of mdm2 and p53 expression in bladder cancer. A comparison with cell proliferation and apoptosis.

BACKGROUND: Clinical significance of immunohistochemically detectable level of p53 protein has been reported, but with some limitation as a prognosticator of bladder cancer patients. Whether or not simultaneous evaluation of mdm2 and p53 expression in bladder cancer exceed the prognostic significance of conventional histological findings, cell proliferation markers and apoptotic parameters remains unclear. MATERIALS AND METHODS: The paraffin-embedded materials taken from 84 patients with transitional cell carcinoma of the bladder who were treated with total cystectomy were used in this study. Immunostainings of p53 protein, mdm2 protein and Ki67 antigen were performed using monoclonal antibodies (clone DO7, clone 1B10 and clone MIB1, respectively). In addition, the apoptotic cells were determined using a terminal deoxynucleotidyl transferase (TdT) mediated dUTP biotin nick end labeling (TUNEL) technique. The results were quantitatively evaluated using a CAS 200 Image Analyzer (Cell Analysis System, Elmhurst, Ill., USA) and were compared with histological findings and clinical course. RESULTS: The mean values of mdm2 expression, p53 immunoreactivity, Ki67 expression and apoptotic index were 19.2, 20.5, 22.4 and 0.96%, respectively. Histological grade and pT category were significantly positively correlated with 53 immunoreactivity (p < 0.05 and p < 0.05, respectively), Ki67 expression (p < 0.005 and p < 0.0001, respectively) and apoptotic index (p < 0.01 and p < 0.0001, respectively), while both were not correlated with mdm2 expression. Using univariate analysis, the prognostic relevance for both survival and disease progression was noted in histological grade, pT category, p53 expression, Ki67 index and apoptotic index, whereas it was not in mdm2 expression. However, when analyzing the simultaneous evaluation of mdm2 and p53 expression (mdm2-p53 category), the relationship of the mdm2-p53 category with Ki67 expression and apoptotic index showed a statistical significance and a borderline significance (p = 0.0085 and p = 0.0652, respectively). In addition, the patients with both mdm2(-) and p53(-) showed a significant better prognosis as compared with either counterpart of mdm2-p53 category (p < 0.05 for both). Multivariate analysis revealed only pT category and mdm2-p53 category as independent factors for both disease progression and survival. CONCLUSIONS: Clinical significance of simultaneous evaluation of mdm2 and p53 immunostaining proved to be superior over that of cell proliferation and/or apoptotic markers when elucidating the biological characteristics of bladder cancer.

Adult↗
PubMed1999

Traumatic dislocation of the testis.

We report on a patient having testis dislocated into the superficial crus caused by an accident on a fishing boat. On physical examination, the left hemiscrotum was empty, and a painful mass was palpable inside the left thigh. On sonography, the testis appeared to be normal. Magnetic resonance imaging showed that the mass was located between subcutaneous tissue and muscle layer of the thigh. Surgical intervention was performed, and the left testis was found within the subcutaneous tissue inside the thigh, with slight torsion of the spermatic cord. The testis was fixed in the left hemiscrotum. To our knowledge, traumatic dislocation of the testis into the superficial crus is rare, and only 2 cases have been reported.

Adult↗
PubMed1999

Inverted papilloma of the urinary bladder in a girl.

We report a case of inverted papilloma of the urinary bladder in a 10-year-old girl. She was referred to us with intermittent asymptomatic gross hematuria. A polypoid, pedunculated mass, which had a thin and long stalk, approximately 6 x 20 mm in diameter, was observed by cystscopic examination at the right paratrigone. The lesion was resected endoscopically. Histological findings were compatible with the trabecular type of inverted papilloma. There have been only 3 cases reported of inverted papilloma in children, and no report has previously been published concerning a girl. Since the biological potential of pediatric inverted papilloma remains unclear, we believe that our patient should undergo periodic and detailed urological examinations.

Child↗
PubMed1999

Electrocochleographic evaluation of hearing loss in acoustic neuromas.

OBJECTIVE: This study aimed to clarify the pathophysiology involved in the cause of hearing impairment due to acoustic neuromas (AN) with electrocochleograph (ECoG). STUDY DESIGN: The study design was a retrospective case study. SETTING: This study was conducted in a tertiary referral center. PATIENT: Thirty-four patients diagnosed as having AN by magnetic resonance imaging between 1988 and 1995. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The authors made a comparison between the patients' ECoG findings and the size of their tumors as determined by magnetic resonance imaging and a pure-tone audiometry (PTA). The disparity between the threshold of PTA and the detective threshold of compound action potential (CAP) or that of the cochlear microphonics (CM) was calculated. When the threshold of the PTA was worse than the detective threshold of the CAP or the CM, the disparity was regarded as indicating a hearing loss of retrocochlear origin. RESULTS: There was no correlation found between tumor size and the detective threshold of CAP or CM. Disparity was found to correlate with tumor size. CONCLUSIONS: These findings seem to indicate that retrocochlear damage in AN increases parallel to the growth of the tumor and that retrocochlear damage can be detected by the ECoG before surgery.

Adult↗
PubMed1998

Comparison of chromosomal aberrations detected by fluorescence in situ hybridization with clinical parameters, DNA ploidy and Ki 67 expression in renal cell carcinoma.

To evaluate the significance of chromosomal aberrations in renal cell carcinoma, fluorescence in situ hybridization (FISH) was used to determine its prevalence and correlation with clinical parameters of malignancy. In addition, correlation of chromosomal aberration with Ki 67 expression was analysed. We performed FISH with chromosome-specific DNA probes, and the signal number of pericentromeric sequences on chromosomes 3, 7, 9 and 17 was detected within interphase nuclei in touch preparations from tumour specimen. The incidence of loss of chromosome 3 was significantly higher than those of chromosomes 7, 9 and 17 (P < 0.001, P = 0.03 and P < 0.001 respectively). Hyperdiploid aberration of chromosomes 3 and 17 was significantly correlated with tumour stage (P = 0.03, P = 0.02 respectively), whereas hyperdiploid aberration of chromosome 9 was associated with nuclear grade (P = 0.04). Disomy of chromosome 7 was correlated with venous involvement (P = 0.04). Ki 67 expression was significantly associated with hyperdiploid aberration of chromosome 17 (P = 0.01), but not with aberration of chromosome 3. There was a significant relationship between hyperdiploid aberration of chromosome 7 and Ki 67 expression (P = 0.01). In conclusions, gain of chromosome 17 may reflect tumour development, and aberration of chromosome 7 may affect metastatic potential of malignancy, whereas loss of chromosome 3 may be associated with early stage of tumour development in renal cell carcinoma.

Adult↗
PubMed1998

The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms.

Arsenic trioxide (As2O3) has recently been shown to induce complete remission in acute promyelocytic leukemia (APL). As2O3 reportedly has dose-dependent dual effects on APL cells, triggering apoptosis at relatively high concentrations and inducing differentiation at lower concentrations. However, its effect is still controversial for other AML cells and hematological neoplasms. We studied the in vitro effect of As2O3 on lymphoid lineage cells: lymphoma cell lines, NOL-3, Raji and Daudi, a myeloma cell line, NOP-1, normal peripheral blood lymphocytes (PBL), non-Hodgkin's lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells, and compared it with the effect on APL cell line, NB4, as well as other myeloid cell lines, HL-60 and NKM-1. As2O3 at a concentration of 1 micromol/l markedly inhibited both proliferation and viability of NB4, NOP-1, NOL-3 and NKM-1 cells, but it reduced only viability in normal PBL, CLL cells and NHL cells. As2O3 induced apoptosis and down-regulated bcl-2 expression in NB4, NOP-1 and NKM-1 cells. On the other hand, in HL-60, Raji and Daudi cells, 1 micromol/l As2O3 inhibited only the proliferation weakly, and neither induced apoptosis nor down-regulated bcl-2 expression, but arrested only cell cycle at G1 phase. As2O3 at a low concentration of 0.1 micromol/l had no effect on proliferation and viability of these cells except for NB4. These results showed that As2O3 exerted variable and definite effects on lymphoid cells and indicated that As2O3 might be clinically useful in lymphoid neoplasms such as malignant lymphoma and CLL.

Antineoplastic Agents↗
PubMed1998

Free groin flap for reconstruction of the tongue and oral floor.

The authors report the use of free groin flaps to close intraoral defects in 24 patients following ablative tongue cancer surgery. The lateral thin portion of the flap was used for tongue reconstruction, and the deepithelialized medial thick portion for filling the mandibular defect and for covering the important vessels in the neck. In lean patients, if the medial deepithelialized portion was too thin for adequate coverage, the proximal sartorius muscle was included to prevent postoperative orocervical fistula. The advantages of the groin flap in reconstructing the tongue and oral floor after hemiglossectomy include the following: (1) a suitable amount of tissue is available for both the tongue and oral floor; (2) the important vessels in the neck may be protected with the flap; (3) the proximal sartorius muscle can be included with the flap, if necessary; (4) donor-site morbidity is less than with other flaps; and (5) flap elevation can be done concurrently with the hemiglossectomy and radical neck dissection.

Adult↗
PubMed1998

A study of growth pattern in giant condyloma acuminatum.

We report a case of giant condyloma acuminatum (CA) of the perianal region. Pathological diagnosis revealed a typical CA with no sign of atypia. In addition, HPV type 11 could be identified by Southern blot analysis. PCNA was highly positive immunohistochemically, but the positivity of p53 protein was not as high as compared with the other control cases. Thus, the high growth rate of tumor cells evaluated by PCNA staining seems to contribute to the marked increase in size, and not only the p53 mutation but also an other cascade may be implicated in cell proliferation.

Adult↗
PubMed1997

Immunohistochemical analysis of estramustine binding protein with particular reference to proliferative activity in human prostatic carcinoma.

BACKGROUND: The estramustine binding protein (EMBP) specifically binds to estramustine and was first discovered in the rat ventral prostate. However, the physiological property of EMBP in the human prostate still remains to be elucidated. To elucidate whether EMBP is interrelated with cellular proliferation in human prostatic carcinoma (PC), the change in EMBP immunostaining during luteinizing hormone-releasing hormone (LH-RH) analog administration or during Cis-platinum-based chemotherapy, and the difference in EMBP immunostaining between hormone refractory (hr-PC) and untreated PC were analyzed. METHODS: Forty-six patients with histologically proven untreated PCs (34 were treated with LH-RH analog and 12 were treated with chemotherapy as an initial therapy) and 14 with hr-PC were used in this study. PC tissues were obtained before and 3 months after the initial therapy. The changes in immunostainings for EMBP, proliferating cell nuclear antigen (PCNA), and nm23 protein were compared with the change in serum prostate-specific antigen (PSA) level and the histological response during the treatment. RESULTS: The increased EMBP expression was observed in tumors with high histological grade and high clinical stage as well as in hr-PC. In untreated PC, EMBP expression weakly correlated with PCNA or nm23 protein immunoreactivity. In PC receiving LH-RH analog, EMBP expression was significantly reduced after treatment, however, no significant changes were observed in PCNA or nm23 protein immunoreactivity. In addition, EMBP expression before the treatment significantly correlated with the serum PSA change, while PCNA expression and nm23 protein immunoreactivity did not. On the other hand, no significant relationship was observed between histological changes induced by the LH-RH analog and immunostainings for EMBP, PCNA, and nm23 protein before treatment. In PC patients receiving chemotherapy, immunostainings for EMBP, PCNA, and nm23 protein were not significantly changed during the treatment. EMBP immunoreactivity was significantly higher in hr-PC than in untreated PC with paralleled change of PCNA expression and nm23 protein immunoreactivity. CONCLUSIONS: These observations indicate that EMBP is androgen regulated in some PCs. However, EMBP expression is demonstrated even in hr-PC and is interrelated with cellular proliferation especially in hr-PC.

Aged↗
PubMed1997

Chromosome aberrations in renal tumors detected by fluorescence in situ hybridization.

The aim of this study was to investigate the relationship between chromosome aberrations detected by fluorescence in situ hybridization (FISH) and tumor grade, stage, venous involvement, and DNA ploidy status in 18 renal tumors. Using FISH with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 3, 7, 9, and 17 was detected within interphase nuclei in touch preparations from tumor specimens. Monosomy for chromosome 3 was detected in seven of 9 DNA diploid tumors, whereas all DNA aneuploid tumors demonstrated trisomy or tetrasomy for chromosome 7. Moreover, monosomy for chromosome 3 was more frequently shown in the diploid and low-stage tumors than in the aneuploid and high-stage tumors. The percentage of hyperdiploid cells significantly correlated with DNA ploidy status in the case of chromosomes 3 and 7 (p = 0.030, p = 0.007, respectively). The percentage of hyperdiploid cells for chromosome 3 had borderline significance with tumor stage. On the other hand, the percentage of diploid cells for chromosome 17 was significantly correlated with DNA ploidy status and tumor stage (p = 0.030, p = 0.027, respectively). Moreover, the percentage of diploid cells for chromosome 7 in renal cell carcinoma (RCC) with venous involvement was significantly lower than those without venous involvement (p = 0.023). These results suggest that the incidence of chromosomal aberrations detected by FISH is more frequent than the chromosomal aneuploidy reported previously by conventional cytogenetics. Therefore, loss of chromosome 3 may be associated with an early event in RCC carcinogenesis. Gain of chromosomes 3 and 7 is correlated with tumor progression as well as gain and loss of chromosome 17. Study of the chromosomal aberrations may provide a greater understanding of tumor carcinogenesis and progression in RCC.

Adult↗
PubMed1997

[A reversible posterior leukoencephalopathy syndrome in a patient with classical polyarteritis nodosa].

We report a case of a reversible posterior leukoencephalopathy syndrome (RPLS). A 57-year-old male had classical polyarteritis nodosa with mononeuritis multiplex, renal insufficiency, and a high titer of p-ANCA (MPO). He was normotensive. He was treated with high dose methylprednisolone and then with oral prednisolone and cyclophosphamide. Despite the treatment, his renal function rapidly deteriorated and hypertension progressed. He had two generalized seizures; at that time his blood pressure was 200/140 mmHg. CT scan revealed bilaterally symmetric hypodensities in the thalamus, the occipital white matter, and the brainstem. T2-weighted MRI showed increased signal intensities in the temporo-occipital white matter, the thalamus, the posterior limbs of the internal capsules, the external capsules, the midbrain, the pons, and the middle cerebellar peduncles. T1-weighted images showed hypointensities in these areas. Treatment with nifedipine improved his blood pressure; 5 days later he was only moderately disoriented. Follow-up CT demonstrated an ill-defined hypodense area only in the left parietal lobe. To our knowledge, there are only two reported cases of RPLS associated with systemic vasculitides. Interestingly, thalamic lesions are outstanding also in these cases. Under these circumstances, treatment of hypertension is of primary importance, and steroid therapy should not be withdrawn or reduced.

Brain Diseases↗
PubMed1996

Evaluation of the argyrophilic nucleolar organizer region, nuclear DNA content and mean nuclear area in transitional cell carcinoma of bladder using a quantitative image analyzer.

To search for reliable parameters that reflect the biological potential of bladder cancer, the argyrophilic nucleolar organizer region (AgNOR), nuclear DNA content and mean nuclear area (MNA) were studied in paraffin-embedded materials of 75 primary transitional cell carcinomas (TCCs) using a quantitative image analyzer, and were also compared with histological findings and prognosis. The AgNOR parameters studied were the mean AgNOR count (C-AgNOR) and the percentage of cells exhibiting more than 4 AgNOR dots within nuclei (P-AgNOR), whereas the DNA parameters were the 2c deviation index (2cDI) and 5c exceeding rate (5cER). These 5 parameters significantly correlated with the histological grade (p < 0.0001, respectively). Similarly, these 5 parameters correlated with the histological stage, but the correlation was higher in 2cDI and 5cER (p < 0.0001, respectively) in comparison with the AgNOR parameters and MNA. Using univariate analysis, the prognostic relevance was noted in all but P-AgNOR. The 5cER value could discriminate histological grade-II tumors in relation to prognosis, whereas the remaining parameters could not. In addition, the significant difference between noninvasive and invasive tumors was noted in 2cDI and 5cER (p < 0.05, respectively), but not in C-AgNOR, P-AgNOR and MNA. These results suggest that (i) 2cDI and 5cER exhibit superiority over the AgNOR parameters and MNA in predicting survival, and (ii) in histological grade-II tumors, evaluation of the 5cER value is most important when predicting survival as well as judging the necessity for further aggressive treatment in patients with TCCs of the bladder.

Adult↗