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Biomedical subjects

T Koshikawa

Publications and source records attributed to T Koshikawa.

At least 19 recordsLinked to original sources

[Pulmonary sequestration associated with fungal infections; report of a case].

A 45-year-old female was admitted to our hospital complaining of cough and purulent sputum. Enhanced chest computer tomography(CT) showed that abnormal mass shadow in left lower lobe of the lung and an aberrant artery originated from the discending aorta and penetrated the lesion. Left lower lobectomy was performed and intralobar sequestration was diagnosed. Moreover, fungus which were suspected Aspergillus were found in the cystic lesion. The postoperative course was uneventful and she was discharged.

Adult↗

Study by scanning tunneling microscopy of hydrogen adsorption and desorption on Si111 7 x 7 at room temperature and at high temperature.

An overview is given on the use of scanning tunneling microscopy (STM) for investigation of the adsorption of hydrogen on Si(111)7 x 7 both at room temperature and at elevated temperature to finally obtain a hydrogen-saturated surface of Si(111). The initial stages are characterized by high reactivity of Si adatoms of the 7 x 7 structure. After adsorption of hydrogen on the more reactive sites in the beginning of the adsorption experiments a regular pattern, which is different for room and elevated temperature, is observed for the less reactive sites. In agreement with previous work, local 1 x 1 periodicity of the rest atom layer and the presence of di- and trihydride clusters is observed for hydrogen-saturated surface. STM has also been used to characterize surfaces from which the hydrogen atoms have been removed by thermal desorption. Finally, tip-induced desorption by large positive sample-bias voltages and by increasing the tunneling current will be described.

Journal Article↗

[Multiple lung cancer with cavity; report of a case].

A case of multiple lung cancer with cavity was reported. Chest X-ray and chest computed tomography (CT) showed two abnormal shadows with consolidation in the right S1 and S2b. The shadow in S2b had a cavity. Right upper lobectomy and right middle lobe partial resection was performed and the histopathological examination revealed adenocarcinoma. This case deserves attention of difficulty in differentially diagnosis on the chest X-ray and chest CT from pulmonary tuberculosis.

Adenocarcinoma↗

Virtual endoscopy of the labyrinth, using a 3D-FastASE sequence.

Virtual endoscopy (VE) of the labyrinth was performed using three-dimensional (3D)-fast asymmetric spin-echo MR imaging. The spatial resolution requirements and the usefulness of zero-fill interpolation (ZIP) were evaluated, and VE was used to examine three patients. The (0.6-mm) voxel data with ZIP satisfies the minimum requirements for VE for evaluation of the complex 3D anatomy and pathology of the labyrinth. J. Magn. Reson. Imaging 2001;13:792-796.

Adolescent↗

Immunohistochemical demonstration of cyclin D1 in bladder cancers as an inverse indicator of invasiveness but not an independent prognostic factor.

BACKGROUND: Cyclin D1 is essential for G1 progression through the cell cycle phase. It is a possible proto-oncogene whose aberrant expression may be responsible for the occurrence of some types of human neoplasms. The objective of the present study was to demonstrate immunohistochemically cyclin D1 expression in bladder cancer tissues and establish any relationship with the histologic findings and the clinical course. METHODS: Tissue from 102 patients with bladder cancers and bladder tissue from five normal subjects were used for an immunohistochemical study of cyclin D1 using the avidin-biotin complex method. RESULTS: Nuclear staining of cyclin D1 was found in 79 (77%) out of the 102 cases of bladder cancer. The five cases of normal epithelium had no immunostaining for cyclin D1. All grade 1 tumors were positive for cyclin D1. With the advance of tumor grade the incidence of cyclin D1 decreased. All pTa tumors stained positively for cyclin D1, whereas the positive staining rates of invasive tumors were 47% in pT1, 73% in pT2, 31% in pT3 and 0% in pT4 tumors. Although a univariate analysis revealed patients with lesions positive to cyclin D1 had more favorable survival rates than those with negative findings, a multivariate analysis showed that positivity for cyclin D1 is not an independent prognostic factor. No relationship was discovered between positivity for cyclin D1 and tumor recurrence in patients with superficial bladder cancers. CONCLUSIONS: These findings suggest that cyclin D1 demonstrated immunohistochemically could be used as an inverse indicator for the level of invasiveness of bladder cancer, but not as an independent prognostic factor.

Adult↗

Cytological changes induced by intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer.

To evaluate cytological changes of urothelial cells with intravesical instillation therapy of the bacillus Calmette-Guérin (BCG), cytological specimens of voided urine from patients with superficial bladder cancer (pTa and pT1) treated with intravesical BCG therapy were examined. The following three groups of patients who had no evidence of recurrence more than 2 years after the treatment were studied: groups 1 and 2, patients who were treated with BCG (n = 22) and epirubicin, a derivative of doxorubicin (n = 22), respectively, for prophylaxis of intravesical recurrence after transurethral resection (TUR); and group 3, patients receiving no intravesical therapy after TUR (n = 12). Sixteen cytological characteristics were studied before and after the treatment in each group. In group 1 patients translucent nuclei and prominent nucleoli, vacuolization of cytoplasm, and eosinophilic cytoplasmic inclusions were frequently observed in urothelial cells as well as an increase in granulocytes, especially within 3 months after BCG instillation therapy. In group 2 patients an increased nuclear/cytoplasmic ratio, hyperchromatic nuclei and prominent nucleoli of urothelial cells were transiently found within 1-2 months after intravesical epirubicin therapy. In group 3, translucent nuclei and prominent nucleoli of urothelial cells were found within 1-2 months after TUR. In conclusion, cytological changes induced by BCG therapy are nonspecific and reactive in nature, different from those due to chemotherapeutic agents and distinguishable from malignant changes of urothelial cells.

Administration, Intravesical↗

MR imaging of the enlarged endolymphatic duct and sac syndrome by use of a 3D fast asymmetric spin-echo sequence: volume and signal-intensity measurement of the endolymphatic duct and sac and area measurement of the cochlear modiolus.

BACKGROUND AND PURPOSE: In enlarged endolymphatic duct (EED) and sac (EES) syndrome, deformity of the EED and EES is congenital; however, hearing loss is acquired. To investigate the pathophysiology of progressive sensorineural hearing loss in EED and EES syndrome, we measured the volume of the EED and EES, the diameter of the EED and EES, the area of the cochlear modiolus, and the signal intensity of the EES and compared our findings against degree of hearing loss. METHODS: Thin-section MR images of 33 ears in 17 patients with EED and EES syndrome were studied. All studies were obtained on a 1.5-T MR unit using a quadrature surface phased-array coil. Heavily T2-weighted 3D fast asymmetric spin-echo images were obtained with a voxel size of 0.3 x 0.3 x 0.8 mm without zero-fill interpolation. Two radiologists traced the areas of the EED and EES manually, and the volume was calculated. The area of the cochlear modiolus, diameter of the EED and EES, and signal intensity of the EES were also measured by drawing regions of interest manually. The signal intensity ratio of EES/CSF was calculated. These measured values were compared against audiographic data, and the degree of linear correlation was determined. RESULTS: The volume of the EED and EES, the area of the modiolus, the diameter of the EED and EES, and the signal intensity of the EES did not show significant correlation with degree of hearing loss. CONCLUSION: These findings suggest that there is a microscopic area of damage or fragility in the inner ear not visible even with thin-section heavily T2-weighted MR imaging.

Adolescent↗

High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis.

In patients with multiple synchronous lung tumors, discrimination of multicentric lung cancers from intrapulmonary metastasis is important for treatment decision, but this is sometimes difficult. The aim of this study was to retrospectively distinguish multicentric lung cancers from intrapulmonary metastases in 14 such cases by loss of heterozygosity (LOH) and p53 mutational status. DNA was extracted from microdissected tumor cells in paraffin-embedded archival tissue, and 3p14.2, 3p21, 3p25, 9p21, and 18q21.1 were investigated for LOH. Exons 5-8 of the p53 gene were examined for mutations by the PCR, followed by single-strand conformation polymorphism analysis and DNA sequencing. For cases with the same LOH pattern, we calculated a clonality index, the probability of the given LOH pattern when these tumors were hypothesized to be independent in origin. Eleven of 14 cases (79%) were thus diagnosed as having pulmonary metastasis and only one case as having genuinely multicentric lung cancers. Two cases presented difficulty in diagnosis. In several cases, the LOH patterns conflicted with p53 mutation patterns, suggesting that clonal evolution is directly affected by certain genetic changes. The combination of p53 with LOH helped increase both the sensitivity and specificity of the assay.

Adult↗

[Comparative genomic hybridization for analysis of chromosomal changes in cisplatin-resistant ovarian cancer].

In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators and regulators of the apoptotic pathway are found to be located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy.

Antineoplastic Agents↗

Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers.

We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mutation, which substitutes alanine (GCG) for threonine (ACG) at codon 299, together with a number of amino acid substituting, single nucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potential target, although with low frequency, for genetic alterations in lung cancer. Thus, further studies of hMAD1 dysfunction caused by other mechanisms appear to be warranted, as well as potential involvement of other components of the mitotic checkpoint.

Base Sequence↗

Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases.

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.

Adolescent↗

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).

Adolescent↗

Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.

The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.

Antineoplastic Agents↗

p27KIP1 in human lung cancers: differential changes in small cell and non-small cell carcinomas.

Small cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs), two major categories of human lung cancers, have been shown to exhibit considerably different clinicopathological, biological, and molecular genetic characteristics. Inactivation of cyclin-dependent kinase inhibitors is now thought to play an important part in the pathogenesis of this fatal disease. In the present study, we show that in vitro p27KIP1 expression was associated with cell density-dependent growth inhibition in human lung epithelial cells in vitro, whereas in vivo, p27KIP1 expression in lung cells showed an inverse correlation with proliferative activity in the developing and adult normal lungs. Our immunohistochemical examination of 166 lung tumor specimens also revealed a striking difference in p27KIP1 expression between SCLCs and NSCLCs. Of 149 NSCLCs, 107 (72%) showed reduced p27KIP1 expression, with 8 being virtually negative. Furthermore, p27KIP1 expression status was found to be a significant prognostic factor for patient survival in the analysis of the 149 primary, resected NSCLC cases (P = 0.03 by the log-rank test). In contrast, all SCLC specimens thus far examined exhibited significantly increased staining when compared to the corresponding normal lung epithelium. These findings provide additional evidence for the heterogeneity prevalent in human lung cancers and suggest that p27KIP1 might play distinct biological roles in the pathogenesis of the two major histological categories, warranting additional studies to elucidate the functional consequences of such differences.

Adult↗

Different distributions of immunoreactive S100-alpha and S100-beta protein expression in human breast cancer.

BACKGROUND AND OBJECTIVES: Although the localization of S100 protein in breast carcinoma has previously been studied, the immunohistochemical expression of the S100-alpha and -beta subunits has not been examined. METHODS: Immunohistochemical staining for S100-alpha and S100-beta proteins was performed on 72 benign breast lesions and 72 infiltrating ductal carcinoma of the breast. Noncross-reactive anti-S100-alpha and anti-S100-beta antibodies purified by affinity chromatography were used in the studies. RESULTS: More than 30% of the epithelial cells comprising all the benign lesions were either S100-alpha or S100-beta positive. In breast carcinoma cases, however, >30% of malignant cells were S100-alpha positive in 70/72 cases (97.2%), whereas the number of S100-beta positive cells exceeded 30% in only 3/72 cases (4.0%). CONCLUSIONS: Immunohistochemical staining for S 100-alpha and S100-beta proteins may help to differentiate benign proliferative breast lesions from breast cancers in difficult cases.

Breast Neoplasms↗

Multiple polypoid lesions of primary mucosa-associated lymphoid-tissue lymphoma of colon.

AIMS: This study was focused on unusual cases of mucosa-associated lymphoid tissue (MALT) lymphoma presenting with multiple polypoid lesions of the colon and rectum with a special reference to the differential diagnosis of mantle cell lymphoma. METHODS AND RESULTS: The lesions of these five cases grossly showed a segmental distribution of nodular protrusions in three patients and of innumerable small polyps in two. These patterns of involvement simulated those of multiple lymphomatous polyposis, known as the gastrointestinal presentation of mantle cell lymphoma (MCL), and caused a differential diagnostic problem between MALT lymphoma and MCL, which have different prognostic and therapeutic implications. Their histological features are almost indistinguishable from each other, especially in the small biopsy specimens via endoscope. The most important procedure for their differentiation is cyclin D1 immunohistochemistry and its negative reaction provides strong indication of MALT lymphoma. Of interest, one case showed a rare karyotypic abnormality of t(11;18)(q21;q21), which has been reported specifically in MALT lymphoma. CONCLUSIONS: This study has indicated that the multiple polypoid lesions of the colon occur not only in MCL, but also in MALT lymphoma, making differential diagnosis between the two entities necessary, and cyclin D1 immunohistochemistry is indispensable for distinguishing between them.

Adult↗

Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its malignant transformation.

AIMS: To clarify the association of p53 and CD34 expression with development of malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous tumour arising in the pleura, retroperitoneum and pelvic cavity with clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were localized solid masses with or without necrosis in eight and they nearly totally occupied the pleural cavity in two. Basic histology of the tumours was the proliferation of spindle cells arranged in 'patternless' pattern or in interlacing bundles with nuclear atypia and mitotic activities of various degree. In two, high-grade foci were present within low or intermediate-grade tumours. Recurrent tumours also showed more atypical features than primary tumours in two. Immunohistochemical studies showed CD34 positivity in seven, but three of them showed marked diminution or complete loss of CD34 expression in high-grade foci or a recurrent tumour. Three high-grade cases showed totally negative staining for CD34. p53 was strongly expressed in cases with fatal outcome, clinical recurrence, nuclear atypia, high mitotic activity or local invasion, whereas almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous tumours may occur de novo or by transformation within benign or low-grade tumours and may be associated with p53 mutation. Although CD34 is a useful marker in the diagnosis of solitary fibrous tumour, one should bear in mind that its expression can be lost in high-grade tumours.

Adult↗

[An immunohistochemical study of RB tumor suppressor gene protein and bcl-2 gene protein in carcinomas of the thyroid gland].

The expression of RB and bcl-2 proteins was investigated in 135 thyroid carcinomas (130 papillary carcinomas and five follicular carcinomas) by the immunohistochemical technique with RB and bcl-2 monoclonal antibodies. The results were as follows: 1) RB protein nuclear staining was shown in 117 of the 135 thyroid carcinomas (87%). Bcl-2 protein staining was shown in 82 of the carcinomas (61%). 2) There was a higher incidence of recurrence in RB-negative cases than in RB-positive cases (chi 2 test p = 0.001). But there is no significant relationship between the incidence of recurrence and the results of bcl-2 staining (chi 2 test p = 0.287). 3) The expression of RB protein was related to age and clinical N and M categories. Bcl-2 protein expression was related to clinical T categories. 4) The 10-year overall survival rate for RB-positive patients was higher than that for negative patients (long-rank test p < 0.0001). But the survival rate was not associated with bcl-2 expression (log-rank test p = 0.3). Our results suggest that assessment of RB protein expression by the immunohistochemical technique may be useful to determine the possibility of recurrence and to predict the outcome of thyroid carcinomas. We think that assessment of RB protein expression by the immunohistochemical technique can be applied as a more sensitive prognostic factor.

Adenocarcinoma, Follicular↗