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Biomedical subjects

T Koshikawa

Publications and source records attributed to T Koshikawa.

At least 73 records · Page 4Linked to original sources

Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet-derived growth factor.

Phenotypic change of aortic smooth muscle cells (SMC) is a key step for their abnormal proliferation in atheromatous lesions. In this study modulation of the growth properties of SMC by macrophages was investigated to clarify the mechanism regulating the SMC phenotype. Cultured rabbit SMC preincubated with either macrophages derived from human peripheral monocytes, or conditioned medium from macrophages grew faster than control SMC in the absence of either macrophages or conditioned medium. SMC preincubated with purified platelet-derived growth factor (PDGF) also grew faster than control SMC in the absence of PDGF, and their rapid growth was maintained for at least two passages. SMC preincubated with conditioned medium of macrophages plus anti-PDGF antibody did not grow faster than control SMC. Furthermore SMC preincubated with PDGF acquired the ability to secrete some mitogen, which differed from PDGF. These results suggest that macrophages modulate the phenotype of SMC by a mechanism mediated by PDGF. As a result the SMC grow faster and at the same time secrete some mitogen probably distinct from PDGF in an autocrine manner.

Animals↗

Peripheral T-cell lymphoma of AILD (angioimmunoblastic lymphadenopathy with dysproteinemia) type involving gastrointestinal tract. A morphologic, phenotypic and genotypic study.

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki-67 antibody and antibodies against surface antigens demonstrated that CD3+, CD4+, and/or T-cell receptor (TCR) beta+ cells were predominant (67-68%) among the population of proliferating Ki-67% cells, rather than CD8+ or CD22+ cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T-cell lymphoma.

Antigens, CD↗

Extremely well differentiated papillary adenocarcinoma of the lung with prominent cilia formation.

We describe a 54-year-old woman with primary pulmonary adenocarcinoma showing a characteristic papillary architecture and prominent cilia formation. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and Leu-M1, and negative for lactoferrin and surfactant apoprotein. An ultrastructural study also indicated differentiation toward bronchial surface epithelial cells. To our knowledge, this type of neoplasm has not been reported as peripheral-type adenocarcinoma of the lung.

Adenocarcinoma, Papillary↗

[Determination of ER-D5 (estrogen receptor related antigen) in prostatic cancer and its significance].

The existence of an estrogen receptor and various other sex steroid receptors has been confirmed in prostatic cancer. However, the action mechanism of hormone therapy and relationship between the disappearance of hormone response, which is observed in the recurrence of prostatic cancer, and various sex steroid receptors have yet to be identified. The use of monoclonal antibody ERICA is known as a method of detecting the estrogen receptor in the immuno-histological chemistry method. However, this monoclonal antibody is difficult to use on paraffin sections. Therefore, using monoclonal antibody D5, which allows ER-D5 detection of the estrogen receptor related antigen on paraffin sections, we investigated whether or not estrogen receptors are present in the prostatic cancer preparation and studied the survival rate of prostatic cancer as well as relationship with recurrence. Positive ER-D5 results were obtained in 37 of 93 prostatic cancer cases (39.8%) and in all 20 prostatic hypertrophy cases (100%). ER-D5 tended to be more densely stained in prostatic hypertrophy than in prostatic cancer. The survival rate was obviously higher in the ER-D5 positive prostatic cancer cases than in ER-D5 negative cases for a certain period of time after the start of treatment. Despite differences in the histo-differentiation degree and clinical stage of prostatic cancer, the ER-D5 positive percentage did not change and remained between 35% and 45%. In cases where another prostatic cancer preparation was taken because of recurrence of prostatic cancer, there were no ER-D5 positive cases at the time of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Effects of transforming growth factor-beta 1 on growth of aortic smooth muscle cells. Influences of interaction with growth factors, cell state, cell phenotype, and cell cycle.

Transforming growth factor (TGF)-beta 1 may have different effects on cell proliferation depending on many conditions. This paper clarifies the effects of various conditions on the effect of TGF-beta 1 on proliferation of cultured rabbit aortic smooth muscle cells (SMC) and also the time of its action during the cell cycle. TGF-beta 1 at 10-10,000 pg/ml inhibited DNA synthesis of SMC in the G0 stage derived from normal media or atheromatous intima stimulated by either platelet-derived growth factor (PDGF), fibroblast growth factor, SMC-derived growth factor, or fetal bovine serum (FBS). TGF-beta 1 also inhibited the growth of SMC in the growing state stimulated by either PDGF or FBS. TGF-beta 1 was effective only when added to the culture within 2 h after stimulation of the G0 state SMC with PDGF. It also inhibited increase in transcription of the c-myc protooncogene on stimulation of SMC with PDGF. These data suggest that TGF-beta 1 inhibited proliferation of SMC irrespective of the cell phenotype, growth conditions, and growth factors present and that it exerted this inhibitory effect during the time of the G0/G1 transition.

Animals↗

Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC.

Migration of smooth muscle cells (SMC) in the arterial wall is important in the formation of intimal thickening. In this work, cultured SMC from the rat and rabbit aortic media at 2nd to 12th passages were found to secrete a potent migration factor for SMC which was named SMC-derived migration factor (SDMF). This factor stimulated the migration of SMC dose-dependently and its maximum activity was 2-8 times that of PDGF. Checker board analysis showed that SDMF was chemotactic, but not chemokinetic. In further studies, SDMF was found to be inactivated at 100 degrees C for 10 min or by trypsinization, but not inactivated by mercaptoethanol. This factor was not dialyzable. Molecular weight was approximately 500 kDa by a gel filtration. The activity was not inhibited by an anti-PDGF antibody or a fibronectin antiserum. These data suggest that SDMF is a potent migration factor for SMC and that SDMF is distinct from PDGF, fibronectin or other known migration factors. This autocrine system of secretion of SDMF by SMC and its induction of SMC migration may contribute to intimal thickening of the arterial wall in atherosclerosis.

Animals↗

Comparison of immunochemical specificities of Vibrio parahaemolyticus O10 and O12 antigens using monoclonal antibodies.

The monoclonal antibodies against Vibrio parahaemolyticus O10 and O12 antigens (lipopolysaccharide, LPS) were prepared and specificities of the antibodies were examined. Five of six anti-O10 antibodies reacted with O10 antigen, but none of them reacted with O12 antigen. On the contrary all of the five anti-O12 antibodies reacted with O10 antigen as well as homologous O12 antigen. O10 and O12 antigens were subjected to alkali treatment or periodate oxidation, and reactivities of these chemically modified preparations with the monoclonal antibodies were examined. Reactivities of O10 with anti-O10 and anti-O12 antibodies were reduced by the above two chemical treatments, but that of O12 with anti-O12 was not. O-Deacetylation of O10 LPS by the alkaline treatment was confirmed by NMR spectroscopy. These results suggest contributions to O10-specificity of O-acetyl group and periodate sensitive sugar residue. Inhibition experiments of O10 and O12 homologous precipitations were also carried out with various sugars. From the results we concluded that O10 and O12 antigenic determinants were distinct entities, although O10 and O12 antigens have been reported to be similar and cross-reactive.

Antibodies, Monoclonal↗

Benign mixed mesenchymal tumor of the spermatic cord.

We report a case of benign mixed mesenchymal tumor consisting of spindle cells and an area involving osseous elements. Immunohistochemical investigation revealed the spindle tumor cells to express vimentin and the alpha-subunit of S100 protein, but no staining for other specific antigens. The findings thus suggest that the spindle tumor cells are undifferentiated in nature and derived from mesenchyma, the osseous component being interpreted as evidence of a specific differentiation.

Antigens, Neoplasm↗

Serum concentration and immunohistochemical localization of SPan-1 antigen in pancreatic cancer. A comparison with CA19-9 antigen.

We studied SPan-1 antigen in 64 patients with pancreatic cancer by measuring serum concentrations with RIABEAD and examining the intratumor staining patterns immunohistochemically. Serum concentrations were elevated (greater than 30 U/ml) in 46 patients (72.0%), roughly the same percentage as with elevated serum CA19-9 concentrations. Ten out of 19 patients without CA19-9 antigen expressed SPan-1, and the combined rate of positivity was 86% (55/64). Immunohistochemically, CA19-9 was localized to the apical surface and the supranuclear cytoplasm of normal epithelial cells, but SPan-1 was localized to the supranuclear cytoplasm or throughout the cytoplasm. After malignant degeneration, both antigens were found over the entire plasma membrane, throughout the cytoplasm (loss of polar distribution) and in the stroma surrounding the cells. SPan-1 was detected in 48 out of 54 adeno-carcinomas of the pancreas (89%), and all cases with an elevated serum concentration displayed stromal staining in the cancer tissues. The utility of SPan-1 antigen as a tumor marker for diagnosing pancreatic cancer was found to be equal to that of CA19-9.

Adenocarcinoma↗

[Study of growth fraction on fine needle aspirated prostatic tissue smear using monoclonal antibody Ki-67].

Immunohistochemical staining using monoclonal antibody Ki-67 was performed in 30 patients with benign prostatic hypertrophy (BPH), one with prostatic tuberculosis (TB), 22 with prostatic adenocarcinoma, one with prostatic transitional cell carcinoma and one with prostatic invasion from a bladder cancer. Specimens were aspirated from the prostate transrectally and a cytological smear were made. This antibody is specific for a proliferation-associated nuclear antigen. Alkaline phosphatase anti-alkaline phosphatase stained immunopositive nuclei red making positive or negative specimens easy to recognize. In BPH and TB smears, no immunopositive cell was reactive with Ki-67. In prostatic malignancy were found many immunopositive cells ranging from 2.5 to 10.2% (mean 5.9%) in prostatic adenocarcinoma (n = 22), and from 11.9 to 24.3% (mean 18.1%) in prostatic transitional cell carcinoma. Transitional cell carcinoma may have a much greater growth fraction than adenocarcinoma in prostatic tissue. Poorly differentiated adenocarcinoma showed a higher growth fraction (from 4.2 to 10.2%, mean 6.9%) than well differentiated (from 3.1 to 8.9%, mean 5.8%) and moderately differentiated adenocarcinoma (from 2.5 to 10.1%, mean 5.6%), but this difference was not significant. There was no correlation with age, clinical stage, bone metastasis or Böcking's cytological grade. In conclusion, immunohistochemical staining using Ki-67 on aspirated prostatic smear is visualizes the growth fraction of prostatic disease well and is useful to diagnose prostate cancer.

Adenocarcinoma↗

Bifunctional effects of transforming growth factor-beta on migration of cultured rat aortic smooth muscle cells.

Migration of smooth muscle cells (SMC) in the arterial wall is important in the pathogenesis of atherosclerosis and is presumably regulated in both normal and atherosclerotic tissues. In this study, the effect of transforming growth factor-beta (TGF-beta) on the migration of rat aortic SMC was examined. TGF-beta alone enhanced the migration of SMC at concentrations of 10 to 50 pg/ml and its maximal effect was similar to that of platelet-derived growth factor (PDGF). Checker board analysis showed that TGF-beta had a chemotactic, but not a chemokinetic effect. PDGF also enhanced the migration in a dose-dependent manner and TGF-beta inhibited the PDGF-induced migration dose-dependently at 1.0 pg/ml to 1.0 ng/ml. These data suggest that TGF-beta is a bifunctional regulator of the migration of aortic SMC.

Animals↗

Enolase isozymes in seminoma.

We determined concentrations of alpha and gamma-enolases in normal testis and in seminoma tissues by enzyme immunoassay. Concentrations of alpha-enolase were 4,170 +/- 2,040 ng/mg protein in normal testis (n = 8) and 8,140 +/- 4,480 ng/mg protein in seminoma (n = 8). Concentrations of gamma-enolase in seminoma (460 +/- 571 ng/mg protein) were significantly higher than those of normal testis (59 +/- 15 ng/mg protein). Immunohistochemistry showed positive tumor cells for gamma-enolase in 6 of 8 seminoma cases (75%). Serum gamma-enolase levels were elevated (greater than 6.0 ng/ml) in 9 of 12 patients (75%) with seminoma: 60% of stage I, and 100% of stages II and III. In 10 patients treated by surgical excision and chemotherapy, serum gamma-enolase was significantly reduced after the treatment. These findings indicate that elevated serum gamma-enolase is derived from enhanced gamma-enolase in seminoma tissues, and that serum gamma-enolase could be a useful biomarker for staging and monitoring clinical course in patients with seminoma.

Adult↗

Primary transitional cell carcinoma of prostate: case with lymph node metastasis eradicated by neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy.

A case of transitional cell carcinoma of the periurethral prostatic ducts received neoadjuvant chemotherapy consisting of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), which eradicated pelvic lymph node metastasis, followed by cystoprostatectomy. M-VAC therapy may be indicated for metastatic transitional cell carcinoma of the periurethral prostatic ducts.

Antineoplastic Combined Chemotherapy Protocols↗

Growth fractions of transitional cell carcinomas of the bladder defined by the monoclonal antibody Ki-67.

We used an immunohistochemical technique with the monoclonal antibody Ki-67, which recognizes nuclear antigen expressed in proliferating cells to determine the growth fractions of 5 normal mucosa specimens and 55 transitional cell carcinomas of the bladder. Normal mucosa had a mean value of 0.37 +/- 0.35% cells positive for Ki-67, whereas 9 histological grade 1 tumors showed 2.2 +/- 1.5%, 31 grade 2 tumors averaged 10.1 +/- 7.5% and 15 grade 3 tumors yielded 19.5 +/- 9.0%. These values were significantly different from each other (p less than 0.01), with Ki-67 indexes for grade 2 varying from 0.3 to 24.6%. Nonpapillary tumors had significantly higher indexes than papillary tumors (20.1 +/- 8.0 versus 6.7 +/- 5.9, p less than 0.01). The Ki-67 indexes were 4.6 +/- 4.5% for stage Ta (20 cases), 7.8 +/- 4.7% for stage T1 (14) and 20.2 +/- 7.8% for stages equal to or higher than T2 (21). Significant differences were noted between stages Ta and T1 (p less than 0.05) and between stages T1 and T2 or greater (p less than 0.01). Tumors with muscle layer invasion often showed more than 15% Ki-67 positive cells. Our results imply that Ki-67 indexes not only provide objective information to determine a malignant potential but also help to select the treatment.

Antibodies, Monoclonal↗

Expression of aldolase C isozyme in renal cell carcinoma.

The authors localized aldolase C in renal tubules and renal cell carcinoma by immunohistochemical study and quantitative analysis by an enzyme immunoassay. Aldolase C was localized in epithelial cells of loops of Henle and collecting ducts and in those of Bowman's capsules. In renal cell carcinoma, aldolase C was immunohistochemically demonstrated in 95% (41 of 43) of cases, including one sarcomatoid variant. The tissue concentrations of aldolase C in the renal cortex (n = 8) were 12.7 +/- 6.2 micrograms/g protein (mean +/- standard deviation), and those of the medulla (n = 8) were 20.3 +/- 6.9 micrograms/g protein. On the other hand, the concentrations in renal cell carcinoma (n = 26) were 93.5 +/- 95.9 micrograms/g protein: about seven times higher than that in renal cortex (P less than 0.001). These findings indicate that aldolase C was first expressed in renal cell carcinoma, which is derived from proximal renal tubules, because proximal renal tubules had aldolase B but not aldolase C.

Carcinoma, Renal Cell↗

[Clinical study of urinary cytology in bladder tumors--analysis of factors related with positivity of urinary cytology].

To clarify the clinical and pathological determinants affecting the sensitivity of urinary cytology, we reviewed cytological findings from 119 patients with bladder cancer who were initially treated between January 1982 and March 1988. Cytological specimens obtained from voided urine were stained by the Giemsa and Papanicolaou techniques, and were classified into three categories of malignant cells: positive, suspicious, and negative. Of 311 specimens examined, 114 (37%) were positive, 81 (26%) were suspicious, and the remaining 116 (37%) were negative. The overall positive rate, or sensitivity, was 50% (60 out of 119 patients). The sensitivities were 7% for patients with grade 1 tumors, 42% for grade 2 tumors, and 97% for grade 3 tumors. Univariate analysis by logistic regression analysis revealed that grade, stage, histological pattern of growth, size and number of tumors, and patient age were significantly related with the positivity of voided urinary cytology. The logistic regression model, as a multivariate analysis, demonstrated that grade was the most important determinant affecting the positive cytologic finding, followed by number of tumors with statistical significance. We conclude that the lower sensitivity in conventional urinary cytology for low-grade tumors necessitates new adjuncts, including immunocytochemistry and flow cytometry, to lower the false-negative rate.

Adult↗