Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 19 recordsLinked to original sources

PubMed1992

Abundant expression of immunoreactive endothelin 1 in mammary phyllodes tumor: possible paracrine role of endothelin 1 in the growth of stromal cells in phyllodes tumor.

Immunoreactive endothelin 1 (irET-1) concentrations were measured in extracts prepared from 4 phyllodes tumors and 14 fibroadenomas. irET-1 was detectable in all tissue extracts by specific radioimmunoassay, and the mean concentration of irET-1 was 18-fold and 27-fold higher in tissue extracts from phyllodes tumors than in those from intracanalicular fibroadenomas and pericanalicular fibroadenomas, respectively. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay in the extracts from phyllodes tumors revealed one major irET-1 component corresponding to human standard ET-1. Furthermore, immunocytochemical staining for ET-1 revealed that numerous ET-1-immunoreactive cells were seen in the epithelial cells but not in the stromal cells, suggesting that ET-1 is synthesized by the epithelial component of phyllodes tumors. A possible paracrine role of ET-1 in the growth of this rare tumor which is characterized by its prominent stromal cellularity is discussed.

Adenofibroma↗

PubMed1992

CD45 isoform expression during T cell development in the thymus.

Various isoforms of leukocyte common antigen, or CD45, are expressed differentially on T cells at different stages of development and activation. We report studies on CD45 isoform expression on various subsets of human T cells using two- and three-color flow cytometry and cell depletion. Bone marrow cells that were depleted of CD3+ and HLA-DR+ cells were CD45RA-RO-. The earliest CD3-CD4-CD8-CD19- thymocytes were CD45RO- with 20%-30% CD45RA+ cells. The most prominent population of CD4+CD8+ double-positive thymocytes were CD45RA-RO+. Even the CD4+CD8+ blasts were greater than 90% CD45RO+. About 80% of single-positive thymocytes (CD4+CD8- or CD4-CD8+) were also CD45RO+. Only 4.3% of CD4+ and 18% of CD8+ single-positive thymocytes were CD45RA+. In contrast, cord blood T cells which represent the stage that immediately follows single-positive thymocytes, contained 90% CD45RA+ cells. Thus, in terms of CD45 isoform expression, single-positive thymocytes are more like double-positive cells than cord blood T cells. These results suggest the following sequence of CD45 isoform switching during T cell development: CD45RA-RO- or RA+RO- (double-negative thymocytes)----RA-RO+ (double-positive and most single-positive thymocytes)----RA+RO- (cord blood T cells), the last switch from CD45RO to CD45RA occurring as a final step of maturation in the thymus.

Antigens, CD↗

PubMed1992

CD45RA-R0+ subset is the major population of dividing thymocytes in the human.

CD45, or leukocyte common antigen, is expressed in different isoforms on different subsets of thymocytes, suggesting its involvement in the process of T cell development in the thymus. We report studies on CD45 isoform expression on human thymocytes at various stages of development using three-color flow cytometric analysis and cell cycle analysis. Among CD45R0+ cells 18.4% were in S+G2/M phase and represented more than 80% of the dividing cells in the thymus. Among the CD45R0- cells 10.9% were also in cell cycle. Because the CD45R0+ population is almost exclusively CD45RA-, the CD45RA-R0+ subset constitutes the major portion of dividing cells in the thymus. Both the CD1high and the CD3- populations were actively cycling. However, the former was almost 100% and the latter only 50% CD45RA-R0+. Dividing CD45RA-R0+ cells contain, therefore, many cells that have not yet expressed the CD3/T cell receptor complex and presumably have not yet undergone selective procedures. These results are hard to reconcile with the previously presented hypothesis that CD45R0 represents a marker for cells that are destined to die in the thymus. Instead, these results suggest an alternative possibility that CD45R0+ cells may contain cells that can mature and, thus, also constitute the thymic generative lineage.

Antigens, CD↗

PubMed1992

Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content.

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer.

This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus.

Bone Neoplasms↗

PubMed1992

Reversal of CD45R isoform switching in CD8+ T cells.

Both CD4+ and CD8+ T cells express either CD45RA or CD45R0 isoform of CD45R in an exclusive way. Recent reports have shown that CD45RA+ T cells lose CD45RA and gain CD45R0 upon activation. This switching has been suggested to be irreversible although more recently, examples of reversal of CD45R isotype switching in CD4+ T cells have been reported. We report here that freshly isolated unprimed CD8+ T cells, when activated with PHA, temporarily lose CD45RA but reexpress an intermediate level of CD45RA 2-3 weeks after activation with PHA. This reversal seems to take place much more slowly in unprimed CD4+ T cells: the majority of CD4+ T cells that had lost CD45RA and gained CD45R0 remained CD45RA-CD45R0+ in 3 weeks after the stimulation. Also, long-term CD8+ CD45RA+ T cell lines stimulated with PHA or OKT3 showed even more rapid recovery of CD45RA while PPD-specific CD4+ T cell clones retained the original CD45R0 phenotype 3 weeks after stimulation with PPD or PHA.

Antigens, CD↗

PubMed1992

Are plasma endotoxin levels related to burn size and prognosis?

Plasma endotoxin concentrations were determined in 42 patients with burns covering more than 20 per cent of the body surface area, using the endotoxin-specific Endospecy assay and treatment of plasma by a new method developed by ourselves. The normal endotoxin level was 9.8 pg/ml or less. In the early period after injury when no infection was present, very few patients had an endotoxin level above 9.8 pg/ml and endotoxin levels did not correlate with the area of the burns or with prognosis. However, later in the clinical course, endotoxin levels were correlated significantly with the burned area and with the prognosis.

Adolescent↗

PubMed1992

Hormone control of total plasminogen activator activity is specific to malignant DMBA-induced rat mammary tumours.

Hormonal regulation of plasminogen activator expression in 7,12-dimethylbenz[a]anthracene (DMBA)--induced rat mammary carcinomas was studied both in vivo and in vitro and was compared to that in DMBA-mammary dysplasia induced in neonatally androgenised rats. The plasminogen activator activity in DMBA-mammary carcinomas, but not in DMBA-mammary dysplasia, was regulated by oestrogen. This suggests that expression of this enzyme is hormonally regulated in carcinoma cells. Furthermore, in two of six DMBA-mammary carcinoma groups classified in terms of hormonal treatment, plasminogen activator activity was not under the control of oestrogen. Thus, the present results suggest that at the time of carcinogenesis, the hormonal milieu determines the hormone sensitivities of the malignant cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Specific stimulation by estradiol of tissue-type plasminogen activator production in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor cells.

The hormonal regulation of two plasminogen activators, tissue-type plasminogen activator (t-PA) and urokinase (u-PA), was studied both in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma and in DMBA-induced rat mammary dysplasia. t-PA activity in DMBA-mammary carcinoma was decreased markedly by oophorectomy and recovered upon estradiol administration to reach the maximum level at 12 hr. In contrast to its effect on DMBA-mammary carcinoma, estradiol had no effect on t-PA activity in DMBA-mammary dysplasia. Furthermore, DMBA-mammary carcinoma cells in primary culture displayed similar estrogen-dependency in production of t-PA, while t-PA production in DMBA-mammary dysplasia cells was not under the control of estradiol in vitro. Moreover, estrogen-stimulated production of u-PA activity was not observed in DMBA-mammary carcinoma cells or DMBA-mammary dysplasia cells both in vivo and in vitro. Taken together, these results suggest that estrogen stimulates the production of t-PA but not u-PA and that this estrogen dependency of t-PA is limited to malignant DMBA-mammary tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Immunohistochemical analysis of GH-producing adenomas--with special emphasis on plurihormonality of individual tumor cells by double staining.

Forty-four human growth hormone (GH)-producing adenomas were investigated immunohistochemically for the concomitant localization of GH, prolactin (PRL), and glycoprotein hormone alpha subunit. Immunoreactivity for GH, PRL, and the alpha subunit was found in 44, 37, and 36 cases, respectively. By double immunohistochemical staining, 24 of 27 cases showed colocalization of GH and alpha subunit, with the numbers of tumor cells showing double staining varying from case to case. The colocalization of GH and alpha subunit was noted in some normal pituitary cells. In adenoma cells, the colocalization of GH and PRL, and PRL and alpha subunit, was observed in 9 and 12 cases, respectively. The normal pituitary gland showed only occasional colocalization of GH and PRL, or PRL and alpha subunit. We found that GH-producing adenomas are plurihormonal at the individual tumor cell level, with coexpression of GH-alpha subunit, GH-PRL, and PRL-alpha subunit. The colocalization of GH and alpha subunit may be an expression of a subpopulation of normal anterior pituitary cells (with GH-alpha subunit coexpression), but the more frequent coexpression of GH-PRL may be pathological, accompanying tumorigenesis of the anterior pituitary cells, in which a pituitary-specific transcriptional factor, pit-1, may play a role.

Adenoma↗

PubMed1992

Two types of septic shock classified by the plasma levels of cytokines and endotoxin.

We investigated plasma levels of cytokines and endotoxin in septic shock to clarify the roles of various cytokines in this type of shock. Endotoxemia was observed in 16 of 22 septic shock patients. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) IL-2, and IL-6 were significantly higher in septic shock than in sepsis without shock. Strong correlations were noted between TNF-alpha and IL-2 levels and between IL-1 beta and IL-6 levels. Patients with high TNF-alpha and IL-2 levels also showed endotoxemia. We defined two types of septic shock from these data, i.e., endotoxin+TNF-alpha + IL-2 shock and IL-beta + IL-6 shock. In the former type, high TNF-alpha and IL-2 levels were present before the onset of shock, and shock itself was associated with endotoxemia. The second type showed simultaneous elevation of IL-1 beta and IL-6 levels at the onset of septic shock, and endotoxin was detected in some of them. These results suggest that endotoxin and extremely high levels of TNF-alpha and IL-2, or the simultaneous elevation of IL-1 beta and IL-6, are related to the onset of septic shock.

Adolescent↗

PubMed1992

[Immunohistochemical and clinicoendocrinological studies of gonadotropin producing pituitary adenomas].

In order to study the secretion of gonadotropins in clinically non-functioning pituitary adenomas, 83 cases were investigated by immunohistochemistry. Expression of one or more of gonadotropin subunits (alpha-subunit, follicle-stimulating hormone (FSH) beta, luteinizing hormone (LH) beta) was found in 38 (45.8%) of all adenomas studied. alpha subunit and FSH beta were positive in 28 (33.7%) and 27 (32.5%) cases respectively, whereas LH beta was detected in seven (8.4%) adenomas. The presence of both alpha subunit and FSH beta was found in 17 cases, while alpha subunit was singly positive in 11 cases and FSH beta, in 10 cases. LH beta was not detected alone, but was always accompanied by alpha subunit or FSH beta. By the double staining method, alpha subunit and FSH beta were not always colocalized in the same cells. Some cells were found to contain both alpha subunit and FSH beta, but others contained either alpha subunit or FSH beta. Clinical characteristics of gonadotropin positive adenomas (38 cases) were studied in comparison with null cell adenomas (37 cases), which were negative for all anterior pituitary hormones. The former (male 27, female 11) ranged in age from 21-74 years old (mean, 46.5 yr.), and the latter (male 16, female 21) from 28-68 yr (mean, 49.5 yr.). Gonadotropin positive adenomas tended to occur in middle-aged men. All 38 adenomas were macroadenomas, and 29 patients complained of visual failure. Clinical symptoms accompanied by hypersecretion of FSH was infrequent. Hypogonadism (amenorrhea, galactorrhea, loss of libido) were observed in 8 (9.6%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1992

[Human corneal epithelial, stromal and endothelial cells produce interleukin-6].

We have been investigating the production of cytokines in ocular tissues. In this paper, we demonstrated the in vitro production of interleukin-6 (IL-6) by human corneal epithelial, stromal and endothelial cells using enzyme-linked immunosorbent assay (ELISA). In culture supernatant of the stromal cells, the production of immunoreactive IL-6 was induced, depending upon the doses of lipopolysaccharide (LPS) or IL-1 alpha added into the culture. Detectable IL-6 activity in the supernatant of the stromal cells was found 2 hours after addition of IL-1 alpha and the activity increased to a peak level at 48 hours. On the other hand, in the supernatant of the endothelial cells, IL-6 activity was found even in unstimulated-culture, and induced further by LPS stimulation. The molecular weights (MWs) of the IL-6 produced by the epithelial, stromal and endothelial cells were calculated by gel filtration as about 30 kDa. From Western blotting analysis, the MW of IL-6 produced by the stromal cells was also determined to be 30 kDa.

Aged↗

PubMed1991

Hormonal regulation of plasminogen activator and peroxidase activities in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and the rat uterus.

Oophorectomy was found to decrease the plasminogen activator activity of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) to less than 7 per cent, while in vivo estradiol treatment restored its activity in a dose dependent fashion. The peroxidase activity was not changed either by oophorectomy or by the administration of estrogen. In the rat uterus, plasminogen activator activity was not changed by oophorectomy or by the administration of estrogen, however, its peroxidase activity decreased to less than 2 per cent following oophorectomy, while estrogen administration restored its activity. Estrogen regulated plasminogen activator activity in the DMBA-induced rat mammary tumors but not in the uterus and thus, the specific hormonal regulation of this enzyme may be an important factor for the hormonal dependent growth of such tumors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Immunohistochemical studies of chromogranins (A and C) in pituitary adenomas.

Expression of Chromogranin A and C was examined immunohistochemically on 45 surgically obtained pituitary adenomas. Positive rate of chromogranin A was 40.0% and chromogranin C was positive in 8.0% of 45 pituitary adenomas. Chromogranin A was expressed frequently in adenomas in which at least one of the FSH alpha, FSH beta, LH beta and TSH beta subunits was positive. It also expressed frequently in non-functioning adenomas. The positive rate of chromogranin A was low in GH or PRL positive adenomas. These findings suggest that chromogranin could be a parameter of the functional differentiation of the pituitary adenomas.

Adenoma↗

PubMed1991

Establishment of a new perchloric acid treatment method to allow determination of the total endotoxin content in human plasma by the limulus test and clinical application.

We established a new method of plasma treatment for the removal of interfering factors in the plasma to allow detection of endotoxin by limulus test. The limulus test used was an endotoxin-specific chromogenic test, the Endospecy test. Perchloric acid (PCA) treatment and centrifugation (PCA method) is usually used to remove interfering factors from plasma, with the precipitate being discarded and the supernatant used to detect endotoxin. As the solubilized precipitates of endotoxin-spiked plasma and some patient plasma were found to contain the Endospecy activity, we have devised a new method assaying endotoxin in both the supernatant and precipitate. This study confirmed that the solubilized precipitate of endotoxin-spiked plasma had Endospecy activity and found that the precipitate had other endotoxin activities, such as lethality in galactosamine-sensitized mice and pyrogenicity in rabbits. We also confirmed that interfering factors were completely removed from plasma samples by this new method. The endotoxin level after the new PCA method was found to be about 8 times higher than that determined after PCA treatment and the new PCA method surpasses the conventional PCA method with regard to the positive rate of endotoxin contents in clinical samples. These results indicate that the new PCA method is superior to the PCA method as a plasma pretreatment method for limulus test.

Amidohydrolases↗

PubMed1991

Human ciliary body in organ culture.

Ciliary body explants from 30 human eyes were maintained in organ culture up to 14 days. The age of the donors ranged from 45 to 85 years, the post mortem time from 4 to 22 hours. The ciliary epithelium as well as the underlying stroma were studied light- and electronmicroscopically before incubation and after 1, 3, 5, 7 and 14 days of culture. At the same time intervals, the localization of Na/K-ATPase and carbonic anhydrase (CA) were examined histochemically. If the cells were already damaged before incubation in medium (9 cases), they did not recover in culture. Best results were obtained after 3 to 5 days of culture with a survival rate of more than 90% after 3 days and more than 70% after 5 days, respectively. Both the nonpigmented (NPE) and the pigmented epithelium (PE) of the pars plicata in culture retained the morphological characteristics of epithelia involved in active secretion, namely elaborate infoldings of the cell membranes, numerous mitochondria in the cytoplasm and high activity of Na/K-ATPase and CA. In addition the adjacent capillaries were still fenestrated. After longer incubation times (7-14 days) the NPE and PE cells were filled with increasing amounts of lipid droplets and glycogen granules, indicating changes in metabolism.

Adolescent↗

PubMed1991

Development of liver metastasis in colorectal carcinoma. With special reference to venous invasion and basement membrane laminin.

The development of hepatic metastases in 344 patients with colorectal carcinoma was examined for correlation with the presence of both venous invasion by the primary tumor and basement membranes in the tumor tissue. The former was detected by Victoria blue and hematoxylin-eosin staining and the latter by antilaminin antibody. A significant difference in the incidence of venous invasion was noted between patients with and those without liver metastasis at surgery. Basement membrane deposition was found in half of all cases of well differentiated adenocarcinoma, which was significantly high compared with other tumor types. This was more distinct in metastatic foci in the liver and lymph nodes than in the primary lesion, but less marked in intravascular tumor tissue. Basement membrane deposition was seen more frequently in Dukes' A tumors than in B tumors, although this was not statistically significant. No relationship was found between basement membrane laminin positivity and five-year survival, nor was there any correlation between the incidence of liver metastasis and tumor histologic type. Venous invasion was considered to be intimately related to the development of liver metastasis. Deposition of laminin-positive basement membrane was dependent on the grade of tumor differentiation, whereas it had no direct relation to the development of liver metastasis.

Basement Membrane↗