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Biomedical subjects

M Sugimura

Publications and source records attributed to M Sugimura.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase-type plasminogen activator and cathepsin B.

HOC-I ovarian cancer cells express the single-chain form of the urokinase-type plasminogen activator (uPA) and cathepsin B (cath B) on their cell surface. The significance of the expression of cell surface uPA/cath B activity to the invasive potential was examined by preincubating with uPA/cath B-modulating agents in in vitro invasion assay. The anti-uPA monoclonal antibody 394 effectively inhibited invasion in a dose-dependent manner. On the contrary, anti-cath B antibody did not affect the invasive potential of the cells. E-64, a specific inhibitor for cysteine proteases, blocked invasion as effectively as monoclonal antibody 394. The data reveal that the uPA and cysteine proteases contribute significantly to the invasive capacity of the cells. We suggest that the cysteine proteases facilitate the action of uPA, possibly by activating proenzyme uPA produced by cancer cells. Evidence for the role of a cathepsin-uPA activation cascade in HOC-I cell invasion is provided.

Cathepsin B↗
PubMed1992

Morphological and northern blot analysis of juxtaglomerular cells in experimental hydronephrotic mice.

The purpose of this study is to demonstrate the developmental changes of the experimental hydronephrotic kidney using immunohistochemical, histoplanimetrical, and Northern blot techniques. At 1 month after ligation of the ureter, a large number of renin-positive cells were detected immunohistochemically even at a dilution of 1:10,000 in this hydronephrotic kidney; however, there were few renin-positive cells in the non-ligated side. At 6 months after ligation, no difference in reactivity for renin between ligated and non-ligated kidneys was demonstrated. In the morphometrical analysis of the renin-positive region, the numerical value of the ligated side was already increased at 2 weeks, reached the highest value at 1 month, and then decreased gradually to almost the same value as the control kidney by the end of the experiment. On the other hand, the value of the non-ligated side decreased immediately after the unilateral ligation, increased later, and finally reached almost the same value as the control kidney. In the Northern blot analysis, the activity of renin mRNA in the ligated side at 1 month after ligation was markedly higher than that in the non-ligated side. However, the difference between the ligated and the non-ligated sides was not demonstrated at 6 months and the value came to be almost the same as in the non-operated kidney.

Animals↗
PubMed1992

Vascularized fibular graft for reconstruction after resection of aggressive benign and malignant bone tumors.

From 1982 to 1991, 19 patients at Nara Medical University, Kashihara, Japan, underwent resection of aggressive benign and malignant bone tumors, with limb salvage and reconstruction by free vascularized fibula grafts. The patients were followed up for an average of 54 months. The reconstructed site was the jaw in 6 cases, upper extremity in 3, spine in 1, pelvis in 2, and lower extremity in 7. Six patients had aggressive benign lesions, and 13 had malignant lesions. The sizes of the resultant bone defect ranged from 6 to 20 cm, and the lengths of fibular used ranged from 8 to 24 cm. The average time to union was 4.1 months (2-9 months) in the extremities and pelvis. Local recurrence was observed in 3 cases, for whom vascularized fibula grafts were performed for recurrent tumors. In cases of primary untreated tumors, no recurrences occurred. Therefore, this procedure should be performed at the time of primary operation after extensive resection of an aggressive benign or malignant bone tumor.

Adolescent↗
PubMed1992

Characterization and clinical evaluation of tumor-associated antigen CA54/61 identified by monoclonal antibodies MA54 and MA61 in epithelial ovarian cancer.

Monoclonal antibodies (moABs) MA54 and MA61, directed toward the O-linked mucin-type glycoprotein, have been established and showed highly specific reactivity with human ovarian cancer. Fetal intestinal and colonic mucosal cells expressed this antigen and meconium staining was also frequently positive. To investigate the characteristic of an epitopic carbohydrate recognized by these moABs, the reactivity of each moAB with meconium extract was monitored by solid-phase enzyme-linked immunosorbent assay with mono-, di-, and oligosaccharides. MA54 and MA61 react with meconium extract and the reactivities of these moABs are neuraminidase sensitive. Ovine submaxillary mucin had a strong inhibitory activity toward the reaction between meconium extract and MA54 as well as MA61, suggesting that these moABs recognize NeuAc 2-6GalNAc epitope in meconium. The second aim of this study is to investigate the possible application of moABs to diagnose ovarian cancer and to compare these levels with those of the CA125 antigen. While serum CA54/61 antigen levels were elevated in 44.4% of ovarian cancer cases and serum CA125 antigen levels were elevated in 86.7% of the same population, the use of both assays indicated a sensitivity of detection of 97.8% (44 of 45 patients) in the population studied.

Antibodies, Monoclonal↗
PubMed1992

Clinical significance of urokinase-type plasminogen activator (uPA) in invasive cervical cancer of the uterus.

The relationship between the level of urokinase-type plasminogen activator (uPA) and pelvic lymph node metastasis was investigated in 20 patients with invasive cervical cancer of the uterus. Frozen sections from all surgical specimens were stained immunohistochemically by alkaline phosphatase anti-alkaline phosphatase method to detect uPA in cancer tissue. The concentration of uPA, determined immunologically, and the fibrinolytic activity were also examined in supernatants of homogenates of some cancer tissues. uPA was detected immunohistochemically in cancer cells of all specimens. A significant correlation was found between the extent of immunohistochemical staining for uPA and the concentration of uPA determined immunologically in cancer tissues (P less than 0.05). A positive correlation was also found between semiquantitative values determined by immunohistochemical staining for uPA and lymph node metastasis (P less than 0.05). Fibrinolytic activity in cancer tissues was confirmed by casein-plaque assay. These findings indicate that the pro-uPA/uPA contents in cervical cancer tissues are clinically useful for predicting the metastatic potential of these cancers to the pelvic lymph nodes.

Carcinoma, Squamous Cell↗
PubMed1992

An immunoelectron-microscopical observation of mouse juxtaglomerular cells in the case of experimental hydronephrosis.

Changes in juxtaglomerular (JG; renin-containing) cells in experimental hydronephrosis 1 month after ureteral ligation were investigated with immunoelectron-microscopical techniques. Two types of granules, electron dense (D) and lucent (L), were observed. D type granules were labeled more intensely with gold particles than those of L type. Granules intermediate between D and L types and exocytosis of D types were observed. In the cells containing D types exclusively, gold particles were restricted to the granules, whereas in the cells containing both D and L type granules, the particles were scattered throughout the cytoplasmic cytosol. The authors discuss the mechanisms of renin release in JG cells.

Animals↗
PubMed1992

YM-14673, a new thyrotropin-releasing hormone analog, augments long-term potentiation in the mossy fiber-CA3 system of guinea pig hippocampal slices.

Effects of a new thyrotropin-releasing hormone (TRH) analog, N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]L-histidyl-L-prolinamide dihydrate (YM-14673), which improves experimentally induced memory dysfunction, on long-term potentiation (LTP) in the mossy fiber-CA3 system, were investigated using guinea pig hippocampal slices. At concentrations of 10(-7) M and 10(-6) M, YM-14673 significantly augmented LTP in a concentration dependent manner. The magnitude of effect of 10(-6) M YM-14673 was similar to that of 10(-6) M TRH. As LTP in the hippocampus is regarded as an elementary process of memory and learning, the augmenting effect of YM-14673 on LTP in the present study may contribute to this drug's ability to remedy memory dysfunction.

Animals↗
PubMed1992

Are there M cells in the cecal tonsil of chickens?

A unique morphological cell type, "microfold or membranous (M) cell-like cell", was detected electron-microscopically in the cecal tonsil epithelium of the chicken. M cell-like cells possessed a few short microvilli of irregular arrangement and a large number of lymphocytes and macrophages wedged into their basal surfaces. Triticum vulgaris was found to bind to M cell-like cells. With horseradish peroxidase (HRP) treatment, M cell-like cells showed an active HRP uptake just as did the neighbouring usual absorptive epithelial cells. No uptake of colloidal carbon particles from the intestinal lumen was recognized in any part of the intestinal epithelium. These results suggest that M cell-like cells of the chicken possess some M cell-characteristic morphological and histochemical features, but that their active uptake of foreign materials is not so developed as in mammalian M cells.

Animals↗
PubMed1992

[Effects of sex hormones and propylthioracil on growth of transplantable rat thyroid tumor with estrogen receptor (ER)].

UNLABELLED: Effects of hormones (E2: estradiol, TP: testosterone) and propylthiouracil (PTU) on the growth of transplantable rat thyroid tumor (F2D1) having estrogen receptors were studied. Rat thyroid neoplasms, induced by N-bis (2-hydroxypropyl) nitrosamine, were inoculated subcutaneously from donor to recipient rats, in order to establish 16 transplantable rat thyroid tumor lines. The grafts were used for histological studies and for the assay of estrogen receptor (ER) and androgen receptor (AR). Of these lines, we designated papillary carcinoma, which was positive for ER (N: 12.5fmol/mg protein, Kd: 0.4nM) but negative for AR, as F2D1. For studies on the effects of sex hormones and PTU on the growth of transplantable tumors, the rats which had been inoculated with tumors were divided into the following 8 groups; (1) Intact, (2) PTU, (3) ovariectomy (OV), and (4) OV + E2 for female, and (5) Intact, (6) PTU, (7) castration (CA), and (8) CA + TP for male. RESULTS: The growth rate of F2D1 in female rats was decreased by OV, but no change was observed in OV + E2 as compared with Intact. CA and CA + TP in male rats did not influence the growth rate. PTU produced a significant increase in the growth rate in both sexes. These results demonstrate that estrogen and PTU act on the growth of ER-positive rat thyroid tumors.

Animals↗
PubMed1992

Comparative study of renin expression in the coagulating glands of C57BL/6 and Balb/c mice.

The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands.

Animals↗
PubMed1992

[A new method for diagnosis of amniotic fluid embolism by means of monoclonal antibody TKH-2 that recognizes mucin-type glycoprotein, a component in meconium].

Five monoclonal antibodies (moABs TKH-2, MA54, MA61, B72.3, and CC49), directed toward the O-linked mucin-type glycoprotein, showed signs of specific reactivity with human meconium. The reactivity of these moABs with meconium extract was examined by solid-phase ELISA with different native and sialidase-treated glycoproteins. All moABs react with meconium extract, whereas the reactivities of TKH-2, MA54, and MA61 are sialidase sensitive and the reactivity of TKH-2 with meconium extract was only inhibited by ovine submaxillary mucin (OSM), indicating that TKH-2 is the most sensitive and specific antibody clearly directed to the sialyl Tn antigen in meconium. The possible application of TKH-2 to diagnose amniotic fluid embolism (AFE) has been prelimiarily investigated. We demonstrated that the concentration of sialyl Tn antigen in the serum of patients with AFE was significantly increased, indicating that meconium was released into the maternal circulation. Our method for detecting sialyl Tn antigen in the serum of AFE patients is a direct way to demonstrate the release of meconium into the maternal circulation, and is a simple, rapid, non-invasive and sensitive method for the diagnosis of AFE.

Amniotic Fluid↗
PubMed1992

[Immunohistochemical study on the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer of the uterus].

We have investigated the expression of epidermal growth factor receptor (EGF-R) in invasive cervical cancer tissue of the uterus to determine whether there is a relationship between the expression of EGF-R and lymph node metastasis. Frozen sections of surgical specimens from twenty patients with invasive cervical cancer were immunohistochemically stained by the alkalinephosphatase anti-alkalinephosphatase method. The monoclonal antibody 528 we employed reacts with the receptor binding epitope within the EGF molecule, indicating that monoclonal antibody 528 is competitive with ligands such as EGF. Immunohistochemical staining was carried out before and after dissociation of ligands from the cellular surface of the tumor by acid treatment. However, the staining was resulted in no difference between before and after acid treatment. Consequently, the expression of EGF-R was detected in all cancer tissues as well in some normal tissue such as basal cell layers of epidermis. The expression of EGF-R was related inversely with lymph node metastasis by Wilcoxon rank sum test (p less than 0.05). These findings suggest that the expression of EGF-R in cervical cancer does not always lead to tumor growth or tumor invasion, although it does in some types of cancer.

ErbB Receptors↗
PubMed1991

Human renin in transgenic mouse kidney is localized to juxtaglomerular cells.

To examine whether expression of human renin in the transgenic mouse kidney is regulated in a cell-specific manner, we have characterized monoclonal antibodies against human renin and determined the renin-production site by immunohistochemistry. By using a monoclonal antibody specific for human renin, A6-11-6, we demonstrated that human renin in the transgenic mouse kidney is localized to the juxtaglomerular cells of afferent arterioles.

Animals↗
PubMed1991

Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding.

The effects of several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.

Animals↗
PubMed1991

S-100-immunoreactive giant macrophages in lymphoid tissues of the guinea pig.

Giant cells containing S-100 protein of the lymphoid tissues in the guinea pig were studied by immunohistochemistry using S-100 antiserum. S-100-immunoreactive giant cells were dendritic in shape, contained one or two irregular-shaped, euchromatic nuclei, phagosomes of various diameter, numerous mitochondria and microfilaments in the perikaryon, and extended cell processes free of cell organelles. These cells predominantly lined the superficial cortex facing the subcapsular sinus, were less numerously scattered in the medulla of lymph nodes and located at the marginal zone of the spleen. They also stained with S-100 alpha monoclonal antiserum and showed active phagocytosis for aldehyde-fixed red cells or colloidal carbon in the popliteal lymph node and spleen. S-100-immunoreactive giant cells also appeared in the corticomedullary zone of the thymus and in the interfollicular area of the Peyer's patches of the gut. Small sinus macrophages, which exhibited active phagocytosis for colloidal carbon but were less active for red cells in the popliteal lymph node and spleen, were not stained with S-100 antiserum. These findings indicate that S-100-immunoreactive giant cells of the lymph node and spleen are a subpopulation of macrophages different from S-100-negative cells of the small type.

Animals↗
PubMed1991

Immunohistochemical detection of estrogen receptors in paraffin sections of human thyroid tissues.

The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells.

Deoxyribonucleases↗
PubMed1991

An immunohistochemical study of the gastro-entero-pancreatic endocrine cells in the alimentary tract of the Korean tree squirrel, Sciurus vulgaris corea.

The regional distribution and relative frequencies of gastrointestinal endocrine cells were studied immunohistochemically in the gastrointestinal mucosa of Korean tree squirrels. Seven kinds of endocrine cells were identified in this study. Although a large number of 5-hydroxytryptamine-immunoreactive cells were seen throughout the gastrointestinal tract, they were most predominant in the duodenum. A moderate number of glucagon-immunoreactive cells which were restricted to the cardia and fundus of the stomach was also observed. Bovine chromogranin-immunoreactive cells were numerous in the cardia and pylorus of the stomach, found in moderate numbers in the fundus, duodenum and large intestine, but rare in the jejunum. Porcine chromogranin-immunoreactive cells were found in moderate numbers in the stomach but were rare in the duodenum. Gastrin/cholecystokinin-immunoreactive cells were abundant in the pyloric gland region but scarce in the duodenum. Bovine pancreatic polypeptide-immunoreactive cells were observed to be rare and found only in the pyloric gland region. Somatostatin-immunoreactive cells were distributed moderately in the stomach but were few in number in the intestine. No insulin-immunoreactive cells were found in the gastrointestinal tract of Korean tree squirrels. These results suggest that although the Korean tree squirrel is a herbivorous rodent, the distribution pattern of its gastro-entero-endocrine cells is rather similar to that reported for omnivorous animals.

Animals↗