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Biomedical subjects

M Sugimura

Publications and source records attributed to M Sugimura.

At least 91 records · Page 5Linked to original sources
PubMed1995

Expression of gamma delta T cell receptor on caprine globule leukocytes.

Histochemical characteristics and immunological surface phenotypes of globule leukocytes (GLs) of normal goats were investigated in the intestine. In the small intestine, GLs were concentrated in the base of the villus and around the crypt, whereas in the cecum and colon they were randomly distributed. Their cytoplasmic granules exclusively stained with phosphotungstic acid hematoxylin, and were negative for peroxidase and histamine in contrast to those of subepithelial mast cells. The existence of chondroitin sulfate in some granules of GLs and heparin in most granules of mast cells were revealed by alcian blue staining and digestion with chondroitinase ABC. Isolated intestinal GLs were positive for T cell receptor (TcR) 1-N24 (gamma delta) and CD8 alpha, and negative for WC1-N3 and WC1-N4. Cryostat sections of ileum revealed preferential intraepithelial distribution of both TcR1-N24+ cells and CD8+ cells. WC1-N3+ and WC1-N4+ cells were rarely seen in the epithelium and lamina propria. These results indicate that caprine GLs are a gamma delta T cell subset, which is a different cell population from WC1 positive gamma delta T cells.

Animals↗
PubMed1995

Epstein-Barr virus in the proliferative diseases of squamous epithelium in the oral cavity.

The presence of Epstein-Barr virus was analyzed in 79 cases of oral epithelial proliferative diseases by polymerase chain reaction, in situ hybridization for Epstein-Barr virus-deoxyribonucleic acid and Epstein-Barr virus-encoded small messenger ribonucleic acid and immunohistochemistry for Epstein-Barr virus latent membrane protein. These lesions were histologically categorized as invasive squamous cell carcinoma (n = 36), carcinoma in situ (n = 10), verrucous carcinoma (n = 4), leukoplakia (n = 19), and papilloma (n = 10). Epstein-Barr virus genomes were detected in 19 squamous cell carcinoma (52.8%), four carcinoma in situ (40%), and one leukoplakia (5.3%); none of the verrucous carcinoma or papilloma cases were positive with polymerase chain reaction. By deoxyribonucleic acid in situ hybridization, positive signals were observed in the nuclei of cancer cells in 10 cases, in infiltrating lymphocytes in three, and both in one case. In patients with carcinoma in situ, only a single case was positive. In one case of leukoplakia positive signals were found in upper and middle layer squamous cells. The results by Epstein-Barr virus-encoded small messenger ribonucleic acid in situ hybridization revealed the same distribution as that by deoxyribonucleic acid in situ hybridization. Latent membrane protein was expressed only in the epithelial cells of leukoplakia but not in cases with squamous cell carcinoma and carcinoma in situ. These findings suggest that Epstein-Barr virus infection of oral squamous epithelium may be carcinogenic; alternatively, the virus may merely exist in epithelial cells of squamous cell carcinoma, carcinoma in situ, and leukoplakia as a passenger.

Adult↗
PubMed1995

An echocardiographic study of interactions between pindolol and epinephrine contained in a local anesthetic solution.

An increasing number of dental patients are taking beta-adrenergic blockers for the treatment of hypertension or angina pectoris. If epinephrine-containing local anesthetics are administered to such patients, interactions between epinephrine and the beta-blocking agent may induce cardiovascular complications. We assessed in volunteers the effects of intraoral injection with 2% lidocaine containing 1:80,000 epinephrine (L-E) on cardiac function after pretreatment with the beta-blocking agent pindolol. M-Mode echocardiography was used for the assessment. The injection of L-E after administration of pindolol did not alter cardiac preload, whereas it reduced the stroke volume, due to an increase in afterload and a decrease in myocardial contractility. Reductions in stroke volume and heart rate led to a decrease in cardiac output. Because total peripheral vascular resistance increased markedly, blood pressure was elevated despite the reduced cardiac output. These results suggest that cardiac function of dental patients on beta-blocker therapy can be adversely affected by epinephrine-containing local anesthetics. Therefore, when such an anesthetic solution has to be used in patients on beta-blocker therapy, careful systemic monitoring is needed.

Adrenergic beta-Antagonists↗
PubMed1994

Effects of urinary trypsin inhibitor on the invasion of reconstituted basement membranes by ovarian cancer cells.

Using the human ovarian cancer cell line HOC-1, we investigated the effects of urinary trypsin inhibitor (UTI) purified from human urine and its related synthetic peptides on the invasive potential of cancer cells in an in vitro assay. Invasiveness of tumor cells was determined using a modified Boyden chamber and a reconstituted basement membrane Matrigel. Three peptides (peptide 1, peptide 2, and peptide 3), representing sequences within UTI, were synthesized. HOC-1 cells showed detectable and reproducible levels of expression of surface urokinase-type plasminogen activator (uPA) and plasminogen/plasmin by cell ELISAs and enzyme assays. UTI was found to strongly inhibit plasmin and human leukocyte elastase (HLE). Peptide 2 and peptide 3 specifically inhibit HLE and plasmin activity respectively. Peptide 1 has essentially no inhibitory activity. Treatment with UTI and peptide 3 reduces the incidence of invasion, whereas peptide 1 and peptide 2 do not affect invasion. The inhibitory effect on cell invasion is dose-dependent. The proteolytic enzyme plasmin may be involved in human ovarian cancer invasion in extracellular matrix degradation, and the use of UTI and peptide 3 that inhibits plasmin specifically reduces invasion by tumor cells.

Amino Acid Sequence↗
PubMed1994

Role of activated protein C in facilitating basement membrane invasion by tumor cells.

The present study was undertaken to investigate the role of plasminogen activator inhibitor type 1 (PAI-1) and activated protein C (APC) in the regulation of tumor cell invasion. PAI-1 was purified in active form from conditioned medium of human umbilical vein endothelial cells under denaturing conditions (4 M guanidine-HCl). The purified inhibitor reacts with urokinase-type plasminogen activator (uPA) and APC. Two selected human lines, HOC-I (ovarian cancer cells) and SMT-ccl (choriocarcinoma cells), preferentially invaded through reconstituted basement membranes in an in vitro invasion assay using a modified Boyden chamber. The present study determined the efficacy of these two agents (PAI-1 and APC) used alone or in combination in inhibiting or facilitating tumor cell invasion. Active PAI-1 inhibited the tumor cell surface receptor-bound uPA activity. In an in vitro invasion assay, active PAI-1 reduced tumor cell invasive potential in a dose-dependent manner. When SMT-ccl cells saturated with uPA-PAI-1 complexes were treated with a 50-fold molar excess of APC, PAI-1-APC complex was demonstrated in conditioned medium, indicating that PAI-1 was dissociated from receptor-bound uPA on tumor cells and that tumor cell-associated uPA restored its enzymatic activity. Although APC alone had no effect on tumor cell invasion, the addition of APC to the cells saturated with uPA-PAI-1 complexes showed regeneration of tumor cell surface receptor-bound uPA activity and produced substantial and efficient invading effects. These data suggest that PAI-1 activity may be neutralized by APC or that APC may promote tumor cell invasion via inactivation of PAI-1 by formation of a stable PAI-1-APC complex. These observations suggest that APC may play a critical role in the initiation of a hematogenous metastatic process (extravasation step).

Basement Membrane↗
PubMed1994

Immunohistochemical studies of renin-containing cells in the developing sheep kidney.

BACKGROUND: Renin-containing (RC) cells in small ruminant kidneys have been known to be widely distributed along the blood vessels. In the present study, RC cells in developing sheep kidneys were studied to investigate not only the appearance but distribution with the potential physiological significance using immunohistochemical and histoplanimetrical techniques. METHODS: Seven fetal, 12 newborn, and 3 adult metanephric kidneys were used and immunostained by anti-renin antiserum. In the histoplanimetrical analysis, the numerical values of RC cells existing at the walls of 3 major arterial types in the kidneys were calculated. RESULTS: At day 44 of gestation, RC cells were already demonstrated in the walls of renal, interlobar, and afferent vessels, located in the deep cortex and the medulla. In intermediate gestational periods, RC cells were detected throughout the intrarenal arterial trees. In late gestational periods, RC cells expressed in the walls of interlobar/arcuate and interlobular arteries tended to decrease or disappear gradually, while they were distributed predominantly in the afferent glomerular vessels. In newborn lambs, especially days 1 to 3 after birth, increased numbers of RC cells were demonstrated throughout the arterial trees in the kidneys. In older lambs, RC cells located in the interlobar/arcuate arteries and the proximal region of the interlobular arteries decreased in number and gradually disappeared. Some RC cells were still distributed in the distal portion of the interlobular artery even in the adult sheep. CONCLUSIONS: These results suggest that the wide distribution of RC cells in sheep kidney is formed in perinatal life, and that the neuronal regulation is associated with the maintenance of this distribution.

Aging↗
PubMed1994

Plasmin modulators, aprotinin and anti-catalytic plasmin antibody, efficiently inhibit destruction of bovine vascular endothelial cells by choriocarcinoma cells.

The interaction of human gestational choriocarcinoma cell line, SMT-cc1, with bovine vascular endothelial cells, CPAE, was examined in an in vitro coculture model. SMT-cc1 cells have urokinase-type plasminogen activator (uPA) on their cell surface, and more than half of the cell-associated uPA is enzymatically inactive single-chain uPA (pro-uPA). uPA is bound to a specific surface receptor that is not completely saturated. Also, the plasmin activity is detected on their cell surface. We measured the ability of added SMT-cc1 cells to cause morphological changes in CPAE cells, leading to destruction of CPAE cells. SMT-cc1 cells that adhered to CPAE cell monolayers were capable of causing CPAE cell destruction, followed by detachment, within 6 hr after coculture. Nonspecific serine proteinase inhibitor, aprotinin, and anti-catalytic antibody against plasmin(ogen) effectively inhibited the destruction/detachment in a dose-dependent manner. SMT-cc1 cell-mediated CPAE cell destruction was suppressed for 6 hr in the presence of aprotinin, at a concentration of 20 micrograms/ml, or anti-plasmin antibody, at a concentration of > or = 10 micrograms/ml, suggesting that the destruction is closely related to the proteolytic enzyme, plasmin. We suggest that the destruction of endothelial cells by some tumor cells is associated with tumor cell-associated proteolytic activity, and the uPA-plasmin cascade plays an important role as a critical step during blood-borne metastasis.

Animals↗
PubMed1994

Urinary trypsin inhibitor (UTI) and fragments derived from UTI by limited proteolysis efficiently inhibit tumor cell invasion.

We investigated the effects of purified human urinary trypsin inhibitor (UTI) and fragments derived from UTI by proteolysis on the invasive potential of ovarian cancer cells (HOC-I) and gestational choriocarcinoma cells (SMT-ccl) using an in vitro reconstituted basement membrane invasion assay. These cells express cell-associated plasmin and functional uPA receptors that are partially occupied by ligands. SMT-ccl cells, which express threefold higher levels of cell-associated plasmin activity than HOC-I cells, showed approximately twofold increase in their invasive potential. For the invasion assay, HOC-I cells were primed with exogenous plasminogen, but SMT-ccl cells were not. Human leukocyte elastase (HLE)-digested UTI (22 kDa fragment; UTI-22) inhibited plasmin practically with the same strength as native UTI. Trypsin-digested UTI (20 kDa fragment; UTI-20), however, did not inhibit plasmin significantly. Treatment of cells with UTI or UTI-22 reduced the incidence of tumor cell invasive capacity, whereas the inhibitory effect of UTI-20 was not remarkable. The inhibitory effect on tumor cell invasion was dose-dependent and non-toxic; moreover, it was not mediated by inhibition of the tumor cell chemotactic response or of cell attachment to matrigel. These results indicate that inhibition of the proteolytic enzyme plasmin specifically reduced the invasive capacity of tumor cells in vitro.

Amino Acid Sequence↗
PubMed1994

Risk factors for the postoperative local recurrence of tongue carcinoma.

Clinical and histologic studies on the risk factors for the postoperative local recurrence of tongue carcinoma were analyzed in 51 patients. Postoperative local recurrence occurred in 12 (23.5%), with almost all developing within the first 12 months after surgery. A comparison of patients with and without recurrence indicated that the risk factors for recurrence were 1) endophytic tumor growth, 2) grade 4 pattern of histologic invasion, and 3) tumor within 5 mm of the surgical margin (especially the deep margin). All T1 tumors were less than 5 mm deep, indicating that it is reasonable for partial glossectomy to be performed in patients with T1 carcinoma. However, for T2 through T4 carcinoma it seems that more extensive surgery should be performed because of the variability in depth of tumor invasion. The 5-year survival rate of the patients with recurrence was 45% and that of patients without recurrence was 73.7% (P < .01). The overall prognosis of tongue carcinoma should improve when surgeons take a more prudent attitude to the treatment of patients with these risk factors.

Adult↗
PubMed1994

Anatomical and histological re-examination of Appendices colli in the goat.

Appendices colli (App. colli) were investigated by anatomical and histological methods in the goat. App. colli were composed of elastic cartilage located at central and the skin covering the cartilage, which included arterioles along the cartilage and nerve bundles. Three types of muscles connected to App. colli; superficial muscle bundles, a branch of the omohyoideus muscle, and a muscle arising from the pharyngeal raphe (appendico-pharyngeal muscle). The latter two muscles were connected to the root of the App. colli where the muscle fibers transformed into the perichondrium of the elastic cartilage. The appendico-pharyngeal muscle was innervated by branches from the glossopharyngeal nerve which were composed of myelinated nerve fibers. The subcutaneous area of the App. colli was supplied by cutaneous rami of the vagus and the second cervical nerves. The innervation and the musculature confirmed that the cartilage of the App. colli were derived from third and fourth branchial arches.

Animals↗
PubMed1994

Perforin-like immunoreactivity in feline globule leukocytes and their distribution.

Distributional and immunohistochemical characteristics of the feline globule leukocyte (GL) were investigated by light microscopy. The GL, which contained eosinophilic large granules in the cytoplasm, was frequently found in the epithelia of the intestine and gall bladder, and less frequently found in those of the gastric pit, intrahepatic bile duct, and interlobular secretory duct of the pancreas. No GL was seen in the respiratory and urogenital organs. The GLs composed a homogeneous cell population including no mast cells according to the following histochemical stainings; phosphotungstic acid hematoxylin, alcian blue and peroxidase. The feline GL showed perforin-like immunoreactivity to anti-human perforin monoclonal antibody, but did not show histamine-immunoreactivity to anti-histamine polyclonal antibody. The results suggest that the feline GL is a lineage of large granular lymphocytes. The epitheliotropism and characteristics as granular lymphocytes of the feline GLs were similar to those of the intestinal gamma delta T cells of the mouse.

Animals↗
PubMed1994

A case report of synchronous triple cancer resected simultaneously.

We report a unique case of a patient with synchronous renal cell carcinoma, hepatocellular carcinoma and squamous cell carcinoma of the oral floor. All three tumors were resected during a single operation. The patient was a 75-year-old man with masses in the liver and right kidney discovered by ultrasound examination during a routine checkup. Further examination also revealed a squamous cell carcinoma of the oral floor. The patient underwent a simultaneous radical nephrectomy, enucleation of the liver tumor and resection of the tumor of the oral floor. The diagnoses were histopathologically confirmed. The number of patients with multiple cancers has recently been increasing. The possibility of a second or third malignant lesion should be considered, not only in patients with a known malignancy but also in those without malignancy. The importance of screening procedures in the early detection of malignancy before the appearance of clinical symptoms should be emphasized.

Aged↗
PubMed1994

Annexin V as a probe of the contribution of anionic phospholipids to the procoagulant activity of tumour cell surfaces.

The ability of anionic phospholipids (especially phosphatidylserine, PS) on the outer membrane leaflet of four tumour cell lines to support different stages of the extrinsic pathway of coagulation was probed using annexin V as an inhibitor. The procoagulant activity of two tumorigenic (MKN-28, human gastric carcinoma, Hep3B, human hepatoblastoma) and two non-tumorigenic (HepG2, human hepatocellular, HOC-1, human ovarian carcinoma) cell lines were observed to be inhibited by annexin V, although significant differences (observed as IC50 with respect to annexin V) were noted for each stage of coagulation and between different cell types. This was considered to suggest a restricted accessibility of PS in the vicinity of coagulation factors on the surface of the cell. PS levels, as estimated by binding of 125I-annexin V, were high on two of the cell lines tested, equivalent to 24 x 10(6) sites per cell for HepG2 (Kd 128 nM) and 6.5 x 10(6) sites per cell for MKN-28 (Kd 50 nM). During 9 days' culturing of HepG2 and MKN-28, the number of sites per cell remained constant. However, perhaps supporting a proposal of reduced availability, there was an observed fall in PS-dependent procoagulant activity of HepG2 and MKN-28 cells, subsequent to a peak on reaching confluency at 3 days. Both prothrombinase activity and total procoagulant activity fell, even though the number of 125I-annexin V binding sites remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Anions↗
PubMed1994

[Antiestrogen therapy of patients with uterine cancer].

It has been widely accepted that the estrogen is one of the contributing factors to the development of endometrial cancer of the uterus. The objective responsiveness of recurrent endometrial cancer to medroxyprogesterone acetate (MPA) has been substantiated. Many researchers have examined whether the anti-estrogenic agents could be the choice of treatment of endometrial cancer including tamoxifen (TAM), aromatase inhibitors, danazol and luteinizing releasing hormone (LHRH)-agonist as an adjunctive endocrine therapy. In this review, we discussed the pharmacological and clinical aspects of these new agents.

Danazol↗
PubMed1993

Effects of membrane-associated cathepsin B on the activation of receptor-bound prourokinase and subsequent invasion of reconstituted basement membranes.

The present study was undertaken to assess the role of membrane-associated cathepsin B as an activator of receptor-bound single-chain urokinase-type plasminogen activator (pro-uPA) and to determine the importance of receptor-bound uPA activity in the destruction of extracellular matrix by tumor cells with subsequent invasion through basement membranes. Ovarian cancer HOC-I cells express pro-uPA/HMW-uPA and cathepsin B on their surface. uPAs are bound to a specific surface receptor, about 30% of which is saturated. 60% of the receptor-bound uPA is pro-uPA. No reduction in the specific binding of biotinylated DFP-HMW-uPA was observed when cells were cultivated in the presence of E-64, a cysteine proteinase inhibitor, for 24 h. Inhibition of cell-surface cathepsin B activity was associated with a decrease in cell-bound uPA activity to undetectable levels, and > 95% of the membrane-associated uPA was pro-uPA in cells cultivated with E-64. This suggested that receptor-bound pro-uPA cannot be converted to HMW-uPA in the absence of enzymatically-active cathepsin B. The significance of the expression of cell-surface uPA activity regarding invasive potential was examined in an in-vitro Matrigel invasion assay. Decreased cell-surface uPA activity was associated with a decrease in invasive potential. These data support our hypothesis that membrane-associated cathepsin B may be important for the conversion of pro-uPA to HMW-uPA and that receptor-bound uPA activity constitutes an efficient mechanism which contributes to tumor cell invasion. As HOC-I cells produce both uPA and cathepsin B, the implications of tumor-cell-derived pro-uPA activation by cellular proteinase cathepsin B should be considered.

Basement Membrane↗
PubMed1993

Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation.

Histological and immunohistological prognostic factors for well-differentiated oral squamous cell carcinoma (SCC) were examined in 31 patients. They included 18 males and 13 females aged 42-84 (median 63) years. The tumors were located in the tongue in 13 cases, gingiva in 7, floor of the mouth in 5, cheek mucosa in 4, and palate in 2. Advanced disease (stages III and IV) was found in 92% of patients; 22 were treated by radical surgery and nine by excisional or incisional biopsy, followed by adjuvant chemotherapy and external radiation. The 5-year survival rate in patients with stages III and IV disease was 58% and 33%, respectively. Histologic factors evaluated were tumor cell mitotic counts, degree of lymphocyte and eosinophil infiltration around the tumor, mast cell counts, HLA-DR expression on tumor cells, or surrounding lymphocytes. Multivariate analysis revealed that degree of eosinophilic infiltration and expression of HLA-DR antigen on the tumor cells were significant factors for prognosis (P < 0.05); i.e., heavy eosinophilic infiltration and expression of HLA-DR antigen on tumor cells were signs of an unfavorable prognosis. The interpretation of the present findings are discussed with a review of the literature.

Adult↗
PubMed1993

Monoclonal antibodies MA54 and MA61 as potential reagents in the prognosis of patients with ovarian cancer.

Monoclonal antibodies (moABs) MA54 and MA61 directed to the O-linked NeuAc alpha 2-6GalNAc epitope were generated by immunization with culture supernatants of lung adenocarcinoma cells. We have examined the correlation between the prognosis of patients (overall survival and progression-free survival) and circulating serum levels of CA54/61 antigen by comparison with CA125 in patients with epithelial ovarian cancer. Circulating serum CA54/61 antigen levels were determined by sandwich enzyme immunoassay kits. Serum antigen levels were elevated in 44.4% of the patients. Survival at 3 years for ovarian cancer patients with CA54/61-negative (serum CA54/61 levels < 15.2 U/ml) versus CA54/61-positive (CA54/61 > or = 15.2 U/ml) tumors was 64% versus 25% (P < 0.05). In contrast, there is no significant difference in the prognosis of patients based upon positive or negative CA125 antigen values (51% vs 67%). The overall survival rate was worse in patients with CA54/61-positive sera, indicating that positive CA54/61 levels in serum is an independent predictor of poor prognosis in ovarian cancer. In addition, CA54/61 status has been shown to be associated with early relapse of this malignancy.

Adult↗