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Biomedical subjects

S Kanda

Publications and source records attributed to S Kanda.

At least 19 recordsLinked to original sources

Induction of fibroblast growth factor receptor-1 mRNA and protein by platelet-derived growth factor BB.

Expression levels of growth factor receptors are subject to complex regulation, which is of consequence for their signaling capacity in physiological and pathological processes. We examined the regulation of expression levels of fibroblast growth factor receptor 1 (FGFR-1) in human fibroblasts treated with a panel of growth regulatory factors. Only platelet-derived growth factor BB (PDGF-BB) treatment had a significant effect and induced FGFR-1 mRNA levels fourfold, with a peak around 8 h of stimulation. The increase in mRNA levels was followed by an increased synthesis of FGFR-1 protein, which responded to basic FGF (bFGF) stimulation with induction of kinase activity and biological signaling. Thus, murine brain endothelial cells displayed an augmented induction of plasminogen activator activity in response to bFGF, following treatment with PDGF-BB. These data suggest that PDGF-BB could support FGFR-1-mediated biological responses in processes such as angiogenesis.

Animals

Expression of manganese superoxide dismutase mRNA in reproductive organs during the ovulatory process and the estrous cycle of the rat.

Expression of manganese superoxide dismutase (Mn-SOD) mRNA during the pregnant mare serum gonadotrophin (PMSG)/human chorionic gonadotrophin (HCG)-induced ovulatory process, and during the estrous cycle was examined in rat female reproductive organs. Mn-SOD mRNA levels in theca interna cells markedly increased in PMSG-primed rats and high levels of the transcripts were maintained after HCG injection. The PMSG-enhanced expression of Mn-SOD mRNA in follicular epithelial cells increased concomitantly with luteinization of these cells. The levels of Mn-SOD mRNA remained high and became equivalent in both granulosa and theca lutein cells 24 h after HCG injection. Neither luteinization nor the expression of Mn-SOD mRNA was observed in the epithelial cells of unovulated follicles. Luteal bodies had formed 3 days after HCG injection, and the same level of Mn-SOD mRNA expression continued in lutein cells, but not in stromal cells. During the estrous cycle, Mn-SOD mRNA was localized to theca interna cells on proestrus, to the epithelial cells of luteinizing follicles on estrus, and to newly formed luteal bodies on diestrus. The epithelial cells in the oviduct did not express Mn-SOD mRNA throughout the ovulatory process or the estrous cycle. Expression of Mn-SOD mRNA in the luminal epithelial cells of the uterus increased after PMSG injection, reaching a maximum after 24 h, and became relatively negative 3 days after HCG injection when corpora lutea had formed in the ovary. During the estrous cycle, uterine epithelial cells and leukocytes showed marked increases in Mn-SOD mRNA expression on estrus and on proestrus, respectively. Expression in the vaginal epithelium became apparent 3 days after HCG injection and continued for at least 12 days after HCG injection. The expression was localized to the superficial layer of the epithelium. During the estrous cycle, expression occurs in the basal layer on proestrus and estrus, transferring to the superficial layer on diestrus day 1, and expression stops on diestrus day 2. The relationship between the expression of Mn-SOD mRNA and hormone-induced metabolic changes, including steroidogenesis, is discussed.

Animals

Human simple renal cyst fluid contains a cyst formation-promoting activity for Madin-Darby canine kidney cells cultured in collagen gel.

Simple renal cysts are commonly observed in the elderly, but few examinations have been performed to study the mechanism of this disease. We have previously shown that simple renal cyst fluid contains some growth factors, including epidermal growth factor (EGF; less than 54 pg mL-1) and insulin-like growth factor I (IGF-I; 30-2070 pg mL-1) (M. Taide et al. Clin Chim Acta, 1993; 217:199-203). In this report, the biological significance of growth factors or of human simple renal cyst fluid on the formation of renal epithelial cyst was determined using Madin-Darby canine kidney (MDCK) cells cultured in collagen gel. Both EGF (200 pg mL-1 or more) and IGF-I (100 pg mL-1 or more) were found to stimulate cyst formation in MDCK cells. Additionally, 12/21 human simple renal cyst fluid samples were found to be capable of stimulating cyst formation in MDCK cells. This activity was due to a heat- and acid-labile protein and not inhibited by the anti-IGF-I neutralizing antibody. These results indicate that in some instances simple renal cyst fluid would thus appear to contain specific activity for cyst formation, which may affect cyst formation in vivo.

Animals

Fibroblast growth factor receptor 1-induced differentiation of endothelial cell line established from tsA58 large T transgenic mice.

Angiogenesis of capillary endothelial cells includes at least four sequential cellular responses: digestion of basement membrane, migration, proliferation, and differentiation. To study differentiation of endothelial cells, we established a brain capillary endothelial cell line from H-2Kb-tsA58 transgenic mice. These cells are stable at 33 degrees C and display endothelial cell-specific characters, such as expression of von Willebrand factor and binding sites for the lectin Bandeiraea simplifolia, and uptake of acetylated-low density lipoprotein. We measured the effects of a panel of growth factors on cellular responses. A number of factors, such as hepatocyte growth factor, vascular endothelial growth factor, and platelet-derived growth factor (PDGF)-AA failed to induce biological responses. PDGF-BB, epidermal growth factor, and acidic and basic fibroblast growth factor (FGF) induced proliferation of the cells. Of all the factors tested, only acidic FGF and basic FGF induced differentiation of the cells, visualized as the formation of tube-like structures of cells grown in three-dimensional collagen gels. All factors were also analyzed for their effects on plasminogen activator (PA)-induction and migration of the cells. Transfected cells, expressing a chimeric receptor, composed of the extracellular part from the PDGF alpha-receptor and the intracellular part from FGF receptor-1, responded to PDGF-AA treatment with plasminogen activator induction, migration, proliferation, and tube formation in collagen. These results indicate that FGF receptor-1 coupled to signal transduction pathways, leading to differentiation. This novel cell model offers the potential of detailed dissection of signal transduction pathways involved in the differentiation of endothelial cells.

Animals

Shc and a novel 89-kDa component couple to the Grb2-Sos complex in fibroblast growth factor-2-stimulated cells.

A major pathway for mitogenicity is gated via the small GTP-binding protein Ras. Receptor tyrosine kinases couple to Ras through the Src homology 2 (SH2) domain protein Grb2. The activated fibroblast growth factor receptor-1 (FGFR-1) expressed in L6 myoblasts did not bind Grb2 directly, but indirectly, through the small adaptor protein Shc, which was tyrosine-phosphorylated in response to fibroblast growth factor-2 (FGF-2) stimulation. A FGFR-1 mutant in which Tyr766, a known autophosphorylation site, was changed to Phe, mediated less efficient tyrosine phosphorylation of Shc. FGF-2 stimulation of mutant FGFR-1-expressing cells still allowed formation of complexes containing Shc, Grb2, and the nucleotide exchange factor Sos and mediation of a mitogenic signal. Another pool of Grb2 was found in complex with a tyrosine-phosphorylated 89-kDa component after FGF-2 stimulation. Stimulation with other growth factors did not lead to tyrosine phosphorylation of p89. As shown by "far-Western" analysis, p89 bound directly to the Grb2 SH2 domain, and this interaction was inhibited by a peptide containing the Y(P)-X-N motif. Tyrosine-phosphorylated p89 was found exclusively in the membrane fraction, indicating its role in bringing Grb2, as well as Sos, to the plasma membrane. These data support the concept of growth factor-specific coupling of Grb2 to the Ras pathway.

Adaptor Proteins, Signal Transducing

[Hypertrophy and hyperplasia of renal tubular interstitial cells--regulatory factors].

Renal tubular cells do not proliferate under normal intact conditions, whereas a marked regeneration is evident when tubular cells are injured by renal toxins or by ischemia. In case of compensatory renal growth too, hyperplasia of renal proximal tubular cells is observed. Various growth factors, including epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) seem to be involved in renal regeneration, however, the physiological role of these growth factors for the natural course of the renal regeneration have yet to be established. Hepatocyte growth factor (HGF), a potent mitogen for cultured renal tubular cells, may function as a renotropic factor, which enhances regeneration of the kidney. Once renal tubular cells are damaged by some agents, HGF mRNA, HGF activity and DNA synthesis of renal tubular cells are sequentially increased. Since both HGF mRMA and HGF protein are localized in renal interstitial cells, HGF seems to act on the tubular cells as a paracrine mediator. In addition to these results, HGF has multiple biological functions. This suggests that HGF possesses biological activities essential for renal regeneration.

Animals

Imaging features of maxillary osteoblastoma and its malignant transformation.

We report two cases of osteoblastoma, one of them an unusual case in a 32-year-old woman in whom a maxillary tumor was confidently diagnosed as an osteoblastoma at the time of primary excision and subsequently transformed into an osteosarcoma 7 years after the onset of clinical symptoms. The other patient developed osteosarcoma arising in the maxilla, which was diagnosed 3 years after the primary excision and is very suggestive of malignant transformation in osteoblastoma. We present the radiological features, including computed tomographic and magnetic resonance imaging studies, of this unusual event of transformed tumor and compare imaging features of benign and dedifferentiated counterparts of this rare tumor complex.

Adult

Detection of manganese superoxide dismutase mRNA in the theca interna cells of rat ovary during the ovulatory process by in situ hybridization.

To determine the possible involvement of reactive oxygen species in ovulation, dynamic aspects of superoxide dismutase (SOD) isozyme were studied in the ovaries of rats by in situ hybridization histochemistry. Previously, mRNA levels of ovarian manganese superoxide dismutase (Mn-SOD) were reported markedly to increase whilst enzymic activity of Mn-SOD decreased during the ovulatory process after treating immature rats with 10 and 5 Units, respectively, of pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG). Levels of Cu/Zn-SOD activity and Cu/Zn-SOD mRNA were reported to remain unchanged throughout ovulation. This increase in the Mn-SOD mRNA level was shown in the present study by in situ hybridization to be localized to the theca interna cells throughout the PMSG/HCG-induced ovulatory process. The observations suggest that the turnover rate of Mn-SOD but not Cu/Zn-SOD increases specifically in the mitochondria of these cells. SOD has been postulated to play important roles in steroidogenesis. The relationship is discussed between mitochondrial functions in steroid-secreting cells and superoxide radicals and related metabolite(s).

Animals

Both VH and VL regions contribute to the antigenicity of anti-idiotypic antibody that mimics melanoma associated ganglioside GM3.

Previously we developed a murine monoclonal anti-idiotype (anti-id) antibody (4C10) that mimics the melanoma-associated ganglioside antigen GM3, that is, it carries the internal image of GM3. 4C10 was made against the human monoclonal antibody (HuMAb) L612, which reacts with several types of human cancer cells, including melanoma and breast cancer. To reduce mouse components of 4C10, the constant region was replaced by a human constant domain to form the murine/human chimeric anti-id antibody TVE-1. In the present study, we sought to determine which chain (VH or VL) of the anti-id is responsible for the antigenicity of GM3. The TVE-1 VH and VL expression vectors were simultaneously transfected with either the VH or VL expression vector of a murine-human chimeric IgG antidansyl haptenic antibody, resulting in the construction of three different combinations of VH and VL chimeric antibodies. These IgG molecules were produced from the transfectomas, and their reactivity to HuMAb L612 was tested. Neither of the IgG proteins that had cross-combined the VH-VL pair showed positive results, suggesting that both heavy and light chains are required to express the antigenicity. The in vivo antigenicity of this chimeric anti-id was confirmed by skin tests in melanoma patients receiving active specific immunotherapy.

Animals

Florid cemento-osseous dysplasia. Radiographic study with special emphasis on computed tomography.

This article describes the computed tomographic and conventional radiographic findings for florid cemento-osseous dysplasia. A low-density thin layer or cystlike area was observed around the high-density masses in the tooth-bearing area in the seven cases studied. Expansion of the buccal and lingual cortical plates was observed in association with cystlike areas, but was infrequently observed in florid cemento-osseous dysplasia not having such areas. The computed tomographic number of the high-density masses ranged from 772 to 1587 Hounsfield Units and was equivalent to that of cementum or cortical bone.

Adult

Ultrasonographic evaluation of inflammatory changes in the masseter muscle.

The ultrasonographic images of 32 patients with inflammatory change in the masseteric region were investigated to clarify the characteristic findings and to evaluate the utility of ultrasonography. Inflamed masseter muscles frequently demonstrated reduction of echo intensity and complete or partial absence of hyperechoic bands. The mean thickness of the masseter muscle on the unaffected side was 8.6 mm, whereas that on the affected side was 12.9 mm. Nine of 10 patients with heterogeneous hypoechoic area, but only 1 of 10 patients with homogeneous hypoechoic area, had received surgical treatment before ultrasonographic examination.

Abscess

Radiographic patterns of osteomyelitis in the mandible. Plain film/CT correlation.

Mandibular osteomyelitis often is associated with involvement of the masticator space. Assessment of mandibular osteomyelitis should therefore involve assessment of soft tissue involvement of the lesion. The purpose of this study was to clarify the relationship between computed tomography patterns and the presence of inflammation in soft tissues. Thirty-three cases diagnosed with osteomyelitis of the mandible were analyzed radiologically with conventional radiographs and with computed tomography scans. Computed tomography patterns of osteomyelitis were classified into four types, lytic, mixed, sclerotic, and sequestrum patterns. Location, extent of the lesion, and change of the cortical plate were evaluated and compared with conventional radiographic findings. Mixed pattern cases displayed diffuse bone abnormalities, which sometimes were accompanied by cortical plate disruption and periosteal reaction. In addition, most mixed pattern cases showed soft tissue involvement, especially of the masseter muscle. Inflammation of the masseter muscle was found to be related to periosteal reaction and disruption of the buccal cortical plate. The data demonstrate a close interaction between cortical plate disruption and muscle inflammation. The extent of inflammation including soft tissue involvement was better appreciated with computed tomography in osteomyelitis, especially in mixed pattern cases.

Adolescent

Central squamous cell carcinoma of the mandible. Computed tomographic findings.

Five cases of central squamous cell carcinoma of the mandible were investigated with the use of computed tomography. Bucco-lingual extent and spread along the mandibular division of the trigeminal nerve were evaluated. Three patients with trismus showed involvement of the masseter or medial pterygoid muscle on computed tomography. Involvement of more than two landmarks along the trigeminal nerve were observed in cases with both paresthesia of the lower lip and severe pain that resembled neuralgia. Perineural invasion was confirmed histologically in four cases, and all of these patients had both severe pain and mandibular canal involvement that could be demonstrated with computed tomography. When localized soft tissue changes are evident along the course of the trigeminal nerve in the region between the mandibular foramen and foramen ovale, ascending perineural spread should be suspected. Computed tomography findings correlated well with clinical symptoms but added information about the spread of the lesion within the surrounding soft tissue.

Carcinoma, Squamous Cell

The proliferative activity in dysplasia and carcinoma in situ of the uterine cervix analyzed by proliferating cell nuclear antigen immunostaining and silver-binding argyrophilic nucleolar organizer region staining.

The proliferative activity of dysplasia and carcinoma in situ (CIS) in the uterine cervix was examined using proliferating cell nuclear antigen (PCNA) immunostaining and silver-binding argyrophilic nucleolar organizer region (AgNOR) staining. A significant difference in the labeling index of PCNA immunostaining obtained from dysplastic cells in each histopathologic category was demonstrated between severe dysplasia and CIS. There was no significant difference among each category of dysplasia. The frequency of mitotic figures was highest in CIS, followed in decreasing order by severe, moderate, and mild dysplasia, and was closely correlated with the histopathologic classification. There was an intimate correlation between the PCNA and mitotic indexes in severe dysplasia and CIS. However, the mean numbers of AgNORs in each category of dysplasia and CIS were not significantly different, and there was no apparent relationship with the histologic classification. The PCNA index seemed to be a useful means of evaluating proliferative activity in dysplasia and CIS, and especially in distinguishing CIS from severe dysplasia. In addition, the present PCNA index suggests that a considerable alteration of the biologic behavior involving genetic changes occurs during the progression of carcinogenesis from severe dysplasia to CIS. However, AgNOR staining did not appear to reliably represent the proliferative activity in these lesions.

Antigens, Neoplasm

Studies on the quantitative computed tomography of normal parotid and submandibular salivary glands.

A better understanding of computed tomographic (CT) numbers of normal salivary glands might help make CT diagnosis more accurate. The CT numbers of the parotid and submandibular salivary glands were measured using both non-enhanced and enhanced CT images by setting a circular region of interest (ROI). The normal range of CT numbers, the difference between the CT numbers of right and left glands, and the correlation with age were all investigated. There was a close correlation between the CT numbers of right and left glands. No significant difference was seen between the average of right and left CT numbers in both glands, on either non-enhanced or enhanced CT images. The difference between right and left numbers on enhanced CT were larger than those on non-enhanced CT. A significant difference was seen between the CT numbers of the parotid and submandibular glands. A sex difference was seen on both non-enhanced and enhanced CT images in the parotid gland, while it was only seen on enhanced CT in the submandibular gland. The range as well as the mean of CT numbers in all cases of enhanced CT were larger than those of non-enhanced CT. CT numbers of the parotid glands tended to decrease proportionally with age, up to the age of 40 years; over the age of 40, no relationship could be detected. In the submandibular gland, the difference in the correlation coefficient was not significant between the two age groups. Further investigation into the factors affecting the CT numbers of normal glands is required before they can be used for diagnostic purposes.

Adolescent

Increased attenuation in odontogenic keratocysts with computed tomography: a new finding.

An increased attenuation area (IAA) is sometimes seen in the cystic cavity of odontogenic keratocysts (OKCs) on CT scans. The significance of IAA was compared radiologically and histologically in 26 cysts in which a provisional diagnosis of OKC had been made. First, the presence of IAA in the cystic cavity was assessed. Then, relationship between the presence of IAA and data obtained from the cysts, including the CT and histological findings and the visual appearance of the cyst contents, was evaluated. An IAA was frequently seen in large multilocular cysts. There was no relationship between the presence of IAA and aggressive features of the cyst on CT or the cyst contents. Histologically, subepithelial inflammation was often observed in the cysts with IAA. In order to ascertain whether the IAA was due to the keratin mass, a CT scan of a bundle of hair in a water bath was performed and shown to have a similar density. Our study demonstrated that IAA in cystic cavities results from desquamated keratin. Since this seems to occur in long-standing or inflamed multilocular OKCs, it could be used as a significant finding in the diagnosis of OKC.

Adolescent

Quantitative analysis of masticatory muscles using computed tomography.

Quantitative information on the normal size range of the masticatory muscles needed for successful treatment of facial asymmetry is sparse. Our purpose in this study was to define morphological indicators for the volume of the masticatory muscles on CT. Cross-sectional areas and volumes of the masseter and medial pterygoid muscles were measured from CT scans of 65 patients. The muscles were scanned from origin to insertion and the maximum cross-sectional area (MCSA) and its location together with the total volume were determined. The mandibular foramen was used as a landmark to determine the location of MCSA. The location of MCSA of masseter muscle was centred 8 mm above the mandibular foramen, and that of medial pterygoid muscle at the foramen. The MCSA of both muscles was highly correlated with volume suggesting that this parameter might serve as an indicator of their volume. Knowledge of the location of the MCSA would facilitate its measurement and so reduce radiation exposure. There was a positive correlation between the two muscles for both volume and MCSA. This finding could be relevant for future studies of the relationship between the morphology, biomechanics and pathology of the masticatory muscles.

Adult