Kiyohide Fujita

Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model

Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds of colon carcinoma cell lines were incubated with active matrilysin, this enzyme efficiently bound to the cell surface and induced loose cell aggregation, which led to E-cadherin-mediated tight cell aggregation. Synthetic MMP inhibitors inhibited both the membrane binding of matrilysin and matrilysin-induced cell aggregation, while TIMP-2 inhibited only the cell aggregation. Two other active MMPs, stromelysin and gelatinase A, neither bound to cell membrane nor induced cell aggregation. Tumor cells in loose cell aggregates could reaggregate even after they were freed from matrilysin and dispersed. When injected into the spleen of nude mice, the tumor cells in the stable aggregates produced much larger metastatic nodules in the livers than control cells and those in the loose aggregates. These results suggest that matrilysin may enhance metastatic potential of tumor cells by processing a cell surface protein(s) and thereby inducing loose and then tight aggregation of tumor cells.

Experimental Production of Lingual Carcinomas in Hamsters by Local Application of 9, 10-Dimethyl-l, 2-Benzanthracene

Carcinoma of the tongue was readily induced in hamsters by triweekly applications of a carcinogen and concommitant trauma.

Factors influencing secondary alveolar bone grafting in cleft lip and palate patients: prospective analysis using CT image analyzer.

Objective: To examine the effect of migration of the germ of the lateral incisor into the bone for eruption factors on bone bridge resorption. Methods: Twenty-five subjects who underwent secondary alveolar bone graft were enrolled. The volume of the alveolar bone grafts immediately after the operation (V1), bone bridge formation 6 months postoperatively (V2), and tooth (teeth) migration into the bone bridge (Vt) were measured using a computed tomography (CT) image analyzer. Based upon these measurements, the following points were examined: (1) the correlation between the tooth-occupied ratio (Rt = Vt/V2 × 100) and the ratio of bone bridge resorption (Rv = (V1 − V2)/ V1 × 100); and (2) comparison of the tooth-occupied ratio (Rt) and the ratio of bone bridge resorption (Rv) between the groups with and without the germ of the lateral incisor. Results: A significant negative correlation was found between Rv and Rt (p < .001). Comparison of Rv and Rt between the groups with and without a germ of the lateral incisor revealed that both indices were significantly higher in the former group than the latter one (p < .05). Conclusion: In cleft lip and palate patients with a germ of the lateral incisor, it is beneficial to carry out secondary bone grafting to the alveolar cleft at the age of 5 to 7 years, preceding eruption of the canine, in order to form a good bone bridge that will facilitate eruption of the lateral incisor and subsequent normal dentition and occlusion.

A carrier for clinical use of recombinant human BMP-2: dehydrothermally cross-linked composite of fibrillar and denatured atelocollagen sponge

The clinical applicability of a dehydrothermally cross-linked composite of fibrillar and denatured atelocollagen sponge (DCFD-AS), as a carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated in the rat subcutaneous pouch. After four weeks, DCFD-AS with rhBMP-2 formed compact bone, without undergoing significant changes in shape and size, by means of intramembranous ossification. The ultimate size, shape and location of induced new bone was accurately controlled by the carrier. Low antigenicity of soluble atelocollagen, cross-linking without chemicals, the combination of gelatin with fibrillar collagen, and the spongy structure probably all contributed to new bone formation through intramembranous ossification without inducing an inflammatory response. Atelocollagen sponge is easily sterilized, can be stored at room temperature, and can act as a rhBMP-2 carrier without the need for complex procedures.

Endogenously released DOPA is a causal factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rat striata.

Glutamate is implicated in neuronal cell death. Exogenously applied DOPA by itself releases neuronal glutamate and causes neuronal cell death in in vitro striatal systems. Herein, we attempt to clarify whether endogenous DOPA is released by 10 min transient ischemia due to four‐vessel occlusion during rat striatal microdialysis and, further, whether DOPA, when released, functions to cause glutamate release and resultant delayed neuronal cell death. Ischemia increased extracellular DOPA, dopamine, and glutamate, and elicited neuronal cell death 96 h after ischemic insult. Inhibition of striatal l‐aromatic amino acid decarboxylase 10 min before ischemia increased markedly basal DOPA, tripled glutamate release with a tendency of decrease in dopamine release by ischemia, and exaggerated neuronal cell death. Intrastriatal perfusion of 10–30 nm DOPA cyclohexyl ester, a competitive DOPA antagonist, 10 min before ischemia, concentration‐dependently decreased glutamate release without modification of dopamine release by ischemia. At 100 nm, the antagonist elicited a slight ceiling effect on decreases in glutamate release by ischemia and protected neurons from cell death. Glutamate was released concentration‐dependently by intrastriatal perfusion of 0.3–1 mm DOPA and stereoselectively by 0.6 mm DOPA. The antagonist elicited no hypothermia during and after ischemia. Endogenously released DOPA is an upstream causal factor for glutamate release and resultant delayed neuronal cell death by brain ischemia in rat striata. DOPA antagonist has a neuroprotective action.

A newly developed collagen/silicone bilayer membrane as a mucosal substitute: a preliminary report

A new bilayer membrane proved effective as a mucosal substitute. The membrane is composed of an outer layer of silicone and an inner layer of dehydrothermally cross linked composites of fibrillar and denatured collagen sponge. The membrane was placed on oral mucosal defects of five patients after operations for cancer. Ten to 14 days after application the outer silicone sheet was removed, leaving only the inner collagen sponge layer into which cellular tufts of fibroblasts and capillaries had infiltrated. The infiltrated collagen matrix became a new connective tissue that epithelialised rapidly by migration of peripheral epithelium 4-5 weeks after application. In all cases the postoperative course was unremarkable and the repair was effective.

Soft-diet feeding during development enhances later learning abilities in female rats

We investigated whether a decrease in masticatory work affected not only jaw bone growth but also radial eight-arm maze learning, and whether there was a sexual difference in this effect, if any. Male and female rats, weaned at 3 weeks of age, were fed either pelleted or powdered chow until 16 weeks of age and learning experiments were conducted at 10-13 weeks of age. Almost all of the five dimensions of the jaw bones were greater in rats fed pelleted chow than in rats fed powdered chow in both sexes. The number of correct choices in the last five trials was significantly greater in female, but not in male, rats fed powdered chow, and the number of trials to attain at least seven correct choices in the first eight choices in five consecutive trials was greater in female rats fed pelleted chow than in female rats fed powdered chow and in male rats fed either powdered or pelleted chow. These results suggest that 1) a decrease in masticatory work due to soft-diet feeding during development enhances later learning ability preferentially in female rats, and 2) the reported sexual inferiority of female rats in learning and memory functions is due to hard-diet feeding as the standard laboratory condition.

Diurnal variation of cerebral blood flow in rat hippocampus.

We measured local cerebral blood flow over 24 hours in 10 unanesthetized, freely moving rats to determine whether blood flow in the hippocampus fluctuated as a function of time of day. We measured hydrogen clearance at 1-hour intervals using a polyurethane-coated platinum electrode with a 1-mm bare tip implanted in the dorsal hippocampus. Individual rats displayed a wide range of local cerebral blood flow values (from 30 to 100 ml/min/100 g tissue) in a day. In seven of the 10 rats, the overall mean hippocampal blood flow for the dark cycle (7 PM-5 AM) was significantly (p less than 0.001, 0.01, or 0.05) greater than that for the light cycle (6 AM-6 PM), showing an average increase of 20%. Further, the maximum mean hippocampal blood flow at 11 PM in all 10 rats was 42% greater than the minimum at noon. Our study demonstrates for the first time that local cerebral blood flow in the hippocampus shows diurnal variation.

Oral manifestations and differential diagnosis of isolated hypoglossal nerve palsy: report of two cases

Isolated hypoglossal nerve palsy is rare, but occasionally it appears as the initial or solitary sign of an intracranial or extracranial space-occupying lesion, a head and neck injury, or a vascular abnormality of the internal carotid artery. Therefore it should be considered in differential diagnosis. We report two cases of isolated unilateral hypoglossal nerve palsy. In Case 1 the cause of the palsy appeared to be hypoglossal nerve neurilemmoma within the hypoglossal canal, whereas in Case 2 the cause could not be identified. Neither patient complained of any disability other than slight dysarthria. The tongue deviated toward the healthy side at rest and toward the affected side on protrusion. Hemiatrophy of the tongue with fatty displacement was demonstrated by means of T1-weighted magnetic resonance imaging. Dentists who might at times see patients with isolated hypoglossal nerve palsy should be aware of the significance of its oral manifestation, and they should be able to perform differential diagnosis of patients with the condition who appear for treatment.

Experimental Production of Lingual Carcinomas in Hamsters: Tumor Characteristics and Site of Formation

Lingual carcinomas were produced at various sites on the hamster tongue by local application of 9,10-dimethyl-1,2-benzanthracene. The period of carcinogenesis, degree of infiltration, and frequency of metastases were different according to site. The lateral border of the middle third of the tongue was most sensitive to the carcinogen and showed the most severe infiltration and frequent metastases.