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Biomedical subjects

M Furukawa

Publications and source records attributed to M Furukawa.

At least 73 records · Page 4Linked to original sources

Maxillary sinus development and sinusitis in patients with cleft lip and palate.

OBJECTIVE: Sinusitis is frequently associated with cleft lip and palate. The present study was performed in an attempt to investigate maxillary sinus development in relation to the occurrence of sinusitis in cleft patients. METHODS: Forty-seven consecutive patients with cleft lip and alveolus with or without cleft palate underwent computed tomographic scans of the maxilla. The cross-sectional area of the maxillary sinus at the level of the zygomatic arch was measured, and the soft tissue density shadow of the sinus was scored on a 4-point scale. RESULTS: The cross-sectional area of the sinus was significantly smaller in the child group (10 years or less) than in the adolescent group (11-20 years, P<0.001) and the adult group (over 20 years, P<0.02). The cross-sectional area significantly increased with age in the child group (r=0.552, P<0.001). The growth rate became slower in the adolescent group. The cross-sectional area then gradually decreased with age in the adult group (r=-0.64, P<0.05). Sinusitis was observed in 15 patients (32%) and in 20 sinuses (21%). Severe sinusitis was more common in the child group than in the patients over 10 years of age (P<0.05). CONCLUSION: These results indicate that maxillary sinusitis associated with cleft lip and palate occurs preferably in the developing sinuses of children.

Adolescent↗

Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach.

The relative risk of development of peptic ulcer with the use of nonsteroidal antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs are administered in combination with steroids. We investigated the ulcerogenic potential of a combination of NSAIDs and steroids in rats and the underlying pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the severity of the lesions markedly increased with concomitant administration of prednisolone. However, nimesulide, even in excessive doses, did not produce any gastric lesions, regardless of concomitant administration with prednisolone. Furthermore, we showed that the ulcerogenic potential of indomethacin administered in combination with prednisolone may be related to the induction of physiological changes, such as endogenous prostaglandin deficiency, an increase in neutrophil activation, and gastric hypermotility, by indomethacin and alteration of normal epithelial renewal by the steroid. These results suggest that the ulcerogenic potential of preferential a COX-1 inhibitor increases following concomitant administration with a steroid, whereas, nimesulide, a preferential COX-2 inhibitor, is nonulcerogenic, even when administered concomitantly with a steroid, and is therefore a clinically useful antiinflammatory agent.

Animals↗

Hepatocyte growth factor induces branching tubulogenesis in MDCK cells by modulating the activin-follistatin system.

BACKGROUND: The activin-follistatin system is expressed in tubular cells of the kidney. The present study was conducted to examine the role of the activin-follistatin system in tubulogenesis using Madin-Darby canine kidney (MDCK) cells as a model system. METHODS: Tubulogenesis was assessed using MDCK cells cultured in collagen gel. The effect of recombinant human activin A on tubulogenesis was examined. Blockade of the action of endogenous activin was achieved by either adding follistatin or transfection of dominant-negative mutant of the type II activin receptor. The production of activin A was examined by Northern blotting, in situ hybridization, and Western blotting. RESULTS: MDCK cells expressed mRNA for the betaA subunit of activin. These cells formed spherical cysts when cultured in collagen gel. Hepatocyte growth factor (HGF) added to the spherical cysts induced branching tubulogenesis. When activin A was added together with HGF, activin A blocked the branching tubulogenesis induced by HGF, and the activin-treated cells were scattered. Conversely, follistatin, an antagonist of activin A, induced branching tubulogenesis qualitatively similar to that induced by HGF. Adenovirus vector-mediated transfer of the gene encoding truncated type II activin receptor, which acts as a dominant negative mutant, also induced branching tubulogenesis. Finally, HGF markedly inhibited the production of activin A in MDCK cells cultured in collagen gel. CONCLUSION: Activin A produced in MDCK cells tonically inhibits branching tubulogenesis, and HGF induced branching tubulogenesis mainly by blocking the production of activin A.

Activins↗

Preoperative UFT administration for patients with advanced colorectal cancer--increased uptake of 5-fluorouracil by tumor tissue is a prognostic factor.

The aim of this study was to clarify whether increased 5-fluorouracil (5-FU) uptake by tumor tissue following preoperative UFT administration is a prognostic factor after surgery in colorectal cancer patients. We examined the concentrations of 5-FU in tumor or normal tissue of 96 colorectal cancer patients who received UFT (400 mg/day) orally for 7 days prior to surgery. Patients were divided into two groups with high or low 5-FU concentrations in tumor tissue (defined as higher or lower than the cut-off value, respectively). The cut-off value of 5-FU was established based on the upper limit of the 95% confidence interval of the median of the concentration found in normal tissue (0.106 microg/g). Of the 96 patients, 62 (64.6%) were in the low-5-FU group and 34 (35.4%) in the high-5-FU group. The latter had a more favorable clinical outcome (p=0.0465). Cox regression analysis revealed that two independent variables, stage and 5-FU status in tumor tissue, were significant for prediction of survival. These findings suggest that increased uptake of 5-FU by tumor tissue following preoperative oral administration of UFT is an independent prognostic factor in colorectal cancer patients. This variable needs to be considered in the design of future therapeutic trials.

Administration, Oral↗

Microvascular angiogenesis and apoptosis in the survival of free fat grafts.

OBJECTIVES/HYPOTHESIS: Autologous fat is an ideal material for augmentation in plastic surgery because of its minimal tissue reaction and easy availability, but its long-term graft survival is somewhat unpredictable. This study was conducted to determine how fat grafts get their vascular supply from the recipient bed and why they keep reducing in volume and weight. STUDY DESIGN: Experimental study using animal models. METHODS: The expression of vascular endothelial growth factor (VEGF) in grafted fat tissue was examined by using immunohistochemical staining, and apoptotic cell death in the grafted fat was studied by using terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate (dUTP)-biotin nick end-labeling method. Twenty-five Wistar rats were used as models of free fat grafts. Fat tissue taken from inguinal fat pads was grafted to the back skin with an 18-gauge needle injection. RESULTS: The weight of the injected fat was significantly reduced on the 180th day compared with the original weight (32% +/- 10%). VEGF+ cells were observed in fibrous connective tissue of the grafts on days 7 and 30 but not after day 90. Apoptotic cells were also observed on days 7 and 30. CONCLUSIONS: Angiogenic factors including VEGF started to revascularize the graft around day 7, and the extent of the vasculature was not reduced after the revascularization. In addition to necrosis in the graft's early stages, apoptosis induced by many factors in the graft's environment is also, at least in part, a cause of long-term volume reduction of the fat graft. Thus clinical application of angiogenic factors such as VEGF to fat grafts and control of apoptosis may contribute to improvements in fat-grafting techniques.

Adipose Tissue↗

The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.

Members of the cullin and RING finger ROC protein families form heterodimeric complexes to constitute a potentially large number of distinct E3 ubiquitin ligases. We report here that the highly conserved C-terminal sequence in CUL1 is dually required, both for nuclear localization and for modification by NEDD8. Disruption of ROC1 binding impaired nuclear accumulation of CUL1 and decreased NEDD8 modification in vivo but had no effect on NEDD8 modification of CUL1 in vitro, suggesting that ROC1 promotes CUL1 nuclear accumulation to facilitate its NEDD8 modification. Disruption of NEDD8 binding had no effect on ROC1 binding, nor did it affect nuclear localization of CUL1, suggesting that nuclear localization and NEDD8 modification of CUL1 are two separable steps, with nuclear import preceding and required for NEDD8 modification. Disrupting NEDD8 modification diminishes the IkappaBalpha ubiquitin ligase activity of CUL1. These results identify a pathway for regulation of CUL1 activity-ROC1 and the CUL1 C-terminal sequence collaboratively mediate nuclear accumulation and NEDD8 modification, facilitating assembly of active CUL1 ubiquitin ligase. This pathway may be commonly utilized for the assembly of other cullin ligases.

Amino Acid Sequence↗

Clinical evaluation of staging system for nasopharyngeal carcinoma: comparison of fourth and fifth editions of UICC TNM classification.

Staging nasopharyngeal carcinoma (NPC) by the UICC 4th-edition TNM classification system (the old system) did not give an accurate prognosis because of the uneven distribution of patients in each stage. This system was revised in 1997 (the new system). To evaluate the performance of the new system, 35 patients with NPC who had been staged by the old system were restaged according to the new system. Restaging of the patients resulted in an overall "downstaging." Differences in the overall survival rates of the early group (stages I, II, III), stage IVA, stage IVB, and stage IVC patients were statistically significant (75%, 48%, 74%, and 0%. respectively; p = .01). T4 was a significant factor of poor outcome (hazard rate, 2.932; 95% CI, 1.667 to 8.545), whereas N3 was not (hazard rate, 0.858; 95% CI, 0.281 to 2.618). The new staging system is more useful than the old system.

Biopsy↗

Spinal projections of cat primary afferent fibers innervating caudal facet joints.

The spinal projections of afferent fibers innervating the facet joints between caudal vertebrae were examined by the use of anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Experiments were performed on 5 adult cats in which spinal dorsal roots below the 2nd sacral segment (S2) on the right side were cut. Injections of WGA-HRP into the caudal facet joints gave rise to extensive cranio-caudal distribution of WGA-HRP positive products along the spinal cord, indicating that many afferent fibers innervating unilateral facet joints terminate bilaterally in laminae I-II, V-VI and X of the thoracic, lumbar, sacral and caudal spinal cord. These afferent fibers may convey a series of sensory information from the caudal facet joints to the spinal cord.

Afferent Pathways↗

Comparison of sperm motility test methods (except computer-assisted sperm analysis) in rats under the condition of alfa-chlorohydrin treatment--collaborative investigation.

A comparison among rat sperm motility test methods including percent of motile sperm (% Motile), scoring method (Scoring), Ishii's method, Progressive Motility Test (PMT) and Sperm Quality Analyzer (SQA), was conducted using data gathered from eleven laboratories. As a unified study design, mature male rats were orally treated daily for approximately 1 week with alpha-chlorohydrin (ACH), which is known to affect the sperm motility at the epididymis, at dose levels of 2.5, 5 and 10 mg/kg, and then subjected to more than two test methods for sperm motility in each laboratory. Scoring (4 or 5 grades), Ishii's method, PMT and SQA showed high sensitivity for the detection of the effects of ACH, which were not considered to be inferior to a computer-assisted sperm analyzer (CASA). Longer incubation time before testing was considered to contribute to detecting the effects of ACH. In particular, we realized that Scoring was a favorable method even if the demerit of poor objectivity was allowed for. Percent Motile showed lower sensitivity than other test methods. The differences in sensitivity between % Motile and other methods were considered to be based on whether the defects of progressive motion could be detected. Although % Motile cannot clearly judge whether immotile sperm are dead or alive, the value is a great help for the interpretation of the result from other methods. Based on the characters for detectability, objectivity and efficiency, the most suitable method of sperm motility should be selected according to the purpose of the toxicity study.

Animals↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 16). Effects of short-term administration of carmofur on spermatogenesis.

Since morphological changes in the testes were observed in a 4 week repeated dose toxicity study of carmofur in rats, male Sprague-Dawley rats were administered the compound orally at 200 mg/kg by gavage for 11 days to assess the possibility of detecting abnormalities in spermatogenesis within a 2 week period. For comparison two studies were performed, treatment groups of fifteen and fourteen rats being given carmofur for 28 and 11 days, respectively. There were seven and nine rats that died or were killed in a moribund condition with 28 and 11 days treatment, respectively. Histopathologically, vacuolar degeneration of Sertoli cells, degeneration of elongated spermatids, exfoliation of round spermatids and multinucleated giant cell formation were observed in the testes of all animals and cell debris in ductus epididymidis was noted in almost all rats in the 28 days study. Exfoliation of round spermatids and multinucleated giant cell formation were detectable in two of five rats in the 11 days study, and vacuolar degeneration of Sertoli cells was also evident in four, though the changes were slight. No abnormalities were observed in the epididymides in the 11 days study. These results suggest that effects of carmofur on spermatogenesis can be detected with a treatment period of less than 2 weeks using histopathological examination of the testes. Therefore a 2-week repeated dose toxicity study has validity for detection of effects of carmofur on the male reproductive organs in the rats.

Administration, Oral↗

[Cervical lymph node metastasis from an unknown primary tumor].

Between June/1986 and June/1999, we treated 18 cases of previously untreated metastatic carcinoma in cervical lymph nodes from an unknown primary tumor. Among them, 15 cases were squamous cell carcinoma, 2 were adenocarcinoma, and one was undifferentiated carcinoma. The dose of radiotherapy, which was planned only for the cervical lymph nodes, was 60-70 Gy at the metastatic sites. Preventive radiotherapy at possible primary sites was performed only in one case. After these treatments, a primary lesion appeared in only two cases: in one case a tumor was found in the hypopharynx, and the other, which had been diagnosed as undifferentiated carcinoma, proved to be malignant lymphoma. Outcomes were analyzed except for these two cases. The five-year survival rate was 31%. The loco-regional control rate was 57% after radiation treatment limited to the affected cervical lymph nodes. Distant metastasis appeared more often in open-biopsy cases than in those receiving fine-needle aspirations (FNA). According to these results, treatment of possible primary sites may not be necessary, and for initial pathological diagnosis, FNA is recommended, while open biopsy should be avoided, if possible.

Adenocarcinoma↗

Elevation of antibody against Epstein-Barr virus genes BRLF1 and BZLF1 in nasopharyngeal carcinoma.

PURPOSE: Epstein-Barr virus immediate early genes BZLF1 and BRLF1 encode the Z and R proteins respectively. Elevation of the anti-Z immunoglobulin (Ig) antibody titer is a common feature of nasopharyngeal carcinoma (NPC) in areas where the disease endemic, whereas R levels have not been examined. This study was performed to analyze antibody titers against Z and R in Japan. METHODS: Sera from 14 patients with newly diagnosed NPC, 7 with NPC in complete remission, 15 with head and neck squamous cell carcinoma (HNSCC), and 31 controls were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Both anti-Z and anti-R Ig were significantly increased in sera from patients with NPC compared with those in remission, those with HNSCC, and controls (Z, P = 0.0016, = 0.0344, = 0.0002; R, P = 0.0015, = 0.0004, <0.0001 respectively). By immunoblot analysis, anti-Z and anti-R Ig were detected in 9 of 9 cases of NPC, 1 of 3 cases NPC in remission, and 2 of 13 cases of HNSCC. Anti-Z and anti-R antibody titers were nine times higher in NPC than in other groups. None of 15 control cases showed positive reactivity against either Z or R. CONCLUSION: Coupled evaluation of anti-Z and anti-R Ig by ELISA might be a useful system for screening NPC.

Carcinoma, Squamous Cell↗

[A case of adenoid cystic carcinoma of the trachea resected surgically after Nd-YAG laser therapy].

A case of primary tracheal tumor ablated by endoscopic Nd-YAG laser prior to tracheal sleeve resection was reported. A 53-year-old man had dry cough, bloody sputum and dyspnea. Bronchoscopic examination revealed polypoid tumor which located 2 cm below the vocal cords and obstructed the airway almost completely. After tumor vaporized by Nd-YAG laser, bronchoscopy type 200 could pass through the tracheal lumen and the length of the lesion was diagnosed within 4 cm. Biopsy specimen was confirmed adenoid cystic carcinoma. Cervical trachea was resected of six tracheal cartilage (first to sixth cartilage) combined with left thyroid lobe under collar incision and median sternotomy. The neck was fixed for ten days by tying the jaw to the anterior chest wall in order to reduce excessive tension to the anastomosis. Pathological examination revealed the tumor residual microscopically, 60 Gy of radiotherapy was conducted.

Carcinoma, Adenoid Cystic↗