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Biomedical subjects

H Enomoto

Publications and source records attributed to H Enomoto.

At least 91 records · Page 5Linked to original sources

[Postoperative swallowing function in tongue and oral floor cancer patients reconstructed with a recto-abdominal myocutaneous free flap after glossectomy--quantitative assessment of reconstructed tissue movement].

We examined the postoperative swallowing function of 12 tongue and oral floor cancer patients reconstructed with a recto-abdominal myocutaneous free flap after glossectomy. On the basis of the resection site, the present cases were classified into either anterior type or lateral type. Subjective evaluation of postoperative swallowing function was obtained from self-reports from patients. The movement of the reconstructed tissue was evaluated videofluorographically during swallowing, by tracking the movement of two small pellets temporarily attached to the anterior and central portions of the reconstructed tongue. The trajectory of the two pellets and the selected point of the hyoid bone were recorded together with the distance between the plate and the tongue dorsum, and between the posterior pharyngeal wall and the tongue base. Using a personal computer, a quantitative study of the video images was performed. The results were summarized as follows. 1) The movement pattern of the reconstructed tissue was generally saccadic rather than smooth. It was suggested that the swallowing pattern of the patients was different to that of normal controls. 2) Postoperative swallowing function was poorer in cases of the anterior type when compared to the lateral type. 3) In general, cases which showed relatively wide movement range appeared to achieve subjectively satisfactory swallowing function.

Adult↗

[Case reports of mucosal melanoma of the head and neck].

Twelve patients with mucosal melanoma in the head and neck were treated at Yokohama city University from 1975 to 1994. The sex distribution was 5 male and 7 female, and the age ranged from 40 to 79 years-old. The highest number of patients were in their sixties. In 10 cases tumors arose in the nasal cavity, in one case in the maxillary sinus and in other case in the oral cavity. The treatment modality for this tumor consisted of various combination therapies including surgery, radiotherapy, chemotherapy and immunotherapy. Combination chemotherapy consisting of dimethyltriazeno imidazole carboxamide (DTIC, Dacarbazine), amino methyl pyrimidinyl methyl chlorethyl nitrorosourea hydrochloride (ACNU) and vincristine (VCR). Cisplatin (CDDP) was recently used for cases where other chemotherapy was not effective. Surgical treatment in the initial therapy was performed in 8 patients. In three of these 8 cases, the surgical margin was positive. One of them was dead after 9 months, another dead with complication after 1 year and the other survived free of any tumor. Immunotherapy using OK-432, interleukin-2, LAK therapy and low dose CPM was effective for some patients. The 5-year survival rate was 44%. Patients with surgical treatments in the initial therapy had longer survival than those without surgical treatments.

Adult↗

[Articulatory function in patients receiving glossectomy followed by reconstruction with a recto-abdominal myocutaneous free flap].

Postoperative articulatory functions of patients with tongue cancer have been improved by reconstructive surgery with a radial forearm or recto-abdominal myocutaneous free flap. We examined the postoperative articulatory functions of 10 patients who received reconstruction with a recto-abdominal myocutaneous free flap after glossectomy. The functions were investigated by standardized tests, i. e. a quentionnaires, the 100 Japanese monosyllable speech intelligibility test and a single-word intelligibility test. A confusion matrix was obtained from the results of the monosyllable test. On the basis of resection sites, the present cases were divided into two types: an anterior type and a lateral type. The results are summarized as follows. There was no significant difference in the results of the quentionnareis between the two types. The mean score of the 100 Japanese monosyllable speech intelligibility test in cases of the anterior type was 48% and in those of the lateral type it was 62%. The mean score of the single-word intellibibility test in cases of the anterior type was 75% and in those of the lateral type it was 83%. In cases of the anterior type, dental and alveolar sounds were often confused with fricatives, whereas in the lateral type, velars sounds were often confused with affricates or flaps. These results suggest that our classification based on resection site was useful for investigating postoperative articulatory functions after partial glossectomy.

Adult↗

[Immunoblastic lymphadenopathy-like T cell lymphoma associated with erythroid hypoplasia and thrombocytopenia].

A 71-year-old female patient was admitted with generalized lymphadenopathy, anemia and thrombocytopenia. On admission a peripheral blood examination showed a red blood cell (RBC) count of 1.95 x 10(6)/microliter, hemoglobin (Hb) 5.0 g/dl, platelet count (Plt) 2.2 x 10(4)/microliter and no reticulocytes. A bone marrow aspiration specimen was hypocellular with a nuclear cell count 1.0 x 10(4)/microliter, erythroblasts less than 0.3% and no megakaryocytes. Serum examination showed polyclonal hypergammaglobulinemia and the results of the direct/indirect Coombs test indicated the existence of auto-antibodies. as immunoblastic lymphadenopathy-like T cell lymphoma was diagnosed based on the lymph node biopsy specimen. Cyclophosphamide, doxorubicin and etoposide obtained improvement of lymphadenopathy, hypergamma globulinemia, hypoplastic bone marrow and thrombocytopenia. On the other hand, the anemia did not improve and the ratio of erythroblasts in total bone marrow cells was remainde 0.5%. The detailed mechanism of this hypoplastic anemia is still unknown, however, our results imply some

Aged↗

A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3.

Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome 1p polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by D1Z2 and proximally by D1S228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of 1p36, and from a neuroblastoma cell line with a small 1p36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of 1p36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes--DAN, ID3 (heir-1), CDC2L1 (p58), and TNFR2--were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within 1p36.2-36.3, eliminating 33 centimorgans of proximal 1p36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with 1p36 LOH.

Base Sequence↗

Overexpression of DAN gene product in normal rat fibroblasts causes a retardation of the entry into the S phase.

Differential screening-selected gene aberrative in neuroblastoma (DAN) gene (previously named N03 gene), whose expression is significantly reduced in transformed cells, has recently been demonstrated to have a tumor-suppressive activity in vitro. In order to investigate biological roles of DAN gene product in normal rat fibroblasts (3Y1), marker-selected transfectants that expressed the high amount of DAN gene product were generated from 3Y1 cell lines. These clones did not exhibit morphological changes compared with parental 3Y1 cells; however, they showed a decrease in growth rate and a remarkable reduction in saturation density. Cell cycle analysis revealed that the overexpression of DAN gene product causes the retardation of the entry into the S phase. These results suggest that DAN gene product may have an important role in regulation of the entry of cells into the S phase.

Animals↗

Expression of parathyroid hormone-related peptide in human thyroid tumours.

The purpose of this study was to evaluate the distribution of parathyroid hormone-related peptide (PTHrP) in human thyroid tissues. The presence of PTHrP was studied immunohistochemically in 107 consecutive patients with human thyroid tumours. PTHrP expression was revealed in 97.6 per cent of carcinomas, but not in paranodal normal thyroid epithelial cells. Although there were no differences in the incidence of PTHrP positivity among papillary, follicular, and anaplastic carcinoma cases, PTHrP expression levels were correlated with the growth pattern of thyroid cancer. Strong immunopositivity was detected in 67.3 per cent of papillary growth tissues in papillary carcinomas. A tissue growth pattern consisting of colloid-absent follicles had a high incidence of strong immunopositivity irrespective of the histological type of tumour. Anaplastic carcinoma without colloid production also showed strong immunoreactivity in all cases. In contrast, a growth pattern of colloid-rich follicles did not show strong immunopositivity in either papillary or follicular carcinomas. Follicular adenomas showed positive immunostaining in only one case, and no adenomatous goitres showed PTHrP antigens. In situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) revealed strong PTHrP mRNA in thyroid cancer tissues, but not in normal thyroid tissues. PTHrP expression was not associated with metastasis, calcification, or hypercalcaemia in thyroid cancers. These results suggest that the expression of PTHrP in human thyroids is closely related to the malignant alteration of normal thyroid epithelial cells, especially in the growth pattern of thyroid carcinoma tissues.

Base Sequence↗

Expression of parathyroid hormone-related protein in rat articular cartilage.

Expression and localization of parathyroid hormone-related protein (PTHrP) in rat articular cartilage during fetal and postnatal periods were investigated by immunohistochemistry and in situ hybridization. PHTrP displayed distinct distribution and intensity of staining at different ages. In fetal (18-day-old) and young (3-week-old) rats, articular chondrocytes expressed abundant PTHrP throughout the entire thickness of cartilage. In contrast, in 60-week-old rats, PTHrP was expressed in a few articular chondrocytes of superficial and middle layers. Regulation of PTHrP and PTH/PTHrP receptor mRNA was also studied in cultured rat articular chondrocytes. Northern blot analysis revealed that both transforming growth factor-beta (TGF-beta), an important stimulator for chondrocyte proliferation and differentiation, and 10% fetal bovine serum (FBS) stimulated the expression of PTHrP mRNA with down-regulation of its receptor mRNA. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) down-regulated the expression of receptor without changes of PTHrP mRNA level. These results suggest that the changes in abundance and localization of PTHrP and its receptor may be directly involved in the cell growth and differentiation of articular cartilage.

Animals↗

Comparison of granisetron alone and granisetron plus hydroxyzine hydrochloride for prophylactic treatment of emesis induced by cisplatin chemotherapy.

The efficacy and safety of granisetron alone (group G) and granisetron plus hydroxyzine hydrochloride (group G/H) as prophylactic therapy for acute and delayed nausea and vomiting were evaluated in an open trial in head and neck cancer patients undergoing chemotherapy with cisplatin. The severity of nausea was significantly reduced on days 1 and 4 in patients receiving combination therapy, but the frequency of vomiting was not significantly different between the two groups. The only side-effect observed was headache in 1 patient from group G, and no drug-related laboratory test abnormalities were observed. These results suggest that the anti-emetic efficacy of granisetron can be augmented by hydroxyzine hydrochloride.

Acute Disease↗

[A randomized crossover comparison of azasetron and granisetron in the prophylaxis of emesis induced by chemotherapy including cisplatin].

The clinical application of 5-HT3 receptor antagonists has enabled continuation of the course of chemotherapy including cisplatin, which induces strong nausea and vomiting, and to prevent the delay of curative treatment for cancer patients receiving neoadjuvant chemotherapy. However, with the development of basic research on the mechanisms of vomiting, each 5-HT3 receptor antagonist has appeared to have different pharmacological actions and, subsequently, the difference in the clinical efficacy of each drug has been reported in Europe and USA. In freshly advanced head and neck carcinoma cases, a randomised crossover study was performed to compare the efficacy and safety profile of a single intravenous dose for 7 days of azasetron (10 mg/day) or granisetron (3 mg/day) in the prophylaxis of nausea and vomiting induced by multi-drug chemotherapy including cisplatin (50 mg/m2 or 60 mg/m2). Anti-emetic effects were evaluated by the protective rates for nausea and vomiting for 7 days following the start of cisplatin administration. Both 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute and delayed emesis induced by chemotherapy, whereas the efficacies of azasetron on day 3 and 4 were superior to those of granisetron. No adverse effect of either drug was observed in this study.

Aged↗

[Comparison of granisetron alone and granisetron plus dexamethasone or hydroxyzine hydrochloride for the prevention of nausea and vomiting during chemotherapy including cisplatin].

The comparative study among granisetron alone and granisetron combined with hydroxyzine hydrochloride or dexamethasone was undertaken for the prevention of nausea and vomiting during chemotherapy including cisplatin in patients with advanced head and neck carcinomas. The results indicated that the combination antiemetic therapies were more effective than granisetron alone for acute nausea and vomiting, whereas a significant difference was not observed among these three groups in the acute adverse effects. Otherwhile, there were statistically significant improvements in the prevention of delayed nausea and vomiting for patients receiving granisetron combined with the other antiemetic drugs, especially the combination antiemetic therapy with dexamethasone. These results confirm the antiemetic activity of granisetron in acute nausea and vomiting induced by cisplatin and show that it has an additive effect in combination with dexamethasone.

Adult↗

Coronary atherosclerotic smooth muscle cells overexpress human parathyroid hormone-related peptides.

Parathyroid hormone-related peptide (PTHrP) was originally characterized as a tumor product responsible for hypercalcemia of malignancy and was subsequently found to be produced in many normal tissues. PTHrP is now suggested to play a critical role in the local modulation of vascular smooth muscle function. To elucidate the involvement of PTHrP in coronary atherosclerosis, we immunohistochemically examined coronary arteries obtained from 76 patients with various grades of atherosclerosis and compared the correlation between PTHrP staining and the percent stenosis. Smooth muscle cells at sites of coronary atherosclerosis overexpressed PTHrP, while cells from normal coronary arteries did not. The in situ hybridization using PTHrP riboprobe has also proven the overexpression of PTHrPmRNA in the affected lesions following atherectomy. The intensity of PTHrP expression by smooth muscle cells was significantly correlated with the degree of coronary artery stenosis. Coronary arterial PTHrP overexpression is closely related to the severity and/or progression of coronary atherosclerosis.

Adult↗

Effect of transforming growth factor-beta on the insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes.

Transforming growth factor-beta (TGF-beta) and insulin-like growth factor-I (IGF-I) are essential anabolic factors in articular cartilage. In this study, we concentrated on the elucidation of TGF-beta interaction with IGF-I on cell growth and differentiation in monolayer articular chondrocytes obtained from 5-week-old rats. TGF-beta (1 ng/ml) and IGF-I (25 ng/ml) stimulated DNA synthesis about 6.5- and 2.1-fold over control values, respectively. When TGF-beta and IGF-I were added in combination, DNA synthesis was enhanced about 10.4-fold, indicating that the two peptides act in synergism. This synergistic action was also present in the expression of aggrecan mRNA. To study the mechanism of synergistic action, the effect of TGF-beta on the IGF-I autocrine/paracrine axis was investigated. Administration of increasing concentrations of TGF-beta (0.1-10 ng/ml) resulted in a dose-dependent decrease in medium IGF-I concentration that was reflected by decreased levels of IGF-I mRNA. TGF-beta also inhibited the production of a 41-kDa IGF-binding protein into the culture medium. Pretreatment with TGF-beta (1 ng/ml) for 12 h increased the binding of [125I]IGF-I to 140% of control by increasing the number of receptors without changes of affinity. Immunoprecipitation against phosphorylated tyrosine indicated that IGF-I-dependent autophosphorylation of IGF-I receptor beta-subunit was inhibited by simultaneous TGF-beta stimulation. These observations demonstrate that TGF-beta acts synergistically with IGF-I and regulates the IGF-I autocrine/paracrine axis via a complex regulatory mechanism with decreased production of IGF-I and IGFBPs and dephosphorylation of IGF-I receptor, whereas there is an apparent up-regulation of the binding of [125I]IGF-I.

Aggrecans↗

Effects of prophylactic intrathecal administrations of nicardipine on vasospasm in patients with severe aneurysmal subarachnoid haemorrhage.

Calcium antagonists are currently most widely used for chronic cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). However, the vasodilatory effects of systemically administered calcium antagonists can be limited secondary to hypotension. We previously compared intrathecal and intravenous routes of administration of nicardipine. Intrathecal administration of nicardipine significantly dilated spastic basilar arteries on day 7 in a two-haemorrhage canine model of vasospasm. In the present communication, the effects of prophylactic, serial administration of intrathecal nicardipine on vasospasm was examined in 50 patients. Patients were classified as Fisher SAH group 3 and all had their aneurysms clipped within 3 days of SAH. Following placement of a cisternal drain, 2 mg of nicardipine was injected, three times each day for an average of 10 days. The control group consisted of 91 similar patients with cisternal drainage not treated with nicardipine. Intrathecal administration of nicardipine decreased the incidence of symptomatic vasospasm by 26%, angiographic vasospasm by 20% and increased good clinical outcome at one month after the haemorrhage by 15%. Postoperative angiograms revealed that patients in the nicardipine group showed less vasospasm of major cerebral arteries, near the tip of a drain in the basal cistern, but vasospasm in the A2 and M2 segments was not decreased. Radio-isotope cisternography suggested that nicardipine might not reach the subarachnoid space around A2 and M2 segments. Nine patients complained of headache probably secondary to nicardipine induced vasodilation. Two patients suffered from meningitis, both were successfully treated. Intrathecal administration nicardipine appears to be effective in the treatment of vasospasm, but side effects were significant.

Adult↗

Molecular cloning and characterization of a cDNA showing tumor-suppressive activity in V-SRC-transformed 3Y1 rat fibroblasts.

Differential screening procedure was employed to isolate new genes specifically down-regulated in RSV-transformed rat 3Y1 cells (SR-3Y1) compared with parental 3Y1 cells. Among those, one clone termed N03 showed nearly complete down-regulation in v-src-, v-mos and SV40-transformed 3Y1 cells. Nucleotide sequence analysis showed that N03 protein is novel and is composed of 178 amino acid residues in length. Introduction of N03 cDNA into SR-3Y1 cells using an expression vector resulted in suppression of transformed phenotypes such as high growth rate, colony-forming ability in soft agar and tumorigenicity in nude mice.

Amino Acid Sequence↗

Induction chemotherapy in advanced head and neck cancer.

Induction chemotherapy, followed by definitive treatment, was performed in patients with advanced squamous-cell carcinoma of the head and neck. In this study, carried out between 1984 and 1991, testing the effectiveness of multimodality therapy in patients with previously untreated advanced (stage III and IV) squamous-cell carcinoma of the pharynx, patients received two different induction chemotherapy regimens: cisplatin, vincristine (Oncovin) plus peplomycin (COP), and cisplatin plus continuous 120-hr 5-fluorouracil (5-FU) infusion (CF) for two courses. Overall response rates (complete response plus partial response) to each of the two induction chemotherapy regimens were high: 76 and 82%, respectively. Superior complete response rate in the group receiving CF therapy was 16% versus 10% for COP therapy. Responders to induction chemotherapy had significantly better survival compared with non-responders. The toxicity of these two regimens was tolerable and manageable. It is indispensable to develop the more efficacious chemotherapy regimen with the potential to induce complete disappearance of tumors in patients with advanced head and neck carcinomas.

Adolescent↗

Growth hormone directly and indirectly stimulates articular chondrocyte cell growth.

Although growth hormone (GH) is known to regulate cartilage growth and differentiation during development, it is still unclear whether the cell growth of articular chondrocytes is stimulated directly by GH or mediated by GH-induced insulin-like growth factor-I (IGF-I). In the present study, we focused on whether GH directly or indirectly stimulates articular chondrocyte proliferation. Monolayer articular chondrocytes from 5-week-old male Sprague-Dawley rats were cultured in Ham's F-12/Dulbecco's modified essential medium supplemented with 10% fetal bovine serum. Stimulation of DNA synthesis by GH was dose-dependent between 0.1 and 1 microg/ml, and the maximum active concentration of GH was 500 ng/ml, which induced a 3.5-fold increase over control values. Anti-IGF-I antiserum neutralized about 80% of GH-induced DNA synthesis. GH stimulated the secretion of IGF-I into the conditioned medium in a dose-responsive manner. To determine whether GH stimulated DNA synthesis directly, we investigated the time-course changes in mRNA expression of IGF-I and the proto-oncogene c-myc. Induction of IGF-I mRNA occurred at 4 h, and reached a maximum level at 12 h, whereas the expression of c-myc mRNA was induced within 4 h, and continued to increase until 72 h after GH treatment. Furthermore, administration of cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both IGF-I and c-myc mRNAs. These results suggest that early induction of c-myc is due to a direct stimulatory effect of GH, and that long-term induction of c-myc was attributable to an indirect effect of GH in which GH-induced secondary proliferative factors may act in an autocrine/paracrine manner. The superinduction of c-myc gene by cycloheximide also indicates that fresh protein synthesis of an intermediate protein was not required for GH-induced c-myc expression. Western ligand blot analysis of IGF-binding proteins revealed that cultured rat articular chondrocytes produced a predominant 41 kDa and a faint 32 kDa form, and that GH significantly stimulated the secretion of the 41 kDa form without affecting expression of the 32 kDa form. Furthermore, a specific IGF-I binding study suggested that the increase in DNA synthesis induced by GH was not associated with changes in affinity or in the number of IGF-I binding sites. These results support the conclusion that the stimulatory effect of GH was mainly mediated by GH-induced IGF-I production in monolayer rat articular chondrocytes. However, it is likely that GH may also have a direct stimulatory effect by inducing c-myc proto-oncogene expression.

Animals↗

Effects of interleukin-1 beta on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes.

OBJECTIVE: To clarify the interaction of tissue destruction and repair of articular cartilage during inflammation, the effects of interleukin-1 beta (IL-1 beta) on the expression of insulin-like growth factor I (IGF-I), its receptor, and its binding proteins were examined. METHODS: Articular chondrocytes from five week rats were cultured in serum free medium treated with IL-1 beta (1-100 U/ml) for 24 hours. The concentration of IGF-1 in the conditioned medium was measured by RIA, and IGFBP were analysed by immunoligand blotting method. IGF-I receptors were also examined by [125I]IGF-I binding study. RESULTS: IL-1 beta induced the secretion of IGF-I and IGF-binding protein in chondrocytes; this was not inhibited by indomethacin (5 micrograms/ml). IL-1 beta also increased the number of IGF-I receptors but had no effect on receptor affinity. IL-1 beta inhibited chondrocyte proliferation, while exogenous IGF-I and growth hormone stimulated chondrocyte cell growth. IL-1 beta did not change IGF-I mRNA levels. CONCLUSION: IL-1 beta up-regulated the IGF-I autocrine/paracrine axis in cultured articular chondrocytes. These observations provide insight into the critical role played by IL-1 beta in tissue destruction and repair, and into the direct interaction between cytokines and growth factors associated with inflammatory arthropathy.

Animals↗