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Biomedical subjects

S Komiyama

Publications and source records attributed to S Komiyama.

At least 55 records · Page 3Linked to original sources

Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy.

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been used since 1972 to treat malignant tumors of the head and neck at Kyushu University. Using nick end labeling of tumor specimens, cells of human maxillary sinus carcinomas were observed previously to undergo apoptosis in response to FAR therapy. The present study evaluated the in vitro effects of FAR therapy on a human maxillary sinus cancer (IMC-4) cell line. We further compared the effects of FAR therapy on this cell line with those effects seen on tissue samples taken from patients with maxillary sinus cancers. DNA electrophoresis and electron microscopic examination of the IMC-4 cells after treatment with FAR therapy revealed typical apoptotic features. The effects of 50-100 micrograms/ml 5-FU, 10(-4) M all-trans-retinoic acid and radiation to 6 Gy on IMC-4 cells were evaluated by trypan blue dye exclusion and a cell colony formation assay. 5-FU and radiation caused direct cell death, while vitamin A mainly inhibited cell growth. The combination of these treatment as FAR therapy synergistically enhanced cell death and inhibited cell growth. Flow cytometry demonstrated that FAR-treated cells were arrested in the G1 phase of the cell cycle before undergoing apoptosis. To further investigate possible biological parameters influencing a tumor's apoptotic sensitivity, we also examined the expression of p53 in human maxillary sinus cancer cells and analyzed the relationship between p53 expression and apoptosis. However, no relationship was found between these two markers at the time point studied.

Antineoplastic Agents↗

Stomal recurrence invading the cervicothoracic esophagus and upper mediastinum: resectability and the creation of a safe anterior mediastinal tracheostoma.

Surgical salvage for stomal recurrence is a for midable problem for head and neck surgeons. The two factors of considerable significance are resectability and establishment of a safe anterior mediastinal tracheostoma. A case of stomal recurrence invading the cervicothoracic esophagus and upper mediastinum is presented. Total esophagectomy and upper mediastinal dissection was performed. The esophagus was reconstructed immediately with a pedicled gastric flap. The omentum on the gastric pedicle was wrapped around the trachea to reduce the likelihood of erosion into the great vessels and to supplement the lateral blood supply to the trachea. No serious postoperative complications were observed. We believe that the total esophagectomy improved the resectability, and that the bulk of the gastric pedicle and the use of the omentum prevented significant postoperative complications associated with an anterior mediastinal tracheostoma.

Anastomosis, Surgical↗

Treatment of cholesteatoma in children.

We studied retrospectively 28 cases of cholesteatoma in children whose ages were 3 to 13 years old. All had undergone surgery between 1989 and 1995. The intact canal wall technique was the predominant method used in the initial operation, with long term goals of an anatomically normal and infection-free ear. Cholesteatoma was found postoperatively in 15 cases and was considered to be residual in 6 cases and recurrent in 9. The residual cholesteatoma was relatively uncommon and usually removable in an exploratory second operation. Our findings showed that the intact canal wall technique was the best initial operation if two-stage surgery was planned. Avoidance of a retraction pocket, which tends to progress to a recurrent cholesteatoma, is important to successful treatment.

Adolescent↗

Cases of cutaneous and nasal CD56 (NCAM)-positive lymphoma in Japan have differences in immunohistology, genotype, and etiology.

CD56 (NCAM)-positive lymphoma frequently involves the skin and nasal area. This study shows it is likely that the clinicopathologic features of this lymphoma are distinctive to each of the primarily involved sites. Sixteen cutaneous and 11 nasal cases of CD56-positive lymphoma were examined. In 10 cutaneous cases, the lesions consisted of pleomorphic large-cell lymphoma that expressed CD3epsilon (CD3), CD2 (LFA2), CD4, CD122 (IL-2B receptor), TIA1, perforin, and granzyme B and displayed angiocentric/angiodestructive features. Lobular panniculitis was found in 8 of these cases, and 6 cases showed other organ involvement. The remaining 6 cutaneous cases consisted mostly of CD3epsilon- and CD4-positive, CD2-, CD122-, and TIA1-negative large blastic lymphoma, having less angiodestruction and panniculitis. Bone marrow invasion and leukemic changes were found in 4 of these cases during the clinical course. All 11 nasal cases showed pleomorphic small and medium-size lymphoma cells with angiodestructive features and were positive for CD3epsilon, CD2, CD122, TIA1, perforin, and granzyme B. CD4-positive lymphoma was found in 4 of these cases. Only 3 nasal cases showed other organ involvement. Genotypically, 2 of the 4 cases examined in the first cutaneous group, 3 of the 4 cases examined in the second cutaneous group, and only 1 of the 11 nasal cases showed rearrangement of the TcRCbeta gene by the Southern blot method. Only 2 cutaneous cases with panniculitis and all 11 nasal cases showed a positive nuclear signal for EBV-encoded RNA (EBERs) by in situ hybridization. Thus, two types of cutaneous CD56-positive lymphoma were found, each having a unique cell characteristic, genotype, and EBV infection pattern that differed from that of nasal-type lymphoma.

Adult↗

Superoxide anion impairs Ca(2+) mobilization in cultured human nasal epithelial cells.

We examined the effects of superoxide anion (O(-2)) on the intracellular Ca(2+) concentration in cultured human nasal epithelial cells. The cells were exposed to O(-2) by pretreatment with xanthine (X) and xanthine oxidase (XO); control cells were treated with X alone. When Ca(2+)-containing Krebs solution was reperfused in the thapsigargin-treated, store-depleted cells, reapplication-induced intracellular Ca(2+) concentration elevation was significantly smaller in X/XO-treated cells than in the control cells, suggesting that O(-2) impairs Ca(2+) release-activated Ca(2+) entry (CRAC). Bath application of ATP induced a steep Ca(2+) transient in both control and X/XO-treated cells. However, the concentration-response curve of the ATP-induced Ca(2+) transient was shifted to a higher concentration in X/XO-treated cells. The impairments of CRAC and ATP-induced Ca(2+) transient induced by X/XO were reversed by superoxide dismutase. Furthermore, all these X/XO-induced effects were also observed in cells pretreated with pyrogallol, also an O(-2) donor. These results indicate that O(-2) impairs at least two mechanisms involved in Ca(2+) mobilization in human nasal epithelial cells, i.e., CRAC and ATP-induced Ca(2+) release.

Adenosine Triphosphate↗

A convenient method for library construction: parallel synthesis of beta-amino ester and quinoline derivatives in liquid phase using Ln(OTf)3-catalyzed three-component reactions

A convenient method for library construction in liquid phase, which is based on lanthanide triflate (Ln(OTf)3)-catalyzed three-component reactions, has been developed. Equimolar amounts of each component, an aldehyde, an amine, and a silyl enol ether or an alkene, react smoothly in the presence of Ln(OTf)3, and the work-up and purification processes are performed by simply passing through a short column. The key is to use Ln(OTf)3 as a Lewis acid catalyst, which is not decomposed during the work-up and purification steps, and is easily separated from products by the simple procedure. According to this method, various high-quality beta-amino ester and quinoline derivatives have been prepared in parallel in large quantities. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

Expression of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment.

BACKGROUND: Recent studies suggest that apoptosis is important in the cell death induced by treatment that damages deoxyribonucleic acid (DNA). We assessed the correlation between the expression of the apoptosis-related proteins, p53 and bcl-2, and the clinical outcome of patients with nasopharyngeal carcinomas (NPCs) who were treated with both DNA-damaging treatments. We also assessed the level of Ki-67, a marker of cell proliferation, in these tumors. METHODS: We evaluated statistically the relationships among the expression of p53, bcl-2, and Ki-67 and clinicopathologic factors, the sensitivity to radiation, the incidence of distant metastases, and survival. RESULTS: The group that was positive for p53 tended to be resistant to radiotherapy and to have a significantly poorer prognosis (p = .05). CONCLUSIONS: The enhanced expression of p53 may be a prognostic factor in patients with NPCs whose tumor is resistant to therapy that damages DNA.

Adult↗

Elevation of intracellular calcium induced by the intrapipette perfusion technique modifies membrane ion currents in the chick cochlear hair cell.

The concentration of intracellular calcium ion ([Ca2+]i) was altered in the same hair cell dissociated from a chick cochlea by the intrapipette perfusion technique. At a membrane potential of -40 mV, the elevation of [Ca2+]i generated outward-going currents within 60 sec when the intrapipette solution was based on KCl. In controls, at membrane potentials more positive than -50 mV, outward K+ currents were observed and at large positive potentials, the outward K+ current decreased, showing an N-shaped I-V relationship. This outward K+ current was increased by elevation of [Ca2+]i and was partially suppressed by a TEA-containing extracellular solution. We suggest that the Ca2+ increased by the intrapipette perfusion technique operates directly inside the cell membrane and activates Ca(2+)-activated K+ currents.

Animals↗

[Cyclin D1 overexpression in laryngeal carcinomas].

Overexpression of cyclin D1 has been found in a variety of malignancies and is suggested to be related to tumor progression. We immunohistochemically investigated the overexpression of cyclin D1 protein in 92 laryngeal carcinomas. Twenty-eight (30.4%) of the carcinoma specimens showed overexpression of cyclin D1. This overexpression was not related to the tumor stage, lymph node metastasis, or clinical outcome. However, the overexpression of cyclin D1 in patients with local recurrence was significantly higher than in patients with no recurrence. Cyclin D1 immunohistochemical staining is considered to be a useful marker for predicting tumor recurrence.

Biomarkers, Tumor↗

[A case of adenoid cystic carcinoma in epipharynx which responded to radiation and chemotherapy].

A 45-year-old man visited our hospital complaining of a right hearing loss. The head and neck examination was unremarkable except for right secretory otitis media. Fiberoptic examination of the nose and the epipharynx revealed a mass. Transnasal biopsy was performed and histologic analysis revealed adenoid cystic carcinoma. Invasion of the sphenoid sinus was identified by MRI. He was treated with FAR therapy (5-FU, Vit A, Radiation) and chemotherapy (intra-arterial infusion of ADM). Severe side effects were not seen during treatment. After treatment, the majority of the tumor mass disappeared on fiberoptic examination and MRI. On repeat biopsy specimens, no cancer cells were found. The patient was alive with no evidence of disease as of August 1997.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of mediastinal teratoma discovered availing of pneumonia].

A 42-year-old woman was admitted to our hospital with hemosputum and an abnormal shadow on chest X-ray. Although her hemosputum disappeared after the treatment of pneumonia, the abnormal shadow was not improved. Chest CT showed a mediastinal mass. She underwent thoracotomy and the tumor, measuring 6 x 5 x 5 cm in size, was resected. Pathological diagnosis was a mature type teratoma with direct invasion to the lung. We have to take mediastinal teratoma into consideration as one of the causes of pneumonia.

Adult↗

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus.

We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Animals↗

p53 and bcl-2 expression and argyrophilic nucleolar organizer regions in patients with malignant maxillary sinus tumours.

To investigate the relation between the clinicopathological findings, and the survival of patients with malignant tumours of the maxillary sinus, and the tumour's biological parameters, we examined the expression of p53 and bcl-2 and the number of silver-stainable nucleolar organizer regions (AgNORs) in 23 paraffin-embedded specimens from primary tumours. Fifteen of 23 (65 per cent) maxillary tumours expressed p53 and two of 23 (nine per cent) tumours expressed the bcl-2 gene product. The mean number of AgNORs per nucleus was 5.2 +/- 2.4. There was no relationship between the expression of p53 or bcl-2 and the patient's clinical course. In contrast, there was a statistically significant difference in the survival of patients with a high (> 6) number of AgNORs and patients with a low (< 6) number of AgNORs. These data suggest that the number of AgNORs may be useful in evaluating the prognosis of patients with malignant maxillary sinus tumours.

Carcinoma, Squamous Cell↗

The highly conserved DAD1 protein involved in apoptosis is required for N-linked glycosylation.

BACKGROUND: The tsBN7 cell line is one of the temperature-sensitive mutants for cell proliferation which have been isolated from the BHK21 cell line derived from the golden hamster. It has a mutation in the DAD1 gene encoding a 12.5kDa highly conserved protein through evolution, and enters apoptosis at the restrictive temperature due to this mutation. RESULTS: DAD1 was recovered in light membrane fractions after differential centrifugation. It could not be released from the membrane, even by carbonate extraction, without a detergent. Upon digestion with proteinase K, both N and C terminal portions-but not the middle portions of DAD1- were released from the membrane. Thus, DAD1 appears to be an integral membrane protein in which both termini are located in the cytosol. DAD1 was localized in the endoplasmic reticulum. In accordance with a similarity to the yeast protein Ost2p, which is a subunit of the oligosaccharyltransferase, at the restrictive temperature, loss of DAD1 function caused a defect of N-linked glycosylation in tsBN7 cells resulting in apoptosis. However, tunicamycin, which is known to inhibit N-linked glycosylation did not induce apoptosis in either tsBN7 or BHK21 cells. CONCLUSION: tsBN7 cells have a defect in N-linked glycosylation caused by the loss of DAD1.

Animals↗

All-trans-retinoic acid-dependent inhibition of E-cadherin-based cell adhesion with concomitant dephosphorylation of beta-catenin in metastatic human renal carcinoma cells.

We previously described an in vitro invasion assay model, using a monolayer of vascular endothelial cells grown on collagen gel, that mimics the metastatic abilities of the highly metastatic human renal carcinoma cell lines, MM-1,3 and 8 and their poorly metastatic counterparts, SN12C and Cl-8. MM-1, 3 and 8 cells were observed to penetrate the monolayer of vascular endothelial cells and grew in a spreading or scattering manner with loose cell-cell contact on collagen gel or on vascular endothelial cells. SN12C and Cl-8 cells failed to penetrate and grew in a clustering manner with tight cell-cell contact. Treatment with all-trans-retinoic acid (ATRA) at non-toxic concentrations induced clustering or growth of MM-1, 3 and 8 cells on collagen gel or on vascular endothelial cells with tight cell-cell contact, and inhibited penetration. The clustering induced by ATRA was virtually blocked in the presence of anti-E cadherin antibody. E-Cadherin and beta-catenin were each localized mainly at the cell-cell adherent junctions of colonizing cell populations that had been treated with ATRA. While the cellular levels of E-cadherin and beta-catenin did not change significantly following ATRA treatment, the tyrosine residue of beta-catenin was rapidly dephosphorylated. The concomitant administration of Na vanadate, an inhibitor of tyrosine dephosphorylase, inhibited both the ATRA-induced clustering and the dephosphorylation of beta-catenin tyrosine. ATRA-induced clustering of MM-3 cells may be linked to the state of tyrosine phosphorylation of beta-catenin.

Adult↗

[Changes in arterial blood pressure and hypothalamic neural activity in response to caloric stimulation in guinea pigs].

We investigated the effects of caloric stimulation on arterial blood pressure (AP) and neural activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the labyrinth produced a decrease in AP in 56 of 73 cases tested, and AP decrease followed by increase in 12 cases. In the cases where AP initially decreased and then increased, 92% of PVN neurons responded as excitatory or inhibitory to caloric stimulation. When the AP change was a decrease alone, the responsive rate of the PVN neurons was 63%, and no change in PVN neural activity was seen in the group which showed no AP change after caloric stimulation. The ratio of the PVN neurons showing inhibition in the group that showed AP decrease-increase sequence was significantly higher than that in the group showing AP decrease alone. AP changes following caloric stimulation were greatly reduced after electric destruction of the anterior and middle parts of the hypothalamus. This indicates that the activation of the hypothalamic neurons by the vestibular input is important to produce the vestibulovasomotor response and its pattern. When the same amount of stimulus was applied periodically to the labyrinth, the AP increment component was increased with time. It is suggested that the pattern of AP changes is greatly influenced by level of consciousness. It is suggested that the basal activity level of the autonomic nervous system, and the variety and magnitude of the vestibular stimuli should be synthetically evaluated when the autonomic nerve function test is applied to patients suffering dizziness.

Animals↗

[Quantitative analysis of the gustatory evoked potentials in the guinea pig].

Gustatory evoked potentials were studied in anesthetized guinea pigs to develop an objective and quantitative taste examination for patients with taste disorders. A positive wave was recorded by the application of NaCl, HCl or quinine hydrochloride solution. There was little difference in latency, duration and waveform among these three solutions. No apparent change in activity was seen after the application of sucrose solution or distilled water. The gustatory evoked potentials that excluded the influence of the trigeminal nerve innervating the tongue surface were able to be reproducibly recorded on either the cortical surface or the skull surface. There was a linear relationship between logarithmic values of potential amplitude and those of taste solution concentration. Therefore, it is suspected that the quantitative evaluation of taste detection is possible by measuring the taste solution concentration-potential amplitude relationship.

Animals↗