Synthesis and antitumor activity of cis-dichloroplatinum complexes coordinating nitrogen cyclic or sulfur compounds.
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Animals↗
Biomedical subjects
S Fujieda
Publications and source records attributed to S Fujieda.
Enhancement of cytolytic activity of human peripheral blood lymphocytes by sodium periodate (IO4) possible involvement of protein kinase C.
Sodium periodate (IO4) exerts a number of biological effects including the enhancement of lymphocyte activation. In this study, we investigated its effects on cytotoxicity of human peripheral blood lymphocytes (PBL) and explored the mechanism whereby it exerted these effects. In vitro treatment of human PBL with IO4 augmented their cytotoxicity against K562 myelogenous leukemia cells. IO4 oxidative treatment increased the frequency of effector-to-target cell binding. It also increased cellular ATP levels in effector cells, suggesting that the post-binding cytolytic functions of these cells were also enhanced after treatment with IO4. Moreover, IO4 treatment significantly increased the protein kinase C (PKC) activity of effector cells and induced the translocation of activity in the membrane fraction from the cytosol. H-7, a potent PKC inhibitor, significantly reduced this enhancement of membrane-associated PKC activity at 10 microM and significantly reduced the enhanced cytotoxicity of PBL at the same concentration. These results indicated that IO4 enhanced the binding capacity and post-binding cytolytic functions of PBL and that PKC activation was one mechanism to explain the IO4-induced cellular activation.
Adenosine Triphosphate↗
Platysma myocutaneous flap including the external jugular vein with special reference to neck dissection.
Although platysma myocutaneous flap (PTMCF) is suitable for a small intraoral defect, combination with neck dissection (ND) decreases the viability. Therefore, a version of PTMCF was devised to increase the viability. This version consists of three points: preservation of the external jugular vein (EJV), preservation of the facial artery after skeletonization from the submandibular gland, and a new incision around the flap. This procedure was applied to 21 patients with intraoral cancer. All 21 patients underwent some kind of ND. The average viable area of transferred skin was 80%. This rate was significantly better than that for 46 previous cases using Farr's modification with ND, in which the facial artery was divided. Viability of the flaps was analyzed by the vessels preserved, especially by EJV. ND is not a contraindication with this version.
Humans↗
Numerous transorbital wooden foreign bodies in the sphenoid sinus.
A very rare case of numerous transorbital wooden foreign bodies penetrating into the sphenoid sinus in a 47-year-old male is reported. His right eye was nonreactive to light, and the oculomotor, trochlear and abducens nerves were completely disturbed. Although a minor injury was observed on the inner side of the right eyebrow, the wound was not serious or infectious. Computed tomographic scanning of the orbit and parasinus revealed an isodense linear shadow to muscle and an irregular shadow of the lamina papyracea. However, the findings were difficult to discriminate from an optic canal fracture preoperatively. We detected foreign bodies penetrating the optic nerve rise, which were successfully removed in combination with an endoscopic transethmoidal and transorbital approach. Various and careful imaging examinations are recommended to diagnose and manage paraorbital trauma, when a penetrating wound of the face is observed.
Blindness↗
Antrolithiasis in the frontal sinus.
A very rare case of sinusitis with antrolithiasis in the left frontal sinus of a 63-year-old male patient is reported. Various conservative treatments had no effect on the decrease of his left frontal pain and of postnasal drip. Neither bacteria nor fungus were detected in the discharge. Computed tomographic scanning revealed several high-dense spots in an isodense shadow in the left frontal sinus. At first, endoscopic sinus surgery (ESS) was employed and a stony mass was detected in the nasofrontal duct and sinus. Patency of the nasofrontal duct was insured and a sticky paste and small masses were removed as well as possible. However, the flow of discharge from the frontal duct continued after surgery. We performed a second operation with extranasal approach and additional stones in the sinus were successfully removed. Most cases of antrolithiasis are caused by a foreign body or caseous sinusitis with fungus. The maxillary sinus is the most common site of disease in antrolithiasis. It is unknown why the present case of antrolithiasis was in the frontal sinus. In such cases of antrolithiasis or cases having pastelike contents in the frontal sinuses, we conclude that ESS may be an unsuccessful treatment and a classical surgical approach may be required.
Endoscopy↗
Nasal challenge activates the mucociliary transport system on not only the ipsilateral but also the contralateral side of the nose in patients with perennial allergic rhinitis.
It is controversial whether the mucociliary transport system in the nasal mucosa of persons with allergic rhinitis is upregulated after an allergen challenge in vivo. The aim of this study was to assess the effect of a specific allergen challenge on the mucociliary transport system in allergic rhinitis. We used a challenge of house dust mites or a control substance on one side of the nose of 97 volunteers (54 with allergic rhinitis for house dust mites and 43 without allergies). The mucociliary transport system of the ipsilateral or contralateral side of the nose challenged was evaluated using the saccharin clearance time on the right side of the nose. The saccharin clearance time was significantly shortened after an allergen challenge not only on the ipsilateral (right) side of the nose (from 15.0 +/- 11.6 to 10. 9 +/- 9.2 min, mean +/- SD, p = 0.041) but also on the contralateral (left) side of the nose (from 14.7 +/- 10.1 to 8.1 +/- 7.9 min, p = 0.013) in the allergic group. A reduction of the saccharin clearance time was also seen in the allergic group after a control challenge [ipsilateral (right) challenge: from 13.0 +/- 10.0 to 11.6 +/- 10.6 min, contralateral (left) challenge: from 13.5 +/- 9.0 to 10.2 +/- 10.1 min]. There were no reductions of the saccharin clearance time after an allergen or control challenge in the nonallergic groups. These results suggest that a unilateral nasal challenge accelerates the mucociliary transport system bilaterally in the nose of subjects with a hypersensitivity such as allergic rhinitis.
Adult↗
Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage.
Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661-1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.
Anti-Bacterial Agents↗
Expression of granulocyte colony-stimulating factor receptor and platelet-derived endothelial cell growth factor in oral and oropharyngeal precancerous lesions.
Epithelial hyperplasia and dysplasia have been diagnosed as precancerous lesions and have been discussed in relationship to carcinogenesis. We analyzed the immunohistochemical expression of granulocyte colony-stimulating factor receptor (G-CSFR) and platelet-derived endothelial cell growth factor (PD-ECGF) in oral and oropharynx; 33 samples of normal epithelium, 28 samples of hyperplasia, 16 samples of dysplasia and 58 samples of squamous cell carcinoma. Also, we examined mean vessel density (MVD) by using CD34 staining and proliferating cell nuclear antigen (PCNA) staining. Dysplasia and head and neck Squamous Cell Carcinoma (SCC) exhibited higher G-CSFR expression and MVD than normal or hyperplastic epithelium (p <0.01). In the PD-ECGF staining, significant differences were found between SCC and normal epithelium, hyperplasia and dysplasia (p<0.001). In dysplasia and hyperplasia, PD-ECGF expression was significantly correlated with PCNA expression (r=0.345, p=0.025), however it was not correlated with the MVD. G-CSFR expression was not correlated with either PCNA or MVD. These results suggest that G-CSFR and PD-ECGF might be concerned with different carcinogenesis pathways of the squamous cells in the oral region and that PD-ECGF may be concerned with epithelial proliferation rather than angiogenesis.
Adult↗
Effect of OK-432 on cytotoxic activity in cancer patients without tumor burden.
The present study was designed to determine the optimal therapeutic protocol for OK-432, a streptococcal preparation, and to clarify the kinetics of various immunological parameters following intracutaneous administration of OK-432 in 39 disease-free postoperative patients with early cancer. These patients were randomly divided into 4 groups according to the dose (1KE or 5KE) and the frequency of administration (one or 3 times every other day) of OK-432. NK activity 3-4 days after the first injection increased significantly in patients whose pretreatment baseline activity was below the lower level of normal values (60 LU) in all study groups (P < 0.05). The elevation of post-therapeutic NK activity lasted for 2 weeks in the group of patients given repeated injections. The serum content of cytotoxic activity against L-M cells increased significantly after the injection of OK-432 at doses of more than 5 KE doses (p < 0.05). These findings suggest that repeated injections of OK-432 over a period of a week have important immunotherapeutic results.
Adult↗
Relationship between cellular glutathione level and susceptibility to LAK killing in human pharyngeal carcinoma cell line.
We examined the relationship between cellular glutathione (GSH) level and susceptibility to lymphokine-activated killer (LAK) cell-mediated cytolysis in KB human pharyngeal carcinoma cells. Treatment of KB cells with D,L-buthionine-S,R-sulfoximine (BSO), a gamma-glutamyl cysteine synthetase blocker, resulted in decreased total intracellular GSH levels associated with increased susceptibility to LAK killing. In contrast, treatment with oxothiazolidine-4-carboxylate (OTZ, a precursor of cysteine), which is known to increase cellular GSH level, decreased the susceptibility of KB cells to LAK killing. Both agents had no effects on binding frequency of KB cells to LAK cells. These results suggest that intracellular GSH in tumor cells play a protective role against LAK mediated cytolysis, specially in the post-binding killing phase.
Buthionine Sulfoximine↗
Effects of OK-432 on in vitro secondary responses of the non-adherent cells to IL-2 and OK-432 in cancer patients without tumor burden.
We examined the effect of OK-432 intracutaneous injection on the in vitro responses of non-adherent cells to IL-2 and OK-432, along with changes in lymphocyte subpopulations, in early cancer patients who underwent surgery. We found that 1) repeated injections of OK-432 resulted in an enhancement of LAK activity, the peak of which was seen between 7 and 10 days after the first administration, 2) this augmentation of LAK activity was not associated with changes in lymphocyte subpopulations CD8+ CD11- and CD8+ CD11+ phenotypes, and 3) the cytotoxic activity of lymphocytes stimulated in vitro with OK-432 did not show a definite change in specific pattern after in vitro OK-432 treatment. These findings indicate that repeated injections of OK-432 over a period of a week effectively enhanced LAK activity.
Adult↗
Involvement of intracellular glutathione in induction of apoptosis by cisplatin in a human pharyngeal carcinoma cell line.
We investigated the effect of intracellular glutathione (GSH) levels on apoptosis in KB cells induced by cisplatin (CDDP). The mode of cell death, apoptosis or necrosis, was evaluated by biochemical and morphological criteria. The treatment of KB cells with D,L-buthionine-(S,R)-sulfoximine (BSO, a gamma-glutamyl cysteine synthetase inhibitor) decreased GSH level to 1/7th of that of control cells, and augmented cell death induced by CDDP via a necrotic rather than apoptotic process (the ratio of necrosis to apoptosis; n/a>14). In contrast, treatment with 2-oxothiazolidine-4-carboxylic acid (OTZ, a precursor of cysteine) increased GSH levels 1.7 fold compared with that of untreated cells, inhibited cell death induced by CDDP and switched the mode of cell death from necrosis to apoptosis (n/a<0.8, similar to untreated cells). These results suggest that the GSH level affects the cytotoxicity of CDDP and plays an important role in switching the mode of cell death induced by CDDP.
Antimetabolites, Antineoplastic↗