Biomedical subjects
Publications and source records attributed to S Nakabayashi.
Photoluminescence spectroscopy studies have been performed on self-assembled monolayers (SAMs) on Au(111) of thiophene oligomers with the number of thiophen rings N=3 and N=4. Photoluminescence spectra of SAMs reveal excitonic behavior with different band resolution and temperature dependence. These differences are attributed to different SAMs structure (degree of ordering).
PURPOSE: Previously, we suggested that alkylglucoside can be an effective vector for renal-specific drug delivery (Suzuki et al., J. Pharmacol. Exp. Ther, 288:57-61, 1999). The purpose of the present study is to characterize the membrane protein which is recognized by this alkylglucoside. METHODS: The binding of [125I] tyrosine conjugated with a octylthioglucoside (Glc-S-C8-[125I]Tyr) Glc-S-C8-[125I]Tyr to crude membrane fractions of kidney was determined. In addition, the membrane was cross-linked with this alkylglucoside and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: Glc-S-C8-[125I]Tyr was shown to have a specific binding site on the kidney membrane (Kd = 931 nM and Bmax = 987 pmol/mg protein). Cross-linking of the membrane with Glc-S-C8-[125I]Tyr resulted in the detection of a protein (Mr = 62,000), which was unaffected by reducing agents. The results of this cross-linking study were consistent with previous information on its localization and binding characteristics. CONCLUSIONS: The kidney membrane protein, to which alkylglucoside binds in a specific manner, has a molecular weight of 62,000. Crosslinking is a useful tool for detecting this novel membrane protein in kidney.
PURPOSE: We have previously shown Glc-S-C7-Me (octyl beta-D-thioglucoside) exhibits renal targeting potential in vivo in addition to its specific binding to the renal membrane fraction in vitro. Thus, "alkylglycoside" is considered to be a novel targeting vector for the kidney (1,2). The present study is designed to clarify the structural requirements for alkylglycoside as a renal targeting vector. METHODS: Inhibitory effects of various sugars and glycosides on 3H-Glc-S-C7-Me binding to the kidney membrane fraction were evaluated by a centrifugation method. RESULTS: As far as the sugar moiety is concerned, no other sugars except D-aldohexose and D-aldohexose derivatives (containing F, S, and N) showed greater inhibition than D-glucose. Therefore, octylthio derivatives of various D-aldohexose were prepared and their inhibitory effects were investigated. The following findings were obtained: Equatorial OH at 4 position is essential; OH at 2 position can have either orientation or be deleted. As far as the alkyl moiety is concerned, the length, branching and electrical environment in the region of the glycoside bond are important; aromatic structures can substitute for the alkyl portion; the preferred glycoside bonding atom is as follows: S > NH > O. CONCLUSIONS: The structural requirements for the renal targeting vector have been identified to be as follows: a hydrophobic group (alkyl chain or aromatic ring) should be introduced to a sugar (D-glucose, D-mannose, or 2-deoxy-D-glucose) via a beta-glycoside binding atom (S > NH > O).
Hydrodynamic instability analogous to Rayleigh-Bénard convection is observed in an electrolytic solution between two parallel copper wire electrodes. The laser interferometric technique can reveal the dissipation structure created by the motion of the fluid, which is controlled electrochemically. It is shown that under the presence of horizontal magnetic field the roll cells move horizontally along the electrodes. The electrochemically driven convection is simply controlled and monitored by setting and measuring the electrochemical parameters and forms many kinds of spatiotemporal patterns, especially under the magnetic field. The phenomenon is modeled by considering a Boussinesq fluid under a concentration gradient. The stability of the resulting equations is studied by linear stability analysis. The time dependent nonlinear system is investigated numerically and the main features of the experimental response are reproduced.
We evaluated the clinical efficacy of endonasal endoscopic sinus surgery (ESS) in patients with asthma associated with chronic sinusitis. Twenty-one patients (13 men and 8 women) from 27 to 72 years old were enrolled in this study. All patients had had sinus-related symptoms for more than 3 months and had computed tomographic evidence of paranasal sinus opacification. Fifteen patients underwent bilateral endonasal ESS under local anesthesia, and 6 other patients without surgery were controls. The sinus-related symptoms of the preoperative and postoperative periods were assessed via a questionnaire. The period 6 months prior to surgery was compared with that 6 months postoperatively with regard to peak expiratory flow and total dosage of systemic glucocorticoids. Sinus-related symptoms in the ESS group were significantly improved 6 months postoperatively. The average peak expiratory flow 6 months following surgery was improved in the ESS patients, ranging from 40 to 190 L/min. Seven patients showed a reduction in the need for corticosteroids, whereas 2 patients were unchanged and 2 patients required larger dosages. The remaining 4 patients needed no corticosteroids before or after ESS. No significant changes in sinus-related symptoms or peak expiratory flow were obtained for the control group. Improvement of paranasal sinus disease by successful ESS can alleviate pulmonary dysfunction in asthma associated with chronic sinusitis. We believe that adequate and positive treatment for chronic sinusitis would reduce not only the nasal and sinus-related symptoms evoked by chronic sinusitis, but also some of the signs induced by asthma.
We investigated the relationship between the daily count of pollen scattered, the count of days during the scattering period and the highest temperature during the sugi (Japanese cedar) pollen scattering season from 1983 to 1997, and whether prediction of the count of pollen scattered for the following day is possible. Our studies clearly demonstrated that the count of sugi pollen scattered is small in the early period of the scattering season with some daily variations in amount; this cycle is repeated for several days in the middle period of the season then decreases again in the late period. These findings showed that both the cumulative value of the count of pollen scattered daily and the total count of pollen scattered formed an S-shaped curve when compared with the count of days after the start of the scattering season and the cumulative highest temperature for the season. Predicting the daily count of pollen scattered after the start of the scattering season against the cumulative highest temperature is possible by drawing a regression curve from the S-shaped curve. Also, a regression curve was useful in predicting the total count of pollen scattered during the season from the cumulative count of pollen scattered 10 to 20 days after the start of the scattering season. Using these data, we were able to improve the accuracy for predicting the scattering of sugi pollen.
We present a 73-year-old female with an enlarged mass in the right parotid gland. Fine-needle aspiration cytology suggested pleomorphic adenoma. Diagnostic imaging revealed that the tumour had a well-defined margin arising from the deep lobe of the parotid gland. A total parotidectomy with preservation of the facial nerve was performed. The final histopathological diagnosis including immunohistochemical studies was basal cell adenocarcinoma, which is a recently defined entity and a rare epithelial neoplasm. No sign of local recurrence or metastasis 24 months postoperatively has been observed.
We studied the efficacy of high-dose steroid therapy for severe sudden deafness, and evaluated various factors that affect hearing recovery; i.e., severity of hearing loss, age, presence of vertigo and time to the beginning treatment. Twenty-eight patients with idiopathic sudden sensorineural hearing loss whose hearing levels were 60 dB or more were analyzed. They were given 200 mg of prednisolone per day intravenously according to Stennert's method. Hearing recovery was assessed by the criteria of the Sudden Deafness Research Group of the Japanese Ministry of Health and Welfare. The overall recovery rate and cure rate were 50% and 14%, respectively. Patients whose initial hearing levels were within 90 dB showed a significantly higher cure rate than those with above 90 dB (36% (n = 11) vs 0% (n = 17), p < 0.05). The cure rate was significantly higher in the vertigo (-)-group than in the vertigo (+)-group (40% (n = 10) vs 0% (n = 18), p < 0.02). The cure rate was also higher in patients under 50 years of age who were treated within 7 days after onset than in the others (31% (n = 13) vs 0% (n = 15), p < 0.05). The recovery rate was higher when patients were under 50 years of age (63% vs 33%), treated within 7 days after onset (56% vs 42%), or had an initial hearing level within 90 dB (55% vs 47%); however, the differences were not statistically significant. We conclude that these prognostic factors are important for predicting the hearing recovery of patients with severe sudden deafness who undergo high-dose steroid therapy and, therefore, for determining whether this therapy is indicated.
During the past 2 years, drug-induced interstitial pneumonia was reported in 66 Japanese patients, mainly among chronic hepatitis C patients, undergoing treatment with the Japanese herbal medicine "Sho-saiko-to" (TJ-9). As interstitial pneumonia is also induced by granulocyte colony-stimulating factor (G-CSF), we examined the effects of TJ-9 on G-CSF production in peripheral blood mononuclear cells. In patients with hepatitis B or C, G-CSF production in the absence of any stimulation was significantly lower than healthy controls (p < 0.01). G-CSF production increased along with the increase of TJ-9 levels, and this could induce excessive production of G-CSF in hepatitis C patients, and this may be a cause of interstitial pneumonia.
Endothelial and epithelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. To determine the relationship between recruited leukocytes and adhesion molecules in the paranasal sinus mucosa of nonallergic chronic sinusitis, we surgically obtained mucosa from 16 patients and identified the expression of intercellular adhesion molecules (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin by immunohistochemistry. Neutrophils were significantly dominant in the nasal discharge as compared with eosinophils. The degree of neutrophil infiltration in the paranasal sinus mucosa was prominent in both intraepithelial and subepithelial areas as compared with the lamina propria. In each tissue site, the degree of infiltration of neutrophils was similar to that of eosinophils. These findings suggest that the tissue neutrophils actively and rapidly migrated into the lumen. All the adhesion molecules except VCAM-1 were expressed in the vascular endothelial cells. On the other hand, the surface epithelial cells showed the expression of only ICAM-1. The expression of ICAM-1 on the endothelial cells correlated with the degree of neutrophil infiltration in the mucosa The eosinophil infiltration was not dependent on any adhesion molecules examined here. It was concluded that ICAM-1 expression in the mucosa may be involved in neutrophil recruitment and may contribute to the establishment of the inflammatory cell distribution in the paranasal sinus of nonallergic chronic sinusitis.
A 43-year-old man with a primary leiomyosarcoma of the left sphenoid sinus is presented. To our knowledge, this is an unusual case of leiomyosarcoma, which has never been reported in the literature. Accurate and safe diagnosis was obtained by an endonasal endoscopic approach with minimal tissue invasion.
It is well known that EG2-positive cells, CD68-positive cells and other inflammatory cells significantly increase after antigen provocation in the nasal mucosa of an allergic patient. However, there are few reports of the immunohistological study if the infiltrating cells in nasal lavage fluid are not seen. In this study, the infiltrating cells in nasal mucosa as well as in nasal lavage fluid were immunohistologically examined by means of monoclonal antibodies 30 minutes after the antigen provocation. Seven patients with perennial allergic rhinitis were challenged by an antigen disk placed on one side of the inferior turbinates and each nasal cavity was irrigated separately 30 minutes after the antigen provocation. About seven days later, these patients were operated on and the nasal mucosa was removed 30 minutes after the antigen provocation. No marked change in CD4- and CD8 positive cells in the nasal mucosa and lavage fluid was found after provocation. On cytospin glass slides, there was a slight increase in the number of CD68 (P = 0.1), EG2 (P = 0.09), and neutrophil elastase positive (P = 0.2) cells. A significant increase in EG2-positive cells was also seen in the superficial layer of the lamina propria (P < 0.05) but not in the deep layer. CD22 positive cells were not seen on the cytospin glass slide, whereas many positive cells were observed in the deep layer of the lamina propria. These results indicate that EG2-positive cells participate strongly in the early phase of the allergic response after provocation in spite of the absence of significant changes in CD4- and CD8 positive cells. Immunohistological evaluation of nasal lavage is thought to be beneficial concerning the movement of each kind of cells. Each kind of cell is thought to fulfill the main physiological role in the epithelial layer or the lamina propria in early allergic inflammation.
BACKGROUND: The mechanism of neutrophil recruitment in patients with chronic sinusitis is unclear. OBJECTIVE: This study aims to elucidate the role of IL-8 in inducing neutrophil accumulation in the nasal discharge of patients with chronic sinusitis. METHODS: Nasal discharge and mucosal specimens were obtained from two groups of patients, those with chronic sinusitis and those with allergic rhinitis. The samples were subjected to immunohistochemical examination and in situ hybridization. The IL-8 level in the nasal discharge was measured by enzyme immunoassay. RESULTS: Immunoreactivity to IL-8 was observed in polymorphonuclear cells of nasal smear, in nasal gland duct cells, and in epithelial cells of the chronic sinusitis group; whereas those of the allergic rhinitis group mostly showed little or no reaction. Similar patterns of localization were shown by in situ hybridization for IL-8 messenger RNA. The IL-8 level in nasal discharge was significantly higher in the chronic sinusitis group than in the allergic rhinitis group. CONCLUSION: These results suggest that chemotactic factors in sinus effusion, including IL-8 derived from nasal gland duct cells and epithelial cells, attract neutrophils out of mucosa, and the neutrophils that have emigrated into the sinus effusion secrete IL-8. This induces further neutrophil accumulation in the sinus effusion of patients with chronic sinusitis.
It is well known that an initial treatment with several kinds of antiallergic medicines is useful for patients suffering from Japanese cedar pollinosis to reduce nasal symptoms during the pollen season. Also topical corticosteroids show a preventive effect as antiallergic medicines. In this study, the preventive effect of topical corticosteroids with antiallergic medicine as an initial treatment was evaluated during the 1995 cedar pollen season a season in which a high pollen count was anticipated. Twenty-five patients with cedar pollinosis were selected and divided into two groups. A and B, A topical corticosteroid (fluticasone propionate; Flunase) as well as antiallergic medicine (azelastin) were administered to patients in group A 4 weeks before the beginning of the pollen season. In group B, only antiallergic medicine was given at the same time as group A and a topical corticosteroid was administered after the appearance of the symptoms. Nasal symptoms and mucosal conditions of the nasal cavity were monitored throughout the pollen season. The inflammatory cells in the mucoepithelial layer of the nasal mucosa were also periodically evaluated by immunohistochemical staining. Nasal symptoms and mucosal conditions in group A were significantly improved compared with patients in group B. The infiltration of macrophages in the mucoepithelial layer of the nasal mucosa was strongly inhibited in group A. The numbers of mast cells and EG2-positive cells in group A were not significantly different from those in group B during the pollen season. According to these results, although not all inflammatory cells were inhibited, the initial treatment with Flunase aqueous nasal spray in addition to the conventional initial treatment with antiallergic medicine is very useful for reducing symptoms even in a season with a large amount of cedar pollen.
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Substituted (cyclopentenopyridinium)thiomethyl groups were introduced as C-3 substituents of (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-oxyimino]acetami docephalosporins. Structure-activity relationships of this class of cephalosporins are discussed on the basis of their MIC. The selected compounds, 3a and 4a (ME1221), having an acidic substituent, showed excellent in vivo efficacy and low toxicity.
A series of new aminothiazolylglycylcephalosporins with a mono- or dihydroxypyridonecarbonyl group at the alpha-amino group of the C-7 substituent have been prepared and antibacterial activity of these compounds was investigated. Among them, the compounds having a 1,5-dihydroxy-4-pyridone-2-carbonyl group showed excellent anti-pseudomonal activity. In particular, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4- pyridone-2-carboxamido)- acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4-yl]thiomethyl]ceph-3 -em- 4-carboxylate (MT0703, 7g) was found to be a well balanced compound with respect to antibacterial activity.